Citations

Abstract The Infectious Diseases Society of America Training Program Directors Committee met in October 2022 and discussed an observed increase in clinical volume and acuity on infectious diseases (ID) services, and its impact on fellow education. Committee members sought to develop specific goals and strategies related to improving training program culture, preserving quality education on inpatient consult services and in the clinic, and negotiating change at the annual IDWeek Training Program Director meeting. This paper outlines a presentation of ideas brought forth at the meeting and is meant to serve as a reference document for infectious diseases training program directors seeking guidance in this area.

Abstract Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world‐wide survey to ISEV members to assess methods considered ‘best practices’ for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.

Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid in the blood/urine and acetone in our breath and skin. Monitoring ketone production in the body is essential for people who use caloric intake deficit to reduce body weight or use ketogenic diets for wellness or therapeutic treatments. Current methods to monitor ketones include urine dipsticks, capillary blood monitors, and breath analyzers. However, these existing methods have certain disadvantages that preclude them from being used more widely. In this work, we introduce a novel acetone sensor device that can detect acetone levels in breath and overcome the drawbacks of existing sensing approaches. The critical element of the device is a robust sensor with the capability to measure acetone using a complementary metal oxide semiconductor (CMOS) chip and convenient data analysis from a red, green, and blue deconvolution imaging approach. The acetone sensor device demonstrated sensitivity of detection in the micromolar-concentration range, selectivity for detection of acetone in breath, and a lifetime stability of at least one month. The sensor device utility was probed with real tests on breath samples using an established blood ketone reference method.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.

Abstract Blood is the most commonly used body fluid for extracellular vesicle (EV) research. The composition of a blood sample and its derivatives (i.e., plasma and serum) are not only donor‐dependent but also influenced by collection and preparation protocols. Since there are hundreds of pre‐analytical protocols and over forty variables, the development of standard operating procedures for EV research is very challenging. To improve the reproducibility of blood EV research, the International Society for Extracellular Vesicles (ISEV) Blood EV Task Force proposes standardized reporting of (i) the applied blood collection and preparation protocol and (ii) the quality of the prepared plasma and serum samples. Gathering detailed information will provide insight into the performance of the protocols and more effectively identify potential confounders in the prepared plasma and serum samples. To collect this information, the ISEV Blood EV Task Force created the Minimal Information for Blood EV research (MIBlood‐EV), a tool to record and report information about pre‐analytical protocols used for plasma and serum preparation as well as assays used to assess the quality of these preparations. This tool does not require modifications of established local pre‐analytical protocols and can be easily implemented to enhance existing databases thereby enabling evidence‐based optimization of pre‐analytical protocols through meta‐analysis. Taken together, insight into the quality of prepared plasma and serum samples will (i) improve the quality of biobanks for EV research, (ii) guide the exchange of plasma and serum samples between biobanks and laboratories, (iii) facilitate inter‐laboratory comparative EV studies, and (iv) improve the peer review process.

ImportanceYoung women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.ObjectiveTo investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.Design, Setting, and ParticipantsInternational, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.ExposurePregnancy after breast cancer.Main Outcomes and MeasuresPrimary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer–specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.ResultsOf 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer–specific survival and overall survival.Conclusions and RelevanceIn this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.Trial RegistrationClinicalTrials.gov Identifier: NCT03673306

Introduction: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. Methods: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. Results: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients’ risk profile. Conclusions: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.