Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Auranen A, Powell MA, Sukhin V, Landrum LM, Ronzino G, Buscema J, Bauerschlag D, Lalisang R, Bender D, Gilbert L, Armstrong A, Safra T, Nevadunsky N, Sebastianelli A, Slomovitz B, Ring K, Coleman R, Podzielinski I, Stuckey A, Teneriello M, Gill S, Pothuri B, Willmott L, Sharma S, Dabrowski C, Antony G, Stevens S, Mirza MR, Fleming E.

Ther Adv Med Oncol. 2024 Sep 28;16:17588359241277656. doi: 10.1177/17588359241277656. PMID: 39346117; PMCID: PMC11439170.

• In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

• RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.

Methods: Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.

Results: The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.

Conclusion: The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.

Trial registration: NCT03981796.

For a full text of the article, click here: https://journals.sagepub.com/doi/10.1177/17588359241277656

Opportunities to optimize patient experience in the in vitro fertilization (IVF) clinic and the role of genetic counselors.

Chanouha N, Thoeny R, Summers K, Zorn A, Duran H, Schaa K.

J Assist Reprod Genet. 2024 Nov 15. doi: 10.1007/s10815-024-03313-4. Epub ahead of print. PMID: 39543059.

• To understand factors influencing patient satisfaction with genetics education and psychosocial support in an IVF clinic without a genetic counselor (GC), and how the role of a GC may fill gaps in care using a mixed-method cross-sectional study.
• Previous IVF patients (n = 133) completed a survey assessing satisfaction with genetics education and psychosocial support and decisional conflict about genetic testing. Kruskal-Wallis tests were used to compare satisfaction level to demographic and clinical variables. Spearman's correlation was used to analyze decisional conflict. Focus groups with 12 total participants expanded on themes identified in survey responses. Thematic analysis was performed using interpretive description.

Results: Participants reported satisfaction with their genetics education experience (78.9% somewhat or extremely satisfied). Satisfaction with genetics education was associated with satisfaction with information received about genetic testing results (H = 21.3, p < 0.01) and confidence using results in future decisions (H = 9.9, p < 0.01). Participants desired thorough pre-test and post-test counseling regarding genetic testing and directive guidance. Decision conflict about genetic testing was low (mean of 22.3, range 0-100). Satisfaction with genetics education was inversely correlated with decisional conflict (rs = - 0.42, p < 0.05). In-person GC visit scored highest among proposed education methods (mean score of 84.1).

• Patients felt satisfied with genetics education and psychosocial support provided by clinical providers. Gaps in care included misconceptions regarding genetic testing, a desire for more thorough counseling about genetic testing options, more directive guidance, and increased psychosocial support through external sources such as support groups.

For a full text of the article, click here: https://link.springer.com/article/10.1007/s10815-024-03313-4

Depression in the time of COVID-19: Examination of prenatal and postpartum depression, rurality, and the impact of COVID-19.

Blocklinger KL, Gumusoglu SB, Kenney AS, Faudel AJ, Faro E, Brandt DS, Knosp B, Davis HA, Hunter SK, Santillan MK, Santillan DA.

J Affect Disord. 2024 Oct 28;370:337-347. doi: 10.1016/j.jad.2024.10.081. Epub ahead of print. PMID: 39490676.

• To determine the impact of the COVID-19 pandemic on prenatal and postpartum depressive symptoms in rural versus urban populations.
• A retrospective cohort study was conducted among 24,227 cisgender women who gave birth from 2010 to 2021 at an academic medical center located in a rural midwestern state. Exclusion criteria were <18 years old, incarcerated, or without a documented zip code. The Patient Health Questionnaire-9 (PHQ-9) was administered during pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) during postpartum. A sub-cohort also completed a COVID-related questionnaire. Rurality was defined as living in a county with <50,000 people. The COVID-19 era was defined as 1/1/2020 to 9/25/2021. Chi-square and Fisher exact tests were used as appropriate. Significance was set at α < 0.05.

Results: Rural participants were more likely (p ≤ 0.001) to exhibit clinical depression symptoms before the pandemic in both the prenatal (8.63 % of rural participants vs. 6.49 % of urban participants) and postpartum periods (11.19 % rural vs. 9.28 % urban). During the pandemic, urban participants had increased postpartum depression. Rural participants endorsed more financial and labor concerns, whereas urban participants expressed support system concerns.

Limitations: Study data were gathered from participants who gave birth at a single, midwestern hospital. Results may not be widely generalizable given the homogeneity of participants.

Conclusions: Rural women experienced higher rates of prenatal and postpartum depressive symptoms compared to their urban counterparts. The COVID-19 pandemic was a significant stressor, revealing specific mental health vulnerabilities among birthing people.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0165032724017762?via%3Dihub

Pembrolizumab-induced cytokine release syndrome with severe encephalopathy in the setting of clear cell vaginal carcinoma: A case report.

Metzger S, Ulmer K, Hill EK.

Gynecol Oncol Rep. 2024 Oct 11;56:101529. doi: 10.1016/j.gore.2024.101529. PMID: 39494393; PMCID: PMC11530849.

•Pembrolizumab is increasingly used in the treatment of gynecologic cancers and has a half-life of 26 days.

• Cytokine release syndrome with severe encephalopathy is a rare immune-mediated adverse effect.

•Supportive care remains an important part of treatment of immune-mediated toxicity. It takes 5 half-lives to clear Pembrolizumab from the body.

For a full text of the article, click here: https://pmc.ncbi.nlm.nih.gov/articles/PMC11530849/

Should We Rescue Clubbed Fallopian Tubes?

Kroeger MG, Kresowik JD.

Fertil Steril. 2024 Oct 30:S0015-0282(24)02341-0. doi: 10.1016/j.fertnstert.2024.10.039. Epub ahead of print. PMID: 39486502.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0015028224023410?via%3Dihub

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005.

Lee JM, Brady MF, Miller A, Moore RG, MacKay H, McNally L, Lea J, Street D, Lheureux S, McDonald ME, Duska LR, Cantuaria G, Kavecansky J, Leath CA 3rd, Powell M, Cadungog MG, Rose PG, Kim YM, Huang HQ, Provencher M, Wenzel LB, Bookman MA, Kohn EC, Secord AA

J Clin Oncol. 2024 Oct 3:JCO2400683. doi: 10.1200/JCO.24.00683. Epub ahead of print. PMID: 39361946.

• We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC).

Patients and methods: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes.

• Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725).

Conclusion: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

For a full text of the article, click here: https://ascopubs.org/doi/pdf/10.1200%2FJCO.24.00683

Regulator of G-Protein Signaling 2 Knockout in CD4+ T Cells Promotes Anti-Inflammatory T Cells, Enhancing Ovulation, and Oocyte Yield.

Raff M, Benton T, Brummond D, Kovach D, Bunton O, Janky E, Duran EH, Scroggins DG, Gray G, Scroggins SM.

bioRxiv [Preprint]. 2024 Oct 18:2024.10.15.618561. doi: 10.1101/2024.10.15.618561. PMID: 39464145; PMCID: PMC11507868.

Objective: To determine the downstream effects on ovarian function and immune cell differentiation in the ovary and uterus using a model in which RGS2 was knocked out specifically in CD4+ T cells.

Design: Laboratory based experiments with female mice.

• Female congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout.
• Four-week-old female CD4 RGS2 knockout (CD4 RGS2 KO ) mice and their littermate controls (CD4 RGS2 CTL ) were subjected to superovulation using pregnant mare serum gonadotropins.

Main outcome measures: Oocyte numbers, lymphocyte populations in the ovary and uterus, and serum estradiol and progesterone concentrations.

• In non-congenic (mixed strain) mice, CD4 RGS2 knockout (KO) promoted higher oocyte ovulation and increased uterine total leukocyte numbers. Similarly, congenic (fully backcrossed strain) mice showed higher oocyte numbers and increased uterine total leukocytes in the CD4 RGS2 KO mice compared to CD4 RGS2 CTL mice. Pro-inflammatory CD4+ T helper (T H ) 1 and T H 17 cell frequencies in the ovary and uterus were unchanged, while Treg and T H 2 cell frequencies were elevated, along with increased concentrations of estradiol and progesterone in the serum of CD4 RGS2 KO mice.

Conclusion: Our study highlights the important role of RGS2 in CD4+ T cells within the context of reproduction. The dysregulation of immune responses due to RGS2 knockout in CD4+ T cells appears to enhance oocyte production. Further research is warranted to elucidate the precise mechanisms by which RGS2 influences reproductive outcomes, including its impact on fecundability, endometrial receptivity, and successful implantation.

For a full text of the article, click here: https://www.biorxiv.org/content/10.1101/2024.10.15.618561v1

Load-dependent mechanisms contribute to increased aortic stiffness among women with a history of preeclampsia: relation with cardiovagal baroreflex sensitivity.

Davis KG, Armstrong MK, Nuckols VR, Smith MN, Pewowaruk R, Gimblet CJ, Santillan DA, Santillan MK, Pierce GL.

Am J Physiol Heart Circ Physiol. 2024 Dec 1;327(6):H1406-H1412. doi: 10.1152/ajpheart.00556.2024. Epub 2024 Oct 18. PMID: 39423036.

Preeclampsia, a hypertensive disorder of pregnancy, results in increased lifetime cardiovascular disease (CVD) risk. Total aortic stiffness, a robust risk factor for CVD, is composed of load-dependent (blood pressure load on arterial wall) and structural (intrinsic changes in arterial wall) mechanisms. Total aortic stiffness is also associated with reduced cardiovagal baroreflex sensitivity (BRS). We sought to determine 1) whether elevated total aortic stiffness among women with a history of preeclampsia (hxPE) is attributed to load-dependent or structural stiffness, and 2) whether either mechanism is associated with lower BRS. Total aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal BRS (sequence technique) were measured among women 1-5 yr postpartum (n = 115; age 34 ± 4 yr; hxPE n = 51; controls n = 64). Structural aortic stiffness was calculated from participant-specific exponential models by standardizing aortic stiffness to a "reference" blood pressure. Load-dependent stiffness was calculated as total minus structural stiffness. Total [+0.8 m/s, 95% confidence interval (CI) (-0.99, -0.23), P = 0.002] and load-dependent [+0.4 m/s, 95% CI (-0.56, -0.22), P < 0.001], but not structural [95% CI (-0.52, 0.08), P = 0.16] aortic stiffness were higher among women with a hxPE compared with controls. Women with a hxPE had lower BRS (P = 0.042) that was negatively associated with total [B = -3.24 ms/mmHg, 95% CI (-6.35, -0.13), P = 0.042] and load-dependent [B = -5.91 ms/mmHg, 95% CI (-11.31, -0.51), P = 0.033] aortic stiffness. Load-dependent, not structural, aortic stiffness mechanisms contribute to higher total aortic stiffness among women with a hxPE and are associated with lower cardiovagal BRS. Postpartum monitoring for high BP is critical to reduce increased CVD risk after preeclampsia.NEW & NOTEWORTHY The novel finding is that load-dependent stiffness, not structural stiffness, is the primary mechanism of aortic stiffness, and is associated with reduced baroreflex sensitivity in women with a history of preeclampsia. These findings may help tailor high blood pressure prevention and management strategies in this population to prevent structural aortic stiffening, altered baroreflex control, and increased lifetime cardiovascular disease (CVD) risk.

For a full text of the article, click here: https://journals.physiology.org/doi/full/10.1152/ajpheart.00556.2024

Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Fertil Steril. 2024 Oct 8:S0015-0282(24)02004-1. doi: 10.1016/j.fertnstert.2024.08.351. Epub ahead of print. PMID: 39387775.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0015028224020041?via%3Dihub

Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Am J Obstet Gynecol MFM. 2024 Oct 7:101481. doi: 10.1016/j.ajogmf.2024.101481. Epub ahead of print. PMID: 39393968.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2589933324002076?via%3Dihub

Trustworthiness Criteria for Meta-Analyses of Randomized Controlled Studies: OBGYN Journal Guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Gynecol Obstet Invest. 2024 Oct 3:1-5. doi: 10.1159/000541479. Epub ahead of print. PMID: 39362189.

For a full text of the article, click here: https://karger.com/goi/article/doi/10.1159/000541479/914242/Trustworthiness-Criteria-for-Meta-Analyses-of

Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

BJOG. 2024 Oct 2. doi: 10.1111/1471-0528.17945. Epub ahead of print. PMID: 39356178.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17945

Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Ultrasound Obstet Gynecol. 2024 Oct 2. doi: 10.1002/uog.29118. Epub ahead of print. PMID: 39356156.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.29118

Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN Journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Int J Gynaecol Obstet. 2024 Nov;167(2):475-478. doi: 10.1002/ijgo.15885. Epub 2024 Oct 2. PMID: 39356118.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.15885

Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN Journal guidelines.

OBGYN Editors' Integrity Group (OGEIG); Berghella V.  Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Acta Obstet Gynecol Scand. 2024 Nov;103(11):2118-2121. doi: 10.1111/aogs.14942. Epub 2024 Sep 22. PMID: 39306746; PMCID: PMC11502421.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.14942

ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic.

Streeter J, Persaud L, Gao J, Manika D, Fairman W, García-Peña LM, Marti A, Manika C, Gaddi S, Schickling B, Pereira RO, Abel ED.

Front Endocrinol (Lausanne). 2024 Sep 24;15:1325286. doi: 10.3389/fendo.2024.1325286. PMID: 39381436; PMCID: PMC11458430.

Introduction: Reducing Optic Atrophy 1 (OPA1) expression in skeletal muscle in male mice induces Activation Transcription Factor 4 (ATF4) and the integrated stress response (ISR). Additionally, skeletal muscle secretion of Fibroblast Growth Factor 21 (FGF21) is increased, which mediates metabolic adaptations including resistance to diet-induced obesity (DIO) and glucose intolerance in these mice. Although FGF21 induction in this model can be reversed with pharmacological attenuation of ER stress, it remains to be determined if ATF4 is responsible for FGF21 induction and its metabolic benefits in this model.

• We generated mice with homozygous floxed Opa1 and Atf4 alleles and a tamoxifen-inducible Cre transgene controlled by the human skeletal actin promoter to enable simultaneous depletion of OPA1 and ATF4 in skeletal muscle (mAO DKO). Mice were fed high fat (HFD) or control diet and evaluated for ISR activation, body mass, fat mass, glucose tolerance, insulin tolerance and circulating concentrations of FGF21 and growth differentiation factor 15 (GDF15).
• In mAO DKO mice, ATF4 induction is absent. Other indices of ISR activation, including XBP1s, ATF6, and CHOP were induced in mAO DKO males, but not in mOPA1 or mAO DKO females. Resistance to diet-induced obesity was not reversed in mAO DKO mice of both sexes. Circulating FGF21 and GDF15 illustrated sexually dimorphic patterns. Loss of OPA1 in skeletal muscle increases circulating FGF21 in mOPA1 males, but not in mOPA1 females. Additional loss of ATF4 decreased circulating FGF21 in mAO DKO male mice, but increased circulating FGF21 in female mAO DKO mice. Conversely, circulating GDF15 was increased in mAO DKO males and mOPA1 females, but not in mAO DKO females.
• Sex differences exist in the transcriptional outputs of the ISR following OPA deletion in skeletal muscle. Deletion of ATF4 in male and female OPA1 KO mice does not reverse the resistance to DIO. Induction of circulating FGF21 is ATF4 dependent in males, whereas induction of circulating GDF15 is ATF4 dependent in females. Elevated GDF15 in males and FGF21 in females could reflect activation by other transcriptional outputs of the ISR, that maintain mitokine-dependent metabolic protection in an ATF4-independent manner.

For a full text of the article, click here: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1325286/full

AptamerRunner: An accessible aptamer structure prediction and clustering algorithm for visualization of selected aptamers.

Ruiz-Ciancio D, Veeramani S, Singh R, Embree E, Ortman C, Thiel KW, Thiel WH.

Mol Ther Nucleic Acids. 2024 Oct 9;35(4):102358. doi: 10.1016/j.omtn.2024.102358. PMID: 39507401; PMCID: PMC11539416.

Aptamers are short single-stranded DNA or RNA molecules with high affinity and specificity for targets and are generated using the iterative systematic evolution of ligands by exponential enrichment (SELEX) process. Next-generation sequencing (NGS) revolutionized aptamer selections by allowing a more comprehensive analysis of SELEX-enriched aptamers as compared to Sanger sequencing. The current challenge with aptamer NGS datasets is identifying a diverse cohort of candidate aptamers with the highest likelihood of successful experimental validation. Here we present AptamerRunner, an aptamer sequence and/or structure clustering algorithm that synergistically integrates computational analysis with visualization and expertise-directed decision making. The visual integration of networked aptamers with ranking data, such as fold enrichment or scoring algorithm results, represents a significant advancement over existing clustering tools by providing a natural context to depict groups of aptamers from which ranked or scored candidates can be chosen for experimental validation. The inherent flexibility, user-friendly design, and prospects for future enhancements with AptamerRunner have broad-reaching implications for aptamer researchers across a wide range of disciplines.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2162253124002452?via%3Dihub

Initially categorized 46,XY embryo transfer ending with 45,X products of conception-a case report and a review of discordant result management.

Singh P, Snider A, Kayali R, Mancuso A.

F S Rep. 2024 May 22;5(3):328-332. doi: 10.1016/j.xfre.2024.05.006. PMID: 39381658; PMCID: PMC11456636.

• : To report a case of an initially categorized euploid male embryo screened using preimplantation genetic testing (PGT) resulting in miscarriage and testing of products of conception consistent with Turner syndrome, and to discuss additional workup and considerations in cases of discrepancy.
• : Case report.

Setting: University fertility clinic.

• Frozen single embryo transfer of a euploid male embryo.
• A couple seeking procreative management for a female partner having a balanced translocation 46,XX,t(14;16)(q21;q21) diagnosed after the couple's previous child passed because of segmental duplication in chromosomes 14 and 16 and pursued in vitro fertilization treatment for PGT for structural rearrangements.

Main outcome measures: Miscarriage with discordant chromosomal microarray result.

• Couple conceived with the transfer of a euploid male embryo. After the initial confirmation of pregnancy, repeat imaging indicated a missed abortion. Dilation and curettage were performed, and the products of conception were sent for chromosomal microarray. Results indicated Turner syndrome (45,X). Follow-up short tandem repeat analysis confirmed the products of conception were from the tested embryo. After reevaluation of the data, copy number variations below the reporting threshold for the sex chromosomes were observable and compatible with mosaic 45,X/46,XY.
• The limitations of PGT should be kept in mind when counseling patients because of both the sample provided by biopsy, the sequencing platforms and the laboratory pipeline for diagnosis. We recommend that patients be counseled about these limitations and offered antenatal and postnatal testing as indicated. When discrepancies are seen after PGT, collaboration with the reference laboratory and additional testing with short tandem repeat analysis should be considered when possible.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2666334124000576?via%3Dihub

Intracytoplasmic sperm injection versus conventional in vitro fertilization in unexplained infertility.

Iwamoto A, Summers KM, Sparks A, Mancuso AC

F S Rep. 2024 Jun 19;5(3):263-271. doi: 10.1016/j.xfre.2024.06.003. PMID: 39381653; PMCID: PMC11456666.

• To compare cumulative live birth rate (CLBR) and cost-effectiveness of intracytoplasmic sperm injection (ICSI) vs. conventional in vitro fertilization (cIVF).

Design: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System.

• Society for Assisted Reproductive Technology (SART) member IVF clinics in the United States.
• Patients with unexplained infertility who underwent first autologous retrieval cycles between January 2017 and December 2019 with linked fresh and frozen embryo transfers through December 2021.
• : ICSI vs. cIVF.

Main outcome measures: The primary outcome was CLBR, defined as ≤1 live birth from a retrieval cycle and all linked embryo transfers. Secondary outcomes included two pronuclear (2PN) per oocyte retrieved, miscarriage rate, and total number of transferred or frozen embryos per 2PN. Subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A) were analyzed. Outcomes were adjusted for age, body mass index, number of oocytes retrieved, length of follow-up, and clinic ICSI use rate.

Results: A total of 18,805 patients with unexplained infertility were included. No difference in CLBR was found among cycles without genetic testing (54.4% ICSI vs. 57.5% cIVF) and with PGT-A (47.6% ICSI vs. 51.8% cIVF). Intracytoplasmic sperm injection cycles without genetic testing had a higher miscarriage rate (16.4% vs. 14.4%) but no difference was seen in cycles with PGT-A (13.9% ICSI vs. 13.2% cIVF). Intracytoplasmic sperm injection cycles had a significantly lower ratio of 2PN per oocyte retrieved without genetic testing (59.7% vs. 60.9%) and with PGT-A (63.3% vs. 65.8%). The ratio of embryos transferred or frozen per 2PN was not significantly different in cycles without genetic testing (49.4% vs. 49.6%) or with PGT-A (54.2% vs. 55.2%). Total fertilization failure occurred in 216 patients (4%) who underwent cIVF and in 153 patients (1.1%) who used ICSI.Compared with cIVF alone, an estimated additional $11,011,500 was charged to patients for ICSI without genetic testing and $9,010,500 was charged to patients for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics. On the basis of total fertilization failure rates, 35 patients would require treatment with routine ICSI to avoid a single cycle of total fertilization failure with cIVF.

• Routine use of ICSI in unexplained infertility is not warranted due to the additional cost and lack of CLBR benefit.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2666334124000746?via%3Dihub

To see or not to see? That is the miscarriage management question.

Salari S, Lindheim SR.

Fertil Steril. 2024 Sep 18:S0015-0282(24)02234-9. doi: 10.1016/j.fertnstert.2024.09.021. Epub ahead of print. PMID: 39299568.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0015028224022349?via%3Dihub

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy

Metz TD, Reeder HT, Clifton RG, Flaherman V, Aragon LV, Baucom LC, Beamon CJ, Braverman A, Brown J, Cao T, Chang A, Costantine MM, Dionne JA, Gibson KS, Gross RS, Guerreros E, Habli M, Hadlock J, Han J, Hess R, Hillier L, Hoffman MC, Hoffman MK, Hughes BL, Jia X, Kale M, Katz SD, Laleau V, Mallett G, Mehari A, Mendez-Figueroa H, McComsey GA, Monteiro J, Monzon V, Okumura MJ, Pant D, Pacheco LD, Palatnik A, Palomares KTS, Parry S, Pettker CM, Plunkett BA, Poppas A, Ramsey P, Reddy UM, Rouse DJ, Saade GR, Sandoval GJ, Sciurba F, Simhan HN, Skupski DW, Sowles A, Thorp JM Jr, Tita ATN, Wiegand S, Weiner SJ, Yee LM, Horwitz LI, Foulkes AS, Jacoby V; NIH Researching COVID to Enhance Recovery (RECOVER) Consortium*.

Obstet Gynecol. 2024 Sep 1;144(3):411-420. doi: 10.1097/AOG.0000000000005670. Epub 2024 Jul 11. PMID: 38991216; PMCID: PMC11326967.

• To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors.
• In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC , defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC.

Results: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC.

Conclusion: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy.

Clinical trial registration: ClinicalTrials.gov , NCT05172024.

For a full text of the article, click here: https://journals.lww.com/greenjournal/fulltext/2024/09000/post_acute_sequelae_of_severe_acute_respiratory.15.aspx

Family Medicine Presence on Labor and Delivery: Effect on Safety Culture and Cesarean Delivery.

VanGompel EW, Singh L, Carlock F, Rittenhouse C, Ryckman KK, Radke S.

Ann Fam Med. 2024 Sep-Oct;22(5):375-382. doi: 10.1370/afm.3157. PMID: 39313350; PMCID: PMC11419729.

Purpose: Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units.

Methods: Using a cross-sectional design, we surveyed Iowa physicians, nurses, and midwives delivering intrapartum care at hospitals participating in a quality improvement initiative to decrease the incidence of cesarean delivery. We linked respondents with their hospital characteristics and outcomes data. The primary outcome was the association between FM physician, obstetrician (OB), or both disciplines' presence on labor and delivery and hospital low-risk, primary cesarean delivery rate. Unit culture was compared by hospital type (FM-only, OB-only, or Both).

• A total of 849 clinicians from 39 hospitals completed the survey; 13 FM-only, 11 OB-only, and 15 hospitals with both. FM-only hospitals were all rural, with <1,000 annual births. Among hospitals with <1,000 annual births, births at FM-only hospitals had an adjusted 34.3% lower risk of cesarean delivery (adjusted incident rate ratio = 0.66; 95% CI, 0.52-.0.98) compared with hospitals with both. Nurses endorsed unit norms more supportive of vaginal birth and stronger safety culture at FM-only hospitals (P <.05).

Conclusions: Birthing hospitals staffed exclusively by FM physicians were more likely to have lower cesarean rates and stronger nursing-rated safety culture. Both access and quality of care provide strong arguments for reinforcing the pipeline of FM physicians training in intrapartum care.

For a full text of the article, click here: https://www.annfammed.org/content/22/5/375.long

Results of a randomized phase II trial of paclitaxel and carboplatin versus bleomycin, etoposide and cisplatin for newly diagnosed and recurrent Chemonaive stromal ovarian tumors: An NRG oncology/gynecologic oncology group study14.

Brown J, Miller A, Holman LL, Backes F, Nagel C, Bender D, Miller DS, Powell MA, Westin SN, Bonebrake A, Muller CY, Secord AA, Crane E, Schorge J, Tew WP, Sood AK, Bookman MA, Aghajanian C, Gershenson DM.

Gynecol Oncol. 2024 Sep 11;190:283-290. doi: 10.1016/j.ygyno.2024.09.002. Epub ahead of print. PMID: 39265466.

Objectives: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST).

• This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522.
• At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%).
• The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0090825824011090?via%3Dihub

Adherence to Labor Arrest and Failed Induction of Labor Guidelines: The Impact of a Quality-Improvement Educational Intervention.

Cate JJM, Arkfeld CK, Campol M, Campbell KH, Pettker CM, Illuzzi JL.

J Clin Med. 2024 Aug 12;13(16):4720. doi: 10.3390/jcm13164720. PMID: 39200862; PMCID: PMC11355156.

• To evaluate adherence to labor arrest and failed induction of labor (IOL) criteria in nulliparous, term, singleton, and vertex (NTSV) cesarean deliveries at an academic medical center and to measure the impact of a quality-improvement educational initiative that focused on obstetric provider education of modern labor arrest and failed IOL criteria.

Methods: This is a retrospective cohort study using electronic health record (EHR) data with a pre- (1 September 2018-30 September 2019) and post-intervention (1 October 2019-31 March 2020) study design of all NTSV cesarean deliveries for labor arrest or failed IOL performed at an academic medical center in the northeastern United States. The quality-improvement educational intervention consisted of the distribution of educational pocket cards outlining modern labor arrest and failed IOL criteria to obstetric providers. Outcomes included adherence to labor arrest and failed IOL criteria pre- and post-intervention with secondary outcomes evaluating adherence by provider type (Maternal-Fetal Medicine (MFM) or generalist obstetrician). Descriptive and bivariate statistics were used in the analysis.

• Pre-intervention, 272 NTSV cesarean deliveries were performed for labor arrest or failed IOL versus 92 post-intervention. Adherence improved post-intervention amongst failed IOL (OR 6.5, CI 1.8-23.8), first-stage arrest (OR 4.5, CI 2.2-10.8) and second-stage arrest (OR 3.7, CI 1.5-9.4). When comparing provider type, MFM physicians were more likely to be adherent to labor arrest and failed IOL criteria compared to generalist obstetricians pre-intervention (OR 3.1, CI 1.7-5.5); however, post-intervention, there was no longer a difference in adherence (OR 3.3, CI 0.9-12.3).

Conclusions: Adherence to labor arrest criteria was suboptimal in the pre-intervention period; however, a targeted quality-improvement educational intervention improved adherence rates to labor arrest and failed IOL criteria among obstetric providers.

For a full text of the article, click here: https://www.mdpi.com/2077-0383/13/16/4720

Is Histopathology Deep Learning Artificial Intelligence the Future of Precision Oncology?

Wagner VM.

J Clin Oncol. 2024 Sep 11:JCO2401271. doi: 10.1200/JCO-24-01271. Epub ahead of print. PMID: 39259925.

For a full text of the article, click here: https://ascopubs.org/doi/pdf/10.1200%2FJCO-24-01271

Delivery outcomes in super morbid obesity

Foster M, Vemulapalli R, Santillan DA, Greiner AL.

Proc Obstet Gynecol. 2024;13(1):Article 7 [ 3 p.]. https://doi.org/10.17077/2154-4751.33870  Extended Abstract

For a full text of the article, click here: https://pubs.lib.uiowa.edu/pog/article/id/33870/

Quality of life and survivorship in patients with low-grade ovarian cancer.

Lemieux M, Telles R, Goodheart M, Dahmoush L, Hagemann I, Penedo FJ, Nandakumar R, Cole SW, Sood AK, Lutgendorf SK, Thaker PH.

Gynecol Oncol. 2024 Aug 21;190:96-103. doi: 10.1016/j.ygyno.2024.08.010. Epub ahead of print. PMID: 39173565.

• High-grade (HGOC) and low-grade ovarian carcinoma (LGOC) are distinct malignancies with different biological features, treatment paradigms, and life expectancies. However, differences in quality of life (QOL), sleep, and depressive symptoms have not been examined by grade, and neither have inflammatory profiles associated with these symptoms. We aim to characterize QOL and biomarkers by OC grade.

Methods: Participants included patients with HGOC (N = 578) or LGOC (N = 85). Participants completed baseline assessments of psychosocial factors prior to primary surgery or neoadjuvant chemotherapy and contributed saliva for cortisol and blood for interleukin-6 (IL-6) quantification. Samples were collected intraoperatively to quantify tumor cortisol. General linear models were used to examine differences in biological and psychological variables by grade.

• At baseline, patients with LGOC reported less depression (p = 0.018) and sleep disturbances (p = 0.014), but no significant difference in depressive mood (p = 0.11) or QOL (p = 0.51) compared to patients with HGOC, adjusting for age and disease stage. There were trends towards lower tumor cortisol levels (p = 0.078) in LGOC compared to HGOC. One-year post-diagnosis, we found a significant improvement in QOL and fatigue, and a decrease in vegetative depression and IL-6 levels irrespective of grade.

Conclusions: We present the first characterization of psychosocial experiences of patients with LGOC. Despite having a better disease prognosis, patients with LGOC were just as likely to have mood disturbances as those with HGOC. There was a trend towards differences in tumor cortisol by grade. Our findings highlight the need to address well-being in patients with both low- and high-grade ovarian malignancies.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0090825824010643?via%3Dihub

Pelvic floor disorder prevalence and risk factors in a cohort of parous Ugandan women.

Vemulapalli R, Ngobi MD, Kiweewa FM, Jensen JE, Fleecs JD, Steffen HA, Wendt LH, Jackson JB, Kenne KA.

Int J Gynaecol Obstet. 2024 Aug 15. doi: 10.1002/ijgo.15853. Epub ahead of print. PMID: 39148276.

Objectives: The aim of this study was to determine the prevalence of pelvic floor disorders (PFDs) and associated risk factors among parous Ugandan women.

• We performed a cross-sectional study of parous Ugandan women. Demographics and assessment for PFD were obtained. The presence of PFD was defined by participant symptom report, standardized questionnaires, and standard physical examination (pelvic organ prolapse quantification [POP-Q] and cough stress test [CST]).
• A total of 159 women were enrolled in the study between June 2022 and June 2023. The median age was 35 years and median parity was 4. Forty-four (28%) women in the cohort reported symptoms of urinary incontinence. No women reported symptoms of pelvic organ prolapse or anal incontinence. Seventy-two (46%) participants had a positive CST and 93 (58.3%) had stage II or greater prolapse based on the POP-Q. Cesarean section was found to have a protective effect for the development of PFD (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.59, P = 0.004).
• PFDs are prevalent among parous Ugandan women at rates similar to cohorts in other low- and middle-income countries. Cesarean section seems to be a protective factor against developing PFDs.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.15853

DermDx: Painful Vulvar Cyst.

Stockdale CK, Elas DE.

Clinical Advisor June 27, 2024.

For a full text of the article, click here: https://www.clinicaladvisor.com/slideshow/derm-dx/dermdx-painful-vulvar-cysts/

​Verrucous Keratosis of the Vulva: Clinical Image.

Elas DE, Stockdale CK.

Clin Image Case Rep J. 2024; 6(6): 403

For a full text of the article, click here: https://www.literaturepublishers.org/archive/Verrucous-Keratosis-of-the-Vulva:-Clinical-Image.html

Changing the paradigm: Elimination – Not only of cervical cancer.

Bornstein J, Sacinti KG, Preti M, Billan S, Razeghian H, Stockdale CK.

Gynecol Oncol Rep. 2024 Jul 3;54:101445. doi: 10.1016/j.gore.2024.101445. PMID: 39045263; PMCID: PMC11263942.

The WHO’s initiative to eliminate cervical cancer by 2030 does not address the increasing incidence of vulvar, anal, and oropharyngeal cancers linked to high-risk HPV. Currently, the prevention of these three cancers faces various obstacles, such as a lack of specialized screening programs, well-defined management guidelines, and widespread public awareness. Without any interventions, the incidence of these three cancers will likely rise in the upcoming years, increasingly affecting younger individuals. We recommend expanding the WHO’s initiative to include vulvar, anal, and oropharyngeal cancers. This involves developing screening and management protocols similar to those for cervical cancer, implementing gender-neutral HPV vaccination programs, establishing clear referral pathways to specialized centers, promoting public awareness, and providing education to healthcare providers and high-risk individuals.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2352578924001243

Diagnosis of pregnancy disorder in the first-trimester patient plasma with Raman spectroscopy and protein analysis

Mathew AP, Cutshaw G, Appel O, Funk M, Synan L, Waite J, Ghazvini S, Wen X, Sarkar S, Santillan M, Santillan D, Bardhan R.

Bioeng Transl Med. 2024;e10691. doi:10.1002/btm2.10691.

Gestational diabetes mellitus (GDM) is a pregnancy disorder associated with short- and long-term adverse outcomes in both mothers and infants. The current clinical test of blood glucose levels late in the second trimester is inadequate for early detection of GDM. Here we show the utility of Raman spectroscopy (RS) for rapid and highly sensitive maternal metabolome screening for GDM in the first trimester. Key metabolites, including phospholipids, carbohydrates, and major amino acids, were identified with RS and validated with mass spectrometry, enabling insights into associated metabolic pathway enrichment. Using classical machine learning (ML) approaches, we showed the performance of the RS metabolic model (cross-validation AUC 0.97) surpassed that achieved with patients' clinical data alone (cross-validation AUC 0.59) or prior studies with single biomarkers. Further, we analyzed novel proteins and identified fetuin-A as a promising candidate for early GDM prediction. A correlation analysis showed a moderate to strong correlation between multiple metabolites and proteins, suggesting a combined protein-metabolic analysis integrated with ML would enable a powerful screening platform for first trimester diagnosis. Our study underscores RS metabolic profiling as a cost-effective tool that can be integrated into the current clinical workflow for accurate risk stratification of GDM and to improve both maternal and neonatal outcomes.

For a full text of the article, click here: https://aiche.onlinelibrary.wiley.com/doi/10.1002/btm2.10691

Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN): An introduction to the Urinary Urgency Phenotyping Protocol LURN II.

Cameron AP, Yang CC, Bradley CS, Griffith JW, Kirkali Z, Clemens JQ, Kreder KJ, Kenton KS, Andreev VP, Amundsen CL, Jelovsek JE, Helfand BT, Lai HH; LURN Study Group.

Neurourol Urodyn. 2024 Jul 29. doi: 10.1002/nau.25566. Epub ahead of print. PMID: 39075835.

Aims: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls.

• This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies.
• This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population.

Conclusions: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency.

For a full text of the article, click here: https://onlinelibrary.wiley.com/doi/10.1002/nau.25566

​Outcomes Related to Prenatal Zika, Dengue, and Other Flavivirus Infections in the Zika en Embarazadas y Niños Prospective Cohort Study in Colombia.

Tannis A, Newton S, Rico A, Gonzalez M, Benavides M, Ricaldi JN, Rodriguez H, Zambrano LD, Daza M, Godfred-Cato S, Thomas JD, Acosta J, Maniatis P, Daniels JB, Burkel V, Ailes EC, Valencia D, Gilboa SM, Jamieson DJ, Mercado M, Villanueva JM, Honein MA, Ospina ML, Tong VT.

Am J Trop Med Hyg. 2024 Jul 9:tpmd230873. doi: 10.4269/ajtmh.23-0873. Epub ahead of print. PMID: 38981499.

Zika virus (ZIKV) infection in pregnancy is associated with severe abnormalities of the brain and eye and other adverse outcomes. Zika en Embarazadas y Niños was a prospective cohort study conducted in multiple Colombian cities that enrolled pregnant women in their first trimester. Specimens collected from pregnant women (n = 1,519) during February 2017-September 2018 and their infants (n = 1,080) during June 2017-March 2019 were tested for prenatal ZIKV infection by nucleic acid amplification tests or IgM antibody testing. Zika virus infection in pregnancy was present in 3.2% of pregnant women (incidence rate [IR] per 1,000 person-months = 5.9, 95% CI: 4.3-7.8). Presumptive ZIKV infection was present in 0.8% of infants (IR = 1.6, 95% CI: 0.7-2.9). Five percent of infants with prenatal ZIKV exposure or infection presented with Zika-associated abnormalities; 4.7% were small for gestational age. Understanding the risk of ZIKV infection during pregnancy and associated adverse outcomes can help inform counseling efforts.

For a full text of the article, click here: https://www.ajtmh.org/view/journals/tpmd/aop/article-10.4269-ajtmh.23-0873/article-10.4269-ajtmh.23-0873.xml

Reply to Editorial Comment on "A Single Injection of Platelet-Rich Plasma Injection for the Treatment of Stress Urinary Incontinence in Females: A Randomized Placebo-Controlled Trial".

Ashton L, Nataksuka H, Johnson CM, Kenne K, Kreder KJ, Kruse R, Wendt L, Takacs EB, Vollstedt AJ.

Urology. 2024 Jul 24:S0090-4295(24)00596-X. doi: 10.1016/j.urology.2024.07.030. Epub ahead of print. PMID: 39059587.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S009042952400596X?via%3Dihub

Predictors of Postpartum Hemorrhage and Associated Outcomes at a Midwest Academic Medical Center.

Mooberry M, Voss N, Wendt L, Kenne KA, Jackson JB, Rysavy MB.

Womens Health Rep (New Rochelle). 2024 Apr 26;5(1):358-366. doi: 10.1089/whr.2023.0192. PMID: 39035139; PMCID: PMC11257117.

• Postpartum hemorrhage (PPH) remains a significant cause of maternal morbidity and mortality around the world, with rates increasing in the United States. The objective of this study was to determine predictors of, and outcomes associated with, PPH at a Midwest academic health center.
• : Demographic and clinical data were obtained from the electronic medical record on all consecutive delivering patients between May 1, 2020, and April 30, 2021. Associations between PPH and perinatal characteristics and outcomes were assessed using logistic regression models. A significance threshold of 0.05 was used for all comparisons.

Results: Of the 2497 delivering patients during the study period, 437 (18%) experienced PPH. Chronic hypertension, gestational hypertension, and preeclampsia with and without severe features were all associated with increased odds of PPH (odds rations [ORs], respectively, 1.61 (95% CI:1.13-2.24, p = 0.006), 1.62 (95% CI 1.18-2.21, p = 0.003), 1.81 (95% CI 1.14-2.80, p ≤ 0.001), and 1.92 (95% CI 1.29-2.82, p = 0.009). There were also increased odds of PPH with type I diabetes: 2.83 (95% CI 1.45-5.30, p = 0.001), type II diabetes: 2.14 (95% CI 1.15-3.82, p = 0.012), twin delivery: 3.20 (95% CI 2.11-4.81, p ≤ 0.001), cesarean delivery: 5.66 (95% CI 4.53-7.09, p ≤ 0.001), and assisted vaginal delivery: 3.12 (95% CI1.95-4.88, p ≤ 0.001). Infants of mothers with PPH had high odds of NICU admission (CI = 1.34-2.07, p < 0.001) and hypoxic ischemic encephalopathy (CI = 1.64-7.14, p < 0.001).

• Our findings confirm previous literature that preexisting and pregnancy-related hypertension, diabetes mellitus, multiple gestation, cesarean delivery, and assisted vaginal delivery are important predictors of PPH. In addition, we found that neonates of mothers with PPH had more adverse outcomes. These results may help to inform clinical care as rates of PPH continue to rise in the United States.

For a full text of the article, click here: https://www.liebertpub.com/doi/pdf/10.1089/whr.2023.0192

Association Between Physical Activity and Pelvic Floor Disorders in Parous Ugandan Women.

Fleecs JD, Ngobi MD, Kiweewa FM, Vemulapalli R, Jensen JE, Steffen HA, Wendt LH, Jackson JB, Kenne KA.

Int Urogynecol J. 2024 Jul 13. doi: 10.1007/s00192-024-05859-4. Epub ahead of print. PMID: 39002045.

Introduction and hypothesis: The aim was to assess the association between the degree of physical activity (PA) and the presence of pelvic floor disorders (PFDs) in a cohort of parous Ugandan women.

• In this cross-sectional study, PFDs were measured using symptom assessment, standardized questionnaires (Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire), and a standardized physical examination (POP-Q and cough stress test [CST]). Degree of PA was assessed using the International Physical Activity Questionnaire. Interquartile ranges were used to describe the age, parity, and body mass index (BMI) of participants. To examine the association between PA and PFDs, a log transformation was applied to the weekly minutes of PA variable and a logistic regression model was constructed with weekly minutes of moderate/vigorous PA, age, BMI, and parity as the predictors.
• : A total of 159 women were enrolled. Median age was 35 (IQR 32-37), median parity 4 (IQR 3-5), and median BMI 29.0 (IQR 24-33). The prevalence of PFD as determined by symptom assessment was 28% (n=44). The most frequent stage of prolapse identified by POP-Q was stage II (57%, n=91). Thirty-six percent of the women (n=58) reported vigorous PA. Ninety-nine percent of the cohort (n=158) reported moderate PA. When controlling for age, parity, and BMI there was a significant positive association between PFD (defined as a combination of stage II prolapse, positive CST, and urinary incontinence (UI)) and moderate PA (OR 2.20, 95% CI 1.08-5.14, p value 0.045).
• Pelvic floor disorders are common among parous Ugandan women and are associated with moderate PA when controlling for age, BMI, and parity. Understanding the risk factors associated with PFD in this population may better equip providers to screen and care for individuals.

For a full text of the article, click here: https://link.springer.com/article/10.1007/s00192-024-05859-4

Reliability and Validation of the PFIQ-7 and PFDI-20 in the Luganda Language

Jensen JE, Ngobi MD, Kiweewa FM, Fleecs JD, Vemulapalli R, Steffen HA, Wendt LH, Jackson JB, Kenne KA.

Int Urogynecol J. 2024 Jul 12. doi: 10.1007/s00192-024-05866-5. Epub ahead of print. PMID: 38995423.

Introduction and hypothesis: Pelvic floor disorders (PFDs) impact women worldwide and are assessed using instruments such as the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7). There are no known valid PFD instruments in Uganda. This study's purpose was to translate and test the reliability and validity of the PFDI-20 and PFIQ-7 in Luganda. It was predicted that these instruments would be reliable and valid to assess the presence and impact of PFD in parous Luganda-speaking women.

• The translated PFDI-20 and PFIQ-7 were administered to parous Luganda-speaking women and readministered 4-8 months after. The Pelvic Organ Prolapse Quantification (POP-Q) examination determined the presence of pelvic organ prolapse (POP) and a cough-stress test (CST) measured urinary leakage. Analysis was completed using Cronbach's α co-efficient for internal consistency and Spearman's correlation coefficients and Wilcoxon rank sum tests for construct validity.
• Of the 159 participants, 93 (58.3%) had stage II POP or higher. The PFDI-20 and PFIQ-7 demonstrated minimal bother and impact on activities of daily living respectively. The Urinary Distress Inventory 6 (UDI-6) scores on the PFDI-20 showed a strong positive association with the presence of urinary incontinence. When PFD was defined by responses to symptom assessment, the translated PFDI-20 and PFIQ-7 could differentiate between individuals with and without PFD.
• The UDI-6 section of the PFDI-20 was found to be valid in Luganda. The PFIQ-7 and the entirety of the PFDI-20 were not found to be reliable or valid, likely because of the low prevalence of PFDs in the study population.

For a full text of the article, click here: https://link.springer.com/article/10.1007/s00192-024-05866-5

A Single Injection of Platelet-Rich Plasma Injection for the Treatment of Stress Urinary Incontinence in Females: A Randomized Placebo-Controlled Trial.

Ashton L, Nakatsuka H, Johnson CM, Kenne K, Kreder KJ, Kruse R, Wendt L, Takacs EB, Vollstedt AJ.

Urology. 2024 Jun 26:S0090-4295(24)00499-0. doi: 10.1016/j.urology.2024.06.047. Epub ahead of print. PMID: 38942391.

• To determine the efficacy of a single injection of platelet-rich plasma (PRP) into the anterior vaginal wall at the mid-urethra compared to placebo, as there is emerging evidence that PRP may help treat female stress urinary incontinence (SUI).
• This was a single-blind, randomized, placebo-controlled clinical trial at a single institution. Females with bothersome, demonstrable stress-predominant urinary incontinence were enrolled. Participants were randomized to either injection of 5 mL autologous PRP or saline at the anterior vaginal wall at the mid-urethra. The primary outcome was composite treatment success at 6 months, defined as a negative cough stress test and an answer of "much better" or "very much better" on the Patient's Global Impression of Improvement.

Results: Fifty patients were enrolled in the study and randomized to the PRP group (n = 25) or the saline placebo group (n = 25). There was no statistically significant difference in the primary outcome between the 2 groups. Adverse events were minor, and the rate of adverse events was similar between both groups.

Conclusion: In this randomized placebo-controlled study, we were unable to demonstrate a difference in SUI treatment success between PRP and saline injections. At this time, there is insufficient evidence to offer a one-time PRP injection into the anterior vaginal wall for treatment of female SUI.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0090429524004990?via%3Dihub

Living well: Protocol for a web-based program to improve quality of life in rural and urban ovarian cancer survivors.

Pennington KP, Schlumbrecht M, McGregor BA, Goodheart MJ, Heron L, Zimmerman B, Telles R, Zia S, Penedo FJ, Lutgendorf SK.

Contemp Clin Trials. 2024 Jun 22:107612. doi: 10.1016/j.cct.2024.107612. Epub ahead of print. PMID: 38914309.

Background: Ovarian cancer (OC) survivors commonly experience chronic symptoms including anxiety, depression, sleep disturbances, fatigue, physical symptoms, poor health-related quality of life (HRQOL), and a generally poor prognosis. Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival. Accessible psychosocial interventions to improve HRQOL and clinical outcomes are needed. This need is particularly true in rural settings where survivors may have less access to clinic-based support systems.

Methods: The Living Well Study, a cluster-randomized Phase II multi-site clinical trial, is designed to evaluate the efficacy of a group-based, web-delivered psychosocial intervention (Mindful Living) verses a Health Promotion active control (Healthy Lifestyles) in increasing HRQOL and decreasing perceived stress (primary outcomes), depressive mood, anxiety, and fatigue (secondary outcomes) for 256 OC survivors who are <5 years post-primary therapy. Mindful Living targets key concerns of OC survivors and teaches stress reduction skills and coping strategies utilizing cognitive behavioral, mindfulness, and acceptance and commitment therapies. Healthy Lifestyles provides lifestyle information including exercise, nutrition, sleep, and other survivorship topics. Interventions consist of 11 consecutive weekly group sessions lasting 1.5-2 h led by trained facilitators and two booster sessions. Participants complete psychosocial questionnaires at baseline, post-intervention, at 6-months, and at 12-months. A subset completes bloodspots for analysis of inflammatory biology.

Conclusion: Easily accessible psychosocial interventions addressing key concerns of OC survivors are an unmet need. The Mindful Living intervention has the potential to substantially enhance HRQOL and decrease distress in OC survivors. Trial registrationclinicaltrials.gov Identifier: NCT04533763.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S1551714424001952?via%3Dihub

Planning for the forgotten fourth trimester of pregnancy: A parallel group randomized control trial to test a postpartum planning intervention vs. standard prenatal care.

Stanhope KK, Stallworth T, Forest AD, Vuncannon D, Juarez G, Boulet SL, Geary F, Dunlop AL, Blake SC, Green VL, Jamieson DJ.

Contemp Clin Trials. 2024 Jun 3;143:107586. doi: 10.1016/j.cct.2024.107586. Epub ahead of print. PMID: 38838985.

• Black and brown birthing people experience persistent disparities in adverse maternal health outcomes, partially due to inadequate perinatal care. The goal of this study is to design and evaluate a patient-centered intervention for obstetric patients with one or more cardiometabolic risk factors for severe maternal morbidity [gestational diabetes, diabetes mellitus, hypertensive disorders of pregnancy (chronic hypertension, preeclampsia, eclampsia, or gestational hypertension), or preconception obesity (BMI > 30)] to promote postpartum visit attendance.

Methods: To address identified unmet needs for postpartum support and barriers to postpartum care, we developed 20 thematic postpartum planning modules, each with corresponding patient educational materials, community resources, care coordination protocols, and clinician support tools (decision aids, electronic medical record prompts and fields). During prenatal care encounters, a research coordinator delivers the educational content (in English or Spanish), facilitates the participant's planning and shared decision-making, provides the participant with resources, and documents decisions in the electronic medical record. We will randomize 320 eligible patients with a 1:1 ratio to the intervention or standard prenatal care and evaluate the impact on postpartum visit attendance at 4-12 weeks and secondary outcomes (postpartum mental health, perceived future maternal and cardiometabolic risk, contraceptive use, primary care use, readmission, and patient satisfaction with care).

• Through engagement with patients and community stakeholders, we developed a guideline-based, locally tailored intervention to address drivers of engagement with postpartum care for high-risk obstetric patients. If demonstrated to be effective, the educational materials and electronic medical record based-tool can be adapted to other settings.

Trial registration: This trial was registered on ClinicalTrials.gov (NCT05430815) on June 23, 2022.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S1551714424001691?via%3Dihub

Return to Running for Postpartum Elite and Subelite Athletes.

Woodroffe L, Slayman T, Paulson A, Kruse N, Mancuso A, Hall M.

Sports Health. 2024 Jun 12:19417381241256973. doi: 10.1177/19417381241256973. Epub ahead of print. PMID: 38864285.

Context: There is little evidence to guide elite athletes who desire returning to competition after giving birth to a child. Ultimately, this can result in decreased performance and increased risk of injury. This paper addresses aspects that must be considered when building and monitoring a return to running program for a postpartum elite or subelite athlete, including pelvic floor and core stability, progressive reloading of the musculoskeletal system, monitoring of nutritional parameters, and considerations for lactation.

Evidence acquisition: PubMed and CINAHL (Cumulative Index for Nursing and Allied Health Literature) were searched with the following search strategy: (extreme sports OR elite athletes OR running OR exercise) AND (breastfeeding OR lactation OR bone density OR fetal weight OR gestational weight gain OR postpartum or post-partum OR postnatal OR post-natal OR pregnancy OR childbirth). The following information is based on best available evidence and clinical experience.

Study design: Clinical review.

Level of evidence: Level 4.

• Due to the interplay between cardiovascular fitness, postpartum nutrition, lactation, and progressive reloading of the muscular and skeletal system, we propose a multimodal, multidisciplinary approach to safely and successfully allow an athlete to return to an elite level of competition.
• Return to running in the postpartum period is a highly individualized process that benefits from multidisciplinary, individualized care. This includes monitoring of nutrition, core and pelvic floor function, bone reloading, muscle and tendon reloading, and breastfeeding care when applicable.

Strengh of recommendation taxonomy (sort): C.

For a full text of the article, click here: https://journals.sagepub.com/doi/10.1177/19417381241256973

The implications of using maternity care deserts to measure progress in access to obstetric care: a mixed-integer optimization analysis.

Meredith ME, Steimle LN, Radke SM.

BMC Health Serv Res. 2024 May 30;24(1):682. doi: 10.1186/s12913-024-11135-4. PMID: 38811929; PMCID: PMC11137923.

Background: Lack of access to risk-appropriate maternity services, particularly for rural residents, is thought to be a leading contributor to disparities in maternal morbidity and mortality. There are several existing measures of access to obstetric care in the literature and popular media. In this study, we explored how current measures of obstetric access inform the number and location of additional obstetric care facilities required to improve access.

• We formulated two facility location optimization models to determine the number of new facilities required to minimize the number of reproductive-aged women who lack access to obstetric care. We define regions with a lack of access as either maternity care deserts, designated by the March of Dimes to be counties with no obstetric care facility or obstetric providers, or regions further than 50 miles from critical care obstetric (CCO) services. We gathered information on hospitals with obstetric services from Georgia Department of Public Health public reports and estimated the female reproductive-age population by census block group using the American Community Survey.
• Out of the 1,910,308 reproductive-aged women who live in Georgia, 104,158 (5.5%) live in maternity care deserts, 150,563 (7.9%) reproductive-aged women live further than 50 miles from CCO services, and 38,202 (2.0%) live in both maternity care desert and further than 50 miles from CCO services. Our optimization analysis suggests that at least 56 new obstetric care facilities (a 67% increase) would be required to eliminate maternity care deserts in Georgia. However, the expansion of 8 facilities would ensure all women in Georgia live within 50 miles of CCO services.
• Current measures of access to obstetric care may not be sufficient for evaluating access and planning action toward improvements. In a state like Georgia with a large number of small counties, eliminating maternity care deserts would require a prohibitively large number of new obstetric care facilities. This work suggests that additional measures and tools are needed to estimate the number and type of obstetric care facilities that best match practical resources to meet obstetric care needs.

For a full text of the article, click here: https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-024-11135-4

Machine Learning: a new era for cardiovascular pregnancy physiology and cardio-obstetrics research.

Ricci CA, Crysup B, Phillips NR, Ray WC, Santillan MK, Trask AJ, Woerner AE, Goulopoulou S.

Am J Physiol Heart Circ Physiol. 2024 Jun 7. doi: 10.1152/ajpheart.00149.2024. Epub ahead of print. PMID: 38847756.

The maternal cardiovascular system undergoes functional and structural adaptations during pregnancy and postpartum to support increased metabolic demands of offspring and placental growth, labor, and delivery, as well as recovery from childbirth. Pregnancy thus poses physiological stress upon the maternal cardiovascular system, and in the absence of an appropriate response it imparts potential risks for cardiovascular complications and adverse outcomes. The proportion of pregnancy-related maternal deaths from cardiovascular events has been steadily increasing, contributing to high rates of maternal mortality. Despite advances in cardiovascular physiology research, there is still no comprehensive understanding of maternal cardiovascular adaptations in healthy pregnancies, and with far less known about pregnancy with complications. Further, current tools for prognosis of cardiovascular complications during pregnancy are limited. Machine learning (ML) offers new and effective tools for investigating mechanisms involved in pregnancy-related cardiovascular complications as well as the development of potential therapies. The main goal of this review is to summarize existing research that uses ML to understand mechanisms of cardiovascular physiology during pregnancy and develop prediction models for clinical application in pregnant patients. We also provide an overview of ML fundamentals and a discussion about platforms that can be used to enhance understanding of cardiovascular adaptations to pregnancy. Finally, we address the interpretability and explainability of ML outcomes, consequences of model bias, and ethics of ML use.

For a full text of the article, click here: https://journals.physiology.org/doi/abs/10.1152/ajpheart.00149.2024

The Association of Female and Male Preconception Dyslipidemia with Live Birth in Couples Seeking Fertility Treatment.

Bollig KJ, Barnhart KT, Schisterman EF, Johnstone EB, Peterson CM, Hotaling JM, Ryan G, Van Voorhis BJ, Carrell DT, Mendola P, Mills JL, Harhay MO, Zee J, Mumford SL.

J Clin Endocrinol Metab. 2024 Jun 24:dgae427. doi: 10.1210/clinem/dgae427. Epub ahead of print. PMID: 38913692.

Context: Dyslipidemia is common, and resultant endothelial dysfunction may impact reproductive outcomes. No prospective study has examined the effect of preconception lipid parameters in both female and male partners or their interaction on live birth.

• To determine whether live birth is associated with preconception lipids in both partners by planned fertility treatment.
• Secondary analysis of the Folic Acid and Zinc Supplementation Trial, conducted between June 2013-December 2017. Couples were followed for nine months after randomization and until delivery.

Setting: Multicenter study.

• Couples seeking fertility treatment (n = 2370; females 18-45 years, males ≥18 years).
• Female, male, and couple abnormal versus normal preconception lipid concentrations (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides [TG]).

Main outcome measures: Live birth.

• Among 2370 couples, most males (84%) and females (76%) had at least one abnormal lipid parameter. Males planning in vitro fertilization (IVF, n = 373) with elevated LDL had lower probability of live birth than those with normal levels (47.4% vs. 59.7%, aRR 0.79, 95% CI 0.65-0.98). In couples planning IVF where both partners had elevated TC or LDL, live birth was lower than those with normal levels (TC: 32.4% vs. 58.0%, aRR 0.53, 95% CI 0.36-0.79; and LDL: 41.9% vs. 63.8%, aRR 0.69, 95% CI 0.55-0.85). Lipid parameters were not associated with live birth for couples planning non-IVF treatments.
• Couples planning IVF where both partners had elevated TC or LDL and males planning IVF with elevated LDL had decreased probability of live birth. These findings may support lipid screening in patients seeking fertility treatment for prognostic information for reproductive outcomes.

For a full text of the article, click here: https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgae427/7697985

Postoperative venous thromboembolism risk in patients with vulvar carcinoma: An analysis of the National surgical Quality Improvement Program (NSQIP) database.

Kistenfeger Q, Felix AS, Meade CE, Wagner V, Bixel K, Chambers LM.

Gynecol Oncol Rep. 2024 May 12;54:101411. doi: 10.1016/j.gore.2024.101411. PMID: 38803657; PMCID: PMC11128827.

• Due to low incidence of vulvar cancer (VC), incidence and predictors for development of venous thromboembolism (VTE) are poorly understood. We examined incidence and risk factors associated with VTE in patients undergoing surgery for VC.

Methods: We included patients who underwent surgery for VC from the National Surgical Quality Improvement Program database. VTE within the 30-day postoperative period was captured with Current Procedural Terminology codes. Baseline demographics and clinical characteristics were compared between patients with and without VTE. Univariable and multivariable-adjusted exact logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and VTE.

• We identified 1414 patients undergoing procedures for VC from the NSQIP database. Overall, 11 (0.8 %) patients developed VTE. Univariable predictors of VTE included surgery type [compared with simple vulvectomy: radical vulvectomy only (OR = 7.97, 95 % CI = 1.44, infinity) and radical vulvectomy plus unilateral IFN (OR = 15.98, 95 % CI = 2.70, infinity)], unplanned readmission (OR = 11.56, 95 % CI = 2.74, 46.38), deep surgical site infection (OR = 16.05, 95 % CI = 1.59-85.50), and preoperative thrombocytosis (OR = 6.53, 95 % CI = 0.00, 34.86). In a multivariable-adjusted model, longer operative time (≥72 min OR = 11.33, 95 % CI = 1.58-499.03) and preoperative functional status [compared with complete independence: total dependence (OR = 53.88, 95 % CI = 0.85, infinity) and partial dependence (OR = 53.88, 95 % CI = 0.85, infinity)] were associated with VTE.
• In this cohort of patients with VC undergoing radical vulvectomy, VTE incidence was low. Surgery type, longer operative time, dependent functional status, and wound disruption were identified as risk factors. Our findings highlight opportunities for prophylactic intervention in certain patients.

For a full text of the article, click here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11128827/

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

Klopp AH, Enserro D, Powell M, Randall M, Schink JC, Mannel RS, Holman L, Bender D, Kushnir CL, Backes F, Zweizig SL, Waggoner S, Bradley KA, Lawrence LD, Hanjani P, Darus CJ, Small W Jr, Cardenes HR, Feddock JM, Miller DS.

J Clin Oncol. 2024 Apr 25:JCO2301279. doi: 10.1200/JCO.23.01279. Epub ahead of print. PMID: 38662968.

Purpose: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy.

Materials and methods: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS.

• The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression.
• Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

For a full text of the article, click here: https://ascopubs.org/doi/10.1200/JCO.23.01279

A Statewide Mobile Simulation Program For Improving Obstetric Skills in Rural Hospitals.

Thenuwara K, Santillan D, Henkle J, Forman J, Dunbar A, Faro E, Hunter S.

Anesth Analg. 2024 May 17. doi: 10.1213/ANE.0000000000006883. Epub ahead of print. PMID: 38758671.

Background: Closure of rural obstetric (OB) units has led to maternal care deserts, causing mothers to travel long distances for maternity care. Emergency departments (EDs) in hospitals where OB units have closed require regular training for personnel to maintain OB skills, as do rural Level-1 OB units with low volumes of maternity cases. We used a federal grant to develop an OB mobile simulation program to bring simulation-based training to rural providers. Our goal was to improve OB skills and standardize care through the framework of the Alliance for Innovation in Maternal Health (AIM) Patient Safety Bundles.

Methods: We conducted needs assessments and built a mobile simulation unit. We defined 2 groups of learners: those in Level-1 OB units and those in EDs without OB units. For Level-1 OB units, we created a train-the-trainer curriculum, to create a statewide cohort of simulation experts to implement simulations in their facilities between our visits. We gifted each Level-1 unit an OB task trainer, implemented virtual train-the-trainer simulation and task trainer workshops, and conducted post-workshop assessments. We then traveled to each Level-1 unit and helped the cohort implement in situ simulations for their staff using facility-specific resources. We conducted assessments for the cohort and the hospital staff after the simulations. For EDs, we delivered virtual didactics to improve basic OB knowledge, then traveled to ED units, implemented in situ simulations, and conducted post-simulation assessments. We chose a postpartum hemorrhage (PPH) scenario for our first round of simulations.

After train-the-trainer simulation workshops, 98% of participants surveyed agreed that workshop goals and objectives were achieved. After the task trainer workshop, 95% surveyed agreed that their knowledge of using the simulator had improved. After implementing in situ simulations in Level-1 OB units, 98.8% of the train-the-trainer cohort found that their ability to implement simulations had improved. The hospital staff participating in the simulations identified a 30% increase in ability to manage PPH. For the ED staff, postdidactic evaluations identified that 95.4% of participants reported moderate improvement in basic OB knowledge and after participation in the simulations >95% reported better skills as an ED team member when caring for pregnant patients.

Conclusions: These results demonstrate improved skills of hospital staff in simulated PPH in Level-1 OB units and simulated OB emergencies in EDs that no longer have OB units. Further studies are warranted to assess improvement in maternal outcomes.

For a full text of the article, click here: https://journals.lww.com/anesthesia-analgesia/fulltext/9900/a_statewide_...

Not all operative time is created equal: operative time in relation to 30-day complications in benign laparoscopic hysterectomies.

Ikoma D, Ikoma M, Haugsdal ML.

Proc Obstet Gynecol. 2024;13(1): Article 2 [17 p.]. doi: https://doi.org/10.17077/2154-4751.33790.

STUDY OBJECTIVE: To assess the relationship between operative time and specific 30-day postoperative complications across different intervals of operation duration in total laparoscopic hysterectomies (TLHs).

• A retrospective cohort study.
• American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2011 to 2020.
• 131,146 TLH cases.
• Eligible cases included benign laparoscopic hysterectomies with operative times between 20 and 499 min. We excluded cases involving disseminated cancer, emergency surgery, supracervical approaches, or concomitant procedures.
• Multivariable logistic regression analysis was used to evaluate the relationship between specific postoperative complications and operative time. Spline regression was used to analyze differences in the association between postoperative complications and operative time across different tertiles of operative duration.

MAIN RESULTS: Multivariable logistic regression analysis demonstrated a significant association between operative time and complication occurrence for each complication type investigated, including unplanned readmission, urinary tract infections, superficial surgical site infections, blood transfusion administration, return to the operating room, and deep organ space infections. Multivariable logistic spline regression demonstrated that operative time contributed more strongly to the odds of a complication for shorter procedures than longer procedures. This relationship was more pronounced for major complications than minor complications.

1. : Operative time is a stronger risk factor for developing complications for shorter duration procedures than longer procedures. This is especially evident in major complications such as return to the operating room and deep organ space infections. Our results suggest that longer procedure duration may not affect the likelihood of a complication as much as previously thought, and operative times should not be a primary factor in deciding to convert to laparotomy or alter post-operative management.

For a full text of the article, click here: https://pubs.lib.uiowa.edu/pog/article/id/33790/

Surgical management of cornual heterotopic using intraoperative sonography depth resection guidance: case report.

Hagenow A, Shaffer SA, Jain SC.

Proc Obstet Gynecol. 2024;13(1): Article 3 [7 p.]. doi: https://doi.org/10.17077/2154-4751.33791.

Heterotopic pregnancy is an uncommon phenomenon in which an ectopic and intrauterine pregnancy coexist. This condition can be life-threatening and poses a significant therapeutic challenge. Here we describe management of a heterotopic pregnancy with the ectopic pregnancy located in the right cornua. Resection of the ectopic pregnancy was performed via open laparotomy with intraoperative sonography. A sonography guided approach may optimize resection depth while secondarily allowing monitoring of the intrauterine pregnancy and prevention of disruption in cases in which the gestational sacs are in close proximity. After resection, the course of the pregnancy was uncomplicated, and a healthy baby was delivered via planned cesarean delivery at 36 weeks. While the optimal management of heterotopic pregnancies is often individualized, prompt diagnosis and treatment can result in favorable outcomes. The use of ultrasound intraoperatively allows for more precise resection depth, and which may lead to improved outcomes including increased intrauterine fetal survival rates and decreased myometrial scarring.

For a full text of the article, click here: https://pubs.lib.uiowa.edu/pog/article/id/33791/

Letter from the Editor.

Santillan DA.

Proc Obstet Gynecol. 2024;13(1):Article 1 [ 1 p.]. doi: https://doi.org/10.17077/2154-4751.33789.

For a full text of the article, click here: https://pubs.lib.uiowa.edu/pog/article/id/33789/

Contraception utilization and barriers to use in an Iowan population.

Johnson JC, Ramesh A, Radke SM.

Proc Obstet Gynecol. 2024;13(1): Article 5 [1 p.]. doi: https://doi.org/10.17077/2154-4751.33797.

Extended Abstract

For a full text of the article, click here: https://pubs.lib.uiowa.edu/pog/article/id/33797/

The effect of race and rurality on poor pregnancy outcomes.

Meierding K, Santillan, MK.

Proc Obstet Gynecol. 2024;13(1): Article 6 [2 p.]. doi: https://doi.org/10.17077/2154-4751.33798.

Extended Abstract

For a full text of the article, click here: https://pubs.lib.uiowa.edu/pog/article/id/33798/

Emergency department use in the postpartum period: a retrospective cohort study.

Reische E, Santillan M, Cunningham V, Blocklinger K, Hunter S, Faro E, Davis H, Knosp B, Santillan D.

Res Sq . 2024 Mar 12:rs.3.rs-4014132. doi: 10.21203/rs.3.rs-4014132/v1. PMID: 38558986; PMCID: PMC10980109.

Background: Visits to the emergency room (ED) by women in the postpartum period may reflect gaps in postpartum care and disparities in access to obstetric and primary care services. This study aimed to characterize the patients who visited the ED in the first year after delivery, their reasons for coming to the ED, and the care they received.

• The electronic health record was reviewed for all patients who delivered at University of Iowa Health Care between 2009 and 2023 and visited the ED within 365 days after delivery. Data drawn directly from the EHR included patient demographics and medical history, pregnancy and delivery information, and newborn characteristics. The charts were then reviewed manually for information regarding ED visits including time from delivery, chief complaint, diagnosis, and disposition.
• 555 pregnancies had ED visits within one year of delivery, with a total 814 ED visits across the study sample. 46.7% of ED visits occurred in the first 30 days following delivery, and 35% of ED visits for obstetric complaints occurred in the first 2 weeks after delivery. Black patients visited the ED more often (mean=1.84 visits, SD=1.30) than white (mean=1.34, SD=0.92, p<0.001) or Hispanic patients (mean=1.35, SD=0.67, p = 0.004). The most common categories of chief complaint were obstetric (34.6%) and gastrointestinal (18.8%), while the most common categories of diagnosis were obstetric (31.8%) and immune/infectious (28.1%).

Conclusions: Visits to the ED are common in the year following delivery. Almost half of these visits occur in the first 30 days after birth. The plurality of postpartum ED visits are due to obstetric complaints, especially in the first few weeks. Black women are more likely to use the ED during this period, potentially due to disparities in healthcare access. These findings suggest that some of these ED visits may be preventable, and that there is room for improvement in post-delivery follow-up, communication between patients and the obstetrics team, and access to outpatient obstetric care.

ATF4-dependent increase in mitochondrial-endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle.

Hinton A Jr, Katti P, Mungai M, Hall DD, Koval O, Shao J, Vue Z, Lopez EG, Rostami R, Neikirk K, Ponce J, Streeter J, Schickling B, Bacevac S, Grueter C, Marshall A, Beasley HK, Do Koo Y, Bodine SC, Nava NGR, Quintana AM, Song LS, Grumbach IM, Pereira RO, Glancy B, Abel ED.

J Cell Physiol. 2024 Apr;239(4):e31204. doi: 10.1002/jcp.31204. Epub 2024 Feb 28. PMID: 38419397.

Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein- and lipid-enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle-specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin-2, a known MERC protein. In the present study, we tested the hypothesis that Opa1 downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice and Drosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. Reducing Atf4 expression prevented the OPA1-loss-induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4-dependent manner.

Cosmetic and functional impact of fascia lata harvest for use in surgery for stress urinary incontinence.

Johnson C, Vollstedt A, Nakatsuka H, Orzel J, Takacs EB.

Neurourol Urodyn. 2024 Apr 8. doi: 10.1002/nau.25462. Epub ahead of print. PMID: 38587244.

• There has been increased interest in using autologous tissues since the Food and Drug Administration banned transvaginal mesh for pelvic organ prolapse in 2019. Our study aims to assess patients' perspective of functional and cosmetic impact on the fascia lata harvest site in patients undergoing fascia lata harvest for the treatment of stress urinary incontinence (SUI).

Methods: This is a prospective survey study of a retrospective cohort of patients who underwent a fascia lata pubovaginal sling between 2017 and 2022. Participants completed a survey regarding the functional and cosmetic outcomes of the harvest site.

• Seventy-two patients met the inclusion criteria. Twenty-nine patients completed the survey for a completion rate of 40.3%. For functional symptoms, 24.1% (7/29) of patients reported leg discomfort, 10.3% (3/29) reported leg weakness, 10.3% (3/29) reported a bulge, 17.2% (5/29) reported scar pain, 14.8% (4/27) reported scar numbness, and 17.2% (5/29) reported paresthesia at the scar. For cosmetic outcomes, 72.4% (21/29) reported an excellent or good scar appearance. On the PGI-I, 75.9% (22/29) reported their condition as very much better (48.3%, 14/29) or much better (27.6%, 8/29).

• The majority of patients reported being satisfied with the functional and cosmetic outcomes of their harvest site as well as satisfied with the improvement in their SUI. Less than 25% of patients report harvest site symptoms, including leg weakness, scar bulging, scar pain, scar numbness, or paresthesia in the scar. This is important in the context of appropriate preoperative discussion and counseling regarding fascia lata harvest.

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Where is the "counseling" in prenatal genetic counseling?

Schaa KL, Biesecker BB         

Patient Educ Couns. 2024 Mar 29;124:108278. doi: 10.1016/j.pec.2024.108278. Epub ahead of print. PMID: 38593481.

• Prenatal genetic testing is routinely offered to all pregnant patients in the United States and is variably offered to certain pregnant populations globally [1]. To achieve value-based, informed decision-making, we argue for a shift away from the predominant "teaching" model of genetic counseling practice that prioritizes information and counselor dominance, toward a "counseling" model of practice that prioritizes the patient's narrative, values and beliefs.

Discussion: Since prenatal testing began, genetic counseling has aimed to facilitate informed decision-making. Many patients are not familiar with the conditions which can be screened for prenatally or the quality of life of affected children. This lack of understanding can leave expectant parents unprepared to make informed decisions about prenatal testing. As the number of prenatal genetic tests expands, genetic counselors and all healthcare providers who discuss prenatal testing face a growing amount of information that is not feasible to explain to patients in a routine appointment. Research demonstrates that the common approach to genetic counseling, including in the prenatal setting, is the provision of biomedical information. Yet, genetic counseling outcome studies suggest that attending to the relational aspects of genetic counseling are associated with more positive patient outcomes, including enhanced knowledge, informed decision-making and greater patient satisfaction [2,3]. Through case vignettes, we illustrate the application of a counseling model of practice using Accreditation Council for Genetic Counseling (ACGC) practice-based competencies in the domain of "Interpersonal, Psychosocial and Counseling Skills" [4]. Finally, we propose changes across the genetic counseling profession to move clinical practice toward a more relational model of care.

Practice implications: A counseling model of genetic counseling practice leads to more positive patient outcomes [2,3]. Genetic counselors and other prenatal healthcare providers can leverage existing counseling and communication skills to support clients in value-based, informed decision-making in prenatal genetic counseling practice.

Skin-to-Skin Contact and Breastfeeding After Planned Cesarean Birth Before and During the COVID-19 Pandemic

Costello S, Santillan D, Shelby A, Bowdler N.

Breastfeed Med. 2024 Mar;19(3):166-176. doi: 10.1089/bfm.2023.0195. Epub 2024 Feb 27. PMID: 38416483.

• Benefits of early skin-to-skin contact (SSC) between mother and newborn are widely documented, including improved breastfeeding outcomes. While promoting immediate SSC is standard practice for vaginal birth, it happens less often after cesarean birth. It is not known how changes in hospital practices and staffing shortages during the COVID-19 pandemic have influenced the practice of SSC in the operating room (OR). This study aims to identify the relationship between SSC after cesarean birth and breastfeeding and compare SSC before and during the COVID-19 pandemic at a single institution.

Materials and Methods: This was a retrospective cohort study of 244 subjects who had scheduled cesarean births during 2019 and 2020. The primary outcome was newborn feeding at hospital discharge. Secondary outcomes were time to initiate breastfeeding, newborn feeding at 4-8-weeks postpartum, and location of SSC initiation in 2019 versus 2020. 

• SSC within 3 days of birth was significantly associated with feeding type on discharge and/or 4-8 weeks postpartum. More subjects intending to exclusively breastfeed met this intention at discharge with SSC in the OR. Newborns who had SSC in the OR had significantly earlier initiation of breastfeeding. There was an increase in SSC in the OR between 2019 (27%) and 2020 (39%). 

• SSC in the OR was associated with improved short-term breastfeeding outcomes in our study. If immediate SSC is not possible, SSC within 3 days of birth may have breastfeeding benefits. The increase in SSC in the OR during the COVID-19 pandemic indicates that SSC practices can be implemented, despite challenging circumstances.

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Evaluation of ChatGPT for Pelvic Floor Surgery Counseling

Johnson CM, Bradley CS, Kenne KA, Rabice S, Takacs E, Vollstedt A, Kowalski JT.

Urogynecology (Phila). 2024 Mar 1;30(3):245-250. doi: 10.1097/SPV.0000000000001459. PMID: 38484238.

• Large language models are artificial intelligence applications that can comprehend and produce human-like text and language. ChatGPT is one such model. Recent advances have increased interest in the utility of large language models in medicine. Urogynecology counseling is complex and time-consuming. Therefore, we evaluated ChatGPT as a potential adjunct for patient counseling.

Objective: Our primary objective was to compare the accuracy and completeness of ChatGPT responses to information in standard patient counseling leaflets regarding common urogynecological procedures.

Study design: Seven urogynecologists compared the accuracy and completeness of ChatGPT responses to standard patient leaflets using 5-point Likert scales with a score of 3 being "equally accurate" and "equally complete," and a score of 5 being "much more accurate" and much more complete, respectively. This was repeated 3 months later to evaluate the consistency of ChatGPT. Additional analysis of the understandability and actionability was completed by 2 authors using the Patient Education Materials Assessment Tool. Analysis was primarily descriptive. First and second ChatGPT queries were compared with the Wilcoxon signed rank test.

• The median (interquartile range) accuracy was 3 (2-3) and completeness 3 (2-4) for the first ChatGPT query and 3 (3-3) and 4 (3-4), respectively, for the second query. Accuracy and completeness were significantly higher in the second query (P < 0.01). Understandability and actionability of ChatGPT responses were lower than the standard leaflets.

• ChatGPT is similarly accurate and complete when compared with standard patient information leaflets for common urogynecological procedures. Large language models may be a helpful adjunct to direct patient-provider counseling. Further research to determine the efficacy and patient satisfaction of ChatGPT for patient counseling is needed.

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The AUGS Presidential Address and State of the Society in 2023: Coming Together.

Bradley CS.

Urogynecology (Phila). 2024 Mar 1;30(3):167-173. doi: 10.1097/SPV.0000000000001490. PMID: 38484228.

The Interdisciplinary Doula Project: Innovations in Nursing Clinical Education.

Vignato J, Horak T, Goodrich A, Shier E, Coleman L, Nicholson A, Thompson M.

Nurs Educ Perspect. 2024 Feb 23. doi: 10.1097/01.NEP.0000000000001248. Epub ahead of print. PMID: 38407243.

People giving birth report overwhelmingly positive experiences with nursing students acting as doulas. However, no programs report on improving diversity among students, pregnant people, and curricula. This article describes the Interdisciplinary Doula Project, a program to enhance diverse perspectives and clinical skills of university students. Nursing (n = 21, 77.8%) and other health students (n = 6, 22.2%) completed doula training, diversity seminars, and 36 hours of intrapartum care. Seven nursing students were hired to work on labor and delivery upon graduation. This innovative program may increase registered nurses trained to provide culturally congruent labor support for vulnerable pregnant populations.

Rural-urban disparities in psychosocial functioning in epithelial ovarian cancer patients.

Telles R, Zimmerman MB, Thaker PH, Slavich GM, Ramirez ES, Zia S, Goodheart MJ, Cole SW, Sood AK, Lutgendorf SK.

Gynecol Oncol. 2024 Feb 2;184:139-145. doi: 10.1016/j.ygyno.2024.01.024. Epub ahead of print. PMID: 38309031.

Objective: Although rural residence has been related to health disparities in cancer patients, little is known about how rural residence impacts mental health and quality of life (QOL) in ovarian cancer patients over time. This prospective longitudinal study investigated mental health and QOL of ovarian cancer patients in the first-year post-diagnosis.

• Women with suspected ovarian cancer completed psychosocial surveys pre-surgery, at 6 months and one-year; clinical data were obtained from medical records. Histologically confirmed high grade epithelial ovarian cancer patients were eligible. Rural/urban residence was categorized from patient counties using the USDA Rural-Urban Continuum Codes. Linear mixed effects models examined differences in psychosocial measures over time, adjusting for covariates.

Results: Although disparities were not observed at study entry for any psychosocial variable (all p-values >0.22), urban patients showed greater improvement in total distress over the year following diagnosis than rural patients (p = 0.025) and were significantly less distressed at one year (p = 0.03). Urban patients had a more consistent QOL improvement than their rural counterparts (p = 0.006). There were no differences in the course of depressive symptoms over the year (p = 0.17). Social support of urban patients at 12 months was significantly higher than that of rural patients (p = 0.04).

Conclusion: Rural patients reported less improvement in psychological functioning in the year following diagnosis than their urban counterparts. Clinicians should be aware of rurality as a potential risk factor for ongoing distress. Future studies should examine causes of these health disparities and potential long-term inequities and develop interventions to address these issues.

The role of the placenta-brain axis in psychoneuroimmune programming.

Gumusoglu SB.

Brain Behav Immun Health. 2024 Feb 6;36:100735. doi: 10.1016/j.bbih.2024.100735. PMID: 38420039; PMCID: PMC10900837.

Gestational exposures have enduring impacts on brain and neuroimmune development and function. Perturbations of pregnancy leading to placental structure/function deficits, cell stress, immune activation, and endocrine changes (metabolic, growth factors, etc.) all increase neuropsychiatric risk in offspring. The existing literature links obstetric diseases with placental involvement to offspring neuroimmune outcomes and neurodevelopmental risk. Psychoneuroimmune outcomes in offspring brain include changes to microglia, cytokine/chemokine production, cell stress, and long-term immunoreactivity. These outcomes are altered by structural, anti-angiogenic/hypoxic, inflammatory, and metabolic diseases of the placenta. This fetal programming occurs via direct placental passage or production of factors which can act directly on fetal brain substrates, or indirectly via action of circulating factors on intermediates in the placenta. Placental neuroendocrine, vascular/angiogenic, immune, and extracellular vesicular mechanisms are detailed. These mechanisms interact within various placental and pregnancy conditions. An increased understanding of the placental origins of psychoneuroimmunology will yield dividends for human health. Identifying maternal and placental biomarkers for fetal neuroimmune health may also revolutionize early diagnosis and precision psychiatry, empowering patients to make the best healthcare decisions for their families. Targeting placental mechanisms may be a valuable approach for the prevention and mitigation of intergenerational, lifelong neuropathology.

Maternal RSV Vaccine - Weighing Benefits and Risks.

Rasmussen SA, Jamieson DJ.

N Engl J Med. 2024 Mar 14;390(11):1050-1051. doi: 10.1056/NEJMe2401072. PMID: 38477994

Childhood maltreatment and trajectories of cardiometabolic health across the reproductive life span among individuals with a first birth during the Coronary Artery Risk Development in Young Adults Study.

Stanhope KK, Gunderson EP, Suglia SF, Boulet SL, Jamieson DJ, Kiefe CI, Kershaw KN.

Prev Med. 2024 Mar;180:107894. doi: 10.1016/j.ypmed.2024.107894. Epub 2024 Feb 10. PMID: 38346564; PMCID: PMC10896584.

Objective: Childhood adversity is associated with poor cardiometabolic health in adulthood; little is known about how this relationship evolves through childbearing years for parous individuals. The goal was to estimate differences in cardiometabolic health indicators before, during and after childbearing years by report of childhood maltreatment in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study.

• : Including 743 individuals nulliparous at baseline (1985-1986) with one or more pregnancies >20 weeks during follow-up (1986-2022), we fit segmented linear regression models to estimate mean differences between individuals reporting or not reporting childhood maltreatment (physical or emotional) in waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, fasting glucose, and body mass index (BMI) prior to, during, and following childbearing years using generalized estimating equations, allowing for interaction between maltreatment and time within each segment, and adjusting for total parity, parental education, and race (Black or white, self-reported).

Results: Individuals reporting maltreatment (19%; 141) had a greater waist circumference (post-childbearing: +2.9 cm, 95% CI (0.7, 5.0), higher triglycerides [post-childbearing: +8.1 mg/dL, 95% CI (0.7, 15.6)], and lower HDL cholesterol [post-childbearing: -2.1 mg/dL, 95% CI (-4.7, 0.5)] during all stages compared to those not reporting maltreatment. There were not meaningful differences in blood pressure, fasting glucose, or BMI. Individuals who reported maltreatment did not report faster changes over time.

• : Differences in some aspects of cardiometabolic health between individuals reporting versus not reporting childhood maltreatment were sustained across reproductive life stages, suggesting potentially persistent impacts of childhood adversity.

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Understanding the role of childhood nurture, abuse, and stability on gestational diabetes in the Coronary Artery Risk Development in Young Adults study (CARDIA).

Stanhope KK, Gunderson EP, Suglia SF, Boulet SL, Jamieson DJ, Kiefe CI, Kershaw KN.

Ann Epidemiol. 2024 Mar;91:30-36. doi: 10.1016/j.annepidem.2024.01.007. Epub 2024 Jan 23. PMID: 38266664; PMCID: PMC10922764.

• To estimate associations between facets of the maternal childhood family environment with gestational diabetes (GDM) and to test mediation by pre-pregnancy waist circumference.
• We used data from CARDIA, a cohort of individuals aged 18-30 years at baseline (1985-86), followed over 30 years (2016). We included participants with one or more pregnancies ≥ 20 weeks after baseline, without pre-pregnancy diabetes. The primary exposure was the Childhood Family Environment Scale (assessed year 15), including the total score and abuse, nurture, and stability subscales as continuous, separate exposures. The outcome was GDM (self-reported at each visit for each pregnancy). We fit log binomial models with generalized estimating equations to calculate risk ratios (RR) and 95% confidence intervals (CI), adjusting for age at delivery, parity, race (Black or White), and parental education. We used regression models with bootstrapped CIs to test mediation and effect modification by excess abdominal adiposity at the last preconception CARDIA visit (waist circumference ≥ 88 cm).

Results: We included 1033 individuals (46% Black) with 1836 pregnancies. 130 pregnancies (7.1%) were complicated by GDM. For each 1 point increase on the abuse subscale (e.g., from "rarely or never" to "some or little of the time") there was a 30% increased risk of GDM (RR: 1.3, 95% CI: 1.0, 1.7). There was evidence of effect modification but not mediation by preconception abdominal adiposity.

Conclusions: A more adverse childhood family environment was associated with increased risk of GDM, with a stronger association among individuals with preconception waist circumference ≥ 88 cm.

Increased Maternal BMI at Time of Delivery Associated with Poor Maternal and Neonatal Outcomes.

Steffen H, Swartz S, Kenne K, Wendt L, Jackson JB, Rysavy M.

Am J Perinatol. 2024 Feb 22. doi: 10.1055/a-2274-0463. Epub ahead of print. PMID: 38387610.

Objective: Current literature on the risks and outcomes of obesity in pregnancy almost exclusively utilizes pre-pregnancy body mass index (BMI). Given the rising obesity rate across the United States along with a paucity of available information on the relationship between delivery BMI and maternal and neonatal outcomes, our study aimed to determine the association of maternal BMI at delivery with antepartum, intrapartum, and neonatal complications at an academic referral hospital.

Study design: This study is a secondary analysis of data collected for a prospective cohort study of COVID-19 in pregnancy. This analysis included all patients who delivered term singleton infants between May 1, 2020, and April 30, 2021, at the University of Iowa Hospitals and Clinics. Demographic and clinical data were obtained from the electronic medical record. The relationship between maternal BMI and maternal and neonatal characteristics of interest was assessed using logistic regression models. A statistical significance threshold of 0.05 was used for all comparisons.

• : There were 1,996 women who delivered term singleton infants during the study period. The median BMI at delivery was 31.7 (interquartile range 27.9, 37.2), with 61.1% of women having a BMI >30.0. Increasing BMI was significantly associated with non-reassuring fetal status, unscheduled cesarean birth, overall cesarean birth rate, postpartum hemorrhage, prolonged postpartum stay, hypertensive diseases of pregnancy, neonatal hypoglycemia, neonatal intensive care unit admission, decreased APGAR score at one minute, and increasing neonatal birth weight. Even when controlling for pre-existing hypertension in a multivariate model, increasing BMI was associated with gestational hypertension and pre-eclampsia.

Conclusion: Increased maternal BMI at delivery was associated with adverse perinatal outcomes. These findings have implications for clinical counseling regarding risks of pregnancy and delivery for overweight and obese patients and may help inform future studies to improve safety, especially by examining reasons for high cesarean rates.

Learning to lead: The evolution of a pilot leadership curriculum for gynecologic oncology fellows at the Ohio State University.

Levine MD, Wagner VM, Riedinger CJ, Khadraoui W, Haight PJ, Morton M, Barrington DA, Calo CA, Castaneda AV, Lightfoot M, Chalif J, Gonzalez A, Cohn DE.

Gynecol Oncol Rep. 2024 Jan 29;52:101327. doi: 10.1016/j.gore.2024.101327. PMID: 38390623; PMCID: PMC10881305.

•Leadership training is under-emphasized in traditional medical education.

•An effective leadership curriculum must be dynamic and requires genuine investment from participants.

•Through didactic education, self-reflection, and real-world perspective we can actively mold future leaders in gynecologic oncology.

Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

Pothuri B, Han S, Chase DM, Heitz F, Burger RA, Gaba L, Van Le L, Guerra E, Bender D, Korach J, Cloven N, Churruca C, Follana P, DiSilvestro P, Baurain JF, Jardon K, Pisano C, Peen U, Mäenpää J, Gupta D, Bacqué E, Li Y, Compton N, Antonova J, Monk BJ, González-Martín A

Gynecol Oncol. 2024 Feb 6;184:168-177. doi: 10.1016/j.ygyno.2024.01.021. Epub ahead of print. PMID: 38325276.

• To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy.

Methods: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment.

Results: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires.

• Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.

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The use of immunomodulation therapy in women with recurrent implantation failure undergoing assisted conception: A multicentre cohort study.

Khairy M, Harb H, Eapen A, Melo P, Kazem R, Rajkhowa M, Ndukuwe G, Coomarasamy A.

Am J Reprod Immunol. 2024 Feb;91(2):e13819. doi: 10.1111/aji.13819. PMID: 38348954.

• Recurrent implantation failure (RIF) after multiple embryo transfers remains a vexing problem and immunomodulators have been used with conflicting results. This study aims to assess the effect of immunomodulation therapy on live birth rate (LBR) in women with RIF undergoing assisted reproduction treatment (ART).

Method of study design: This is a retrospective cohort study in multicentre network of private assisted conception units in the UK. The study included women who had at least two failed attempts of embryo transfers at CARE fertility network in the period from 1997 to 2018. Women in the treatment group had immunomodulator drugs in the form of corticosteroids, low molecular weight heparin (LMWH), and intravenous intralipid (IVIL) infusions, either separately or in combination, after immunological testing, in addition to standard ART whilst women in the control group had only ART without immunomodulators. The primary outcome was LBR per cycle. Secondary outcomes included the rates of clinical pregnancy (CPR), cumulative live birth (CLBR), and miscarriage.

• A total of 27 163 ART cycles fulfilled the inclusion criteria, of which 5083 had immunomodulation treatment in addition to standard ART treatment, and 22 080 had standard ART treatment alone. Women in the treatment group were significantly older (mean age 38.5 vs. 37.1 years, p < .001), and had a higher number of previous failed ART cycles (mean 4.3 vs. 3.8, p < .01). There was a higher LBR in women who received immunomodulation therapy when compared with the control group (20.9% vs. 15.8%, odds ratio [OR] 1.4, 95% confidence interval [CI] 1.29-1.53, p < .001). Multivariate regression analysis showed that immunomodulation treatment was a significant independent predictor of live birth after adjusting for other confounders (adjusted OR [aOR] 1.33, 95% CI 1.15-1.54, p < .001). Survival analysis showed a higher CLBR in the treatment group (adjusted hazard ratio [aHR] 1.78, 95% CI 1.62-1.94, p < .001).

• : This study provides evidence of a potential beneficial effect of immunomodulation therapy in women with RIF after immunological testing. There remains a need for high quality, adequately powered multicentre RCTs to robustly address the role of immunomodulation in women with RIF. There is also an urgent need for standardised screening tests for immune disorders that could preclude implantation.

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Longitudinal Outcomes of Malignant Ureteral Obstruction Secondary to Ovarian Cancer: Predictors of Resolution and the Role of Surgical Management.

Faidley KN, Botkin HE, Loeffler BT, Mott SL, Hansen SC, Hill EK, Erickson BA.

Urology. 2024 Feb 11:S0090-4295(24)00066-9. doi: 10.1016/j.urology.2024.02.001. Epub ahead of print. PMID: 38350551.

Purpose: To review the management of ovarian cancer (OCa) associated hydronephrosis (HN). Specifically, we aim to identify optimal management of HN in the acute setting, predictors of HN resolution, and the role of surgery (tumor debulking/(+/-)ureterolysis/hysterectomy).

Materials/methods: The study cohort included OCa patients managed at our institution from 2004-19 that developed OCa-associated HN. Initial HN management was recorded as none, retrograde ureteral stent (RUS) or percutaneous nephrostomy tube (PCN). Primary outcomes included 1) HN management failure 2) HN management complications and 3) HN resolution. Patient, cancer, and treatment predictors of outcomes were assessed using logistic regression and Fine-Gray competing risk models.

• : Of 2580 OCa patients, 190 (7.4%) developed HN. HN was treated in 121; 90 (74.4%) with RUS, 31 (25.6%) with PCN. Complication rates were similar between PCN and RUS (83% v. 85.1%; p = 0.79; all Clavian Grade I/II). Initial HN treatment failure occurred in 28 patients, predicted by renal atrophy (HR 3.27, p<0.01). HN resolution occurred in only 52 (27%) patients and was predicted by lower FIGO stage (FIGO III/IV HR 0.42 p<0.01) and surgical tumor debulking/ureterolysis (HR 2.83 p = 0.02).

Conclusions: Resolution of HN associated with malignant obstruction from OCa is rare and is most closely associated with tumor debulking and FIGO stage. Initial endoscopic treatment modality was not significantly associated with complications or resolution, though RUS failures were slightly more commonly. Ureteral reconstruction at time of debulking/ureterolysis is potentially underutilized.

Care from Birth to Discharge of Infants Born at 22 to 23 Weeks' Gestation.

Dagle JM, Hunter SK, Colaizy TT, McElroy SJ, Harmon HM, McNamara PJ, Klein JM.

Crit Care Nurs Clin North Am. 2024 Mar;36(1):23-33. doi: 10.1016/j.cnc.2023.08.007. Epub 2023 Sep 19. PMID: 38296373.

The clinical care of infants born at 22 weeks' gestation must be well-designed and standardized if optimal results are to be expected. Although several approaches to care in this vulnerable population are possible, protocols should be neither random nor inconsistent. We describe the approach taken at the University of Iowa Stead Family Children's Hospital neonatal intensive care unit with respect to preterm infants born at 22 weeks' gestation. We have chosen to present our standardize care plan with respect to prenatal, neurologic, nutritional, gastrointestinal, and skin management. Respiratory and cardiopulmonary care will be briefly reviewed, as these strategies have been published previously.

Radiation exposure during sacral neuromodulation lead placement: Multi-institutional descriptive study.

Burns RT, Orzel J, Wadensweiler P, Kenne K, Nakastuka H, Kovacevic N, Aswani Y, Ann Gormley E, Padamanabhan P, Powell CR, Vollstedt A, Takacs E.

Neurourol Urodyn. 2024 Feb 6. doi: 10.1002/nau.25408. Epub ahead of print. PMID: 38318969.

• Fluoroscopy has significantly improved lead placement and decreased surgical time for implantable sacral neuromodulation (SNM). There is a paucity of data regarding radiation and safety of fluoroscopy during SNM procedures. Our study aims to characterize fluoroscopy time and dose used during SNM surgery across multiple institutions and assess for predictors of increased fluoroscopy time and radiation dose.

Methods: Electronic medical records were queried for SNM procedures (Stage 1 and full implant) from 2016 to 2021 at four academic institutions. Demographic, clinical, and intraoperative data were collected, including fluoroscopy time and radiation dose in milligray (mGy). The data were entered into a centralized REDCap database. Univariate and multivariate analysis were performed to assess for predictive factors using STATA/BE 17.0.

Results: A total of 664 procedures were performed across four institutions. Of these, 363 (54.6%) procedures had complete fluoroscopy details recorded. Mean surgical time was 58.8 min. Of all procedures, 79.6% were performed by Female Pelvic Medicine and Reconstructive Surgery specialists. There was significant variability in fluoroscopy time and dose based on surgical specialty and institution. Most surgeons (76.4%) were considered "low volume" implanters. In a multivariate analysis, bilateral finder needle testing, surgical indication, surgeon volume, and institution significantly predicted increased fluoroscopy time and radiation dose (p < 0.05).

Conclusions: There is significant variability in fluoroscopy time and radiation dose utilized during SNM procedures, with differences across institutions, surgeons, and subspecialties. Increased radiation exposure can have harmful impacts on the surgical team and patient. These findings demonstrate the need for standardized fluoroscopy use during SNM procedures.

2019 ASCCP Risk-Based Management Consensus Guidelines: Updates Through 2023.

Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, Huh WK, Kim JJ, Moscicki AB, Nayar R, Saraiya M, Sawaya GF, Wentzensen N, Schiffman M; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. {Stockdale on Committee}

J Low Genit Tract Dis. 2024 Jan 1;28(1):3-6. doi: 10.1097/LGT.0000000000000788. PMID: 38117563; PMCID: PMC10755815.

This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

Authentic leadership in action: Experience gained from a gynecologic oncology fellowship leadership curriculum.

Levine MD, Wagner VM, Riedinger CJ, Khadraoui W, Haight PJ, Morton M, Cohn DE.

Gynecol Oncol. 2024 Feb 7;182:176-178. doi: 10.1016/j.ygyno.2024.01.036. Epub ahead of print. PMID: 38330810.

Psychosocial outcomes of children born via embryo donation.

Salari S, Lee S, Mangels J, Flyckt R, Madeira J, Gordon J, Keenan J, Lee M, Lin P, Pennings G, Sweet C, Klock S, Lindheim SR.

Hum Reprod. 2024 Feb 19:deae023. doi: 10.1093/humrep/deae023. Epub ahead of print. PMID: 38373211.

Study question: What are parents' perceptions of their relationships with and the psychosocial adjustments of their children who are born via embryo donation?

Summary answer: Families created through embryo donation have well-adjusted parent-child relationships and reassuring child psychosocial outcomes.

What is known already: Embryo donation is an effective and growing form of third-party reproduction, but there is limited research in this field. Prior studies suggest that families created through gamete donation function well regarding parent-child relationship quality and child behavioral and socioemotional adjustment.

Study design, size, duration: This is a cross-sectional survey study with 187 total participants.

Participants/materials, setting, methods: Parents of children born via embryo donation were recruited nationally by contacting all embryo donation programs registered with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) as well as medically directed embryo donation or 'embryo adoption' centers. Participants completed three online Qualtrics questionnaires. The first was a survey including 33 questions on demographics, the procurement process, and self-reported obstetric outcomes. Participants also completed two standardized measures assessing children's behavior and parents' adjustment to parenthood: the Strengths and Difficulties Questionnaire (SDQ) and the Parental Acceptance-Rejection Questionnaire (PARQ). Scoring of the SDQ and PARQ was totaled and compared to standardized values (SDQ) or previously published results on other forms of gamete donation (PARQ), such as oocyte donation and sperm donation.

Main results and the role of chance: On the SDQ (n = 46), the average total difficulties scores by age were: 8.2 ± 0.98 for ages 2-4, 7.6 ± 0.93 for ages 5-10, and 3.5 ± 0.77 for ages 11-17; this is compared to the normal reported range of 0-13, which indicates that clinically significant psychosocial problems are unlikely. Across all ages and individual categories (emotional symptoms, conduct problem, hyperactivity, peer problem, prosocial), scores on the SDQ were within the normal ranges. The average PARQ score (n = 70) for all respondents was 27.5 ± 1.18 (range: 24-96), suggesting perceived parental acceptance.

Limitations, reasons for caution: Because this study was cross-sectional, it could not capture familial relationships over time. This survey-based study design allows for potential selection bias (parents of well-adjusted children may be more likely to participate). Additionally, the overall sample size is relatively small; however, it remains one of the largest published to date. Another significant limitation to this study is the lack of generalizability: most participants were recruited from private, faith-based, embryo donation programs who are demographically similar.

Wider implications of the findings: Though embryo donation is an established form of third-party reproduction, it is significantly less robustly studied compared to other forms of gamete donation (oocyte or sperm donation). This study provides a larger data set with a more expanded age range of children compared to the limited number of previously published studies. Furthermore, these findings indicate a high parental disclosure rate with respect to the use of embryo donation which contrasts previous findings.

A role for adverse childhood experiences and depression in preeclampsia.

Myers M, Gumusoglu S, Brandt D, Stroud A, Hunter SK, Vignato J, Nuckols V, Pierce GL, Santillan MK, Santillan DA.

J Clin Transl Sci. 8:e25, 1–8. doi: 10.1017/cts.2023.704.

Introduction: Adverse childhood experiences (ACEs) are a measure of childhood adversity and are associated with life-long morbidity. The impacts of ACEs on peripartum health including preeclampsia, a common and dangerous hypertensive disorder of pregnancy, remain unclear, however. Therefore, we aimed to determine ACE association with peripartum psychiatric health and prevalence of preeclampsia using a case–control design.

Methods: Clinical data were aggregated and validated using a large, intergenerational knowledgebase developed at our institution. Depression symptoms were measured by standard clinical screeners: the Patient Health Questionnaire-9 (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS). ACEs were assessed via survey. Scores were compared between participants with (N = 32) and without (N = 46) prior preeclampsia.

Results: Participants with ACE scores ≥4 had significantly greater odds of preeclampsia than those with scores ≤ 3 (adjusted odds ratio = 6.71, 95% confidence interval:1.13–40.00; p = 0.037). Subsequent speculative analyses revealed that increased odds of preeclampsia may be driven by increased childhood abuse and neglect dimensions of the ACE score. PHQ-9 scores (3.73 vs. 1.86, p = 0.03), EPDS scores (6.38 vs. 3.71, p = 0.01), and the incidence of depression (37.5% vs. 23.9%, p = 0.05) were significantly higher in participants with a history of preeclampsia versus controls.

Conclusions: Childhood sets the stage for life-long health. Our findings suggest that ACEs may be a risk factor for preeclampsia and depression, uniting the developmental origins of psychiatric and obstetric risk.

NRG-GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer.

Rimel BJ, Enserro D, Bender DP, Jackson CG, Tan A, Alluri N, Borowsky M, Moroney J, Hendrickson AW, Backes F, Swisher E, Powell M, MacKay H.

Cancer. 2023 Dec 21. doi: 10.1002/cncr.35151. Epub ahead of print. PMID: 38127487.

• This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer.
• This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel.
• A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response.

Conclusion: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity.

Ecological momentary assessment of pelvic pain and urinary urgency variability in urologic chronic pelvic pain syndrome and their association with illness impact and quality of life: Findings from the multidisciplinary approach to the study of chronic pelvic pain symptom patterns study.

Erickson BA, Griffith JW, Wensheng G, Mengying Y, Herman T, Bradley CS, Quentin Clemens J, Farrar JT, Gupta P, Kreder KJ, Henry Lai H, Naliboff BD, Newman DK, Rodriguez LV, Spitznagle T, Sutcliffe S, Sutherland SE, Taple BJ, Richard Landis J.

Neurourol Urodyn. 2024 Jan 22. doi: 10.1002/nau.25363. Epub ahead of print. PMID: 38247366.

Purpose: This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM).

Materials and methods: A previously validated smart phone app (M-app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M-app notifications were sent 4-times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined.

• A total of 204 participants enrolled in the M-app study (64% female). M-app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability.

• PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses.

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Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

Weber MA, Kerr G, Thangavel R, Conlon MM, Gumusoglu SB, Gupta K, Abdelmotilib HA, Halhouli O, Zhang Q, Geerling JC, Narayanan NS, Aldridge GM.

J Parkinsons Dis. 2023 Dec 30. doi: 10.3233/JPD-230129. Epub ahead of print. PMID: 38189765.

• Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD.
• : To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn.

Methods: We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions.

Results: We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration.

• This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.

Hereditary Breast Cancer, Genetics, and Fertility Preservation.

Huber-Keener KJ

Curr Breast Cancer Rep. 2023 Dec 20;15(4):329–336. doi: 10.1007/s12609-023-00515-0

Purpose of Review Fertility preservation is an important consideration in patients with hereditary breast cancer. Breast cancer mutation carriers may present with their cancers at younger ages and require more gonadotoxic treatments. The intent of this review is to discuss the data and research behind the particular fertility challenges mutation carriers may encounter.

Recent Findings Limited data exist for the impact of hereditary breast cancer genes on fertility in breast cancer patients. Data is conflicting on baseline fertility of BRCA1/2 carriers, but breast cancer patients with these mutations become pregnant more often than noncarrier patients. Artificial reproductive technologies (ART) appear to be safe in this patient population, and these patients may benefit from preimplantation genetic testing.

• Discussion of future fertility is important at time of diagnosis of a cancer mutation and breast cancer. Additional research is needed on mutation carriers to determine how their pathogenic variants affect fertility and risks of fertility preservation options.

For a full text of the article, go here: S:\Applications\Departmental Publications, 2024\Hereditary Breast Cancer, Genetics, and Fertility Preservation. Curr Breast Cancer Rep 2023

Postpartum healthcare expenditures for commercially insured deliveries with and without severe maternal morbidity.

Boulet SL, Stanhope KK, Platner M, Costley LK, Jamieson DJ.

Am J Obstet Gynecol MFM. 2024 Jan;6(1):101225. doi: 10.1016/j.ajogmf.2023.101225. Epub 2023 Nov 14. PMID: 37972925.

• Although severe maternal morbidity is associated with adverse health outcomes in the year after delivery, patterns of healthcare use beyond the 6-week postpartum period have not been well documented.

Objective: This study aimed to estimate healthcare utilization and expenditures for deliveries with and without severe maternal morbidity in the 12 months following delivery among commercially insured patients.

Study design: Using data from the 2016 to 2018 IBM Marketscan Commercial Claims and Encounters Research Databases, we identified deliveries to individuals 15 to 49 years of age who were continuously enrolled in noncapitated health plans for 12 months after delivery discharge. We used multivariable generalized linear models to estimate adjusted mean 12-month medical expenditures and 95% confidence intervals for deliveries with and without severe maternal morbidity, accounting for region, health plan type, delivery method, and obstetrical comorbidities. We estimated expenditures associated with inpatient admissions, nonemergency outpatient visits, outpatient emergency department visits, and outpatient pharmaceutical claims.

• We identified 366,282 deliveries without severe maternal morbidity and 3976 deliveries (10.7 per 1000) with severe maternal morbidity. Adjusted mean total medical expenditures for deliveries with severe maternal morbidity were 43% higher in the 12 months after discharge than deliveries without severe maternal morbidity ($5320 vs $3041; difference $2278; 95% confidence interval, $1591-$2965). Adjusted mean expenditures for readmissions and nonemergency outpatient visits during the 12-month postpartum period were 61% and 39% higher, respectively, for deliveries with severe maternal morbidity compared with deliveries without severe maternal morbidity. Among deliveries with severe maternal morbidity, adjusted mean total costs were highest for patients living in the western region ($7831; 95% confidence interval, $5518-$10,144) and those having a primary cesarean ($7647; 95% confidence interval, $6323-$8970).

Conclusion: Severe maternal morbidity at delivery is associated with increased healthcare use and expenditures in the year after delivery. These estimates can inform planning of severe maternal morbidity prevention efforts.

Effects of rurality and distance to care on perinatal outcomes over a 1-year period during the COVID-19 pandemic.

Bujimalla PV, Kenne KA, Steffen HA, Swartz SR, Wendt LH, Skibbe AM, Jackson JB, Rysavy MB.

J Rural Health. 2023 Dec 27. doi: 10.1111/jrh.12820. Epub ahead of print. PMID: 38151483.

Purpose: Our aim was to investigate the roles of rurality and distance to care on adverse perinatal outcomes and COVID-19 seroprevalence at the time of delivery over a 1-year period.

Methods: Data were collected from the electronic medical record on all pregnant patients who delivered at a single, large, Midwest academic medical center over 1 year. Rurality was classified using standard Rural-Urban Commuting Area codes. Geographic Information System tools were used to map outcomes. Data were analyzed with univariate and multivariate models, controlling for Body Mass Index (BMI), insurance status, and parity.

• A total of 2,497 patients delivered during the study period; 20% of patients were rural (n = 499), 18.6% were micropolitan (n = 466), and 61.4% were metropolitan (n = 1,532). 10.4% of patients (n = 259) were COVID-19 seropositive. Rural patients did not experience higher rates of any measured adverse outcomes than metropolitan patients; micropolitan patients had increased odds of preterm labor (OR = 1.41, P = .022) and pre-eclampsia (OR = 1.78, P<.001). Patients living 30+ miles away from the medical center had increased odds of preterm labor (OR = 1.94, P<.001), pre-eclampsia (OR = 1.73, P = .002), and infant admission to the neonatal intensive care unit (OR = 2.12, P<.001), as well as lower gestational age at delivery (β = -9.2 days, P<.001) and birth weight (β = -206 grams, P<.001).

Conclusion: Distance to care, rather than rurality, was the key predictor of multiple adverse perinatal outcomes in this cohort of deliveries over a 1-year period. Our study suggests that rurality should not be used as a standalone indicator of access to care without further knowledge of the specific barriers affecting a given population.

The implications of using maternity care deserts to measure progress in access to obstetric care: A mixed-integer optimization analysis.

Meredith ME, Steimle LN, Radke SM.

medRxiv [Preprint]. 2023 Nov 1:2023.10.31.23297779. doi: 10.1101/2023.10.31.23297779. PMID: 37961292; PMCID: PMC10635247.

• Among the factors contributing to the maternal mortality crisis in the United States is a lack of risk-appropriate access to obstetric care. There are several existing measures of access to obstetric care in the literature and popular media. In this study, we explored how current measures of obstetric access inform the number and location of additional obstetric care facilities required to improve access.
• We formulated two facility location optimization models to determine the number of new facilities required to minimize the number of reproductive-aged women living in obstetric care deserts. We define deserts as either "maternity care deserts", designated by the March of Dimes to be counties with no obstetric care hospital or obstetric providers, or regions further than 50 miles from critical care obstetric (CCO) services. We gathered information on hospitals with obstetric services from Georgia Department of Public Health public reports and estimated the female reproductive-age population by census block group using the American Community Survey.

Results: Out of the 1,910,308 reproductive-aged women who live in Georgia, 104,158 (5.5%) live in maternity care deserts, 150,563 (7.9%) reproductive-aged women live further than 50 miles from CCO services, and 38,202 (2.0%) live in both "maternity care desert" and further than 50 miles from CCO services. Our optimization analysis suggests that 16 new obstetric facilities (a 19% increase from the current 83 facilities) are required to reduce the number of reproductive-aged women living in "maternity care deserts" by 50% (from 104,158 to 51,477). At least 56 new obstetric care facilities (a 67% increase) would be required to eliminate maternity care deserts in Georgia. Meanwhile, expansion of 2 obstetric care facilities to offer CCO services would reduce the number of reproductive-aged women living further than 50 miles from CCO services by 50% (from 150,563 to 57,338), and 8 facilities would ensure all women in Georgia live within 50 miles of CCO services.

• Current measures of access to obstetric care may not be sufficient for evaluating access and tracking progress toward improvements. In a state like Georgia with a large number of small counties, eliminating maternity care deserts would require a prohibitively large number of new obstetric care facilities. This work suggests that additional measures and tools are needed to estimate the number and type of obstetric care facilities that best match practical resources to obstetric care needs.

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Multiplexed Live-Cell Imaging for Drug Responses in Patient-Derived Organoid Models of Cancer.

Colling KE, Symons EL, Buroni L, Sumanasiri HK, Andrew-Udoh J, Witt E, Losh HA, Morrison AM, Leslie KK, Dunnill CJ, de Bono JS, Thiel KW.

J Vis Exp. 2024 Jan 5;(203). doi: 10.3791/66072. PMID: 38251777.

Patient-derived organoid (PDO) models of cancer are a multifunctional research system that better recapitulates human disease as compared to cancer cell lines. PDO models can be generated by culturing patient tumor cells in extracellular basement membrane extracts (BME) and plating them as three-dimensional domes. However, commercially available reagents that have been optimized for phenotypic assays in monolayer cultures often are not compatible with BME. Herein, we describe a method to plate PDO models and assess drug effects using an automated live-cell imaging system. In addition, we apply fluorescent dyes that are compatible with kinetic measurements to quantify cell health and apoptosis simultaneously. Image capture can be customized to occur at regular time intervals over several days. Users can analyze drug effects in individual Z-plane images or a Z Projection of serial images from multiple focal planes. Using masking, specific parameters of interest are calculated, such as PDO number, area, and fluorescence intensity. We provide proof-of-concept data demonstrating the effect of cytotoxic agents on cell health, apoptosis, and viability. This automated kinetic imaging platform can be expanded to other phenotypic readouts to understand diverse therapeutic effects in PDO models of cancer.

Cervical Cancer: Preventable Deaths Among American Indian/Alaska Native Communities

Buck DiSilvestro J, Ulmer KK, Hedges M, Kardonsky K, Bruegl AS.

Obstet Gynecol Clin N Am. 2024 Mar;51(1):125–141. doi: 10.1016/j.ogc.2023.11.009.

American Indian/Alaska Native (AI/AN) individuals have twice the mortality rate of cervical cancer than the general US population. Participation in prevention programs such as cervical cancer screening and human papillomavirus (HPV) vaccination are under-utilized in this population. There are high rates of established cervical cancer risk factors among this community, with AI/AN people having a higher likelihood of infection with high-risk HPV strains not included in the 9-valent vaccine. There is a need for more robust and urgent prevention and treatment efforts in regard to cervical cancer in the AI/AN community.

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients.

Lutgendorf SK, Telles RM, Whitney B, Thaker PH, Slavich GM, Goodheart MJ, Penedo FJ, Noble AE, Cole SW, Sood AK, Corn BW.

Brain Behav Immun. 2023 Dec 9:S0889-1591(23)00396-3. doi: 10.1016/j.bbi.2023.12.014. Epub ahead of print. PMID: 38081436.

Introduction: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers.

• Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression.
• Greater hope was significantly related to a steeper cortisol slope, β = -0.193, p = 0.046, and lower night cortisol, β = -0.227, p = 0.018, plasma IL-6, β = -0.142, p = 0.033, and ascites IL-6, β = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = -0.233,p = 0.017 and ascites IL-6, β = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031.

Conclusions: These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.

Low indoleamine 2, 3 dioxygenase (IDO) activity is associated with psycho-obstetric risk.

Gumusoglu S, Meincke CR, Kiel M, Betz A, Nuckols V, DuBose L, Steidele J, Sweezer E, Santillan D, Stroud AK, Pierce GL, Santillan MK.

Pregnancy Hypertens. 2023 Dec 7;35:12-18. doi: 10.1016/j.preghy.2023.11.008. Epub ahead of print. PMID: 38064980.

Objectives: Preeclampsia and depression in pregnancy are among the most prevalent obstetric disorders with no known cures. While depression and preeclampsia each increase risk for the other, shared mechansisms are unclear. One possibility is low levels of Indoleamine 2,3 dioxygenase (IDO), which links immune dysregulation and oxidative arterial damage resulting in poor vascular function in both preeclampsia and depression. We hypothesized low circulating IDO activity levels in pregnancy would correspond to poor vascular function and depression symptoms.

Study design: In this nested case-control study, clinical, demographic, and biologic data from a cohort of pregnant women recruited to longitudinal studies measuring noninvasive vascular function and circulating factors were analyzed.

Main outcome measure: IDO activity across all three trimesters of pregnancy was measured using a colorimetric assay. Carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, was also assessed throughout gestation by non-invasive applanation tonometry. Depression symptoms were assessed in pregnancy via the validated patient health questionnaire 9 (PHQ9).

Results: Participants with low second and third trimester IDO activity had significantly decreased cfPWV. This association remained statistically significant when controlled for confounders such as BMI and chronic hypertension in the third but not second trimester. While PHQ9 scores were not associated with cfPWV differences, IDO activity was lower in moderate and severely depressed relative to non-depressed pregnant individuals.

Conclusion: These results implicate IDO in arterial stiffness and depression symptoms, suggesting that decreased IDO may be a central target for improved psycho-obstetric health.

The Iowa Health Data Resource (IHDR): an innovative framework for transforming the clinical health data ecosystem.

Davis HA, Santillan DA, Ortman CE, Hoberg AA, Hetrick JP, McBrearty CW, Zeng E, Vaughan Sarrazin MS, Dunn Lopez K, Chapman CG, Carnahan RM, Michaelson JJ, Knosp BM.

J Am Med Inform Assoc. 2023 Dec 15:ocad236. doi: 10.1093/jamia/ocad236. Epub ahead of print. PMID: 38102790.

Importance: This manuscript will be of interest to most Clinical and Translational Science Awards (CTSA) as they retool for the increasing emphasis on translational science from translational research. This effort is an extension of the EDW4R work that most CTSAs have done to deploy infrastructure and tools for researchers to access clinical data.

• : The Iowa Health Data Resource (IHDR) is a strategic investment made by the University of Iowa to improve access to real-world health data. The goals of IHDR are to improve the speed of translational health research, to boost interdisciplinary collaboration, and to improve literacy about health data. The first objective toward this larger goal was to address gaps in data access, data literacy, lack of computational environments for processing Personal Health Information (PHI) and the lack of processes and expertise for creating transformative datasets.
• : A three-pronged approach was taken to address the objective. The approach involves integration of an intercollegiate team of non-informatics faculty and staff, a data enclave for secure patient data analyses, and novel comprehensive datasets.
• To date, all five of the health science colleges (dentistry, medicine, nursing, pharmacy, and public health) have had at least one staff and one faculty member complete the two-month experiential learning curriculum. Over the first two years of this project, nine cohorts totaling 36 data liaisons have been trained, including 18 faculty and 18 staff. IHDR data enclave eliminated the need to duplicate computational infrastructure inside the hospital firewall which reduced infrastructure, hardware and human resource costs while leveraging the existing expertise embedded in the university research computing team. The creation of a process to develop and implement transformative datasets has resulted in the creation of seven domain specific datasets to date.
• The combination of people, process, and technology facilitates collaboration and interdisciplinary research in a secure environment using curated data sets. While other organizations have implemented individual components to address EDW4R operational demands, the IHDR combines multiple resources into a novel, comprehensive ecosystem IHDR enables scientists to use analysis tools with electronic patient data to accelerate time to science.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

Welch BM, Keil AP, Buckley JP, Engel SM, James-Todd T, Zota AR, Alshawabkeh AN, Barrett ES, Bloom MS, Bush NR, Cordero JF, Dabelea D, Eskenazi B, Lanphear BP, Padmanabhan V, Sathyanarayana S, Swan SH, Aalborg J, Baird DD, Binder AM, Bradman A, Braun JM, Calafat AM, Cantonwine DE, Christenbury KE, Factor-Litvak P, Harley KG, Hauser R, Herbstman JB, Hertz-Picciotto I, Holland N, Jukic AMZ, McElrath TF, Meeker JD, Messerlian C, Michels KB, Newman RB, Nguyen RHN, O'Brien KM, Rauh VA, Redmon B, Rich DQ, Rosen EM, Schmidt RJ, Sparks AE, Starling AP, Wang C, Watkins DJ, Weinberg CR, Weinberger B, Wenzel AG, Wilcox AJ, Yolton K, Zhang Y, Ferguson KK.

Environ Health Perspect. 2023 Dec;131(12):127015. doi: 10.1289/EHP12831. Epub 2023 Dec 20. PMID: 38117586.

Background: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.

Objectives: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.

• : We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.
• : In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): −34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: −19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.
• Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Multiplexed live-cell imaging for drug responses in patient-derived organoid models of cancer.

Colling KE, Symons EL, Buroni L, Sumanisiri HK, Andrew-Udoh J, Witt E, Losh HA, Morrison AM, Leslie KK, Dunnill CJ, De Bono JS, Thiel KW.

bioRxiv [Preprint]. 2023 Nov 17:2023.11.15.567243. doi: 10.1101/2023.11.15.567243. PMID: 38014133; PMCID: PMC10680710.

Patient-derived organoid (PDO) models of cancer are a multifunctional research system that better recapitulates human disease as compared to cancer cell lines. PDO models can be generated by culturing patient tumor cells in extracellular basement membrane extracts (BME) and plating as three-dimensional domes. However, commercially available reagents that have been optimized for phenotypic assays in monolayer cultures often are not compatible with BME. Herein we describe a method to plate PDO models and assess drug effects using an automated live-cell imaging system. In addition, we apply fluorescent dyes that are compatible with kinetic measurements to simultaneously quantitate cell health and apoptosis. Image capture can be customized to occur at regular time intervals over several days. Users can analyze drug effects in individual Z-plane images or a Z Projection of serial images from multiple focal planes. Using masking, specific parameters of interest are calculated, such as PDO number, area, and fluorescence intensity. We provide proof-of-concept data demonstrating the effect of cytotoxic agents on cell health, apoptosis and viability. This automated kinetic imaging platform can be expanded to other phenotypic readouts to understand diverse therapeutic effects in PDO models of cancer.

AptamerRunner: An accessible aptamer structure prediction and clustering algorithm for visualization of selected aptamers.

Ruiz-Ciancio D, Veeramani S, Embree E, Ortman C, Thiel KW, Thiel WH.

bioRxiv [Preprint]. 2023 Nov 15:2023.11.13.566453. doi: 10.1101/2023.11.13.566453. PMID: 38014343; PMCID: PMC10680646.

Aptamers are short single-stranded DNA or RNA molecules with high affinity and specificity for targets and are generated using the iterative Systematic Evolution of Ligands by EXponential enrichment (SELEX) process. Next-generation sequencing (NGS) revolutionized aptamer selections by allowing a more comprehensive analysis of SELEX-enriched aptamers as compared to Sanger sequencing. The current challenge with aptamer NGS datasets is identifying a diverse cohort of candidate aptamers with the highest likelihood of successful experimental validation. Herein we present AptamerRunner, an aptamer clustering algorithm that generates visual networks of aptamers that are related by sequence and/or structure. These networks can then be overlayed with ranking data, such as fold enrichment or data from scoring algorithms. The ability to visually integrate data using AptamerRunner represents a significant advancement over existing clustering tools by providing a natural context to depict groups of aptamers from which ranked or scored candidates can be chosen for experimental validation. The inherent flexibility, user-friendly design, and prospects for future enhancements with AptamerRunner has broad-reaching implications for aptamer researchers across a wide range of disciplines.