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In this study, we used a compact, high-resolution, and MRI-compatible PET camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five (18)F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of 0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.

Introduction Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition. Methods All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0 – 100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires. Results Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥ 2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid). Conclusion More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA.

Background: Individuals with chronic kidney disease (CKD) have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods: We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age-and sex matched healthy volunteers. Among COMBINE participants, we examined the associations of estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results: Mean (standard deviation [SD]) age of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years. The mean (SD) baseline eGFR in COMBINE participants was 32.1 (8.0) and 85.9 (16.0) ml/ min/1.73m2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3 - 540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared to healthy volunteers (β estimate -0.13 CKD vs. non-CKD, 95% confidence interval [CI] -0.24, -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β-estimate per 1 unit increase in natural log UACR -0.06, 95% CI -0.09, -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions: Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction assessed by mitral valve E/A ratio in individuals with CKD with and without clinical CVD, but was not associated with change in any cMRI parameter.

Background: During the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, COVID-19 hospitalization was associated with high mortality. It is unknown how palliative care wa...

BackgroundGangliosides are glycosphingolipids highly enriched in the brain, with important roles in cell signaling, cell-to-cell communication, and immunomodulation. Genetic defects in the ganglioside biosynthetic pathway result in severe neurodegenerative diseases, while a partial decrease in the levels of specific gangliosides was reported in Parkinson’s disease and Huntington’s disease. In models of both diseases and other conditions, administration of GM1—one of the most abundant gangliosides in the brain—provides neuroprotection. Most studies have focused on the direct neuroprotective effects of gangliosides on neurons, but their role in other brain cells, in particular microglia, is not known. In this study we investigated the effects of exogenous ganglioside administration and modulation of endogenous ganglioside levels on the response of microglia to inflammatory stimuli, which often contributes to initiation or exacerbation of neurodegeneration.MethodsIn vitro studies were performed using BV2 cells, mouse, rat, and human primary microglia cultures. Modulation of microglial ganglioside levels was achieved by administration of exogenous gangliosides, or by treatment with GENZ-123346 and L–t-PDMP, an inhibitor and an activator of glycolipid biosynthesis, respectively. Response of microglia to inflammatory stimuli (LPS, IL-1β, phagocytosis of latex beads) was measured by analysis of gene expression and/or secretion of pro-inflammatory cytokines. The effects of GM1 administration on microglia activation were also assessed in vivo in C57Bl/6 mice, following intraperitoneal injection of LPS.ResultsGM1 decreased inflammatory microglia responses in vitro and in vivo, even when administered after microglia activation. These anti-inflammatory effects depended on the presence of the sialic acid residue in the GM1 glycan headgroup and the presence of a lipid tail. Other gangliosides shared similar anti-inflammatory effects in in vitro models, including GD3, GD1a, GD1b, and GT1b. Conversely, GM3 and GQ1b displayed pro-inflammatory activity. The anti-inflammatory effects of GM1 and other gangliosides were partially reproduced by increasing endogenous ganglioside levels with L–t-PDMP, whereas inhibition of glycolipid biosynthesis exacerbated microglial activation in response to LPS stimulation.ConclusionsOur data suggest that gangliosides are important modulators of microglia inflammatory responses and reveal that administration of GM1 and other complex gangliosides exerts anti-inflammatory effects on microglia that could be exploited therapeutically.

Rationale: Early mobilization of ECMO-supported patients is increasingly common, but it remains unknown whether there are factors predictive of achieving higher intensity mobilization among those a...

The textile and dyeing industry have shown dramatic growth alongside synthetic chemistry in the last century. With operations and economic importance, challenges also increase, including environmental pollution, work safety, and consumer health. Change of perspectives in the industry is on the rise, so environmentally-friendly solutions for safer processes and more circularity are urgently sought-after. A possible solution for the pressing issue of textile dyeing is the use of natural colourants obtained in fermentation processes. In this contribution, a comparison between biologically-derived dyes and their synthetic counterparts is conducted on several levels. The structural diversity of biogenic dyes is potentially high enough to pose an alternative on a broad front. Matching fundamental properties concerning dyeing, (bio)synthesis and toxicity give an impression of the advantages of developing this natural alternative. The most important topics for the future are outlined. Major challenges and potential solutions that limit the implementation of biogenic dyes into the textile dyeing value chain are discussed. Biotechnology offers numerous methods to increase reliable production or engineer molecular properties elegantly. The biggest advantage from a Green Chemistry perspective is the possibility to switch to renewable starting materials and obtain more biodegradable dyes. A more sustainable alternative in textile dyeing is afoot. It needs to be embraced and developed to provide the world population with a sustainable way into the future.

Background Anticoagulation therapy management during venoarterial extracorporeal membrane oxygenation (ECMO) is particularly difficult in postcardiotomy shock patients given a significant bleeding risk. We sought to determine the effect of anticoagulation treatment on bleeding and thrombosis risk for postcardiotomy shock patients on ECMO. Methods We retrospectively reviewed patients who received ECMO for postcardiotomy shock from July 2007 through July 2019. Characteristics of patients who had bleeding and thrombosis were investigated, and risk factors were assessed by multilevel logistic regression. Results Of the 152 patients who received ECMO for postcardiotomy shock, 33 (23%) had 40 thrombotic events and 64 (45%) had 86 bleeding events. Predictors of bleeding were intraoperative packed red blood cell transfusion (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.01 to 1.09), platelet transfusion (OR 1.10; 95% CI, 1.05 to 1.16), international normalized ratio (OR 1.18; 95% CI, 1.02 to 1.37), and activated partial thromboplastin time greater than 60 seconds (OR 2.32; 95% CI, 1.14 to 4.73). Predictors of thrombosis were anticoagulant use (OR 0.39; 95% CI, 0.19 to 0.79), surgical venting (OR 3.07; 95% CI, 1.29 to 7.31), hemoglobin (OR 1.38; 95% CI, 1.06 to 1.79), and central cannulation (OR 2.06; 95% CI, 1.03 to 4.11). The daily predicted probability of thrombosis was between 0.075 and 0.038 for patients who did not receive anticoagulation and decreased to between 0.030 and 0.013 for patients who received anticoagulation treatment at activated partial thromboplastin times between 25 and 80 seconds. Conclusions Anticoagulation therapy can reduce thromboembolic events in postcardiotomy shock patients on ECMO, but bleeding risk may outweigh this benefit at activated partial thromboplastin times greater than 60 seconds.

The Radiology Research Alliance (RRA) of the Association of University Radiologists (AUR) convenes Task Forces to address current topics in radiology. In this article, the AUR-RRA Task Force on Academic-Industry Partnerships for Artificial Intelligence, considered issues of importance to academic radiology departments contemplating industry partnerships in artificial intelligence (AI) development, testing and evaluation. Our goal was to create a framework encompassing the domains of clinical, technical, regulatory, legal and financial considerations that impact the arrangement and success of such partnerships.

Objectives This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation by using temporary percutaneous endovascular mechanical circulatory support (tMCS) through a status 2 designation (cardiogenic shock and exception). Background The 2018 donor heart allocation policy change granted a status 2 designation to patients supported with tMCS. Methods Adult patients in the United Network for Organ Sharing registry after October 18, 2018 who received a status 2 designation for tMCS were included and grouped by their status 2 criteria: cardiogenic shock with hemodynamic criteria (CS-HD), cardiogenic shock without hemodynamic criteria before tMCS (CS-woHD), and exception. Baseline characteristics, waitlist events (death and delisting), and post-transplant outcomes were compared. Results A total of 2,279 patients met inclusion criteria: 68.6% (n = 1,564) with CS-HD, 3.2% (n = 73) with CS-woHD, and 28.2% (n = 642) with exceptions. A total of 64.2% of patients underwent heart transplantation within 14 days of status 2 listing or upgrade, and 1.9% died or were delisted for worsening clinical condition. Among the 35.8% who did not undergo transplantation following 14 days, only 2.8% went on to receive a left ventricular assist device (LVAD). The 30-day transplantation likelihood was similar among groups: 80.1% for the CS-HD group vs 79.7% for the exception group vs 73.3% for the CS-woHD group; P = 0.31. However, patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.10-4.75; P = 0.03) compared with CS-HD patients after multivariable adjustment. Pre-tMCS hemodynamics were not associated with adverse waitlist events. Conclusions The use of tMCS is an efficient, safe, and effective strategy as a bridge to transplantation; however, patients with CS-woHD may represent a high-risk cohort. Transition to a durable LVAD was a rare event in this group.

Can we reduce the damage from climate change by investing in seawalls, stilts, or other forms of adaptation? Focusing on the case of severe storms in the US, I develop a macro heterogeneous-agent model to quantify the interactions between adaptation, federal disaster policy, and climate change. The model departs from the standard climate damage function and incorporates the damage from storms as the realization of idiosyncratic shocks. Using the calibrated model, I infer that adaptation capital comprises approximately 1$\%$ of the US capital stock. I find that while the moral hazard effects from disaster aid reduce adaptation in the US economy, federal subsidies for investment in adaptation more than correct for the moral hazard. I introduce climate change into the model as a permanent increase in either or both the severity or probability of storms. Adaptation reduces the damage from this climate change by approximately one-third. Finally, I show that modelling the idiosyncratic risk component of climate damage has quantitatively important implications for adaptation and for the welfare cost of climate change.

Background Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population. Methods and Results We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00–3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14–5.28, P = .021) and death (HR 2.36, 95% CI 1.17–4.79 P = .016) at 6 months of follow-up. Conclusions The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population.

Purpose We sought to evaluate the association between postoperative cam lesion measured by the femoroacetabular impingement resection (FAIR) arc and show 2-year patient outcomes following hip arthroscopy. Methods A retrospective review of prospectively gathered data from 2013-2017 was performed. All patients who underwent hip arthroscopy for femoroacetabular impingement resection (FAI) with ≥2-year follow-up were included. Cam FAIR arc measurements were made preoperatively and postoperatively on a 45° Dunn view radiograph. The clinical effect of postoperative cam maximal radial distance (MRD) was assessed using the modified Harris Hip Score (mHHS) and Non-Arthritic Hip Score (NAHS). Patients were divided into subgroups based on relationship to the mean and standard deviations for cam MRD. One half standard deviation above the mean was found to be 3.15 mm. Results Sixty-one hips in 59 consecutive patients (age 38.1 ± 13.1; body mass index [BMI]: 25.5 ± 4.3; 36 females) were included. Mean preoperative and postoperative cam maximal radial distances (MRD) were 4.5 ± 1.7 mm and 2.3 ± 1.7 mm (P .9) for all measurements. There were no differences in age, sex, BMI or preoperative mHHS/NAHS between 3.15 mm cam MRD groups (P > .05). Using linear regression, cam MRD was found to be significantly associated with 2-year outcomes for both mHHS (R2 = .21, P 3.15 mm group. Additionally, more patients in the 3.15 mm group. Conclusion Patients with a lower postoperative cam MRD relative to the FAIR arc demonstrated significantly improved outcomes as compared to those with higher postoperative MRD at two-year follow-up. Level of Evidence Level IV, retrospective case series.

Prior studies have reported increased cortical excitability in people with Alzheimer’s disease (AD), but findings have been inconsistent, and how excitability relates to dementia severity remains incompletely understood. The objective of this study was to investigate the association between a transcranial magnetic stimulation (TMS) measure of motor cortical excitability and measures of cognition in AD. A retrospective cross-sectional analysis tested the relationship between resting motor threshold (RMT) and the Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) across two independent samples of AD participants (a discovery cohort, n=22 and a larger validation cohort, n=129) and a control cohort of cognitively normal adults (n=26). RMT was correlated with ADAS-Cog in the discovery-AD cohort (n=22, β=−.70, p

PURPOSE The purpose of this study was to evaluate the outcomes of athletes 5-years post-operatively following arthroscopic Bankart repair, and to evaluate factors associated with satisfaction and shoulder function, as defined by subjective shoulder value. METHODS A retrospective review of athletes who underwent arthroscopic Bankart repair, with a minimum of 5-year follow-up was performed. Recurrence, Visual Analogue Scale (VAS) score, Subjective Shoulder Value (SSV), satisfaction, and whether they would undergo the same surgery again, and rate, level and timing of return to play, and Shoulder Instability-Return to Sport after Injury (SIRSI) score were evaluated. Multi-linear regression models were used to evaluate factors affecting postoperative Satisfaction, and SSV level. RESULTS Overall, 144 athletes who underwent arthroscopic Bankart repair were included, with a mean age of 26.9 years (SD: 8.1), 132 (91.7%) were males, and mean follow-up of 75.7 months. At final follow up, 82.6% were satisfied/very satisfied, and the mean SSV was 85.8 (SD: 14.4). Overall, the rate of return to play was 80.5%, with 63.9% returning at the same level at a mean of 6.2 months (SD: 2.7). Overall, there was 18 (12.5%) had recurrent instability, and a further procedure was performed in 15 (10.4%) patients. Linear regression revealed that the SIRSI score (p

The purpose of this study was to determine and establish the MCID for the NAHS at 2 years in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Patients that underwent primary hip arthroscopy for FAIS between 2010 and 2016 were analyzed for eligibility. Data were collected from a single surgeon’s hip arthroscopy database. MCID was calculated for the NAHS utilizing a distribution-based method. The study included 298 patients (184 females) with an average age of 40.4 ± 13.0 years and average body mass index (BMI) of 25.7 ± 4.2 kg/m2. At baseline, the cohort’s average NAHS score was 48.7 ± 13.6 and demonstrated an improvement of 36.5 ± 17.0 for NAHS at follow-up. This resulted in MCID values of + 8.5 for NAHS. This is the first study to report the MCID (+ 8.5) for NAHS following primary hip arthroscopy, and as such, is a valuable contribution to future hip arthroscopy research. IV.

Background Patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis. Aims To investigate the completeness of real-world NASH-related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy-diagnosed NASH and a pragmatic clinical definition of NASH. Methods Liver pathology reports from 222 patients across 38 TARGET-NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over-read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET-NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m2 , type 2 diabetes mellitus and dyslipidaemia. Results Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight-to-fair concordance (weighted kappa 0.01-0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56-0.57) for fibrosis staging. Clinical definition of NASH was 75%-91% concordant (94%-95% sensitive) with biopsy-diagnosed NASH. Conclusions There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET-NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice.

Background Surgical peer coaching has been associated with high rates of practice change but remains largely unutilized. The purpose of this study was to survey surgeons internationally to investigate attitudes regarding peer coaching and to identify any international differences to inform the design of future coaching programs. Methods Practicing surgeons in general surgery or related subspecialties were eligible to participate. Invitations to complete the survey were distributed through 13 surgical associations, social media, and personal e-mail invitations. Responses were obtained between June 1st and August 31st, 2020. Results A total of 521 surveys were collected. The majority of participants practiced in North America (263; 50%) with remaining respondents from Asia (81; 16%), Europe (34;7%), South America (21; 4%), Africa (17; 3%), and Oceania (6; 1%). Duration of practice was equally distributed across 4 intervals (0–5 years; 6–15 years; 16–25 years; > 25 years). Respondents most frequently identified as general surgeons (290; 67%) and 325 (75%) were male. Awareness of peer coaching was reported by 275 (53%) respondents, with 197 (44%) never seeking formal feedback from peers. The majority of respondents (372; 84%) would be willing to participate in a peer coaching program, with monthly interactions the most desirable frequency reported (193; 51%). Coaching in the operating room was preferred by most participants (360; 86%). Few respondents (67; 14%) would accept coaching from someone unknown to them. Participants identified key coaching program elements as: feedback kept private and confidential (267; 63%); opportunity to provide feedback to the coach (247; 59%); personalized goal setting (244; 58%); and the option to choose one’s own coach (205; 49%). The most commonly cited potential barrier to participation was logistical constraints (334; 79%). Conclusion This international survey of practicing surgeons demonstrated that peer feedback is rarely used in practice, but there is high interest and acceptance of the peer coaching model for continuous professional development. Findings regarding preferred program structure may be useful to inform the design of future peer coaching programs. Supplementary Information The online version contains supplementary material available at 10.1007/s00464-021-08760-z.

Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well defined TBS protocols, continuous TBS (cTBS) and intermittent TBS (iTBS), especially in relation to sham TBS, within and across the same 24 participants. All TBS protocols were repeated after approximately 1 month to assess the magnitude and reliability of the modulatory effects of each TBS protocol. Baseline and post-TBS changes in motor evoked potentials (MEP—measure of corticospinal excitability) amplitudes were compared across the cTBS, iTBS and sham TBS protocols and between the initial and retest visits. Overall, across participants, at the initial visit, iTBS facilitated MEPs as compared to baseline excitability, with sham eliciting the same effect. cTBS did not show a significant suppression of excitability compared to baseline MEPs at either visit, and even facilitated MEPs above baseline excitability at a single time point during the repeat visit. Otherwise, effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. However, no protocol demonstrated consistent intra-individual modulation of corticospinal excitability upon retest. As the first study to test both iTBS and cTBS against sham TBS across repeat visits, our findings challenge the efficacy and reliability of TBS protocols and emphasize the importance of accounting for sham effects of TBS. Furthermore, given that therapeutic effects of TBS are hypothetically derived from consistent and repeated modulation of brain activity, the non-replicability of plasticity and sham effects call into question these basic mechanisms.

Background & Aims Retreatment with glecaprevir/pibrentasvir (G/P) resulted in a rate of sustained virologic response 12 weeks after treatment completion (SVR12) of >90% in HCV genotype 1 (GT1) patients who previously failed a regimen of sofosbuvir plus an NS5A inhibitor (NS5Ai). This study investigated the prevalence and impact of baseline NS3 and NS5A resistance-associated substitutions (RASs) on the efficacy of G/P in prior GT1 sofosbuvir+NS5Ai failures and the persistence of treatment-emergent RASs. Methods Longitudinal samples from 177 patients enrolled in a phase IIIb, randomized pragmatic clinical trial were analyzed. Patients without cirrhosis were randomized to 12 or 16 weeks of G/P, and patients with compensated cirrhosis were randomized to G/P and ribavirin for 12 weeks or G/P for 16 weeks. Linkage of RAS was identified using Primer-ID next-generation sequencing at a 15% cut-off. Results Of 177 patients, 169 (95.5%) were PI-naive. All 33 GT1b-infected patients achieved SVR12. In GT1a-infected patients, baseline NS5A RASs were prevalent (74.5%, 105/141) but NS3 RASs were uncommon. Baseline NS3 RASs had no impact on G/P efficacy and patients with baseline NS5A RASs showed a numerically but not statistically significantly lower SVR12 rate compared to those without NS5A RASs (89% vs. 97%). SVR12 was achieved in 34 of 35 (97%) patients without NS5A baseline substitution, and 53 of 57 (93%), 35 of 40 (88%), 5 of 8 (63%) with single, double-linked, and triple-linked NS5A substitutions, respectively. Among 13 patients with virologic failure, 4 acquired treatment-emergent NS3 RASs and 10 acquired NS5A RASs. Conclusion Baseline NS5A RASs were highly prevalent. The presence of an increasing number of linked NS5A RASs in GT1a showed a trend in decreasing SVR12 rates, although no specific NS5A RASs or their linkage pattern were associated with lower SVR12 rates. Lay summary Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C infection, but treatment failure occurs in some patients. Retreatment of patients who previously failed a regimen consisting of sofosbuvir and an NS5A inhibitor with a regimen of glecaprevir and pibrentasvir (G/P) is >90% effective. Herein, we analyzed samples from these patients and showed that retreatment efficacy with G/P is lower in patients with double- or triple-linked NS5A resistance mutations than in patients with single or no NS5A resistance mutations. Clinical trial number NCT03092375 .

Background: Owing to the COVID-19 pandemic, there has been a large shift in health care toward virtual platforms. This study analyzed patient and physician satisfaction with telehealth during the height of the pandemic within the division of sports medicine. Methods: All sports medicine patients who completed a telemedicine visit from March 30, 2020, through April 30, 2020, were sent a 14-question Likert scale (1-5/5) survey. Sports medicine physicians who used telemedicine were sent a separate 14-question Likert scale (1-5/5) survey at the end of the study period. Factors influencing patient satisfaction were determined using a multivariate linear regression model. Results: A total of 143 patients and 9 sports medicine attendings completed the surveys. Most patients were "satisfied" (4/5) or "very satisfied" (5/5) (88.8%). A multivariate linear regression determined that patients who believed they had a greater ability to adopt new technology and were more effective at communicating questions/concerns to their physicians had greater satisfaction (p = 0.009 and p = 0.015, respectively). Most physicians were either "satisfied" (4/5) or "very satisfied" (5/5) (75.0%). On average, physicians felt that physical examinations conducted through telemedicine were "moderately effective" (2.75/5.00 ± 1.3), that they were "fairly confident" (3.86/5.00 ± 0.83) in their diagnoses, and that most sports medicine attendings plan to use telemedicine in the future (87.5%). Conclusion: Telehealth emerged as a valuable tool for the delivery of health care to sports medicine patients during the COVID-19 pandemic. Patients and physicians reported high levels of satisfactions with its use, and this study further identifies areas that can improve the patient and physician experience.

Context While medical end-of-life planning has been well characterized, less is known about non-medical planning to prepare for the end of life. Objectives To determine the prevalence of engagement in non-medical end-of-life (EOL) planning and its relationship to medical EOL planning. Methods Three hundred and four persons age 65 and older recruited from physician offices and a senior center were administered an in-person interview asking about participation in the following non-medical EOL planning behaviors: moving to a location with more help, teaching someone to do things around the house, purchasing long-term care insurance, telling someone the location of important documents, preparing a financial will, conveying wishes for funeral arrangements, purchasing a cemetery plot, and prepaying for a funeral. Results Prevalence of participation in the different non-medical EOL planning activities varied widely, from 8% for prepaying for a funeral to 84% for telling someone the location of important documents. There was little overlap in the factors associated with participation in each activity. Conveying wishes for funeral arrangements and completing a financial will were associated with completing a living will (OR 2.69, 95% CI 1.51, 4.78; OR 6.70, 95% CI 3.18, 14.15) and communication about quality versus quantity of life (OR 4.52, 95% CI 2.54, 8.04; OR 2.47, 95% CI 1.25, 4.86). Conclusion There is variability in both the prevalence of and factors associated with engagement in non-medical EOL planning activities. The association of non-medical with medical planning activities supports the utility of programs assisting individuals with broad engagement in EOL planning.

The impact of gamma radiation on a commercial off the shelf microcontroller board has been investigated. Three different tests have been performed to ascertain the radiation tolerance of the device from a nuclear decommissioning deployment perspective. The first test analyses the effect of radiation on the output voltage of the on-board voltage regulator during irradiation. The second test evaluated the effect of gamma radiation on the voltage characteristics of analogue and digital inputs and outputs. The final test analyses the functionality of the microcontroller when using an external, shielded voltage regulator instead of the on-board voltage regulator. The results suggest that a series of latch-ups occurs in the microcontroller during irradiation, causing increased current drain which can damage the voltage regulator if it does not have short-circuit protection. The analogue to digital conversion functionality appears to be more sensitive to gamma radiation than digital and analogue output functionality. Using an external, shielded voltage regulator can prove beneficial when used for certain applications. The collected data suggests that detaching the voltage regulator can extend the lifespan of the platform up to approximately 350 Gy.

Study design Secondary data analysis of wheelchair failures and service repair logs from a network of wheelchair suppliers. Objective To determine the frequency of wheelchair caster failures and service repairs across wheelchair manufacturers and models and investigate the relationships between them. Setting Wheelchair caster failures and service repairs occurred in the community. Methods Reported caster failure types were classified based on the risk they pose for user injuries and wheelchair damage. Caster failures experienced by users of tilt-in-space and ultralightweight manual wheelchair models and Group 2, 3 and 4 power wheelchair models between January 2017 and October 2019 were analyzed using Chi-Square tests for independence. Correlational analysis of failures and service repairs was performed. Results A total of 6470 failures and 151 service repairs reported across four manufacturers and five models were analyzed. Failure types were significantly associated with manufacturers and models, respectively. Users of tilt-in-space wheelchairs, who require greater seating support, experienced twice the proportion of high-risk caster failures than the ultralightweight manual wheelchair users. Similarly, Group 3 and 4 power wheelchair users, who have complex rehabilitation needs, experienced 15-36% more high-risk failures than Group 2 users. Service repairs negatively correlated with high-risk manual wheelchair caster failures. Conclusions Wheelchair users who have greater seating and complex rehabilitation needs are at a higher risk for sustaining injuries and secondary health complications due to frequent caster failures. The study findings call for significant reforms in product quality and preventative maintenance practices that can reduce wheelchair failures and user consequences.

Aims We aimed to detail the early clinical experience with pVAD 5.5 at a large academic medical centre. Impella® 5.5 (Abiomed) is a temporary peripherally inserted left ventricular assist device (pVAD) used for the treatment of cardiogenic shock (CS). This system has several modifications aimed at improving deliverability and durability over the pVAD 5.0 system, but real‐world experience with this device remains limited. Methods and results We collected clinical and outcome data on all patients supported with pVAD 5.5 at our centre between February and December 2020, including procedural and device‐related complications. Fourteen patients with pVAD 5.5 were included. Aetiology of CS was acute myocardial infarction (n = 6), decompensated heart failure (n = 6), suspected myocarditis (n = 1), and post‐cardiotomy CS (n = 1). Four patients received pVAD 5.5 after being on inotropes alone, two were escalated from intra‐aortic balloon pump, two were escalated from pVAD CP, and six patients were transitioned to pVAD 5.5 from extracorporeal membrane oxygenation. Median duration of pVAD 5.5 support was 12 (interquartile range 7, 25) days. Complications included axillary insertion site haematoma (n = 3), acute kidney injury (n = 3), severe thrombocytopenia (n = 1), and stroke (n = 1). No valve injury or limb complications occurred. Survival to device explant for recovery or transition to another therapy was 11/14 (79%) patients. Conclusions In this early experience of the pVAD 5.5, procedural and device‐related complications were observed but were manageable, and overall survival was high in this critically ill cohort, particularly when the device was used as a bridge to other therapies.

We present an algorithm for producing a seamless animated loop from a single image. The algorithm detects periodic structures, such as the windows of a building or the steps of a staircase, and generates a non-trivial displacement vector field that maps each segment of the structure onto a neighboring segment along a user- or auto-selected main direction of motion. This displacement field is used, together with suitable temporal and spatial smoothing, to warp the image and produce the frames of a continuous animation loop. Our cinemagraphs are created in under a second on a mobile device. Over 140,000 users downloaded our app and exported over 350,000 cinemagraphs. Moreover, we conducted two user studies that show that users prefer our method for creating surreal and structured cinemagraphs compared to more manual approaches and compared to previous methods., Comment: SIGGRAPH 2021. Project page: https://pub.res.lightricks.com/endless-loops/ . Video: https://youtu.be/8ZYUvxWuD2Y

Summary Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vsz 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. Funding National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.

MEMS inductors are used in a wide range of applications in micro- and nanotechnology, including RF MEMS, sensors, power electronics, and Bio-MEMS. Fabrication technologies set the boundary conditions for inductor design and their electrical and mechanical performance. This review provides a comprehensive overview of state-of-the-art MEMS technologies for inductor fabrication, presents recent advances in 3D additive fabrication technologies, and discusses the challenges and opportunities of MEMS inductors for two emerging applications, namely, integrated power electronics and neurotechnologies. Among the four top-down MEMS fabrication approaches, 3D surface micromachining and through-substrate-via (TSV) fabrication technology have been intensively studied to fabricate 3D inductors such as solenoid and toroid in-substrate TSV inductors. While 3D inductors are preferred for their high-quality factor, high power density, and low parasitic capacitance, in-substrate TSV inductors offer an additional unique advantage for 3D system integration and efficient thermal dissipation. These features make in-substrate TSV inductors promising to achieve the ultimate goal of monolithically integrated power converters. From another perspective, 3D bottom-up additive techniques such as ice lithography have great potential for fabricating inductors with geometries and specifications that are very challenging to achieve with established MEMS technologies. Finally, we discuss inspiring and emerging research opportunities for MEMS inductors.

OBJECTIVE To examine the prevalence of hearing impairment in children with hypothyroidism, and to characterize clinical and subclinical hearing loss by examining cochlear function, auditory brainstem pathways, and integration of the auditory system as a whole. DESIGN An electronic search was conducted using PubMed, Scopus, and Cochrane Library databases. This systematic review was performed in accordance with the PRISMA guidelines. Original observational studies that utilized audiological tests for auditory system evaluations in hypothyroidism were included. A total of 2004 studies were found in the search, with 23 studies meeting the inclusion criteria. RESULTS The pooled prevalence of hearing loss was 16.1% [95% confidence interval 10.7, 22.4] for children with congenital hypothyroidism. Hearing thresholds at pure-tone averages (0.5-2 kHz) were 1.6 dB [95% confidence interval 1.7, 4.8] higher for children with hypothyroidism compared to age-matched controls. Cochlear dysfunction was detected at middle frequencies (1-3 kHz) by otoacoustic emission testing, indicating abnormalities of hair cell function or cochlear integration. Retrocochlear involvement was detected on auditory brainstem response (ABR), with prolonged Wave I indicating a peripheral conduction abnormality localized to the middle or inner ear and eighth cranial nerve. CONCLUSIONS Children with hypothyroidism have a higher prevalence of hearing loss than children without hypothyroidism. For children with congenital hypothyroidism, evidence of subclinical abnormalities at the level of the cochlea and eighth cranial nerve are present despite early initiation of levothyroxine therapy. Dysfunction of the auditory system might begin with predominance of peripheral conduction abnormalities early in development.

Background Over the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability despite their short duration and low number of stimuli. However, this assumption, and thus the experimental validity of studies using TBS, is challenged by recent work showing large inter- and intra-subject variability in response to TBS protocols. Objectives To date, the reproducibility of TBS effects in humans has been exclusively assessed with motor evoked potentials (MEPs), which provide an indirect and limited measure of cortical excitability. Here we combined TMS with electroencephalography (TMS-EEG) and report the first comprehensive investigation of (1) direct TMS-evoked cortical responses to intermittent (iTBS) and continuous TBS (cTBS) of the human motor cortex, and (2) reproducibility of both iTBS- and cTBS-induced cortical response modulation against a robust sham control across repeat visits with commonly used cortical responsivity metrics. Results We show that although single pulse TMS generates stable and reproducible cortical responses across visits, the modulatory effects of TBS vary substantially both between and within individuals. Overall, at the group level, most measures of the iTBS and cTBS-induced effects were not significantly different from sham-TBS. Most importantly, none of the significant TBS-induced effects observed in visit-1 were reproduced in visit-2. Conclusions Our findings suggest that the generally accepted mechanisms of TBS-induced neuromodulation, i.e. through changes in cortical excitability, may not be accurate. Future research is needed to determine the mechanisms underlying the established therapeutic effects of TBS in neuropsychiatry and examine reproducibility of TBS-induced neuromodulation through oscillatory response dynamics.

Background Benefits of physical activity are well recognized for youth with type 1 diabetes mellitus (T1DM), but being active is challenging. In this study, we aimed to investigate the challenges experienced by adolescents, their parents and young adults with T1DM when they are physically active. Methods Six focus groups involving adolescents (13 to 18 years old, n=14) and young adults (19 to 25 years old, n=7) and 4 focus groups with parents (n=14) of the adolescents (13 to 18 years) were established. Data were analyzed using content analysis. Results Adolescents and young adults with T1DM identified challenges of unpredictability, knowledge, trust and stigma when they were physically active. Parent challenges were specifically unpredictability and trust. Conclusions Interventions are needed that provide adolescents and young adults with T1DM and parents of adolescents with T1DM more in-depth information about managing physical activity in a manner that enhances their perceived competence and builds autonomy. Interventions can also target peer and community support.

As the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) increases, decisions regarding withdrawal from VA-ECMO increase.To evaluate the clinical characteristics of patients withdrawn from VA-ECMO and the role of palliative care consultation in the decision.We retrospectively reviewed adult patients with cardiogenic shock requiring VA-ECMO at our institution, who were withdrawn from VA-ECMO between January 1, 2014 and May 31, 2019. The relationship between clinical characteristics and palliative care visits was assessed, and documented reasons for withdrawal were identified.Of 460 patients who received VA-ECMO, 91 deceased patients (19.8%) were included. Forty-two patients (44.8%) had a palliative care consultation. The median duration on VA-ECMO was 4.0 days (interquartile range 8.8), and it was significantly longer for patients with palliative care consultation than those without (8.8 days vs. 2.0 days, P 0.001). Among those with palliative care consultation, those with early consultation (within three days) had significantly shorter duration of VA-ECMO compared with those with late consultation (7.6 days vs. 13.5 days, t = 2.022, P = 0.008). Twenty-two (24.2%) had evidence of brain injury, which was significantly associated with patient age, number of comorbidities, duration of VA-ECMO, number of life-sustaining therapies, and number of palliative care visits (Wilks lambda 0.8925, DF 5,121, P = 0.016). Presence of brain injury was associated with fewer palliative care visits (t = 2.82, P = 0.006).Shorter duration of VA-ECMO support and presence of brain injury were associated with fewer palliative care visits. Decisions around withdrawal of VA-ECMO support might be less complicated when patient's medical conditions deteriorate quickly or when neurological prognosis seems poor.

Purpose The purpose of this double-blind, randomized, controlled trial was to evaluate the use of intravenous (IV) tranexamic acid (TXA) in patients undergoing primary bone–patellar tendon–bone (BPTB) anterior cruciate ligament reconstruction (ACLR) regarding postoperative hemarthrosis, pain, opioid consumption, and quadriceps atrophy and activation. Methods A controlled, randomized, double-blind trial was conducted in 110 patients who underwent ACLR with BPTB autograft. Patients were equally randomized to the control and experimental groups. The experimental group received two 1-g boluses of IV TXA, one prior to tourniquet inflation and one prior to wound closure; the control group did not receive TXA. If a clinically significant hemarthrosis was evident, the knee was aspirated and the volume of blood (in milliliters) was recorded. Additionally, we recorded perioperative blood loss (in milliliters); visual analog scale scores on postoperative days 1, 4, and 7 and at postoperative weeks 1, 6, and 12; postoperative opioid consumption on postoperative days 1, 4, and 7; range of motion (ROM) and ability to perform a straight leg raise at postoperative weeks 1, 6, and 12; and preoperative and postoperative thigh circumference ratio. Results There was no significant difference in perioperative blood loss between the TXA and control groups (32.5 mL vs 35.6 mL, P = .47). In the TXA group, 23 knees were aspirated; in the control group, 26 knees were aspirated (P = .56). No significant difference in postoperative hemarthrosis volume was seen in patients who received IV TXA versus those who did not (26.7 mL vs 37.3 mL, P = .12). There was no significant difference in visual analog scale scores between the 2 groups (P = .15); in addition, there was no difference in postoperative opioid consumption (P = .33). No significant difference in ROM, ability to perform a straight leg raise, or postoperative thigh circumference ratio was observed (P > .05 for all). Conclusions IV TXA in patients who undergo ACLR with BPTB autograft does not significantly impact perioperative blood loss, postoperative hemarthrosis, or postoperative pain levels. Additionally, no significant differences were seen in early postoperative recovery regarding ROM or quadriceps reactivation. Level of Evidence Level I, randomized controlled trial.

Symptomatic femoroacetabular impingement is one of the most common hip pathologies in young athletes. Intraoperative fluoroscopy is commonly used during hip arthroscopy to aid with portal placement and resection of the cam and pincer lesions. However, there are currently no universally agreed-on tools to allow for the assessment of adequacy of femoral and acetabular osteoplasty. Despite the general lack of consensus among hip arthroscopists, the senior author recommends using the femoroacetabular impingement resection arc to guide the adequacy of cam and pincer resection in hip arthroscopy. Using intraoperative fluoroscopy, one should aim to create a continuous “Shenton’s line”-type arc along the inferior aspect of the anterior–inferior iliac spine and superolateral femoral neck base by resecting any bone that causes a break in the continuity of this arc., Technique Video Video 1 Case presentation and complete surgical technique of a right hip arthroscopy with cam and pincer resection and labral repair using the femoroacetabular impingement resection arc tool.

Purpose To explore the relationship between generalized joint hypermobility and hip labrum width. Methods A retrospective review was performed of a single-surgeon database containing patients who underwent hip arthroscopy between 2014 and 2017. Patients were assessed for generalized laxity via Beighton Test Scoring (BTS), which tests for hyperextension of the fifth metacarpophalangeal joint, thumb apposition, elbow hyperextension, knee hyperextension, and trunk flexion on a 9-point scale. Patients were stratified into a “high BTS cohort” with a BTS ≥4, and a control cohort with BTS

Real-world evidence includes all health-related information, such as electronic health records, insurance claims, pharmacy records and wearables that are obtained outside of clinical trials. These data can provide critical insights into the natural history of disease and evaluate the safety and effectiveness of treatment regimens used in clinical practice. Real-world data have been applied to varying degrees by global regulatory agencies to inform and expedite many phases of drug development and help refine the use of therapeutic regimens after marketing, especially in populations that are under-represented in registration trials. For the management of hepatocellular carcinoma, early detection provides the best chance for curative therapies, whose success has been evaluated in numerous cohorts. The availability of novel systemic therapies, including kinase inhibitors and immunotherapies, has provided new treatment options and improved survival in patients with advanced stage hepatocellular carcinoma. Real-world longitudinal observational studies can help understand the long-term safety and effectiveness of these agents.

Nucleos(t)ide analogues, with a proven record of safety and efficacy, have been the therapy of choice for over a decade for the treatment of chronic hepatitis B. The approval of tenofovir alafenamide (TAF) in 2016 provided an additional treatment option. The aim of this study was to evaluate the characteristics and clinical outcomes of patients treated with TAF in usual clinical practice. Retrospective data from electronic health records was obtained from those enrolled in TARGET-HBV, a longitudinal observational cohort study of patients with chronic hepatitis B managed according to local practice standards at community and academic medical centers throughout the U.S. Of 500 patients enrolled, most were male (66%) and of Asian race (66%) with median age of 55 years. Cirrhosis was evident in 15%. Most patients (82%) had switched to TAF after treatment with other antivirals. The perceived safety profile of TAF was cited as the primary reason for changing therapy (32%). TAF was well tolerated and only 4 patients discontinued therapy due to adverse event during a median duration of TAF dosing of 74 weeks. Among those with paired laboratory data 12–18 months after switching to TAF, biochemical response and HBV DNA suppression was maintained. Most patients had normal renal function which was essentially unchanged throughout follow-up. TAF is frequently utilized in routine clinical practice due to the perception of its improved safety profile. The current study supports the growing body of evidence regarding the safety and effectiveness of TAF. Trial Registration ClinicalTrials.gov identifier: NCT03692897, https://clinicaltrials.gov/ct2/show/NCT03692897 .

Background Patients hospitalized for coronavirus disease 2019 (COVID-19) may experience complications following hospitalization and require readmission. In this analysis, we estimated the rate and risk factors associated with COVID-19–related readmission and inpatient mortality. Methods In this retrospective cohort study, we used deidentified chargemaster data from 297 hospitals across 40 US states on patients hospitalized with COVID-19 from 15 February 2020 through 9 June 2020. Demographics, comorbidities, acute conditions, and clinical characteristics of first hospitalization are summarized. Multivariable logistic regression was used to measure risk factor associations with 30-day readmission and in-hospital mortality. Results Among 29 659 patients, 1070 (3.6%) were readmitted. Readmitted patients were more likely to have diabetes, hypertension, cardiovascular disease (CVD), or chronic kidney disease (CKD) vs those not readmitted (P 60 vs 18–40 years (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.48–2.50) and those admitted in the Northeast vs West (OR, 1.43; 95% CI, 1.14–1.79) or South (OR, 1.28; 95% CI, 1.11–1.49). Comorbidities including diabetes (OR, 1.34; 95% CI, 1.12–1.60), CVD (OR, 1.46; 95% CI, 1.23–1.72), CKD stage 1–5 (OR, 1.51; 95% CI, 1.25–1.81), and CKD stage 5 (OR, 2.27; 95% CI, 1.81–2.86) were associated with higher odds of readmission; 12.3% of readmitted patients died during second hospitalization. Conclusions Among this large US population of patients hospitalized with COVID-19, readmission was associated with certain comorbidities and acute conditions during first hospitalization. These findings may inform strategies to mitigate risks of readmission due to COVID-19 complications.

Background Hospital admissions for severe hypoglycemia are associated with significant healthcare costs, decreased quality of life, and increased morbidity and mortality, especially for older adults with diabetes. Understanding the reasons for hypoglycemia hospitalization is essential for the development of effective interventions; yet, the causes and precipitants of hypoglycemia are not well understood. Methods We conducted a qualitative study of non-nursing home patients aged 65 years or older without cognitive dysfunction admitted to a single tertiary-referral hospital with diabetes-related hypoglycemia. During the hospitalization, we conducted one-on-one, in-depth, semi-structured interviews to explore: (1) experiences with diabetes management among patients hospitalized for severe hypoglycemia; and (2) factors contributing and leading to the hypoglycemic event. Major themes and sub-themes were extracted using the constant comparative method by 3 study authors. Results Among the 17 participants interviewed, the mean age was 78.9 years of age, 76.5% were female, 64.7% African American, 64.7% on insulin, and patients had an average of 13 chronic conditions. Patients reported: (1) surprise at hypoglycemia despite living with diabetes for many years; (2) adequate support, knowledge, and preparedness for hypoglycemia; (3) challenges balancing a diet that minimizes hyperglycemia and prevents hypoglycemia; (4) the belief that hyperglycemia necessitates medical intervention, but hypoglycemia does not; and (5) tension between clinician-prescribed treatment plans and self-management based on patients’ experience. Notably, participants did not report the previously cited reasons for hypoglycemia, such as food insecurity, lack of support or knowledge, or treatment errors. Conclusions Our findings suggest that some hypoglycemic events may not be preventable, but in order to reduce the risk of hypoglycemia in older individuals at risk: (1) healthcare systems need to shift from their general emphasis on the avoidance of hyperglycemia towards the prevention of hypoglycemia; and (2) clinicians and patients need to work together to design treatment regimens that fit within patient capacity and are flexible enough to accommodate life’s demands.

Increased stressful experiences are pervasive among healthcare providers (HCPs) during the COVID-19 pandemic. Identifying resources that help mitigate stress is critical to maintaining HCPs’ well-being. However, to our knowledge, no instrument has systematically examined how different levels of resources help HCPs cope with stress during COVID-19. This cross-sectional study involved 119 HCPs (64 nurses and 55 physicians) and evaluated the perceived availability, utilization, and helpfulness of a list of personal, hospital, and healthcare system resources. Participants also reported on their level of burnout, psychological distress, and intentions to quit. Results revealed that HCPs perceived the most useful personal resource to be family support; the most useful hospital resources were a safe environment, personal protective equipment, and support from colleagues; the most useful system resources were job protection, and clear communication and information about COVID. Moreover, HCPs who perceived having more available hospital resources also reported lower levels of psychological distress symptoms, burnout, and intentions to quit. Finally, although training and counseling services were perceived as useful to reduce stress, training was not perceived as widely available, and counseling services, though reported as being available, were underutilized. This instrument helps identify resources that support HCPs, providing implications for healthcare management.

Background In malaria-endemic areas, pregnant women and especially first-time mothers are more susceptible to Plasmodium falciparum. Malaria diagnosis is often missed during pregnancy, because many women with placental malaria remain asymptomatic or have submicroscopic parasitemia, masking the association between malaria and pregnancy outcomes. Severe maternal anemia and low birthweight deliveries are well-established sequelae, but few studies have confirmed the relationship between malaria infection and severe outcomes like perinatal mortality in high transmission zones. Methods Pregnant women of any gestational age enrolled at antenatal clinic into a longitudinal cohort study in Ouelessebougou, Mali, an area of high seasonal malaria transmission. Follow-up visits included scheduled and unscheduled visits throughout pregnancy. Blood smear microscopy and polymerase chain reaction (PCR) analysis were employed to detect both microscopic and submicroscopic infections, respectively. Intermittent preventative treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) was documented and prompt treatment regardless of symptoms given upon malaria diagnosis. Results Of the 1850 women followed through delivery, 72.6% of women received 2 or more IPTp-SP doses, 67.2% of women experienced at least 1 infection between enrollment up to and including delivery. Malaria infection increased the risks of stillbirth (adjusted hazard ratio [aHR] 3.87, 95% confidence interval [CI]: 1.18–12.71) and preterm delivery (aHR 2.41, 95% CI: 1.35–4.29) in primigravidae, and early neonatal death (death within 7 days) in secundigravidae and multigravidae (aHR 6.30, 95% CI: 1.41–28.15). Conclusions Malaria treatment after diagnosis, alongside IPTp-SP, is insufficient to prevent malaria-related stillbirth, early neonatal death and preterm delivery (PTD). Although IPTp-SP was beneficial in Mali during the study period, new tools are needed to improve pregnancy outcomes. Clinical Trials Registration NCT01168271.

Chronic pain is a highly prevalent symptom associated with the autoimmune disorder multiple sclerosis (MS). The central nucleus of the amygdala plays a critical role in pain processing and modulation. Neuropathic pain alters nociceptive signaling in the central amygdala, contributing to pain chronicity and opioid tolerance. Here, we demonstrate that activated microglia within the central amygdala disrupt nociceptive sensory processing and contribute to pain hypersensitivity in experimental autoimmune encephalomyelitis (EAE), the most frequently used animal model of MS. Male and female mice with EAE exhibited differences in microglial morphology in the central amygdala, which was associated with heat hyperalgesia, impaired morphine reward, and reduced morphine antinociception in females. Animals with EAE displayed a lack of morphine-evoked activity in cells expressing somatostatin within the central amygdala, which drive antinociception. Induction of focal microglial activation in naive mice via injection of lipopolysaccharide into the central amygdala produced a loss of morphine analgesia in females, similar to as observed in EAE animals. Our data indicate that activated microglia within the central amygdala may contribute to the sexually dimorphic effects of morphine and may drive neuronal adaptations that lead to pain hypersensitivity in EAE. Our results provide a possible mechanism underlying the decreased efficacy of opioid analgesics in the management of MS-related pain, identifying microglial activation as a potential therapeutic target for pain symptoms in this patient population.

Identifying the etiology of an acute respiratory infection in children is a well-known challenge. In this study, we evaluated the correlation between salivary C-reactive protein (CRP) and its serum counterpart, which is known to be higher in bacterial infections but necessitates a venipuncture. Salivary and serum CRPs were measured in children with an acute respiratory illness, aged 2 months to 18 years. Pearson's correlation coefficients were used to measure correlation. Discrimination of the salivary CRP levels for predicting serum levels above 100 mg/L was calculated and compared to serum CRP levels. Sensitivity and specificity were similarly calculated. Salivary CRP was measured in 104 samples. Levels correlated significantly and positively with serum CRP levels (r = 0.670, p

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 ( n = 74) compared to the same period in 2019 ( n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Objective Electrical cardioversion of ED patients is a well-described treatment strategy for certain patients presenting with atrial fibrillation (AF). The objective of this study was to describe the safety and outcomes of this practice in a cohort of patients undergoing ED electrical cardioversion for AF. Methods This retrospective health records survey investigated a 5-year cohort of consecutive ED patients presenting with AF who underwent electrical cardioversion in an academic, tertiary ED. Electronic and manual abstraction strategies were used, extracting data on demographics, clinical features, interventions, complications, and return visits within 1 month. Data were analyzed using descriptive statistics and agreement between trained abstractors on key variables was excellent (k = 0.94–0.98). Results Data from 887 patients were analyzed. Electrical cardioversion was successful in 781 (88%) encounters. There were 3 major complications (3/887; 0.3%) and 123 minor complications (123/887; 14%). Major complications included one post-cardioversion stroke (1/887; 0.1%), one jaw thrust maneuver for hypoxia (0.1%), and one overnight observation for hypotension (0.1%). 741 patients (84%) were discharged following cardioversion with a mean ED LOS of 218 min (95% CI: 206–231 min). 57 (6.4%) patients returned to the ED within 30 days; 43 (4.8%) returned with in AF or flutter. Conclusions In this cohort of ED patients with atrial fibrillation, ED electrical cardioversion followed by discharge to home was largely safe and effective. Most complications were transient and mild. There were remarkably few serious complications.