Recent Research Publications- March 2024
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.
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.
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.
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.
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.