Vassar Brothers Medical Center

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

BACKGROUND: Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. PURPOSE: The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. METHODS: New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). RESULTS: New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. CONCLUSIONS: Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

OBJECTIVE: To determine what factors predispose patients with retrosternal goiters to median sternotomy. STUDY DESIGN: Retrospective review. METHODS: Analysis of a single surgeon experience with 113 substernal goiters operated upon during a 10-year period. RESULTS: 108 goiters were successfully removed through a cervical approach. Four patients required sternotomy, and it was concluded that one patient who did not receive sternotomy might have been better managed with sternotomy. Factors that led to sternotomy were malignancy, involvement of the posterior mediastinum, extensive substernal extension, and the presence of an ectopic nodule. The latter two were the most important factors. Revision surgery and tracheal compression did not influence the need for sternotomy. CONCLUSIONS: On the basis of preoperative imaging, it is possible to predict which patients with retrosternal goiters are likely to require median sternotomy. These factors are malignancy, extension into the posterior mediastinum, substernal extension inferior to the level of the aortic arch, and the lack of a solid attachment between the cervical and mediastinal components of the thyroid gland. Although previously reported, the latter factor has not received sufficient recognition in the management of retrosternal goiter.

BACKGROUND: Procedural success and clinical outcomes after transcatheter aortic valve replacement (TAVR) have improved, but residual aortic regurgitation (AR) and new permanent pacemaker implantation (PPI) rates remain variable because of a lack of uniform periprocedural management and implantation. OBJECTIVES: The Optimize PRO study evaluates valve performance and procedural outcomes using an "optimized" TAVR care pathway and the cusp overlap technique (COT) in patients receiving the Evolut PRO/PRO+ (Medtronic) self-expanding valves. METHODS: Optimize PRO, a nonrandomized, prospective, postmarket study conducted in the United States, Canada, Europe, Middle East, and Australia, is enrolling patients with severe symptomatic aortic stenosis and no pre-existing pacemaker. Sites follow a standardized TAVR care pathway, including early discharge and a conduction disturbance management algorithm, and transfemoral deployment using the COT. RESULTS: A total of 400 attempted implants from the United States and Canada comprised the main cohort of this second interim analysis. The mean age was 78.7 ± 6.6 years, and the mean Society of Thoracic Surgeons predictive risk of mortality was 3.0 ± 2.4. The median length of stay was 1 day. There were no instances of moderate or severe AR at discharge. At 30 days, all-cause mortality or stroke was 3.8%, all-cause mortality was 0.8%, disabling stroke was 0.7%, hospital readmission was 10.1%, and cardiovascular rehospitalization was 6.1%. The new PPI rate was 9.8%, 5.8% with 4-step COT compliance. In the multivariable model, right bundle branch block and the depth of the implant increased the risk of PPI, whereas using the 4-step COT lowered 30-day PPI. CONCLUSIONS: The use of the TAVR care pathway and COT resulted in favorable clinical outcomes with no moderate or severe AR and low PPI rates at 30 days while facilitating early discharge and reproducible outcomes across various sites and operators. (Optimize PRO; NCT04091048).

BackgroundCytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.MethodsIn this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta).FindingsBetween June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations.InterpretationInitially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals.FundingUS Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

BACKGROUND: The objective of this trial was to determine how a mucoadhesive hydrogel (MuGard), a marketed medical device, would fare when tested with the strictness of a conventional multi-institutional, double-blind, randomized, placebo-controlled study format. METHODS: A total of 120 subjects planned to receive chemoradiation therapy (CRT) for treatment of head and neck cancers were randomized to receive either MuGard or sham control rinse (SC) during CRT. Subjects completed the validated Oral Mucositis Daily Questionnaire. Weight, opiate use, and World Health Organization (WHO) oral mucositis (OM) scores were recorded. Subjects who dosed at least once daily during the first 2.5 weeks of CRT were included in the efficacy analysis. RESULTS: Of 120 subjects enrolled, 78 (SC, N=41; MuGard, N=37) were eligible for efficacy analysis. Both cohorts were similar in demographics, baseline characteristics, primary tumor type, and planned CRT regimen. MuGard effectively mitigated OM symptoms as reflected by area under the curve of daily patient-reported oral soreness (P=.034) and WHO scores on the last day of radiation therapy (P=.038). MuGard was also associated with nonsignificant trends related to therapeutic benefit including opioid use duration, and OM scores (WHO criteria) at CRT week 4. Rinse compliance was identical between cohorts. No significant adverse events were reported, and the adverse event incidence was similar between cohorts. CONCLUSIONS: Testing MuGard, a rinse marketed as a device, in a standard clinical trial format demonstrated its superiority to SC in mitigating OM symptoms, delaying OM progression, and its safety and tolerability.

BACKGROUND: Percutaneous, vacuum-assisted, large-gauge core needle biopsy (VACNB) provides an alternative to open surgical biopsy as an initial diagnostic tool for breast lesions, yet rates of underestimating malignant diagnoses remain sufficiently high to warrant surgical biopsy in some cases. The current study was performed to determine if the Breast Lesion Excision System (BLES) provides a feasible alternative to VACNB. METHODS: A retrospective review was conducted of 742 consecutive mammographic lesions with microcalcifications classified as Breast Imaging Reporting and Data System (BIRADS) IV or V that had stereotactic percutaneous biopsy using BLES. Initial diagnoses obtained from the histopathologic examination of tissues retrieved at biopsy were compared with the histopathologic examination of tissues received from surgical excision or lumpectomy. Underestimation rates for atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were recorded if open surgical biopsy revealed DCIS or invasive cancer, and invasive cancer, respectively. RESULTS: Of the 742 breast lesions, 34 displayed ADH upon biopsy with the BLES device. Two patients did not receive open surgical biopsy. Of the 32 patients who had open surgical excision, 3 (9.4%) had DCIS or invasive cancer. There were 119 diagnoses of DCIS upon biopsy with the BLES device. Four patients did not receive open surgical biopsy. Of the 115 patients who had open surgical excision, 6 (5.2%) had invasive cancer. CONCLUSIONS: Breast biopsy can be performed accurately using the BLES device. Compared with VACNB, it does not alter the need for surgical excision in women diagnosed with ADH or DCIS at core biopsy.

Tobacco smoking is a chief cause of preventable deaths worldwide, accounting for various cancers, cardiovascular and respiratory diseases. Tobacco smoking accounts for more than seven million deaths every year. Worldwide statistics show that about 1.1 billion active smokers exist; 80% live in low- and middle-income countries. Nicotine is the addictive ingredient with the least harm compared to other active ingredients in tobacco, albeit not completely benign. Nicotine acts on the nicotinic cholinergic receptors (nAChRs) and produces the release of neurotransmitters. The mechanism by which it affects the cardiovascular system involves endothelial dysfunction by reducing nitrogen monoxide production, pro-thrombotic conditions, and activating inflammatory routes. These factors, along with the increased amounts of coronary atherosclerosis, have addictive adverse effects. Smoking has been shown to cause increased amounts of coronary atherosclerosis which may be responsible for the increased risk of hypertension, coronary heart disease, and atrial fibrillation, potentially contributing to the association of current smokers with a higher incidence of heart failure. This has led to worsened burdens and outcomes of cardiovascular disease among smokers. Smoking cessation has been associated with a reduction in cardiovascular mortality. This ranges from the reduction in the incidence of hypertension, type 2 diabetes, and heart failure. As regards behavioral and mental health, smoking cessation reduces the risk of cardiovascular disease in people experiencing mental illness. The prevalence of smoking continues to trend downward over the past couple of decades. Despite this downtrend, cigarette smoking is responsible for approximately half a million deaths per year in the United States and billions of dollars spent in healthcare. This buttresses the need to explore the various effects of smoking cessation on cardiovascular health and suggest ways to curb the disease burden.

Background The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial. Methods We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. Results We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the “other strategies” group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237–0.816) (p=0.009; I 2 =35.2%) versus other reperfusion strategies and 0.368 (95% CI 0.185–0.733) (p=0.004; I 2 =32.9%) for surgical embolectomy versus thrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the “other strategies” group (OR 1.27, 95% CI 0.54–2.96; I 2 =7.7%). The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy”, “ECMO implantation before pulmonary reperfusion therapy”, “clinical presentation of PE” or “cancer-associated PE” and the associated outcomes. Conclusions The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04323800.

BACKGROUND: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTS: A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSION: Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. Trial Registration: ClinicalTrials.gov number, NCT04373460.

The emergence of inpatient neurologic specialists including neurohospitalists and neurointensivists has led to an increased focus on the quality of neurologic care delivered in the hospital. Each year, there are over 1.5 million nonsurgical neurologic hospital discharges in the United States, making neurology a large inpatient specialty even without accounting for nonadmitted emergency patients.1 National quality metrics in other non-neurologic specialties have focused primarily on inpatient care since hospitals, insurers, professional organizations, and the general public have turned their attention to outcomes achieved during and following hospitalization. Many of these metrics have been applied to neurology patients, despite their not being developed with neurology-specific patient populations or disorders in mind. This gap highlights the need for measures for neurology patients in both inpatient and emergency settings. The authors thank the Inpatient and Emergency Neurology Quality Measurement Set Work Group members for their dedication, time, energy, contributions, and work that supported the development of this manuscript: John Ferro, MD, MS, FAAN (co-chair) (American Academy of Neurology); S. Andrew Josephson, MD, FAAN (co-chair) (Neurohospitalist Society); Paul Vespa, MD, FAAN (co-chair) (Neurocritical Care Society); Rohit Das, MD, MPH (American Academy of Neurology); David Gloss, MD (American Academy of Neurology); David Jones, MD (American Academy of Neurology); William Mack, MD, MS, FAANS, FAHA (American Association of Neurological Surgeons; Congress of Neurological Surgeons); Virginia Prendergast, PhD, NP-C (American Association of Neuroscience Nurses); Chip Truwit, MD (American College of Radiology/American Society of Neuroradiology); Paul Van Ness, MD (American Epilepsy Society); Michael Perskin, MD (American Geriatrics Society); Sanjeev Sockalingam, MD, FRCPC (American Psychiatric Association); Charlotte Jones, MD, PhD, MSPH (Child Neurology Society); Kevin Sheth, MD, FAAN, FNCS, FAHA (Neurocritical Care Society); Navaz Karanjia, MD (Neurocritical Care Society); Salvador Cruz-Flores, MD, MPH, FAAN (Neurocritical Care Society); Corey Fehnel, MD, MPH (Neurocritical Care Society); John Probasco, MD (Neurohospitalist Society); Mark Rubin, MD (Neurohospitalist Society); Jennifer Simpson, MD (Neurohospitalist Society); Jana Wold, MD (Neurohospitalist Society); Adam Cohen, MD (American Academy of Neurology facilitator); Adam Webb, MD (American Academy of Neurology facilitator); Amy Bennett, JD (American Academy of Neurology staff); Gina Gjorvad (American Academy of Neurology staff); Erin Lee (American Academy of Neurology staff); Becky Schierman, MPH (American Academy of Neurology staff).

Population pharmacokinetic analyses can be applied to predict optimized dosages for individual patients. The aim of this study was to compare the prediction performance of the published population pharmacokinetic models for meropenem in critically ill patients. We coded the published population pharmacokinetic models with covariate relationships into dosing software to predict unbound meropenem concentrations measured in a separate cohort of critically ill patients. The agreements between the observed and predicted concentrations were evaluated with Bland-Altman plots. The absolute and relative bias and precision of the models were determined. The clinical implications of the results were evaluated according to whether dose adjustments were required from the predictions to achieve a meropenem concentration of >2 mg/liter throughout the dosing interval. A total of 157 free meropenem concentrations from 56 patients were analyzed. Eight published population pharmacokinetic models were compared. The models showed an absolute bias in predicting the unbound meropenem concentrations from a mean percent difference (95% confidence interval [CI]) of -108.5% (-119.9% to -97.3%) to 19.9% (7.3% to 32.7%), while absolute precision ranged from -249.1% (-263.4% to -234.8%) to 31.9% (17.6% to 46.2%) and -178.9% (-196.9% to -160.9%) to 175.0% (157.0% to 193.0%). A dose change was required in 44% to 64% of the concentration results. Seven of the eight equations evaluated underpredicted free meropenem concentrations. In conclusion, the overall accuracy of these models supports their inclusion in dosing software and application for individualizing meropenem doses in critically ill patients to increase the likelihood of achievement of optimal antibiotic exposures.

INTRODUCTION: Globally, electronic medical records are central to the infrastructure of modern healthcare systems. Yet the vast majority of electronic medical records have been designed for resource-rich environments and are not feasible in settings of poverty. Here we describe the design and implementation of an electronic medical record at a public sector district hospital in rural Nepal, and its subsequent expansion to an additional public sector facility.DevelopmentThe electronic medical record was designed to solve for the following elements of public sector healthcare delivery: 1) integration of the systems across inpatient, surgical, outpatient, emergency, laboratory, radiology, and pharmacy sites of care; 2) effective data extraction for impact evaluation and government regulation; 3) optimization for longitudinal care provision and patient tracking; and 4) effectiveness for quality improvement initiatives. APPLICATION: For these purposes, we adapted Bahmni, a product built with open-source components for patient tracking, clinical protocols, pharmacy, laboratory, imaging, financial management, and supply logistics. In close partnership with government officials, we deployed the system in February of 2015, added on additional functionality, and iteratively improved the system over the following year. This experience enabled us then to deploy the system at an additional district-level hospital in a different part of the country in under four weeks. We discuss the implementation challenges and the strategies we pursued to build an electronic medical record for the public sector in rural Nepal.DiscussionOver the course of 18 months, we were able to develop, deploy and iterate upon the electronic medical record, and then deploy the refined product at an additional facility within only four weeks. Our experience suggests the feasibility of an integrated electronic medical record for public sector care delivery even in settings of rural poverty.

OBJECTIVE: To determine whether there is a "dose-dependent" relationship between coronary atherosclerosis and the burden of exercise. BACKGROUND: Recent data have suggested there may be negative consequences related to strenuous exercise. Previous studies evaluating the presence of coronary atherosclerosis as assessed by coronary calcium scores have been confounded by the presence of other cardiovascular risk factors. We aimed to assess whether there was a relationship between the burden of coronary calcium and the amount of running in a local cohort. PATIENTS AND METHODS: Eighty-five runners were screened on the basis of an exercise questionnaire that was later used to determine the experimental groups from January 2016 through October 2016. Twenty-nine individuals were excluded from the study because of the presence of preexisting cardiovascular risk factors. Runners were divided into 3 categories: Group A comprised runners who had competed in at least 10 ultramarathons and/or Ironman competitions in 10 years. Group B included runners who had participated in more than 9 marathons over 10 years. Group C comprised runners who had competed in more than 9 shorter races over 10 years. Coronary artery calcium (CAC) scores were assessed by computed tomography. Statistical analysis was performed using chi-square analyses. Logistic regression models were used to assess the relationship between runner groups and calcium score greater than 100, calcium score percentile, and calcium score greater than 0. RESULTS: =.03). CONCLUSION: A significantly higher rate of coronary artery calcification existed in long-term marathon, ultramarathon, and extreme runners than in submarathon runners. Marathoners and ultramarathoners also had a higher incidence of calcification, as well as higher average plaque burden, as compared to a standard database. Marathoners and ultramarathoners also had above-average coronary calcium scores as compared to a national database.

Exposure of a very rostral carotid bifurcation for endarterectomy may occasionally be difficult. We are reporting a simple yet effective way to gain several centimetres of exposure of the distal cervical portion of the internal carotid artery in this circumstance.

OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

Bayesian methods for voriconazole therapeutic drug monitoring (TDM) have been reported previously, but there are only sparse reports comparing the accuracy and precision of predictions of published models. Furthermore, the comparative accuracy of linear, mixed linear and nonlinear, or entirely nonlinear models may be of high clinical relevance. In this study, models were coded into individually designed optimum dosing strategies (ID-ODS) with voriconazole concentration data analyzed using inverse Bayesian modeling. The data used were from two independent data sets, patients with proven or suspected invasive fungal infections (n = 57) and hematopoietic stem cell transplant recipients (n = 10). Observed voriconazole concentrations were predicted whereby for each concentration value, the data available to that point were used to predict that value. The mean prediction error (ME) and mean squared prediction error (MSE) and their 95% confidence intervals (95% CI) were calculated to measure absolute bias and precision, while ΔME and ΔMSE and their 95% CI were used to measure relative bias and precision, respectively. A total of 519 voriconazole concentrations were analyzed using three models. MEs (95% CI) were 0.09 (-0.02, 0.22), 0.23 (0.04, 0.42), and 0.35 (0.16 to 0.54) while the MSEs (95% CI) were 2.1 (1.03, 3.17), 4.98 (0.90, 9.06), and 4.97 (-0.54 to 10.48) for the linear, mixed, and nonlinear models, respectively. In conclusion, while simulations with the linear model were found to be slightly more accurate and similarly precise, the small difference in accuracy is likely negligible from the clinical point of view, making all three approaches appropriate for use in a voriconazole TDM program.

BACKGROUND AND OBJECTIVES: Plasma biomarkers of Alzheimer disease (AD), neuroinflammation, and neurodegeneration are increasingly being used in clinical trials for diagnosis and monitoring of dementia. However, their association with longitudinal structural brain MRI changes, an important outcome measure across neurodegenerative and cerebrovascular diseases, is less known. We investigated how baseline plasma biomarkers reflect MRI markers of progression over time in patients with neurodegenerative and cerebrovascular diseases. METHODS: ) diplotypes, waist-hip circumference ratio, and disease duration. RESULTS: = 0.049 to <0.001) in the pooled disease-agnostic group. Within disease-specific cohorts, GFAP and NfL were associated with cerebral atrophy and/or small vessel disease copathology in AD/MCI, PD, FTD, or CVD. P-tau181 and p-tau217 were associated with cerebral atrophy and/or small vessel disease copathology in AD/MCI, CVD, PD-MCI, or PD-dementia. DISCUSSION: Selected plasma biomarkers seem useful as prognosis and monitoring tools of longitudinal imaging changes within real-world populations of neurodegenerative and/or cerebrovascular diseases, and provide insight into overlap across diseases in shared pathologic burden.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.