Iltamiocel Autologous Cell Therapy for the Treatment of Female Stress Urinary Incontinence: A Double-Blind, Randomized, Stratified, Placebo-Controlled Trial.

AIMS: This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI). METHODS: Adult females were randomized 2:1 to iltamiocel (150 × 106 cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations. RESULTS: The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants. CONCLUSION: The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41.

Sarcopenia is associated with survival in patients awaiting kidney transplant.

BACKGROUND: The relationship of sarcopenia to frailty and other survival determinants in patients waitlisted for kidney transplant is not well characterized. Our goal was to evaluate the relationship of muscle area to functional and frailty metrics and its impact on survival in patients waitlisted for kidney transplant. METHODS: Among 303 consecutively listed transplant candidates, 172 had a computed scan within 3 months of frailty and biochemical testing that permitted muscle area evaluation. Third lumbar level psoas muscle indices (total bilateral psoas area/height2) were calculated. Testing included frailty metrics, treadmill and pedometer ability, troponin, and brain natriuretic peptide levels. Associations between muscle area, demographic, biochemical, and frailty measures were analyzed. Log-rank test was used to evaluate waitlist survival on the basis of muscle area, and multivariate Cox proportional hazards modeling was used to evaluate factors independently associated with survival. RESULTS: Demographic factors associated with third lumbar level psoas muscle indices include male sex (P < .001), race (P = .02), age (P = .004), and body mass index (P < .0001). Grip strength, treadmill ability, and Sit-Stands positively correlated with third lumbar level psoas muscle indices (P < .01). Brain natriuretic peptide and Up and Go negatively correlated with third lumbar level psoas muscle indices (P < .01). Survival was significantly associated with third lumbar level psoas muscle indices (P = 0.02). Treadmill ability, Sit-Stands, Up and Go, race and muscle area were most closely associated with waitlist survival on multivariate modeling. CONCLUSION: Sarcopenia as assessed with muscle area measurements is independently associated with kidney waitlist survival. Functional ability and muscle area may be overlapping, but noncongruent, determinants of waitlist outcomes and may need to be individually assessed to create the most predictive survival model.

Simulated bupivacaine pharmacokinetics after labor epidural analgesia followed by transversus abdominis plane block with liposomal bupivacaine for intrapartum cesarean delivery.

STUDY OBJECTIVE: To simulate bupivacaine pharmacokinetics in scenarios of labor epidural analgesia (LEA) extended for intrapartum cesarean delivery (CD) with epidural or intrathecal boluses, followed by transversus abdominis plane (TAP) block with liposomal bupivacaine (LB) for postcesarean analgesia. DESIGN: Bupivacaine plasma concentrations were simulated using a 2-compartment distribution model fit to previous study data. SETTING: Virtual pharmacokinetic simulations. PATIENTS: Virtual individuals (1000, each scenario) had uniform weight (80 kg) but varying absorption parameters. INTERVENTIONS: The 6 scenarios varied in LEA infusion duration (6 or 24 h), local anesthetic used for bolus to extend LEA (epidural lidocaine or intrathecal bupivacaine), TAP block regimen, and time between bolus and TAP block. MEASUREMENTS: Scenario outcomes included geometric mean (GM) peak bupivacaine plasma concentration (Cmax) with 95% prediction interval (PI), median (range) Cmax, and number of virtual individuals (per 1000) with Cmax reaching estimated toxicity thresholds (neurotoxicity: 2000 µg/L; cardiotoxicity: 4000 µg/L). MAIN RESULTS: In simulated scenarios of LEA infusion for 24 h with an epidural bolus of lidocaine 400 mg for CD followed 1 h later by TAP block, the GM Cmax for the scenarios with TAP blocks including either LB 266 mg plus bupivacaine hydrochloride 52 mg or bupivacaine hydrochloride 104 mg was 1860 (95% PI, 1107-3124) and 1851 (95% PI, 1085-3157) µg/L, respectively. Among 1000 virtual individuals for each scenario, 404 and 401 had Cmax reaching 2000 µg/L, respectively; 1 and 0 had Cmax reaching 4000 µg/L, respectively. For other scenarios, GM Cmax remained <1000 µg/L. CONCLUSIONS: Across 6 different simulations of TAP blocks for intrapartum CD analgesia, LEA with bupivacaine (with or without boluses for extension and including a conservative modeling of lidocaine without epinephrine), followed by TAP block with LB and/or bupivacaine hydrochloride 0, 1, or 2 h after CD, is unlikely to result in bupivacaine plasma concentrations reaching local anesthetic systemic toxicity thresholds in healthy patients.

Proteogenomic analysis integrated with electronic health records data reveals disease-associated variants in Black Americans.

BACKGROUND: Most genome wide association studies (GWAS) of plasma proteomics have focused on White individuals of European ancestry, limiting biological insight from other ancestry enriched protein quantitative loci (pQTL). METHODS: We conducted a discovery GWAS of ~3,000 plasma proteins measured by the antibody based Olink platform in 1,054 Black adults from the Jackson Heart Study (JHS), and validated our findings in the Multi-Ethnic Study of Atherosclerosis (MESA). The genetic architecture of identified pQTLs were further explored through fine mapping and admixture association analysis. Finally, using our pQTL findings, we performed a phenome wide association study (PheWAS) across two large multi-ethnic electronic health record (EHR) systems in All of Us and BioMe. RESULTS: We identified 1002 pQTLs for 925 proteins. Fine mapping and admixture analyses suggested allelic heterogeneity of the plasma proteome across diverse populations. We identified associations for variants enriched in African ancestry, many in diseases that lack precise biomarkers, including cis-pQTLs for Cathepsin L (CTSL) and Siglec-9 that were linked with sarcoidosis and non-Hodgkin's lymphoma, respectively. We found concordant associations across clinical diagnoses and laboratory measurements, elucidating disease pathways, including a cis-pQTL associated with circulating CD58, white blood cell count, and multiple sclerosis. CONCLUSIONS: Our findings emphasize the value of leveraging diverse populations to enhance biological insights from proteomics GWAS, and we have made this resource readily available as an interactive web portal.

Charting the Molecular Terrain of Exercise: The Power of Multi-Omic Mapping.

Physical activity plays a fundamental role in human health and disease. Exercise has been shown to improve a wide variety of disease states, and the scientific community is committed to understanding the precise molecular mechanisms that underlie the exquisite benefits. This review provides an overview of molecular responses to acute exercise and chronic training, particularly energy mobilization and generation, structural adaptation, inflammation, and immune regulation. Further it offers a detailed discussion on known molecular signals and systemic regulators activated during various forms of exercise and their role in orchestrating health benefits. Critically, the increasing use of multi-omic technologies is explored with an emphasis on how multi-omic and multi-tissue studies contribute to a more profound understanding of exercise biology. These data inform anticipated future advancement in the field and highlight the prospect of integrating exercise with pharmacology for personalized disease prevention and treatment.

Impact of Neuraxial Preservative-Free Morphine in Vaginal Delivery on Opiate Consumption and Recovery: A Randomized Control Trial.

BACKGROUND: Neuraxial opioids are commonly used after cesarean delivery (CD). However, they are not commonly used after vaginal delivery (VD) though some studies have suggested they may be beneficial from a pain perspective. However, they did not evaluate other potential benefits including patient satisfaction, impact on postpartum depression and breastfeeding (BF) success, or side effects such as pruritus. METHODS: Parturients who delivered vaginally with epidural analgesia were randomized to receive either 2 mg of preservative-free morphine (4 mL) or saline (4 mL) via the epidural catheter within 1 hour of VD. Routine analgesics were unchanged and included q 6-hour dosing of acetaminophen 975 mg orally and ketorolac 30 mg intravenous (IV). Hydromorphone 2 mg or oxycodone 10 mg were offered for breakthrough pain. Our primary outcome was opiate consumption in the first 24 hours after drug administration. Secondary outcomes included pain scores at 24 hours and 1 week postpartum as well as opiate consumption up to 1 week postpartum. Additional end points such as obstetric quality of recovery score (OBS-QOR10) breast feeding success, and an Edinburgh Postnatal Depression Score (EPDS) were also obtained. RESULTS: Data were analyzed for 157 parturients, 80 in the morphine group and 77 in the saline group. No difference was observed in the EDPS score predelivery or intention to BF. We found a statistically significant difference in the use of opioids in the first 24 hours, 3.8% (95% confidence interval [CI], 0.9%-11.3%) vs 14.3% (7.7%-24.5%) in the morphine and saline groups, respectively; and in total opioid dose, median (interquartile range, IQR [range]) of morphine milligram equivalent vs 0 (0-0 [0-47.5]) vs 0 (0-0 [0-72]), P = .023, in the morphine and saline groups, respectively. Verbal pain scores (0-10) at 24 hours were lower in the morphine group (median (IQR [range): 2.0 (1-4 [0-10]) vs 3.0 (1.5-5.0 [0-10]), P = .043. There was a greater incidence of pruritus in the morphine group versus saline group, 37.5% (95% CI, 27.1%-49.1%) vs 18.2% (95% CI, 10.6%-29.0%), P = .008. We did not find any differences in the OBS-QOR10, BF success, or EPDS at 6 weeks PP (P < .05). CONCLUSIONS: A single epidural dose of 2 mg preservative-free morphine after VD was effective at decreasing pain and opioid use at 24 hours after VD but came at the cost of increased pruritus. We did not detect any differences in BF, recovery scores, or PPD. Future studies should focus on elucidating the role of neuraxial preservative-free morphine after VD.

Anesthetic management with labor epidural analgesia of the parturient with severe factor VII deficiency: a case report.

BACKGROUND: Factor VII deficiency is considered a contraindication to neuraxial anesthesia due to the risk of an epidural hematoma. CASE REPORT: A 32 year old G1P0 parturient with severe factor VII deficiency presented for an anesthesiology consultation at 32 weeks gestation. Initial coagulation studies were significant for an elevated INR (2.0) and a low factor VII level of 6%. After interdisciplinary discussion, it was decided that neuraxial analgesia could be offered if her coagulation studies corrected after administration of recombinant activated factor VII (rFVIIa). The patient presented at 36 weeks gestation for a rFVIIa challenge. She received 22 mcg/kg rFVIIa and coagulation studies were analyzed 20 minutes later which showed complete correction of the coagulopathy. The patient presented to the hospital at 39 weeks and 3 days for delivery, received 2 mg rFVIIa and 20 minutes later, successfully received an epidural catheter. Her INR was monitored every 3 hours during her labor course and rFVIIa was given if the INR was 1.3 or greater. She required three additional doses over 22 hours. No bleeding or thrombotic events occurred, and the patient was discharged home without complications. CONCLUSION: This case highlights the safe management of an epidural catheter in a parturient with severe factor VII deficiency.

Pollen and viruses contribute to spatio-temporal variation in asthma-related emergency department visits.

BACKGROUND: Asthma exacerbations are an important cause of emergency department visits but much remains unknown about the role of environmental triggers including viruses and allergenic pollen. A better understanding of spatio-temporal variation in exposure and risk posed by viruses and pollen types could help prioritize public health interventions. OBJECTIVE: Here we quantify the effects of regionally important Cupressaceae pollen, tree pollen, other pollen types, rhinovirus, seasonal coronavirus, respiratory syncytial virus, and influenza on asthma-related emergency department visits for people living near eight pollen monitoring stations in Texas. METHODS: We used age stratified Poisson regression analyses to quantify the effects of allergenic pollen and viruses on asthma-related emergency department visits. RESULTS: Young children (<5 years of age) had high asthma-related emergency department rates (24.1 visits/1,000,000 person-days), which were mainly attributed to viruses (51.2%). School-aged children also had high rates (20.7 visits/1,000,000 person-days), which were attributed to viruses (57.0%), Cupressaceae pollen (0.7%), and tree pollen (2.8%). Adults had lower rates (8.1 visits/1,000,000 person-days) which were attributed to viruses (25.4%), Cupressaceae pollen (0.8%), and tree pollen (2.3%). This risk was spread unevenly across space and time; for example, during peak Cuppressaceae season, this pollen accounted for 8.2% of adult emergency department visits near Austin where these plants are abundant, but 0.4% in cities like Houston where they are not; results for other age groups were similar. CONCLUSIONS: Although viruses are a major contributor to asthma-related emergency department visits, airborne pollen can explain a meaningful portion of visits during peak pollen season and this risk varies over both time and space because of differences in plant composition.

FAIR-USE4OS: Guidelines for creating impactful open-source software.

This paper extends the FAIR (Findable, Accessible, Interoperable, Reusable) guidelines to provide criteria for assessing if software conforms to best practices in open source. By adding "USE" (User-Centered, Sustainable, Equitable), software development can adhere to open source best practice by incorporating user-input early on, ensuring front-end designs are accessible to all possible stakeholders, and planning long-term sustainability alongside software design. The FAIR-USE4OS guidelines will allow funders and researchers to more effectively evaluate and plan open-source software projects. There is good evidence of funders increasingly mandating that all funded research software is open source; however, even under the FAIR guidelines, this could simply mean software released on public repositories with a Zenodo DOI. By creating FAIR-USE software, best practice can be demonstrated from the very beginning of the design process and the software has the greatest chance of success by being impactful.

Impact of cell salvage on hematocrit and post-partum anemia in low hemorrhage risk elective cesarean delivery.

BACKGROUND: Postpartum anemia is a significant contributor to peripartum morbidity. The utilization of cell salvage in low risk cases and its impact on postpartum anemia has not been investigated. We therefore aimed to examine the impact of autologous blood transfusion/cell salvage in routine cesarean delivery on postoperative hematocrit and anemia. STUDY DESIGN AND METHODS: Retrospective cohort study from a perfusion database from a large academic center where cell salvage is performed at the discretion of the obstetrical team. Data from 99 patients was obtained. All patients were scheduled elective cesarean deliveries that took place on the labor and delivery floor. Thirty patients in the cohort had access to cell salvage where autologous blood was transfused after surgery. Pre-procedural hemoglobin/hematocrit measurements were obtained along will postpartum samples that were collected on post-partum day one. RESULTS: The median amount of blood returned to cell salvage patients was 250 mL [206-250]. Hematocrit changes in cell salvage patients was significantly smaller than controls (-1.85 [-3.87, -0.925] vs -6.4 [-8.3, -4.75]; p < 0.001). The odds of developing new anemia following surgery were cut by 74% for the cell salvage treatment group, compared to the odds for the control group (OR = 0.26 (0.07-0.78); p = 0.028) DISCUSSION: Despite losing more blood on average, patients with access to cell salvage had higher postoperative HCT, less postpartum anemia, and no difference in complications related to transfusion. The utilization of cell salvage for routine cesarean delivery warrants further research.

Special issue on software citation, indexing, and discoverability.

Software plays a fundamental role in research as a tool, an output, or even as an object of study. This special issue on software citation, indexing, and discoverability brings together five papers examining different aspects of how the use of software is recorded and made available to others. It describes new work on datasets that enable large-scale analysis of the evolution of software usage and citation, that presents evidence of increased citation rates when software artifacts are released, that provides guidance for registries and repositories to support software citation and findability, and that shows there are still barriers to improving and formalising software citation and publication practice. As the use of software increases further, driven by modern research methods, addressing the barriers to software citation and discoverability will encourage greater sharing and reuse of software, in turn enabling research progress.

Immediate vs. multistage revascularization of non-infarct coronary artery(-ies) in patients with hemodynamically stable multivessel disease acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Untreated multivessel disease (MVD) in acute myocardial infarction (AMI) has been linked to a higher risk of recurrent ischemia and death within one year . Current guidelines recommend percutaneous coronary intervention (PCI) for significant non-infarct artery (-ies) (non-IRA) stenosis in hemodynamically stable AMI patients with MVD, either during or after successful primary PCI, within 45-days. However, deciding the timing of revascularization for non-IRA in cases of MVD is uncertain. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023472652). Databases were searched for relevant articles published before 10 November 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 640 studies evaluated, there were 13 RCTs with 5144 patients with AMI with MVD. The immediate non-IRA PCI is associated with a significantly lower occurrence of unplanned ischemia-driven PCI (OR 0.60; confidence interval [CI] 0.44-0.83) and target-vessel revascularization (OR 0.72; CI 0.53-0.97) . Although there is a favorable trend for major adverse cardiovascular and cerebrovascular events (MACCE), nonfatal AMI, cerebrovascular events, and major bleeding in the immediate non-culprit artery (-ies) PCI, those were statistically non-significant. Similarly, all-cause mortality, cardiovascular mortality, stent thrombosis, and acute renal insufficiency did not show significant differences between two groups. CONCLUSION: Among hemodynamically stable patients with multivessel AMI, the immediate PCI strategy was superior to the multistage PCI strategy for the unplanned ischemia-driven PCI and target-vessel revascularization while odds are favorable in terms of MACCE, nonfatal AMI, cerebrovascular events, and major bleeding at longest follow-up.

The role of viscoelastic hemostatic assays for postpartum hemorrhage management and bedside intrapartum care.

Viscoelastic hemostatic assays are point-of-care devices that assess coagulation and fibrinolysis in whole blood samples. These technologies provide numeric and visual information of clot initiation, clot strength, and clot lysis under low-shear conditions, and have been used in a variety of clinical settings and subpopulations, including trauma, cardiac surgery, and obstetrics. Emerging data indicate that these devices are useful for detecting important coagulation defects during major postpartum hemorrhage (especially low plasma fibrinogen concentration [hypofibrinogenemia]) and informing clinical decision-making for blood product use. Data from observational studies suggest that, compared with traditional formulaic approaches to transfusion management, targeted or goal-directed transfusion approaches using data from viscoelastic hemostatic assays are associated with reduced hemorrhage-related morbidity and lower blood product requirement. Viscoelastic hemostatic assays can also be used to identify and treat coagulation defects in patients with inherited or acquired coagulation disorders, such as factor XI deficiency or immune-mediated thrombocytopenia, and to assess hemostatic profiles of patients prescribed anticoagulant medications to mitigate the risk of epidural hematoma after neuraxial anesthesia and postpartum hemorrhage after delivery.

Group authorship, an excellent opportunity laced with ethical, legal and technical challenges.

Group authorship (also known as corporate authorship, team authorship, consortium authorship) refers to attribution practices that use the name of a collective (be it team, group, project, corporation, or consortium) in the authorship byline. Data shows that group authorships are on the rise but thus far, in scholarly discussions about authorship, they have not gained much specific attention. Group authorship can minimize tensions within the group about authorship order and the criteria used for inclusion/exclusion of individual authors. However, current use of group authorships has drawbacks, such as ethical challenges associated with the attribution of credit and responsibilities, legal challenges regarding how copyrights are handled, and technical challenges related to the lack of persistent identifiers (PIDs), such as ORCID, for groups. We offer two recommendations: 1) Journals should develop and share context-specific and unambiguous guidelines for group authorship, for which they can use the four baseline requirements offered in this paper; 2) Using persistent identifiers for groups and consistent reporting of members' contributions should be facilitated through devising PIDs for groups and linking these to the ORCIDs of their individual contributors and the Digital Object Identifier (DOI) of the published item.

Relationship between demographic and social variables and performance in virtual reality among healthcare personnel: an observational study.

BACKGROUND: Virtual reality is emerging as an important component of medical education. Although the benefits of virtual reality are apparent, the optimal strategy to orient to or differentiate learners in the virtual space have not been delineated. The purpose of this study was to investigate the relationships between demographic variables, social variables, and self-perceived comfort with technology to performance on a standardized non-medical virtual reality experience. METHODS: This observational study was performed at the International Meeting on Simulation in Healthcare in 2022. This conference includes medical and non-medical attendees. Participants provided demographic information and participated in a scored non-medical VR experience due to the heterogeneity of the sample. Participants then completed a System Usability Index and NASA Task Load Index form. Participants were dividedintolow scoring, medium scoring, and high scoring groups according to their final game score for further analysis. RESULTS: 95 participants were included in final analysis. 55 (57.9%) of participants had prior virtual reality experience. Higher scores were associated with younger age (11.09, p < 0.001), identifying as male (11.09, p < 0.001), and a higher frequency of playing video games in the past (18.96, p < 0.001). The high score group was more likely to report comfort with virtual reality (6.29, p = 0.003) as well as comfort with new technology (4.61, p = 0.012). NASA Task Load Index scores trended down and System Usability Index scores trended up with increasing score. Being a nurse was a positive predictor of a higher score when compared to physicians in the multivariate analysis. CONCLUSION: Performance during an immersive virtual reality experience was most closely related to age, gender, and frequency of playing video games. Self-perceived comfort with virtual reality was more predictive of score than prior virtual reality experience.

Pregnancy complications and loss: an observational survey comparing anesthesiologists and obstetrician-gynecologists.

OBJECTIVE: While there is increasing information regarding the occupational risks to pregnant physicians, there is inconsistent and limited subspecialty data. Physicians may be at increased risk for pregnancy complications due to occupational exposure, long work hours, nightshifts, and physical/mental demands. Additionally, little is known regarding the education physicians receive pertaining to pregnancy risks respective to their specialties as well as departmental/institutional support for pregnancy loss or complication. Therefore, a survey was developed and distributed across multiple academic sites to ascertain if there is an inherent occupation-associated risk of pregnancy complication(s) and/or pregnancy loss for anesthesiologists (ANES) when compared to obstetrician/gynecologists (OB/GYN). METHODS: A specialty-specific survey was distributed electronically to attending ANES and OB/GYN, via departmental listservs at six participating academic medical centers. Responses were collected from March to October 2022 and included demographic information, practice characteristics, education about pregnancy risks and details of pregnancy complications and loss. The primary comparison between specialty groups was the occurrence of at least one pregnancy complication and/or loss. Logistic regression was used to evaluate specialty outcome associations. Additionally, complication rates and types between specialties were compared using univariate and multivariable models. RESULTS: The survey was distributed to 556 anesthesiology and 662 obstetrics-gynecology faculty members with 224 ANES and 168 OB/GYN respondents, yielding an overall 32.2% response rate. Of the survey respondents, 103 ANES and 116 OB/GYN reported at least one pregnancy. Demographics were similar between the two cohorts. ANES had higher gravidity and parity relative to OB/GYN and tended to be earlier in their career at first pregnancy (p = .008, <.001, and .043, respectively). The rate of any pregnancy complication, including loss, was similar between specialties (65.1% (67/103) vs. 65.5% (76/116), p = .942). Of the respondents reporting at least one pregnancy, 56.7% of ANES and 53.9% of OB/GYN experienced a complication while at work. Obstetrician-gynecologists had higher use of reproductive assistance (28% (47/116) vs. 11% (20/103), p < .001). There were no notable differences between cohorts for complications, prematurity, and neonatal intensive care admission. Forty-one percent (161/392) of total respondents recalled learning about occupational risks to pregnancy, and ANES were more likely than OB/GYN to have recalled learning about these risks (121/224 (54%) and 40/168 (23.8%), respectively, p < .001). CONCLUSIONS: ANES and OB/GYN had similar risks for pregnancy complications and loss. Anesthesiologists were more likely to recall receiving education regarding occupational risk to pregnancy, though fewer than half of all survey respondents recalled learning about these risks. Our survey results are similar to the previously identified higher rate of pregnancy complications and loss in female physicians while uncovering areas of potential knowledge gaps for which institutions and practices could strive to improve upon. More research is needed to examine the relationship between occupation and pregnancy risk pertaining to female physicians with the goal being to identify modifiable risk factors.

Transcarotid versus trans-axillary/subclavian transcatheter aortic valve replacement (TAVR): A systematic review and meta-analysis.

BACKGROUND: Transcatheter Aortic Valve Replacement (TAVR) is the treatment of choice in patients with severe aortic stenosis. Transcarotid (TCa) or Trans-axillary/subclavian (TAx/Sc) are safer and less invasive non-femoral approaches, where transfemoral access is difficult or impossible to obtain. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023482842). This meta-analysis was performed to compare the safety of the transcarotid and trans-axillary/subclavian approach for TAVR including studies from inception to October 2023. RESULTS: Seven studies with a total of 6227 patients were included in the analysis (TCa: 2566; TAx/Sc: 3661). Transcarotid TAVR approach had a favorable trend for composite of stroke and all-cause mortality (OR 0.79, CI 0.60-1.04), all-cause mortality, stroke, major vascular complication, and new requirement of permanent pacemaker though those were statistically insignificant. On sub-analysis of the results of the studies based on the territory (USA vs French), composite outcome of all cause mortality, stroke and major bleeding (OR 0.54, CI 0.54-0.81), composite of stroke and all cause mortality (OR 0.64, CI 0.50-0.81), and stroke/TIA (OR 0.53, CI 0.39-0.73) showed lower odds of occurrence among patient managed with TCa approach in the American cohort. CONCLUSION: Overall, transcarotid approach had favorable though statistically insignificant odds for composite (stroke and all-cause mortality) and individual outcomes (stroke, all-cause mortality, etc.). There are significant variations in observed outcomes based on study's geographic location. Large prospective randomized clinical trials comparing the two approaches with representative samples are necessary to guide the clinicians in choosing among these approaches.