Regenerative Therapy for Corneal Scarring Disorders.

The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions. These can significantly impair vision. The conventional challenges in managing corneal ailments include the limited regenerative capacity (except corneal epithelium), immune response after donor tissue transplantation, a risk of long-term graft rejection, and the global shortage of transplantable donor materials. This review delves into the intricate composition of the cornea, the landscape of corneal regeneration, and the multifaceted repercussions of scar-related pathologies. It will elucidate the etiology and types of dysfunctions, assess current treatments and their limitations, and explore the potential of regenerative therapy that has emerged in both in vivo and clinical trials. This review will shed light on existing gaps in corneal disorder management and discuss the feasibility and challenges of advancing regenerative therapies for corneal stromal scarring.

A Review of Animal Models Investigating the Reproductive Effects of Gender-Affirming Hormone Therapy.

Gender-affirming hormone therapy (GAHT) is an important component in the process of transitioning for many transgender and gender-diverse (TGD) individuals. Multiple medical organizations recommend fertility preservation counseling prior to initiation of GAHT; however, there remains little high-quality data regarding the impact of GAHT on fertility and reproductive function. A PubMed literature review was performed using Boolean search operators linking keywords or phrases such as "mouse", "rat", "primate", "animal model", "transgender", "gender", "estrogen", "testosterone", "fertility", and "fertility preservation". Recent research has produced a number of animal models of GAHT that utilize similar hormonal regimens and produce similar phenotypic results to those used and observed in human patients. Specific to testosterone(T)-containing GAHT, animals demonstrate loss of menstrual cyclicity with therapy, resumption of menses on cessation of therapy, suppression of gonadotropin levels, and physical changes such as clitoromegaly. Models mimicking GAHT for transmasculine individuals in the peripubertal period demonstrate that pretreatment with GnRHa therapy does not modify the effects of subsequent T administration, which were similar to those described in adult models. Both models suggest promising potential for future fertility with cessation of T. With estradiol (E)-containing GAHT, animals exhibit decreased size of testicles, epididymis, and seminal vesicles, as well as ongoing production of spermatocytes, and seminiferous tubule vacuolization. Given the ethical challenges of conducting human studies in this area, high-fidelity animal models represent a promising opportunity for investigation and could eventually transform clinical counseling about the necessity of fertility preservation. Future studies should better delineate the interactions (if any exist) between treatment attributes such as dosing and duration with the extent of reversibility of reproductive perturbations. The development of models of peripubertal feminizing GAHT is an additional area for future work.

Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers.

Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related to epidermal growth factor receptor (EGFR). These tyrosine kinases are involved in the transmission of cellular signals controlling normal cell growth and differentiation. If this transmission goes awry, it can lead to dysregulated growth of the cell. HER2 specifically can be implicated in the pathogenesis of at least eight malignancies. HER2 positivity quickly became a well-characterized indicator of aggressiveness and poor prognosis, with high rates of disease progression and mortality. After realizing the implication of HER2, it first became investigated as a target for treatment in breast cancer, and later expanded to areas of research in other cancer types. To this day, the most therapeutic advancements of anti-HER2 therapy have been in breast cancer; however, there have been strong advancements made in the incorporation of anti-HER2 therapy in other cancer types as well. This comprehensive review dissects HER2 to its core, incorporating the most up to date information. The topics touched upon are discussed in detail and up to 200 published sources from the most highly recognized journals have been integrated. The importance of knowing about HER2 is exemplified by the groundbreaking advancements that have been made, and the change in treatment plans it has brought to the oncological world in the last twenty years. Since its groundbreaking discovery there have been significant breakthroughs in knowledge regarding the actual receptor, the receptors biology, its mechanism of action, and advancements in tests to detect HER2 and significant strides on how to best incorporate targeted treatment. Due to the success of this field thus far, the review concludes by discussing the future of novel anti-HER2 therapy currently in development that everyone should be aware of.

Good manufacturing practice production of human corneal limbus-derived stromal stem cells and in vitro quality screening for therapeutic inhibition of corneal scarring.

BACKGROUND: Mesenchymal stem cells in the adult corneal stroma (named corneal stromal stem cells, CSSCs) inhibit corneal inflammation and scarring and restore corneal clarity in pre-clinical corneal injury models. This cell therapy could alleviate the heavy reliance on donor materials for corneal transplantation to treat corneal opacities. Herein, we established Good Manufacturing Practice (GMP) protocols for CSSC isolation, propagation, and cryostorage, and developed in vitro quality control (QC) metric for in vivo anti-scarring potency of CSSCs in treating corneal opacities. METHODS: A total of 24 donor corneal rims with informed consent were used-18 were processed for the GMP optimization of CSSC culture and QC assay development, while CSSCs from the remaining 6 were raised under GMP-optimized conditions and used for QC validation. The cell viability, growth, substrate adhesion, stem cell phenotypes, and differentiation into stromal keratocytes were assayed by monitoring the electric impedance changes using xCELLigence real-time cell analyzer, quantitative PCR, and immunofluorescence. CSSC's conditioned media were tested for the anti-inflammatory activity using an osteoclastogenesis assay with mouse macrophage RAW264.7 cells. In vivo scar inhibitory outcomes were verified using a mouse model of anterior stromal injury caused by mechanical ablation using an Algerbrush burring. RESULTS: By comparatively assessing various GMP-compliant reagents with the corresponding non-GMP research-grade chemicals used in the laboratory-based protocols, we finalized GMP protocols covering donor limbal stromal tissue processing, enzymatic digestion, primary CSSC culture, and cryopreservation. In establishing the in vitro QC metric, two parameters-stemness stability of ABCG2 and nestin and anti-inflammatory ability (rate of inflammation)-were factored into a novel formula to calculate a Scarring Index (SI) for each CSSC batch. Correlating with the in vivo scar inhibitory outcomes, the CSSC batches with SI < 10 had a predicted 50% scar reduction potency, whereas cells with SI > 10 were ineffective to inhibit scarring. CONCLUSIONS: We established a full GMP-compliant protocol for donor CSSC cultivation, which is essential toward clinical-grade cell manufacturing. A novel in vitro QC-in vivo potency correlation was developed to predict the anti-scarring efficacy of donor CSSCs in treating corneal opacities. This method is applicable to other cell-based therapies and pharmacological treatments.

Unhealthy air quality secondary to wildfires is associated with lower blastocyst yield.

OBJECTIVE: To study the impact of unhealthy air quality from the 2020 Oregon wildfires on outcomes for patients undergoing in vitro fertilization (IVF) treatment. DESIGN: A retrospective cohort study. SETTING: A university-based fertility clinic. PATIENTS: Subjects were undergoing IVF treatment from the 6 weeks preceding the wildfires through a 10-day exposure period. Cohorts were classified on the basis of whether subjects experienced patient and/or laboratory exposure to unhealthy air quality. Patient exposure was defined as at least 4 days of ovarian stimulation overlapping with the exposure, and laboratory exposure was defined as at least 2 days of IVF treatment and embryogenesis overlapping with the exposure. The unexposed cohort consisted of remaining subjects without defined exposure, with cycles in the 6 weeks preceding the wildfires. As some subjects had dual exposure and appeared in both patient and laboratory exposure cohorts, each cohort was separately compared with the unexposed control cohort. INTERVENTION: A 10-day period of unhealthy air quality caused by smoke plumes from a wildfire event. MAIN OUTCOME MEASURES: The primary outcome was the blastulation rate. Secondary outcomes included fertilization rate, number of blastocysts obtained, and cycles with no blastocysts frozen or transferred. RESULTS: Sixty-nine subjects underwent ovarian stimulation and IVF treatment during the 6 weeks preceding the wildfires through the 10-day period of unhealthy air quality. Of these, 15 patients were in the laboratory exposure cohort, 16 were in the patient exposure cohort, and 44 were unexposed. Six subjects appeared in both laboratory and patient exposure cohorts. Although neither exposure cohort had significantly decreased blastulation rate compared with the unexposed, the median number of blastocysts obtained was significantly lower in the laboratory exposure cohort than the unexposed group (2 [range 0-14] vs. 4.5 [range 0-21], respectively). The laboratory exposure cohort had significantly more cycles with no blastocysts obtained (3/15 [20%] vs. 1/44 [2%]). There were no significant differences in IVF treatment outcomes between patient exposure and unexposed cohorts. These findings persisted after controlling for age. There were no significant differences in pregnancy outcomes observed after embryo transfer between the exposure group and the unexposed group. CONCLUSION: For a cohort of patients undergoing IVF treatment, an acute episode of outside wildfire smoke exposure during fertilization and embryogenesis was associated with decreased blastocyst yield.

Time to Cancer Treatment and Chemotherapy Relative Dose Intensity for Patients With Breast Cancer Living With HIV.

Importance: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer. Objective: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV. Design, Setting, and Participants: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023. Exposure: HIV infection detected before or within 90 days of participants' breast cancer diagnosis. Main Outcomes and Measures: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests. Results: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]). Conclusions and Relevance: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.

Strengthening the Reproductive Endocrinology and Infertility Curriculum Through Three Interactive Cases.

Introduction: Improved reproductive endocrinology and infertility (REI) curricula are needed to address educational deficiencies both at our institution and on a national level. To improve REI education for OB/GYN residents and medical students, we developed and piloted a curriculum with in-person and virtual flexibility. Methods: We developed three clinical vignettes for a facilitator-led case-based discussion among OB/GYN residents: two office cases and one emergency scenario. Cases were evaluated by content experts and tested before implementation. Pre- and postsurveys included both multiple-choice questions on content and a Likert-scale self-assessment of comfort, satisfaction, and knowledge. Postsurveys were administered immediately postintervention and at a delayed interval. Responses were compared using paired t tests and McNemar tests. Results: Eighteen learners (16 OB/GYN residents and two medical students) participated, the majority in person, of whom 17 (94%) completed a postsurvey. Self-rated proficiency in evaluating and managing irregular menses, infertility, and amenorrhea all improved significantly immediately following the intervention (p < .05 for all). Learners reported significantly more knowledge and comfort with REI compared to other subspecialties following the intervention (p < .05). More learners responded correctly to knowledge questions postintervention (p < .05 for questions 1 and 2, p = .16 for question 3). All learners were satisfied with and enjoyed the curriculum. Eight learners completed the delayed postsurvey and showed sustained improvements in knowledge and competence with REI content. Discussion: Facilitator-guided case-based learning was effective in improving learners' confidence, comfort, and knowledge in managing REI conditions, and improvements were sustained following a delayed interval.

The COVID-19 impact on severe uncontrolled asthma costs and biologic use.

Background: Patients with severe uncontrolled asthma (SUA) overwhelmingly contribute to the economic burden of asthma and may require biologic therapy. However, the impact of the CoronaVirus Disease of 2019 (COVID-19) on asthma costs and biologic use has yet to be evaluated. Objective: The objective was to test the hypothesis that SUA costs and biologic use decreased during the pandemic. Methods: We analyzed medical costs and biologic use in patients with SUV from January 2017 to December 2021, by using claims data from a large managed care organization and electronic health record data from Robert Wood Johnson Barnabas Health, according to provider specialty. Results: Of the 3817 managed care organization enrollees within Robert Wood Johnson Barnabas Health with a primary diagnosis of asthma, 348 were identified as having SUA. A nested sample of 151 patients revealed that 50% were managed by primary care physicians (PCP) and specialists, 43% by PCPs only, and 4% by specialists only. The total costs of the claims were $10.8 million over 5 years ($2.2 million per year), with 60% generated from patients seeing PCPs and specialists, 27% from PCPs only, and 15% from specialists only. During the pandemic, total average costs decreased for all care groups (34% PCP-only patients and 45% for both specialist-only and PCP and specialist patients). Inpatient and outpatient costs also decreased and were lowest for patients who saw specialists and highest for patients who saw PCPs and specialists. In contrast, prescription costs increased during the pandemic. Biologic use was steadily increasing until a twofold decrease was observed during the pandemic. Thirteen patients were on biologics: two were managed by PCPs, four by specialists, and seven by both. Conclusion: Inpatient and outpatient costs decreased during the COVID-19 pandemic, but prescription costs increased. Biologic use was increasing among patients with SUA before the pandemic but then drastically decreased and remained lower during the observational interval.

Mifepristone-misoprostol combination treatment for early pregnancy loss after embryo transfer: a case series.

Objective: Evidence strongly supports the use of mifepristone-misoprostol combination treatment for early pregnancy loss (EPL) among pregnancies conceived without assisted reproductive technologies. No literature exists, however, regarding the efficacy of this treatment in the medical management of EPL among pregnancies after in vitro fertilization and embryo transfer (IVF-ET). These patients differ as some use exogenous hormonal supplementation to provide pregnancy support. Thus, the management for EPL may differ between unassisted conceptions and those after ET. Mifepristone, a progesterone receptor antagonist, may demonstrate an altered treatment effect when used with misoprostol to manage EPL in assisted reproductive technologie-conceived pregnancies. Objective: To describe our institution's experience using mifepristone-misoprostol to manage EPL after in vitro fertilization with embryo transfer IVF-ET. Design: Retrospective case series. Setting: Single academic institution from 2020 to 2022. Patientss: Nine patients with ultrasound confirmed EPL after IVF-ET. Interventions: All 9 patients underwent in vitro fertilization followed by fresh or frozen embryo transfer. All 9 received 200 mg of mifepristone 24 hours before 800 µg of misoprostol. Main Outcome Measurements: Incomplete abortion, need for surgical management, number of days to negative serum human chorionic gonadotropin (hCG). Results: Of the 9 subjects included, one had a programmed frozen embryo transfer cycle, 6 had modified natural frozen embryo transfer cycles, and 2 underwent fresh ET. Eight subjects had successful expulsion of tissue with one dose of treatment, and one required uterine aspiration. No subjects required additional dosing of misoprostol. The mean number of days elapsed from mifepristone treatment to tissue expulsion was 4.89 ± 11.30 days and the mean days to negative-range serum hCG was 36.89 ± 18.59 days. At the initial ultrasound, all pregnancies had one gestational sac seen; 5/9 had a yolk sac; only 3 had fetal cardiac activity. The mean gestational age at the time of EPL diagnosis was 55.22 ± 8.77 days, with the majority (8/9) having completed 7 weeks gestation. Conclusions: Mifepristone-misoprostol combination treatment appears to be a reasonable option for those with EPL after IVF-ET. Future, larger-scale studies are needed comparing combination treatment with misoprostol only among various ET protocols.

Human corneal stromal stem cells express anti-fibrotic microRNA-29a and 381-5p - A robust cell selection tool for stem cell therapy of corneal scarring.

INTRODUCTION: Corneal blindness due to scarring is treated with corneal transplantation. However, a global problem is the donor material shortage. Preclinical and clinical studies have shown that cell-based therapy using corneal stromal stem cells (CSSCs) suppresses corneal scarring, potentially mediated by specific microRNAs transported in extracellular vesicles (EVs). However, not every CSSC batch from donors achieves similar anti-scarring effects. OBJECTIVES: To examine miRNA profiles in EVs from human CSSCs showing "healing" versus "non-healing" effects on corneal scarring and to design a tool to select CSSCs with strong healing potency for clinical applications. METHODS: Small RNAs from CSSC-EVs were extracted for Nanostring nCounter Human miRNA v3 assay. MicroRNAs expressed > 20 folds in "healing" EVs (P < 0.05) were subject to enriched gene ontology (GO) term analysis. MiRNA groups with predictive regulation on inflammatory and fibrotic signalling were studied by mimic transfection to (1) mouse macrophages (RAW264.7) for M1 phenotype assay; (2) human corneal keratocytes for cytokine-induced fibrosis, and (3) human CSSCs for corneal scar prevention in vivo. The expression of miR-29a was screened in additional CSSC batches and the anti-scarring effect of cells was validated in mouse corneal wounds. RESULTS: Twenty-one miRNAs were significantly expressed in "healing" CSSC-EVs and 9 miRNA groups were predicted to associate with inflammatory and fibrotic responses, and tissue regeneration (P <10-6). Overexpression of miR-29a and 381-5p significantly prevented M1 phenotype transition in RAW264.7 cells after lipopolysaccharide treatment, suppressed transforming growth factor ß1-induced fibrosis marker expression in keratocytes, and reduced scarring after corneal injury. High miR-29a expression in EV fractions distinguished human CSSCs with strong healing potency, which inhibited corneal scarring in vivo. CONCLUSION: We characterized the anti-inflammatory and fibrotic roles of miR-29a and 381-5p in CSSCs, contributing to scar prevention. MiR-29a expression in EVs distinguished CSSCs with anti-scarring quality, identifying good quality cells for a scarless corneal healing.

Patients with Recurrent Pregnancy Loss Have Similar Embryonic Preimplantation Genetic Testing Aneuploidy Rates and In Vitro Fertilization Outcomes to Infertility Patients.

Objective: To evaluate aneuploidy rates and in vitro fertilization (IVF)/pregnancy outcomes for patients undergoing IVF and preimplantation genetic testing for aneuploidy (PGT-A) with a recurrent pregnancy loss (RPL) diagnosis compared to infertility diagnoses without RPL. Design: Retrospective cohort study. Setting: Academic fertility center. Patients: Of 372 patients undergoing IVF/PGT-A between January 2016-December 2018, 294 patients were included in the analysis: 56 patients with an RPL diagnosis and 238 with infertility diagnoses without RPL. Interventions: None. Main Outcome Measures: The primary outcome measured was the embryonic aneuploidy rate. Secondary outcomes included fertilization and blastulation rates, number of blastocysts biopsied, cycles without euploid blastocysts, and rates of pregnancy losses, clinical pregnancies, and live births after a euploid embryo transfer. Results: The cohort included 56 patients with RPL and 238 patients without RPL, including data from their first IVF cycle within the time period. Aneuploidy rates were similar between the groups, with a mean of 55% (±31%) in RPL and 54% (±34%) in non-RPL cycles. Similar rates persisted after controlling for age, ovarian reserve, and infertility diagnosis. Fertilization and blastulation rates, as well as cumulative clinical pregnancy, pregnancy loss, and live birth rates after the transfer of at least one euploid embryo were also similar between the two groups. Conclusions: These results suggest that IVF/PGT-A cycles from patients with an RPL diagnosis have similar IVF and pregnancy outcomes to those of patients with infertility without RPL. This research can help guide counseling for RPL patients considering IVF with PGT-A.

Combined Therapy Using Human Corneal Stromal Stem Cells and Quiescent Keratocytes to Prevent Corneal Scarring after Injury.

Corneal blindness due to scarring is conventionally treated by corneal transplantation, but the shortage of donor materials has been a major issue affecting the global success of treatment. Pre-clinical and clinical studies have shown that cell-based therapies using either corneal stromal stem cells (CSSC) or corneal stromal keratocytes (CSK) suppress corneal scarring at lower levels. Further treatments or strategies are required to improve the treatment efficacy. This study examined a combined cell-based treatment using CSSC and CSK in a mouse model of anterior stromal injury. We hypothesize that the immuno-regulatory nature of CSSC is effective to control tissue inflammation and delay the onset of fibrosis, and a subsequent intrastromal CSK treatment deposited collagens and stromal specific proteoglycans to recover a native stromal matrix. Using optimized cell doses, our results showed that the effect of CSSC treatment for suppressing corneal opacities was augmented by an additional intrastromal CSK injection, resulting in better corneal clarity. These in vivo effects were substantiated by a further downregulated expression of stromal fibrosis genes and the restoration of stromal fibrillar organization and regularity. Hence, a combined treatment of CSSC and CSK could achieve a higher clinical efficacy and restore corneal transparency, when compared to a single CSSC treatment.

Human Milk-Expression Technologies: A Primer for Obstetricians.

Lactation is a powerful tool for improving health trajectories and promoting reproductive justice. Multiple new human milk-expression technologies are available. Although direct feeding is optimal and feasible in many circumstances, understanding human milk-expression technology and counseling patients appropriately represents one of the ways physicians can support patients in meeting their feeding goals. Breast pumps and breast pump accessories may help patients establish and maintain breastfeeding, but these technologies continue to evolve and are not always intuitive. The core components of a pump are the attachment at the breast, valves, tubing, motor, device programming, and reservoir. Whereas closed systems can be used by multiple patients, open systems are single-user and they are not able to be sterilized. Mobile pumps may help support breastfeeding individuals who are unable to remain stationary for the time necessary to express milk. Nonelectric pumps represent an important adjuvant technology. There are a wide variety of pump accessories that may help patients overcome specific breastfeeding challenges. Obstetricians remain uniquely positioned to support patients in achieving their lactation goals, which is enhanced by familiarity with the supportive technologies available.

Biomarker underuse contributes to an inability to phenotype patients with severe uncontrolled asthma.

Background: Biomarker measurements improve the phenotyping of patients with severe uncontrolled asthma (SUA) and predict therapeutic responses. The use of biomarkers in asthma, however, remains underused. Objective: To test the hypothesis that biomarker measurements of patients with SUA remain markedly underused and contributes to asthma morbidity and oral corticosteroid use. Methods: Leveraging claims data linked to electronic health record data, we calculated biomarker use by providers treating patients with SUA from January 2017 to August 2020. Results: From 3.6 million clients, 3817 had a primary diagnosis of asthma; most were between 50 and 60 years old. Also, 63.2% were female patients; those under ages 10 years were primarily boys. Of the 728 patients who reported race, 69.9% were white and 21.8% were African American. Of the 840 who reported ethnicity, 14% were Latinx. A predetermined definition of SUA identified 348 patients with SUA. In a nested sample of 151 patients with SUA, 43% were managed by primary care physicians (PCP), 4% by specialists, and 49.7% by both. Of this sample, 61.5% had a measurement of serum eosinophils, 9.9% total immunoglobulin E values, and 9.3% radioallergosorbent skin tests; 38% received no tests, whereas 9.9% had more than one. Specialists ordered a biomarker test 4.6 times more often than did PCPs, whereas PCPs ordered 70% of the prednisone prescriptions for recurrent asthma exacerbations. Conclusion: Specialists were more likely to order biomarkers than were PCPs. Patients managed exclusively by PCPs were more likely prescribed oral prednisone. Real-world evidence shows that biomarkers are infrequently used to characterize patients with SUA, especially among patients exclusively managed by PCPs. Programs that encouraged biomarker use may improve SUA management and oral corticosteroid burden.

Surgical uterine evacuation in patients with two cervices: a case series.

OBJECTIVES: To describe the clinical circumstances, surgical approach, intraoperative challenges, and outcomes of patients with two cervices undergoing uterine evacuation for spontaneous, incomplete, or induced abortion at our institution. STUDY DESIGN: We used diagnostic and procedure codes related to uterine anomalies and uterine evacuation to identify patients with cervical duplication who underwent uterine evacuation at Penn Medicine from January 2008 to December 2020. RESULTS: We identified 15 patients with cervical duplication in whom we performed uterine evacuations during 19 pregnancies. We describe in detail each patient's first pregnancy with uterine evacuation at our institution, of which providers performed 11 in the first trimester, and four in the second trimester. Ten patients had a known diagnosis of cervical duplication prior to pregnancy. Five patients did not have a diagnosis of cervical duplication prior to pregnancy and providers newly made this diagnosis intraoperatively either at our institution or referring clinics. Providers at outside institutions referred three patients to our institution for incomplete procedures. At our institution, one patient had a procedure notable for a major complication. Eight other cases were notable for surgical challenges including difficulty placing osmotic dilators, difficulty identifying the correct cervix for local anesthesia, and contralateral cervical and uterine horn instrumentation. CONCLUSIONS: This case series suggests surgical abortion in patients with two cervices is rare, but generally safe. The majority of patients did not have major complications, despite presenting a variety of unique procedural challenges. Surgical providers were sometimes the first to make the diagnosis of a second cervix. IMPLICATIONS: Uterine evacuation providers must be aware of the possibility of an undiagnosed cervical duplication, particularly when encountering surgical challenges in patients with congenital reproductive tract anomalies. Providers should consider procedures under ultrasound guidance regardless of gestational age for patients with any congenital reproductive tract anomaly or who had prior incomplete procedures.

The incidence and importance of the pseudogestational sac revisited.

BACKGROUND: In a pregnancy of unknown location, an intrauterine fluid collection may represent either the early gestational sac of an intrauterine pregnancy, or as reported in previous literature, the pseudogestational sac of an ectopic pregnancy. Various sonographic features have been used to distinguish these 2 entities, but the clinical relevance of the pseudogestational sac remains unclear. OBJECTIVE: To establish the incidence and relative rate of intrauterine fluid collection among ectopic and intrauterine pregnancies and to determine if the size of the collection differs between ectopic and intrauterine pregnancies STUDY DESIGN: We performed a retrospective cohort study of women with pregnancies of unknown location and pelvic or abdominal pain or bleeding. We calculated the incidences of intrauterine fluid collections among ectopic and intrauterine pregnancies, including both ongoing pregnancies and spontaneous abortions, given that that our focus was location and not viability. We calculated the relative risk of ectopic pregnancy if an intrauterine fluid collection was present, adjusting for age and vaginal bleeding. We compared the incidences of ectopic and intrauterine pregnancies among those with and without intrauterine fluid collections. Among those with collections, we compared the mean sac diameter between ectopic and intrauterine pregnancies in continuous and categorical fashions. RESULTS: We evaluated 1236 women presenting with a pregnancy of unknown location. The rates of ectopic and intrauterine pregnancies (including spontaneous abortions) were 13.1% and 63.9%, respectively, with the remainder lost to follow-up. On ultrasound, 452 women (36.6%) had an intrauterine fluid collection. Eight of 162 ectopic pregnancies (4.9%) had a collection, compared with 363 of 789 intrauterine pregnancies (46.0%) (P=.01). Of the ectopics with a fluid collection, 5 had an adnexal mass. The presence of intrauterine fluid collection decreased the risk of ectopic pregnancy (adjusted relative risk, 0.09; 95% confidence interval, 0.05-0.19) after adjusting for age and the presence of bleeding. Among those with an intrauterine fluid collection, the rate of ectopic pregnancy was 2.2%, and the rate of intrauterine pregnancy was 97.8%; among those without a collection, the rate of ectopic pregnancy was 26.7%, and the rate of intrauterine pregnancy was 73.3%. The mean sac diameter did not differ between ectopic and intrauterine pregnancies, whether analyzed continuously or categorically. CONCLUSION: In the presence of an intrauterine fluid collection, the rate of ectopic pregnancy is very low. The size of the intrauterine fluid collection in a woman with a pregnancy of unknown location cannot be used to distinguish between a gestational sac and a pseudogestational sac. Pseudogestational sacs are uncommon and of little clinical consequence. In assessing pregnancies of unknown location, clinicians should incorporate the entire clinical picture, including other sonographic findings, to avoid incorrect or delayed diagnoses.

cAIR: Implementation of peer response support for frontline health care workers facing the COVID-19 pandemic.

Purpose: While global pandemics such as the COVID-19 public health crisis are known to increase the likelihood of frontline health care workers experiencing the negative effects of stress and trauma, many health care workers on the frontlines of the COVID-19 pandemic lack adequate support. This paper presents the findings of a social work led peer support model, COVID-19 Am I Resilient (cAIR), developed and deployed during the first wave of the COVID-19 pandemic.Methods: This quality improvement initiative was developed and piloted within the Clinical Education and Practice department at a large urban health care system. The pilot included provision of peer support through synchronous video presentations, one-on-one peer support, and resourcing and referral. Pilot outcomes of feasibility and staff engagement were evaluated using participant responses to an online survey as well as attendance records at project activities.Implications: Developed to help frontline health care workers thrive in the midst, and wake, of the COVID-19 pandemic, the pilot study of the cAIR peer support model has implications for further development and implementation of peer support for typically underrepresented health care disciplines working during the COVID-19 pandemic as well as future public health emergencies.

Detection of COVID-19 in a Vulvar Lesion.

As new information about coronavirus disease 2019 (COVID-19) is rapidly discovered, clinicians are better equipped to make informed decisions for their patients. While current research suggests COVID-19 viral antigen is not found in vaginal secretions, its detectability in the female lower genital tract may have clinical implications for obstetric and gynecologic care for women. We present a case of a woman at 31 weeks' gestation with simultaneous upper respiratory symptoms and vulvovaginitis. She was found to have a vulvar lesion positive for severe acute respiratory syndrome-COVID by viral swab. This case shows that COVID-19 is detectable in the vulva. This may have implications for health care workers' exposure and personal protective equipment needs. While vertical transmission has largely not been reported, the presence of detectable virus in the female lower genital tract makes this a continued possibility and area of study. KEY POINTS: · COVID-19 is detectable in the female lower genital tract.. · The detection of COVID-19 in the vulva may have implications for personal protective equipment use.. · The detection of COVID-19 in vulvovaginal lesions makes vertical transmission a continued possibility..