Metabolic insights at the finish line: deciphering physiological changes in ultramarathon runners through breath VOC analysis.

Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.

Hepatocellular carcinoma risk decreases as time accrues following hepatitis C virus eradication.

BACKGROUND: It is unclear whether the risk of hepatocellular carcinoma (HCC) decreases over time following hepatitis C virus (HCV) eradication. AIM: To determine if patients who have accrued longer time since sustained virologic response (SVR) have a lower risk of HCC than those with less time since SVR METHODS: We conducted a retrospective cohort study of all HCV-infected Veterans Affairs patients who achieved SVR before 1 January 2018 and remained alive without a diagnosis of HCC as of 1 January 2019 (n = 75,965). We ascertained their baseline characteristics as of 1 January 2019 (time zero), including time accrued since SVR and followed them for the subsequent 12 months for incident HCC. We used multivariable Cox proportional hazards regression to determine the association between time since SVR and HCC risk after adjusting for age, race/ethnicity, sex, diabetes, hypertension, body mass index, alcohol use, Charlson Comorbidity Index, Fibrosis-4 score, HCV genotype, hepatitis B virus co-infection and HIV co-infection. RESULTS: 96.0% were male; mean age was 64.6 years. Among those with cirrhosis (n = 19,678, 25.9%), compared to patients who had accrued only ≥1 to 2 years since SVR (HCC incidence 2.71/100 person-years), those who had accrued >2 to 4 years (2.11/100 person-years, aHR 0.80, 95% CI 0.63-1.01) and >4 to 6 years (1.65/100 person-years, aHR 0.61, 95% CI 0.41-0.90) had progressively lower HCC risk. However, HCC risk appeared to plateau for those with >6 years since SVR (1.68/100 person-years, aHR 0.70, 95% CI 0.46-1.07). Among those without cirrhosis, HCC risk was 0.23-0.27/100 person-years without a significant association between time since SVR and HCC risk. CONCLUSIONS: Among patients with cirrhosis and cured HCV infection, HCC risk declined progressively up to 6 years post-SVR-although it remained well above thresholds that warrant screening. This suggests that time since SVR can inform HCC surveillance strategies in patients with cured HCV infection and can be incorporated into HCC risk prediction models.

Lung "Comet Tails" in Healthy Individuals: Accumulation or Clearance of Extravascular Lung Water?

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung "Comet Tails" in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230-233, 2023-Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Risk factors for adverse outcomes in emergency versus nonemergency open umbilical hernia repair and opportunities for elective repair in a national cohort of patients with cirrhosis.

BACKGROUND: Whether to perform umbilical hernia repair in patients with cirrhosis is a common dilemma for surgeons. We aimed to determine the incidence, morbidity, and mortality associated with emergency and nonemergency umbilical hernia repair in patients with and without cirrhosis, and to explore opportunities for nonemergency repair. METHODS: Veterans diagnosed with cirrhosis between 2001 and 2014 and a frequency-matched sample of veterans without cirrhosis were followed through September 2017. Veterans Affairs Surgical Quality Improvement Program data provided outcomes and risk factors for mortality after umbilical hernia repair. We performed chart review of a random sample of patients undergoing emergency umbilical hernia repair. RESULTS: Among 119,605 veterans with cirrhosis and 118,125 matched veterans without cirrhosis, the Veterans Affairs Surgical Quality Improvement Program database included 1,475 and 552 open umbilical hernia repairs, respectively. In patients with cirrhosis, 30-day mortality was 1.2% after nonemergency umbilical hernia repair and 12.2% after emergency umbilical hernia repair, contrasting with zero deaths in patients without cirrhosis undergoing these repairs. In patients with cirrhosis but no ascites in the prior month, 30-day mortality after nonemergency umbilical hernia repair was 0.7%, compared to 2.2% in those with ascites. Chart review of patients requiring emergency umbilical hernia repair revealed that elective umbilical hernia repair may have been feasible in 30% of these patients in the prior year; fewer than half of those undergoing emergency umbilical hernia repair had received a general surgery consultation in the prior 2 years. CONCLUSIONS: Nonemergency open umbilical hernia repair was associated with relatively low perioperative mortality in patients with cirrhosis and no recent ascites. About 30% of patients undergoing emergency umbilical hernia repair may have been candidates for nonemergency repair in the prior year.

Bridging the Chasm between Pregnancy and Health over the Life Course: A National Agenda for Research and Action.

BACKGROUND: Many pregnant people find no bridge to ongoing specialty or primary care after giving birth, even when clinical and social complications of pregnancy signal need. Black, indigenous, and all other women of color are especially harmed by fragmented care and access disparities, coupled with impacts of racism over the life course and in health care. METHODS: We launched the initiative "Bridging the Chasm between Pregnancy and Health across the Life Course" in 2018, bringing together patients, advocates, providers, researchers, policymakers, and systems innovators to create a National Agenda for Research and Action. We held a 2-day conference that blended storytelling, evidence analysis, and consensus building to identify key themes related to gaps in care and root causes of inequities. In 2019, more than 70 stakeholders joined six working groups to reach consensus on strategic priorities based on equity, innovation, effectiveness, and feasibility. FINDINGS: Working groups identified six key strategic areas for bridging the chasm. These include: 1) progress toward eliminating institutional and interpersonal racism and bias as a requirement for accreditation of health care institutions, 2) infrastructure support for community-based organizations, 3) extension of holistic team-based care to the postpartum year and beyond, with integration of doulas and community health workers on the team, 4) extension of Medicaid coverage and new quality and pay-for-performance metrics to link maternity care and primary care, 5) systems to preserve maternal narratives and data across providers, and 6) alignment of research with women's lived experiences. CONCLUSIONS: The resulting agenda presents a path forward to remedy the structural chasms in women's health care, with key roles for advocates, policymakers, researchers, health care leaders, educators, and the media.

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation.

BACKGROUND/AIMS: The development of decompensation in cirrhosis demarcates a marked change in the natural history of chronic liver disease. HMG-CoA reductase inhibitors (statins) exert pleiotropic effects that reduce inflammation and fibrosis as well as improve vascular reactivity. Retrospective studies uniformly have associated statin utilization with improved outcomes for patients with cirrhosis. Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage when added to standard therapy with an acceptable safety profile. This proposal aims to extend these findings to demonstrate that simvastatin reduces incident hepatic decompensation events among cirrhotic patients at high risk for hepatic decompensation. METHODS: We will perform the SACRED Trial (NCT03654053), a phase III, prospective, multi-center, double-blind, randomized clinical trial at 11 VA Medical Centers. Patients with compensated cirrhosis with clinically significant portal hypertension will be stratified based upon the concomitant use of nonselective beta-blockers and randomized to simvastatin 40 mg/day versus placebo for up to 24 months. Patients will be observed for the development of hepatic decompensation (variceal hemorrhage, ascites, encephalopathy), hepatocellular carcinoma, liver-related death, death from any cause, and/or complications of statin therapy. Ancillary studies will evaluate patient-reported outcomes and pharmacogenetic corollaries of safety and/or efficacy. CONCLUSION: Statins have a long track-record of safety and tolerability. This class of medications is generic and inexpensive, and thus, if the hypothesis is proven, there will be few barriers to widespread acceptance of the role of statins to prevent decompensation in patients with compensated cirrhosis. ClinicalTrials.gov Identifier: NCT03654053.

Incidence and Risk Factors of Postoperative Mortality and Morbidity After Elective Versus Emergent Abdominal Surgery in a National Sample of 8193 Patients With Cirrhosis.

OBJECTIVE: To describe the incidence and risk factors for mortality and morbidity in patients with cirrhosis undergoing elective or emergent abdominal surgeries. BACKGROUND: Postoperative morbidity and mortality are higher in patients with cirrhosis; variation by surgical procedure type and cirrhosis severity remain unclear. METHODS: We analyzed prospectively-collected data from the Veterans Affairs (VA) Surgical Quality Improvement Program for 8193 patients with cirrhosis, 864 noncirrhotic controls with chronic hepatitis B infection, and 5468 noncirrhotic controls without chronic liver disease, who underwent abdominal surgery from 2001 to 2017. Data were analyzed using random-effects models controlling for potential confounders. RESULTS: Patients with cirrhosis had significantly higher 30-day mortality than noncirrhotic patients with chronic hepatitis B [4.4% vs 1.3%, adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.57-4.98] or with no chronic liver disease (0.8%, aOR 4.68, 95% CI 3.27-6.69); mortality difference was highest in patients with Model for End-stage Liver Disease (MELD) score ≥10. Among patients with cirrhosis, postoperative mortality was almost 6 times higher after emergent rather than elective surgery (17.2% vs. 2.1%, aOR 5.82, 95% CI 4.66-7.27). For elective surgeries, 30-day mortality was highest after colorectal resection (7.0%) and lowest after inguinal hernia repair (0.6%). Predictors of postoperative mortality included cirrhosis-related characteristics (high MELD score, low serum albumin, ascites, encephalopathy), surgery-related characteristics (emergent vs elective, type of surgery, intraoperative blood transfusion), comorbidities (chronic obstructive pulmonary disease, cancer, sepsis, ventilator dependence, functional status), and age. CONCLUSIONS: Accurate preoperative risk assessments in patients with cirrhosis should account for cirrhosis severity, comorbidities, type of procedure, and whether the procedure is emergent versus elective.

Lower-Dose Propofol Use for MRI: A Retrospective Review of a Pediatric Sedation Team's Experience.

OBJECTIVE: The aim of the study was to evaluate, in children undergoing procedural sedation for magnetic resonance imaging (MRI) scans, whether lower doses of propofol than previously published permitted a high rate of successful MRI completion, whether lower dosages result in a more rapid recovery, and whether age or behavioral diagnosis increases propofol requirements. METHODS: After institutional review board approval, we retrospectively reviewed the pediatric sedation team's sedation database of children receiving propofol infusion for MRI scans between 2007 and 2016. Data collected included propofol induction dose (in milligrams per kilogram), propofol infusion dose (in micrograms per kilogram per hour), total propofol dose (in milligrams per kilogram and in milligrams per kilogram per hour), and the number of administered ancillary sedative medications. Additional data included the American Society of Anesthesiologist status, sedation duration, recovery duration, and successful completion of MRI. Dosing data were also stratified by age. RESULTS: A total of 2354 patients met inclusion criteria. Eight percent of patients received propofol infusion alone, 79% received midazolam before their propofol induction, and 13% received a combination of propofol and other drugs. Mean induction dose was 2.2 + 0.9 mg/kg, mean infusion dose was 93.5 + 29.0 µg/kg per minute, and total mean dose was 9.0 + 3.0 mg/kg per hour. Mean recovery time was 44 minutes, and 99.3% of the scans were completed with good images. We noted an increase requirement in the mean induction dose and total dose in children younger than 1 year. CONCLUSIONS: Propofol infusion doses lower than commonly reported permit successful completion of scans and similar recovery times in a single institution. Younger children require more propofol for successful procedural sedation.

Perioperative Evaluation and Management of Patients With Cirrhosis: Risk Assessment, Surgical Outcomes, and Future Directions.

BACKGROUND AND AIMS: Patients with cirrhosis are at increased risk of perioperative morbidity and mortality. We provide a narrative review of the available data regarding perioperative morbidity and mortality, risk assessment, and management of patients with cirrhosis undergoing non-hepatic surgical procedures. METHODS: We conducted a comprehensive review of the literature from 1998-2018 and identified 87 studies reporting perioperative outcomes in patients with cirrhosis. We extracted elements of study design and perioperative mortality by surgical procedure, Child-Turcotte-Pugh (CTP) class and Model for End-stage Liver Disease (MELD) score reported in these 87 studies to support our narrative review. RESULTS: Overall, perioperative mortality is 2-10 times higher in patients with cirrhosis compared to patients without cirrhosis, depending on the severity of liver dysfunction. For elective procedures, patients with compensated cirrhosis (CTP class A, or MELD <10) have minimal increase in operative mortality. CTP class C patients (or MELD >15) are at high risk for mortality; liver transplantation or alternatives to surgery should be considered. Very little data exist to guide perioperative management of patients with cirrhosis, so most recommendations are based on case series and expert opinion. Existing risk calculators are inadequate. CONCLUSIONS: Severity of liver dysfunction, medical comorbidities and the type and complexity of surgery, including whether it is elective versus emergent, are all determinants of perioperative mortality and morbidity in patients with cirrhosis. There are major limitations to the existing clinical research on risk assessment and perioperative management that warrant further investigation.

Perioperative cardiovascular medicine: 5 questions for 2018.

A MEDLINE search was performed from January 2017 to February 2018, and articles were selected for this update based on their significant influence on the practice of perioperative cardiovascular medicine.

Emotional Distress Among Physician Residents and Fellows: An Observational Study of Trainees Seeking Counseling Visits.

OBJECTIVE: Emotional distress, burnout, and depression occur frequently among graduate medical education (GME) trainees and may negatively affect patient care, education, and well-being. The authors aimed to characterize the causes and severity of distress among GME trainees seeking on-site counseling services at a large, multi-site, university-based training program in the USA. METHODS: The authors analyzed visits of all GME trainees seeking counseling from 2009 to 2012 and described trainee characteristics, level of distress, chief and secondary complaints, and initial visit outcomes. RESULTS: GME trainees (n = 332; 14.1% of total population) attended 2017 counseling visits. Women comprised over half (60.7%) of the clients. Referrals originated from trainees themselves (79.8%), program leadership (16.6%), or partners (1.8%). Mean counselor-assessed distress level at intake was 4.1 (range 1-5). Mental health was the most frequent concern (46.1%), particularly depression (19.3%) or anxiety (11.5%). Other chief complaints included personal relationship (28.6%), career (21.7%), and physical health concerns (2.7%). Counselors referred nearly a quarter (22.7%) of trainees to additional services such as psychiatry, primary care provider, or career mentor. Most trainees (75.3%) returned for ≥1 follow-up counseling visits. CONCLUSION: GME trainees seen in counseling report significant emotional distress from a broad range of sources. Further research should identify effective preventative and therapeutic interventions to reduce trainee emotional distress.

Breast cancer screening: Does tomosynthesis augment mammography?

Digital breast tomosynthesis (DBT) is a relatively new imaging technology that is being adopted widely for breast cancer screening. Initial evidence suggests that it may reduce recall rates and increase cancer detection rates when added to digital mammography screening. However, more rigorous, prospective studies are needed to determine whether it improves long-term clinical outcomes of breast cancer screening.

Association of Previous Clinical Breast Examination With Reduced Delays and Earlier-Stage Breast Cancer Diagnosis Among Women in Peru.

IMPORTANCE: Mammographic screening is impractical in most of the world where breast cancers are first identified based on clinical signs and symptoms. Clinical breast examination may improve early diagnosis directly by finding breast cancers at earlier stages or indirectly by heightening women's awareness of breast health concerns. OBJECTIVE: To investigate factors that influence time to presentation and stage at diagnosis among patients with breast cancer to determine whether history of previous clinical breast examination is associated with earlier presentation and/or earlier cancer stage at diagnosis. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional analysis of individual patient interviews using a validated Breast Cancer Delay Questionnaire, 113 (71.1%) of 159 women with breast cancer treated at a federally funded tertiary care referral cancer center in Trujillo, Peru, from February 1 through May 31, 2015, were studied. MAIN OUTCOMES AND MEASURES: Method of breast cancer detection and factors that influence time to and stage at diagnosis. RESULTS: Of 113 women with diagnosed cancer (mean [SD] age, 54 [10.8] years; age range, 32-82 years), 105 (92.9%) had self-detected disease. Of the 93 women for whom stage was documented, 45 (48.4%) were diagnosed with early-stage disease (American Joint Committee on Cancer [AJCC] stage 0, I, or II), and 48 (51.6%) were diagnosed with late-stage disease (AJCC stage III or IV). Mean (SD) total delay from symptom onset to initiation of treatment was 407 (665) days because of patient (mean [SD], 198 [449] days) and health care system (mean [SD], 241 [556] days) delay. Fifty-two women (46.0%) had a history of clinical breast examination, and 23 (20.4%) had undergone previous mammography. Women who underwent a previous clinical breast examination were more likely to have shorter delays from symptom development to presentation compared with women who had never undergone a previous clinical breast examination (odds ratio, 2.92; 95% CI, 1.30-6.60; P = .01). Women diagnosed with shorter patient delay were more likely to be diagnosed with early-stage disease (AJCC stage 0, I, or II) than those with longer patient delay (31 [58.5%] vs 11 [30.6%], P = .01). Women who underwent a previous clinical breast examination were more likely to be diagnosed with early-stage disease compared with women who had never undergone previous clinical breast examination; this relationship remained significant after controlling for insurance and household income (odds ratio, 2.44; 95% CI, 1.01-5.95; P = .048). CONCLUSIONS AND RELEVANCE: In a population in which most breast cancers are self-detected, previous clinical breast examination was associated with shorter patient delay and earlier stage at breast cancer diagnosis. In regions of the world that lack mammographic screening, the routine use of clinical breast examination may provide a resource-appropriate strategy for improving breast cancer early diagnosis.