Severe functional mitral regurgitation and cardiogenic shock after transcatheter aortic valve replacement.

An 83-year-old woman with symptomatic severe aortic stenosis was referred for transcatheter aortic valve replacement. Diagnostic left heart catheterization documented diffuse 3-vessel coronary artery disease.

Examining the association between urinary triclosan levels and menopausal status: results from the National Health and Nutrition Examination Survey, 2003 to 2016.

OBJECTIVE: To examine the association between urinary levels of triclosan (TCS), a ubiquitous endocrine disrupter, and menopausal status using the National Health and Nutrition Examination Survey. METHODS: A retrospective cross-sectional study from 2003 to 2016 was conducted among US female participants who completed the reproductive health questionnaire and provided TCS-level measurements. Exposure was assessed by urinary TCS levels adjusted for urinary creatinine; levels were log-transformed to achieve normal distribution for parametric analyses. Menopausal status was based on participants' responses to: "What is the reason that you have not had a period in the past 12 months?" Multivariable linear regression analyses examined the association between creatinine-adjusted urinary TCS levels and menopausal status after adjusting for age at survey completion, body mass index, race, ethnicity, and smoking exposure. RESULTS: Of the final sample of female participants (n = 6,958), 40% identified as postmenopausal, of whom 60% had experienced natural menopause, and of these, 11% had become menopausal at under 40 years of age. Triclosan levels correlated positively with advancing age (r = 0.09, P < 0.001) and inversely with body mass index (r = -0.09, P < 0.001). Smoking exposure was associated with significantly lower TCS levels (P < 0.001). Compared with premenopausal women, postmenopausal women had significantly higher log-transformed, creatinine-adjusted TCS levels (mean, -1.22 ± 1.79 vs -1.51 ± 1.79 ng/mg creatinine; P < 0.001). Triclosan levels were unrelated to the duration of menopause and did not differ between women who underwent natural versus surgical menopause, and premature menopause versus menopause at 40 years or older. In unweighted multivariate linear regression analyses, menopausal status was independently associated with higher urinary TCS levels after adjusting for covariates (ß coefficient, 0.17; 95% CI, 0.020-0.323; P = 0.026). CONCLUSIONS: In a nationally representative sample, postmenopausal status was associated with higher urinary TCS levels, observations that merit further investigation into potential exposures and health consequences.

Outcomes of pregnant women exposed to Sotrovimab for the treatment of COVID-19 in the BA.1 Omicron predominant era (PRESTO).

BACKGROUND: Sotrovimab, a monoclonal antibody with efficacy against SARS-CoV-2 including certain Omicron variants, has been used in treatment of mild-moderate COVID-19. Limited data exists regarding its use in pregnant women. METHODS: Electronic medical record review of pregnant COVID-19 patients treated with sotrovimab from 12/30/21 - 1/31/22 (Yale New Haven Health Hospital System [YNHHS]) was performed. Included were pregnant individuals ≥ 12 years, weighing ≥ 40 kg, with positive SARS-CoV-2 test (within 10 days). Those receiving care outside YNHHS or receiving other SARS-CoV-2 treatment were excluded. We assessed demographics, medical history, and Monoclonal Antibody Screening Score (MASS). The primary composite clinical outcome assessed included emergency department (ED) visit < 24 h, hospitalization, intensive care unit (ICU) admission, and/or death within 29 days of sotrovimab. Secondarily, adverse feto-maternal outcomes and events for neonates were assessed at birth or through the end of the study period, which was 8/15/22. RESULTS: Among 22 subjects, median age was 32 years and body mass index was 27 kg/m2. 63% were Caucasian, 9% Hispanic, 14% African-American, and 9% Asian. 9% had diabetes and sickle cell disease. 5% had well-controlled HIV. 18%, 46%, and 36% received sotrovimab in trimester 1, 2, and 3, respectively. No infusion/allergic reactions occurred. MASS values were < 4. Only 12/22 (55%) received complete primary vaccination (46% mRNA-1273; 46% BNT162b2; 8% JNJ-78,436,735); none received a booster. CONCLUSIONS: Pregnant COVID-19 patients receiving sotrovimab at our center tolerated it well with good clinical outcomes. Pregnancy and neonatal complications did not appear sotrovimab-related. Though a limited sample, our data helps elucidate the safety and tolerability of sotrovimab in pregnant women.

Characterizing the lack of diversity in musculoskeletal urgent care website content.

BACKGROUND: Musculoskeletal urgent care centers (MUCCs) are becoming an alternative to emergency departments for non-emergent orthopedic injuries as they can provide direct access to orthopedic specialty care. However, they tend to be located in more affluent geographies and are less likely to accept Medicaid insurance than general urgent care centers. MUCCs utilize websites to drive patients to their centers, and the content may influence patients' consumer behaviors and perceptions of the quality and accessibility of the MUCCs. Given that some MUCCs target insured patient populations, we evaluated the racial, gender, and body type diversity of website content for MUCCs. METHODS: Our group conducted an online search to create a list of MUCCs in the United States. For each MUCC, we analyzed the content featured prominently on the website (above the fold). For each website, we analyzed the race, gender, and body type of the featured model(s). MUCCs were classified according to their affiliation (i.e. academic versus private) and region (i.e. Northeast versus South). We performed chi-squared and univariate logistic regression to investigate trends in MUCC website content. RESULTS: We found that 14% (32/235) of website graphics featured individuals from multiple racial groups, 57% (135/235) of graphics featured women, and 2% (5/235) of graphics featured overweight or obese individuals. Multiracial presence in website graphics was associated with the presence of women on the websites and Medicaid acceptance. CONCLUSION: MUCC website content has the potential to impact patients' perceptions of medical providers and the medical care they receive. Most MUCC websites lack diversity based on race and body type. The lack of diversity in website content at MUCCs may introduce further disparities in access to orthopedic care.

Clinical outcomes following dalbavancin administration in patients with barriers to outpatient parenteral antimicrobial therapy.

Between 2016 and 2021, we retrospectively identified 42 patients receiving ≥1 dose of dalbavancin for osteomyelitis, skin and soft-tissue infection, endocarditis or bacteremia, or septic arthritis. Median antibiotic duration prior to dalbavancin administration was 7 days. Within 90 days, 93% achieved clinical cure, 12% were readmitted, 12% developed hepatotoxicity, and 5% died.

Implications of triclosan for female fertility: results from the National Health and Nutrition Examination Survey, 2013-2016.

Objective: To examine and further characterize the association between urinary levels of triclosan (TCS), a ubiquitous putative endocrine-disrupting chemical, and the risk of infertility. Design: A retrospective cross-sectional study using the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey. Setting: Not applicable. Patients: Female participants in the United States who completed the reproductive health questionnaire and provided urine samples for TCS level measurement from 2013 to 2016. Interventions: None. Main Outcome Measures: Rates of presumed infertility based on participants' affirmative response to survey question RHQ074 ("Have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?"). Results: A total of 11.7% of the overall female and 12.5% of the eligible study population met the criterion for presumed infertility. Creatinine-adjusted urinary TCS levels were significantly higher among those meeting the criterion for infertility compared with the levels among those who did not. On multivariable-adjusted analyses, individuals with undetectable levels of urinary TCS were 35% less likely to meet the specified infertility criterion compared with those with detectable TCS levels. The magnitude of association between TCS levels and infertility was strongest when comparing the lowest and highest quartiles. The directionality and magnitude of the relationship between TCS levels and infertility were maintained on age-restricted and weighted analyses; however, the associations did not retain statistical significance. Conclusions: In a nationally representative sample of women in the United States, an association between TCS exposure and inability to conceive over a period of 1 year is suggested by our analysis of the National Health and Nutrition Examination Survey data. The data infer a dose-response relationship.

Assessment of the COVID-19 vaccine market landscape in 2021 relative to challenges in low- and middle-income countries.

To evaluate the early vaccine landscape relative to challenges faced by low- and middle-income countries (LMIC), we conducted a cross-sectional study of all COVID-19 vaccines in clinical trials in 2021 (n = 123) using a structured 13-point analytic framework. Supply sustainability was defined as a composite metric of four manufacturing and regulation variables. Vaccine desirability was defined as a composite metric of nine development and distribution variables. Ten vaccines in phases 2/3, 3, or 4 and five vaccines in phases 1 and 1/2 had a sustainability score equal to or above 0.5. Ten vaccines in phases 2/3, 3, or 4 and seven vaccines in phases 1 and 1/2 had a desirability score equal to or above 0.5. No vaccines in Phases 2/3, 3, or 4 met more than one distribution criterion. Structured assessment COVID-19 vaccine candidates in clinical trials in 2021 revealed numerous challenges to adequate access in LMICs. Key policy recommendations included increasing technology transfer to LMICs, developing international legal mechanisms to prevent export bans, and increasing investment in vaccine candidates with more favorable distribution profiles.

Long-term quantitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV (PWH).

BACKGROUND: The durability of immune responses to COVID-19 vaccines among older people living with HIV (PWH) is clinically important. METHODS: We aimed to assess vaccine-induced humoral immunity and durability in older PWH (≥ 55 years, n = 26) over 6 months (post-initial BNT162b2 series). A secondary and exploratory objective was to assess T-cell response and BNT162b2 booster reactogenicity, respectively. Our Visit 1 (3 weeks post-initial BNT162b2 dose) SARS-CoV-2 humoral immunity results are previously reported; these subjects were recruited for Visit 2 [2 weeks (+ 1 week window) post-second vaccination] and Visit 3 [6 months (± 2 week window) post-initial vaccination] in a single-center longitudinal observational study. Twelve participants had paired Visit 2/3 SARS-CoV-2 Anti-Spike IgG data. At Visit 3, SARS-CoV-2 Anti-Spike IgG testing occurred, and 5 subjects underwent T-cell immune response evaluation. Thereafter, subjects were offered BNT162b2 booster (concurrent day outside our study) per US FDA/CDC guidance; reactogenicity was assessed. The primary study outcome was presence of detectable Visit 3 SARS-CoV-2 Anti-Spike-1-RBD IgG levels. Secondary and exploratory outcomes were T-cell immune response and BNT162b2 booster reactogenicity, respectively. Wilcoxon signed-rank tests analyzed median SARS-CoV-2 Anti-Spike IgG 6-month trends. RESULTS: At Visit 3, 26 subjects underwent primary analysis with demographics noted: Median age 61 years; male n = 16 (62%), female n = 10 (38%); Black n = 13 (50%), White n = 13 (50%). Most subjects (n = 20, 77%) had suppressed HIV viremia on antiretroviral therapy, majority (n = 24, 92%) with CD4 > 200 cells/µL. At Visit 3, 26/26 (100%) had detectable Anti-Spike-1-RBD (≥ 0.8 U/mL). Among 12 subjects presenting to Visit 2/3, median SARS-CoV-2 Anti-Spike 1-RBD was 2087 U/mL at Visit 2, falling to 581.5 U/mL at Visit 3 (p = 0.0923), with a median 3.305-fold decrease over 6 months. Among subjects (n = 5) with 6-month T-cell responses measured, all had detectable cytokine-secreting anti-spike CD4 responses; 3 had detectable CD4 + Activation induced marker (AIM) + cells. Two had detectable cytokine-secreting CD8 responses, but all had positive CD8 + AIM + cells. CONCLUSIONS: Among older PWH, SARS-CoV-2 Anti-Spike IgG and virus-specific T-cell responses are present 6 months post-primary BNT162b2 vaccination, and although waning, suggest retention of some degree of long-term protective immunity.

Increasing face-mask compliance among healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: Prior studies of universal masking have not measured face-mask compliance. We performed a quality improvement study to monitor and improve face-mask compliance among healthcare personnel (HCP) during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: Mixed-methods study. SETTING: Tertiary-care center in West Haven, Connecticut. PATIENTS: HCP including physicians, nurses, and ancillary staff. METHODS: Face-mask compliance was measured through direct observations during a 4-week baseline period after universal masking was mandated. Frontline and management HCP completed semistructured interviews from which a multimodal intervention was developed. Direct observations were repeated during a 14-week period following implementation of the multimodal intervention. Differences between units were evaluated with χ2 testing using the Bonferroni correction. Face-mask compliance between baseline and intervention periods was compared using time-series regression. RESULTS: Among 1,561 observations during the baseline period, median weekly face-mask compliance was 82.2% (range, 80.8%-84.4%). Semistructured interviews were performed with 16 HCP. Qualitative analysis informed the development of a multimodal intervention consisting of audit and passive feedback, active discussion, and increased communication from leadership. Among 2,651 observations during the intervention period, median weekly face-mask compliance was 92.6% (range, 84.6%-97.9%). There was no difference in weekly face-mask compliance between COVID-19 and non-COVID-19 units. The multimodal intervention was associated with an increase in face-mask compliance (ß = 0.023; P = .002). CONCLUSIONS: Face-mask compliance remained suboptimal among HCP despite a facility-wide mandate for universal masking. A multimodal intervention consisting of audit and passive feedback, active discussion, and increased communication from leadership was effective in increasing face-mask compliance among HCP.

Evaluating musculoskeletal urgent care center triage and transfer of emergency conditions for emergency surgical assessment and intervention.

Musculoskeletal urgent care centers (MUCCs) are an alternative to emergency departments (EDs) for patients to seek care for low acuity orthopedic injuries such as ankle sprains or joint pain, but are not equipped to manage orthopedic emergencies that require a higher level of care provided in the ED. This study aims to evaluate telephone and online triage practices as well as ED transfer procedures for MUCCs for patients presenting with an orthopedic condition requiring urgent surgical intervention. We called 595 MUCCs using a standardized script presenting as a critical patient with symptoms of lower extremity compartment syndrome. We compared direct ED referral frequency and triage frequency for MUCCs for patients insured by either Medicaid or by private insurance. We found that patients presenting with an apparent compartment syndrome were directly referred to the ED by < 1 in 5 MUCCs. Additionally, < 5% of patients were asked additional triage questions that would increase clinician suspicion for compartment syndrome and allow MUCCs to appropriately direct patients to the ED. MUCCs provide limited telephone and online triage for patients, which may result in delays of care for life or limb threatening injuries that require ED resources such as sedation, reductions, and emergency surgery. However, when MUCCs did conduct triage, it significantly increased the likelihood that patients were appropriately referred to the ED. Level of Evidence: Level II, prognostic study.

Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy.

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. Moreover, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.

Severely impaired terminal erythroid differentiation as an independent prognostic marker in myelodysplastic syndromes.

Anemia is the defining feature in most patients with myelodysplastic syndromes (MDS), yet defects in erythropoiesis have not been well characterized. We examined freshly obtained bone marrow (BM) samples for stage-specific abnormalities during terminal erythroid differentiation (TED) from 221 samples (MDS, n = 205 from 113 unique patients; normal, n = 16) by measuring the surface expression of glycophorin A, band 3, and integrin α-4. Clinical and biologic associations were sought with presence or absence of TED and the specific stage of erythroid arrest. In 27% of MDS samples (56/205), there was no quantifiable TED documented by surface expression of integrin α-4 and band 3 by terminally differentiating erythroblasts. Absence of quantifiable TED was associated with a significantly worse overall survival (56 vs 103 months, P = .0001) and SRSF2 mutations (7/23, P < .05). In a multivariable Cox proportional hazards regression analysis, absence of TED remained independently significant across International Prognostic Scoring System-Revised (IPSS-R) categories, myeloid/erythroid ratio, and mutations in several genes. In 149/205 MDS samples, the proportion of cells undergoing TED did not follow the expected 1:2:4:8:16 doubling pattern in successive stages. Absence of TED emerged as a powerful independent prognostic marker of poor overall survival across all IPSS-R categories in MDS, and SRSF2 mutations were more frequently associated with absence of TED.

Bisphenol-A exposure in utero programs a sexually dimorphic estrogenic state of hepatic metabolic gene expression.

Bisphenol-A (BPA) exposure in utero affects fetal development and metabolism leading to obesity. However, the mechanisms are not well characterized. We identified sexually dimorphic developmental programming of genes regulating metabolism in the liver after BPA exposure. Pregnant mice were treated with BPA on days 9-18 of gestation. At six weeks, female offspring were ovariectomized; both sexes were subsequently treated with estradiol (E2). Fetal BPA exposure altered the expression of genes in liver, including those involved in glucose and lipid metabolism, and transporters, in both sexes. Adult gene expression in BPA-exposed mice often resembled normal adult response to E2 stimulation, even in the absence of estrogen treatment. Estrogen receptor alpha and beta gene expression was upregulated in females and downregulated in males. This is the first report demonstrating sexual dimorphism in liver after BPA exposure and our finding of estrogenization may explain the BPA-related increase in incidence of metabolic disorders and obesity.

Donor egg IVF model to assess ecological implications for ART success.

PURPOSE: Environmental influences on reproductive success are recognized. We hypothesized that location of fertility clinics may influence treatment success and explored this hypothesis utilizing donor egg IVF (IVF) embryo transfer (ET) model. METHODS: Publicly accessible national registry data (Society for Assisted Reproductive Technology) on fresh & frozen (FET) ET cycles undertaken at participating clinics across North America (n = 444 IVF centers) for 2007 were utilized. Information on number of donor egg IVF cycles, live birth (LB) rate following fresh and frozen ET(FET), average number (#) of ET and IVF center's location, geographical coordinates (latitude, longitude, altitude), annualized average temperatures and midyear regional ultraviolet B (UVB) radiation intensity were obtained. Multivariable logistic regression analyses assessed relationship between LBR (in tertile and uppermost versus lesser quartiles) following fresh and FET with geographical coordinates (region and altitude of clinic location) and ecological influences (average temperature and midyear UVB intensity), adjusting for #ET and clinic experience with donor egg IVF. RESULTS: Average number of fresh ET, clinic location (region) and midyear UVB intensity were positive predictors of LBR following fresh ET, whereas altitude and annualized average regional temperature demonstrated an inverse relationship with LBR following fresh ET. For FET cycles, #ET, clinic region and altitude were positive determinants of increasing LBR's. Annualized regional temperature and midyear UVB failed to demonstrate any relationship with LB following donor egg FET. CONCLUSION: Our data suggest that ecological influences may relate to donor egg IVF cycle success. Future studies are needed to better elucidate the mechanisms that could explain the observed associations.