Citations

Background: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited. Objectives: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) – the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration – for preventing rCDI in adults. Design: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL. Methods: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively. Results: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants). Conclusion: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL.

Purpose of review Cardiogenic shock (CS) has been recognized for >50 years, most commonly in the setting of myocardial infarction. This review covers recent advances in the definitions, epidemiology and severity assessment of cardiogenic shock. Recent findings In this review, the authors discuss the evolving definitions of cardiogenic shock, detailing the early approaches as well as more contemporary ideas. The epidemiology of CS is reviewed and then granular detail on the assessment of shock severity is provided including the role of lactate measurement and invasive hemodynamic assessment. The development of the Society for Cardiac Angiography and Intervention (SCAI) consensus statement on Classification of Cardiogenic Shock is reviewed by the principal authors. The revised SCAI Shock document is reviewed as well and the future directions for assessment of shock along with clinical applications are reviewed. Summary Cardiogenic shock mortality has not changed in a significant way in many years. Recent advances such as more granular assessment of shock severity have the potential to improve outcomes by allowing research to separate the patient groups which may respond differently to various therapies.

Background: There is limited research on the impact of revisional surgery after breast reconstruction on patient experience and postoperative quality of life (QoL). Methods: Patients undergoing mastectomy with immediate implant-based or autologous free-flap breast reconstruction from 2008 to 2020 were reviewed. These patients were categorized by revisions (0–1, 2–3, and 4+) and surveyed on QoL metrics using BREAST-Q and Was It Worth It? (WIWI) questionnaires. BREAST-Q QoL, satisfaction, and WIWI metrics between revision groups were evaluated. Results: Among 252 patients, a total of 150 patients (60%) underwent zero to one revisions, 72 patients (28%) underwent two to three revisions, and 30 patients (12%) underwent four or more revisions. Median follow-up was 6 years (range, 1–11 years). BREAST-Q satisfaction among patients with four or more revisions was significantly lower ( P = 0.03), while core QoL domains (chest physical, psychosocial, and sexual well-being) did not significantly differ. Analysis of unplanned reoperations due to complications and breast satisfaction showed no significant difference in QoL scores between groups ( P = 0.08). Regarding WIWI QoL metrics, four or more revisions were associated with a higher rate of worse QoL ( P = 0.035) and worse overall experience ( P = 0.001). Most patients in all revision groups felt it was worthwhile to undergo breast reconstruction (86%), would choose breast reconstruction again (83%), and would recommend breast reconstruction to others (79%). Conclusions: Overall, a majority of patients undergoing revisions after breast reconstruction still have a worthwhile experience. Although reoperations after breast reconstruction do not significantly impact long-term BREAST-Q QoL domains, patients undergoing four or more revisions have significantly lower breast satisfaction, worse QoL, and a postoperative experience worse than expected.

AbstractThe coronavirus disease 2019 (COVID‐19) pandemic created unprecedented challenges for anesthesiologists both at work and home. This study examined whether the pandemic affected academic productivity and career satisfaction among anesthesiologists practicing in the United States during the early stages of the pandemic and whether these effects differed by gender. A survey was emailed to 25,473 members of the American Society of Anesthesiologists to learn about their experiences during the beginning of the pandemic. The survey directed respondents to rate their change in academic productivity, clinical care hours, scholarly and leadership opportunities, income, childcare duties, and household responsibilities during the first 5 months of the pandemic (March 1–July 31, 2020). The primary variable was gender, academic productivity was the primary outcome, and data were analyzed by multivariable proportional odds logistic regression models and correlations. Female anesthesiologists reported lower academic productivity and career satisfaction relative to male anesthesiologists during the study period. Career satisfaction positively correlated with academic productivity. Compared to male anesthesiologists, female anesthesiologists also had more household responsibilities before and during the pandemic. Being a female parent reduced academic productivity relative to that reported by nonparents of either gender. In conclusion, the early months of the COVID‐19 pandemic had a greater adverse professional impact on female anesthesiologists than on their male counterparts. Efforts to support and retain female anesthesiologists, particularly those early in their careers and those with children, are essential for the specialty to maintain its workforce and promote gender equity in promotion and leadership.

Breast cancer is the second-leading cause of mortality among women around the world. Ultrasound (US) is one of the noninvasive imaging modalities used to diagnose breast lesions and monitor the prognosis of cancer patients. It has the highest sensitivity for diagnosing breast masses, but it shows increased false negativity due to its high operator dependency. Underserved areas do not have sufficient US expertise to diagnose breast lesions, resulting in delayed management of breast lesions. Deep learning neural networks may have the potential to facilitate early decision-making by physicians by rapidly yet accurately diagnosing and monitoring their prognosis. This article reviews the recent research trends on neural networks for breast mass ultrasound, including and beyond diagnosis. We discussed original research recently conducted to analyze which modes of ultrasound and which models have been used for which purposes, and where they show the best performance. Our analysis reveals that lesion classification showed the highest performance compared to those used for other purposes. We also found that fewer studies were performed for prognosis than diagnosis. We also discussed the limitations and future directions of ongoing research on neural networks for breast ultrasound.

Abstract Objective Previous studies suggested that patients with epilepsy might be able to forecast their own seizures. This study aimed to assess the relationships between premonitory symptoms, perceived seizure risk, and future and recent self‐reported and electroencephalographically (EEG)‐confirmed seizures in ambulatory patients with epilepsy in their natural home environments. Methods Long‐term e‐surveys were collected from patients with and without concurrent EEG recordings. Information obtained from the e‐surveys included medication adherence, sleep quality, mood, stress, perceived seizure risk, and seizure occurrences preceding the survey. EEG seizures were identified. Univariate and multivariate generalized linear mixed‐effect regression models were used to estimate odds ratios (ORs) for the assessment of the relationships. Results were compared with the seizure forecasting classifiers and device forecasting literature using a mathematical formula converting OR to equivalent area under the curve (AUC). Results Fifty‐four subjects returned 10 269 e‐survey entries, with four subjects acquiring concurrent EEG recordings. Univariate analysis revealed that increased stress (OR = 2.01, 95% confidence interval [CI] = 1.12–3.61, AUC = .61, p = .02) was associated with increased relative odds of future self‐reported seizures. Multivariate analysis showed that previous self‐reported seizures (OR = 5.37, 95% CI = 3.53–8.16, AUC = .76, p < .001) were most strongly associated with future self‐reported seizures, and high perceived seizure risk (OR = 3.34, 95% CI = 1.87–5.95, AUC = .69, p < .001) remained significant when prior self‐reported seizures were added to the model. No correlation with medication adherence was found. No significant association was found between e‐survey responses and subsequent EEG seizures. Significance Our results suggest that patients may tend to self‐forecast seizures that occur in sequential groupings and that low mood and increased stress may be the result of previous seizures rather than independent premonitory symptoms. Patients in the small cohort with concurrent EEG showed no ability to self‐predict EEG seizures. The conversion from OR to AUC values facilitates direct comparison of performance between survey and device studies involving survey premonition and forecasting.

The snATAC + snRNA platform allows epigenomic profiling of open chromatin and gene expression with single-cell resolution. The most critical assay step is to isolate high-quality nuclei to proceed with droplet-base single nuclei isolation and barcoding. With the increasing popularity of multiomic profiling in various fields, there is a need for optimized and reliable nuclei isolation methods, mainly for human tissue samples. Herein we compared different nuclei isolation methods for cell suspensions, such as peripheral blood mononuclear cells (PBMC, n = 18) and a solid tumor type, ovarian cancer (OC, n = 18), derived from debulking surgery. Nuclei morphology and sequencing output parameters were used to evaluate the quality of preparation. Our results show that NP-40 detergent-based nuclei isolation yields better sequencing results than collagenase tissue dissociation for OC, significantly impacting cell type identification and analysis. Given the utility of applying such techniques to frozen samples, we also tested frozen preparation and digestion (n = 6). A paired comparison between frozen and fresh samples validated the quality of both specimens. Finally, we demonstrate the reproducibility of scRNA and snATAC + snRNA platform, by comparing the gene expression profiling of PBMC. Our results highlight how the choice of nuclei isolation methods is critical for obtaining quality data in multiomic assays. It also shows that the measurement of expression between scRNA and snRNA is comparable and effective for cell type identification.