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Heart failure is a leading cause of hospitalisations. Integration of palliative care services with medical therapy in the management of hospitalised patients with heart failure is imperative. Unfortunately, there are no standardised criteria for palliative care referrals among hospitalised patients with acute decompensated heart failure. The objective of our quality improvement project was to develop and implement a palliative care consult trigger tool for hospitalised patients with acute decompensated heart failure. We found that among eligible patients, palliative care referrals were underused, likely contributing to misalignment of goals of care and suboptimal advance care planning. We developed a trigger tool and designed and implemented structured multicomponent educational interventions to improve the appropriateness and timeliness of inpatient palliative care consultations in this high-risk population. The educational interventions led to a significant increase in the rate of appropriate inpatient palliative care consultations among hospitalised patients with acute decompensated heart failure (46.3% vs 27.7%; p=0.02). In addition, palliative care referrals resulted in better alignment of goals of care at the time of hospital discharge, as measured by a significant increase in the completion rate of a healthcare proxy form (11.4% vs 47.2%; p

Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection. We therefore tracked comparative IL-12Rβ2+ ILC1, ST2+ ILC2 and NKp46+ natural killer (NK) innate lymphoid cell population expansions during Brugia malayi experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB/c animals, NKp46+ NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2+ ILC2 failed to expand. NKp46+ NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46+ NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adult B. malayi infection. This data was recapitulated using an Onchocerca ochengi male worm peritoneal implant model. When NKp46+ NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks of B. malayi infection, susceptibility to adult B. malayi infection was significantly increased by 2-3 fold with concomitant impairment in eosinophil or neutrophil recruitments. Finally, we demonstrate that in RAG2 deficient mice, drug clearance of a primary adult B. malayi infection followed by challenge infection leads to resistance against early larval B. malayi establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46+ NK cells express markers of memory-like/enhanced activation (increased expression of interferon gamma and Ly6C). Our data promotes a novel functional role for NKp46+ NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation.

Heparin-induced thrombocytopaenia (HIT) is a serious complication of heparin therapy. Evidence-based guidelines recommend the use of the 4Ts scoring system to calculate pretest probability of HIT. However, this scoring system is often underused, and inappropriate testing can lead to increased morbidity, medical costs and length of hospital stay. We identified that inappropriate testing for HIT was common at our institution and implemented structured multicomponent educational interventions to evaluate the impact of education on the appropriateness of HIT testing. The educational interventions led to a significantly increased rate of appropriateness of HIT testing (69% vs 35%; p=0.001). In addition, the 4Ts score documentation rate significantly improved following the intervention (52% vs 17%; p=0.001). The rates of discontinuation of heparin products and initiation of alternative anticoagulation increased, although not statistically significantly. Educational interventions can improve compliance with evidence-based guidelines on appropriateness of testing for HIT.

Abstract Background Onchocerciasis is a priority neglected tropical disease targeted for elimination by 2025. The standard strategy to combat onchocerciasis is annual Community-Directed Treatment with ivermectin (CDTi). Yet, high prevalence rates and transmission persist following > 12 rounds in South-West Cameroon. Challenges include programme coverage, adherence to, and acceptability of ivermectin in an area of Loa loa co-endemicity. Loiasis patients harbouring heavy infections are at risk of potentially fatal serious adverse events following CDTi. Alternative strategies are therefore needed to achieve onchocerciasis elimination where CDTi effectiveness is suboptimal. Methods/design We designed an implementation study to evaluate integrating World Health Organisation-endorsed alternative strategies for the elimination of onchocerciasis, namely test-and-treat with the macrofilaricide, doxycycline (TTd), and ground larviciding for suppression of blackfly vectors with the organophosphate temephos. A community-based controlled before-after intervention study will be conducted among > 2000 participants in 20 intervention (Meme River Basin) and 10 control (Indian River Basin) communities. The primary outcome measure is O. volvulus prevalence at follow-up 18-months post-treatment. The study involves four inter-disciplinary components: parasitology, entomology, applied social sciences and health economics. Onchocerciasis skin infection will be diagnosed by skin biopsy and Loa loa infection will be diagnosed by parasitological examination of finger-prick blood samples. A simultaneous clinical skin disease assessment will be made. Eligible skin-snip-positive individuals will be offered directly-observed treatment for 5 weeks with 100 mg/day doxycycline. Transmission assessments of onchocerciasis in the communities will be collected post-human landing catch of the local biting blackfly vector prior to ground larviciding with temephos every week (0.3 l/m3) until biting rate falls below 5/person/day. Qualitative research, including in-depth interviews and focus-group discussions will be used to assess acceptability and feasibility of the implemented alternative strategies among intervention recipients and providers. Health economics will assess the cost-effectiveness of the implemented interventions. Conclusions Using a multidisciplinary approach, we aim to assess the effectiveness of TTd, alone or in combination with ground larviciding, following a single intervention round and scrutinise the acceptability and feasibility of implementing at scale in similar hotspots of onchocerciasis infection, to accelerate onchocerciasis elimination.

The plastic nature of cat behaviour allows this “friendly symbiont” of humans to adapt to various housing conditions. Beyond daylight, one could wonder if other environmental factors affect its patterns. Yet, how its activity and feeding rhythms are impacted by its environment is rarely studied in standardised conditions between populations. We compared the behaviour of cats living in a 29 m2 indoor room and cats living in a 1145 m2 outdoor enclosure, tracking them simultaneously in summer for 21 days, with advanced technologies. Both populations received daylight but weather fluctuations only occurred outdoors. Bimodality was detected in the activity and feeding rhythms of both groups, while twilight triggered crepuscular peaks. Daily, the outdoor population covered more distance (4.29 ± 0.27 km; p < 0.001) and consumed more food (67.44 ± 2.65 g; p < 0.05) than the indoor population (2.33 ± 0.17 km, 57.75 ± 2.85 g, respectively), but displayed less rhythmic behaviours, assumedly because of rhythm disruptors met only in outdoor conditions. Finally, outdoor housing seemed to promote the exploratory behaviour of the cats at night, while indoor housing increased both meal frequency (p = 0.063) and the impact of human interactions on the feeding rhythms of the cats.

Abstract Background Observational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate. Methods These post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3 months) to daily HD (mean during the first 3 months). Results After transfer from in-center HD to daily HD (data from 345 patients, 51 ± 15 years of age, mean ± standard deviation), predialysis serum potassium decreased (P

Objective: In hospitals, physicians-in-training are major contributors to the burden of tests ordered, increasing cost and resource utilization. We implemented an intervention to discourage overutilization of the complete blood count (CBC) and the basic metabolic panel (BMP). Methods: An intervention was designed, comprising education on high-value care and burden of over-testing, encouragement of competition, and use of positive reinforcement. The intervention was monitored by a test index determined by dividing the total number of a specific laboratory test ordered for a patient by the total number of hospital days. Results: Following a 6-month intervention, the mean CBC index decreased from 1.56 ± 0.02 to 1.45 ± 0.03 (p

Here, the authors develop a mouse model of Loa loa that reflects human infections, including eosinophilia, and determine effects of ivermectin treatment.

Background: Calciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case series, and cohort studies to synthesize the available treatment modalities and outcomes of calciphylaxis in patients with CKD. Methods: Electronic databases were searched for studies that examined the uses of sodium thiosulfate, surgical parathyroidectomy, calcimimetics, hyperbaric oxygen therapy, and bisphosphonates for calciphylaxis in patients with CKD, including end-stage renal disease. For cohort studies, the results were synthesized quantitatively by performing random-effects model meta-analyses. Results: A total of 147 articles met the inclusion criteria and were included in the systematic review. There were 90 case reports (90 patients), 20 case series (423 patients), and 37 cohort studies (343 patients). In the pooled cohorts, case series, and case reports, 50.3% of patients received sodium thiosulfate, 28.7% underwent surgical parathyroidectomy, 25.3% received cinacalcet, 15.3% underwent hyperbaric oxygen therapy, and 5.9% received bisphosphonates. For the subset of cohort studies, by meta-analysis, the pooled risk ratio for mortality was not significantly different among patients who received sodium thiosulfate (pooled risk ratio [RR] 0.89; 95% confidence interval [CI] 0.71–1.12), cinacalcet (pooled RR 1.04; 95% CI 0.75–1.42), hyperbaric oxygen therapy (pooled RR 0.89; 95% CI 0.71–1.12), and bisphosphonates (pooled RR 0.77; 95% CI 0.44–1.32), and those who underwent surgical parathyroidectomy (pooled RR 0.88; 95% CI 0.69–1.13). Conclusion: This systematic review found no significant clinical benefit of the 5 most frequently used treatment modalities for calciphylaxis in patients with CKD. Randomized controlled trials are needed to test the efficacy of these therapies. Keywords: calciphylaxis, chronic kidney disease, meta-analysis, systematic review

La primatologie n'est pas une discipline de la biologie à proprement parler mais est le dénominateur commun de multiples disciplines de la biologie, écologie, éthologie, psychologie comparée, physiologie, recherches biomédicales, paléontologie, anthropologie, etc. : toutes ces disciplines ont les primates comme sujets. Cet article montre, à travers un exemple autobiographique, l'importance du dialogue entre ces différents domaines de la biologie pour aboutir à une connaissance plus approfondie de cet ordre taxinomique auquel nous humains appartenons. Un dialogue permanent entre ces disciplines permet aussi une meilleure protection in situ et ex situ des espèces de primates non humains, pour leur conservation et le respect de leur bien-être dans différents domaines.

Introduction Onchocerciasis is targeted for elimination mainly with annual community-directed treatment with ivermectin (CDTI). High infection levels have been reported in South-West Cameroon, despite ≥15 years of CDTI. The aim of this study was to assess factors associated with continued onchocerciasis transmission and skin disease.Methods A large-scale cross-sectional study was conducted in 2017 in 20 communities in a loiasis-risk area in South-West Cameroon. A mixed-methods approach was used. Associations between infection levels, skin disease and adherence to CDTI were assessed using mixed regression modelling. Different community members’ perception and acceptability of the CDTI strategy was explored using semi-structured interviews.Results Onchocerciasis prevalence was 44.4% among 9456 participants. 17.5% of adults were systematic non-adherers and 5.9% participated in ≥75% of CDTI rounds. Skin disease affected 1/10 participants, including children. Increasing self-reported adherence to CDTI was associated with lower infection levels in participants aged ≥15 years but not in children. Adherence to CDTI was positively influenced by perceived health benefits, and negatively influenced by fear of adverse events linked with economic loss. Concern of lethal adverse events was a common reason for systematic non-adherence.Conclusion CDTI alone is unlikely to achieve elimination in those high transmission areas where low participation is commonly associated with the fear of adverse events, despite the current quasi absence of high-risk levels of loiasis. Such persisting historical memories and fear of ivermectin might impact adherence to CDTI also in areas with historical presence but current absence of loiasis. Because such issues are unlikely to be tackled by CDTI adaptive measures, alternative strategies are needed for onchocerciasis elimination where negative perception of ivermectin is an entrenched barrier to community participation in programmes.

The internal medicine In-Training Exam (ITE) is administered at residency training programs to assess medical knowledge. Our internal medicine residency program witnessed a performance decline on the ITE between 2011 and 2014. The goal of this quality improvement project was to improve medical knowledge among residents as measured by an improvement in performance on the ITE, through the design and implementation of an Academic Enrichment Program (AEP). The AEP was designed in 2014–2015, and entailed a multipronged approach, including strengthening and tailoring of the didactic curriculum, establishment of a minimum conference attendance rate, and adoption of the New England Journal of Medicine Knowledge-Plus Internal Medicine Board Review platform. Residents performing below a pre-specified percentile rank cutoff on the previous year’s ITE in any of the 12 content areas were required to complete a pre-specified percentage of the question bank in that specific topic. We examined a total of 164 residents enrolled in our program under the categorical training track. The mean (± SEM) ITE percentile for the 12 content areas increased significantly from calendar years 2011–2014 to 2015–2018, reflecting implementation of the AEP (p < 0.001). In brief, compared to the AEP-unexposed graduating classes of residents, the AEP-exposed graduating classes of residents displayed a significant improvement in the mean ITE percentile rank. This quality improvement project was carried out at a single institution. The implementation of a structured academic enrichment program significantly improves performance on the ITE.

Visual communication involves specific signals. These include the different positions of mobile body elements. We analyzed visual configurations in cats that involve ears and the tail. We aimed at deciphering which features of these configurations were the most important in cats’ interactions with other cats and with humans. We observed a total of 254 cat–cat interactions within a sample of 29 cats, during a total of 100 h of observation scheduled with the “Behavioral dependent onset of sampling” method and using the “All occurences” sampling method. In addition, we sampled 10 interactions between cats and humans. In cat–cat interactions, we noted the positions of ears and tail of both protagonists, as well as the outcome of the interaction, which was either positive/neutral or negative. In a great majority of the 254 interactions sampled, both cats held their tail down. On the contrary, ear position was a critical element in predicting the outcome. When both partners held their ears erect, the outcome was significantly positive, such as rubbing or close proximity. In all other cases of the position of ears in both cats, the outcome was negative, with increased distance of the partners. Although the tail did not seem to play a significant role in visual configurations in cat interactions, the “tail-up” display was important when a cat approached a human being. In the vast majority of cases the cat rubbed itself on a human’s leg(s). Thus, we may conclude that the presence of a human has a specific meaning in the cat’s world, probably as the result of a long period of commensalism. It is important for pet owners to understand the signals that cats use with other cats and with humans in order to promote the welfare of cats.

The Onchocerca ochengi adult implant and Brugia malayi microfilariemic Severe-Combined Immunodeficient (SCID) mouse models are validated screens to measure macrofilaricidal and microfilaricidal activities of candidate onchocerciasis drugs. The purpose of this study was to assess whether 5 daily sub-cutaneous (s.c.) injections of standard flubendazole (FBZ) suspension (10mg/kg), a single s.c. injection (10mg/kg) or 5 daily repeated oral doses of FBZ amorphous solid dispersion (ASD) formulation (0.2, 1.5 or 15mg/kg) mediated macrofilaricidal efficacy against O. ochengi male worms implanted into SCID mice. The direct microfilaricidal activity against circulating B. malayi microfilariae of single dose FBZ ASD formulation (2 or 40 mg/kg) was also evaluated and compared against the standard microfilaricide, ivermectin (IVM). Systemic exposures of FBZ/FBZ metabolites achieved following dosing were measured by pharmacokinetic (PK) bioanalysis. At necropsy, five weeks following start of FBZ SC injections, there were significant reductions in burdens of motile O. ochengi worms following multiple injections (93%) or single injection (82%). Further, significant proportions of mice dosed following multiple injections (5/6; 83%) or single injection (6/10; 60%) were infection negative (drug-cured). In comparison, no significant reduction in recovery of motile adult O. ochengi adult worms was obtained in any multiple-oral dosage group. Single oral-dosed FBZ did not mediate any significant microfilaricidal activity against circulating B. malayi mf at 2 or 7 days compared with >80% efficacy of single dose IVM. In conclusion, multiple oral FBZ formulation doses, whilst achieving substantial bioavailability, do not emulate the efficacy delivered by the parenteral route in vivo against adult O. ochengi. PK analysis determined FBZ efficacy was related to sustained systemic drug levels rather than achievable Cmax. PK modelling predicted that oral FBZ would have to be given at low dose for up to 5 weeks in the mouse model to achieve a matching efficacious exposure profile.

Forty million adults in the US suffer from anxiety disorders, making these the most common forms of mental illness. Transient receptor potential channel canonical subfamily (TRPC) members 4 and 5 are non-selective cation channels highly expressed in regions of the cortex and amygdala, areas thought to be important in regulating anxiety. Previous work with null mice suggests that inhibition of TRPC4 and TRPC5 may have anxiolytic effects.To assess the potential of TRPC4/5 inhibitors as an avenue for treatment, we invented a highly potent, small molecule antagonist of TRPC4 and TRPC5 which we call HC-070. HC-070 inhibits recombinant TRPC4 and TRPC5 homomultimers in heterologous expression systems with nanomolar potency. It also inhibits TRPC1/5 and TRPC1/4 heteromultimers with similar potency and reduces responses evoked by cholecystokinin tetrapeptide (CCK-4) in the amygdala. The compound is >400-fold selective over a wide range of molecular targets including ion channels, receptors, and kinases.Upon oral dosing in mice, HC-070 achieves exposure levels in the brain and plasma deemed sufficient to test behavioral activity. Treatment with HC-070 attenuates the anxiogenic effect of CCK-4 in the elevated plus maze (EPM). The compound recapitulates the phenotype observed in both null TRPC4 and TRPC5 mice in a standard EPM. Anxiolytic and anti-depressant effects of HC-070 are also observed in pharmacological in vivo tests including marble burying, tail suspension and forced swim. Furthermore, HC-070 ameliorates the increased fear memory induced by chronic social stress. A careful evaluation of the pharmacokinetic-pharmacodynamic relationship reveals that substantial efficacy is observed at unbound brain levels similar to, or even lower than, the 50% inhibitory concentration (IC50) recorded in vitro, increasing confidence that the observed effects are indeed mediated by TRPC4 and/or TRPC5 inhibition. Together, this experimental data set introduces a novel, high quality, small molecule antagonist of TRPC4 and TRPC5 containing channels and supports the targeting of TRPC4 and TRPC5 channels as a new mechanism of action for the treatment of psychiatric symptoms.

Objective: To compare the spectrum of infection, comorbidities, outcomes, and mortality of patients admitted to the intensive care unit (ICU) due to community-acquired or healthcare-associated severe sepsis. Methods: This prospective cohort study was conducted in three university medical centers in Lebanon from February 2005 to December 2006. Patients with severe sepsis were included and followed up until hospital discharge or death. Results: One hundred and twenty patients were included of whom 60% had community-acquired infections (CAI) and 40% had healthcare-associated infections (HAI). The most common infection in both groups was pneumonia. Hematologic malignancies were the only comorbidity more prevalent in HAI than in CAI (p = 0.047). Fungal infections and extended-spectrum beta-lactamase (ESBL) organisms were more frequent in HAI than in CAI (p = 0.04 and 0.029, respectively). APACHE and SOFA scores were high and did not differ between the two groups, nor did the proportion of septic shock, while mortality was significantly higher in the HAI patients than in the CAI patients (p = 0.004). On multivariate analysis for mortality, independent risk factors were the source of infection acquisition (p = 0.004), APACHE II score (p = 0.006), multidrug-resistant Pseudomonas infections (p = 0.043), and fungal infections (p = 0.006). Conclusions: Severe sepsis and septic shock had a high mortality rate, especially in the HAI group. Patients with risk factors for increased mortality should be monitored and aggressive treatment should be administered.

We report the case of a 66-year-old woman who developed acute kidney allograft failure due to thrombotic occlusion of the common iliac artery after hysterectomy requiring emergent allograft rescue. She underwent percutaneous transluminal angioplasty with endovascular balloon expandable covered stent graft placement in the right common iliac artery. Although there are a handful of case reports of acute limb ischemia secondary to acute common iliac artery thrombosis, this is the first case reported in the literature resulting in successful kidney allograft rescue following pelvic surgery.

Cardiac surgery with cardiopulmonary bypass (CS/CPB) is associated with increased risk for postoperative complications causing substantial morbidity and mortality. To identify the molecular mechanisms underlying CS/CPB-induced pathophysiology we employed an integrative systems biology approach using the whole blood transcriptome as the sentinel organ.Total RNA was isolated and globin mRNA depleted from whole blood samples prospectively collected from 10 patients at time points prior (0), 2 and 24 hours following CS/CPB. Genome-wide transcriptional analysis revealed differential expression of 610 genes after CS/CPB (p

BackgroundIn order to maintain cohesion of groups, social animals need to process social information efficiently. Visual individual recognition, which is distinguished from mere visual discrimination, has been studied in only few mammalian species. In addition, most previous studies used either a small number of subjects or a few various views as test stimuli. Dairy cattle, as a domestic species allow the testing of a good sample size and provide a large variety of test stimuli due to the morphological diversity of breeds. Hence cattle are a suitable model for studying individual visual recognition. This study demonstrates that cattle display visual individual recognition and shows the effect of both familiarity and coat diversity in discrimination.Methodology/principal findingsWe tested whether 8 Prim'Holstein heifers could recognize 2D-images of heads of one cow (face, profiles, (3/4) views) from those of other cows. Experiments were based on a simultaneous discrimination paradigm through instrumental conditioning using food rewards. In Experiment 1, all images represented familiar cows (belonging to the same social group) from the Prim'Holstein breed. In Experiments 2, 3 and 4, images were from unfamiliar (unknown) individuals either from the same breed or other breeds. All heifers displayed individual recognition of familiar and unfamiliar individuals from their own breed. Subjects reached criterion sooner when recognizing a familiar individual than when recognizing an unfamiliar one (Exp 1: 3.1+/-0.7 vs. Exp 2: 5.2+/-1.2 sessions; Z = 1.99, N = 8, P = 0.046). In addition almost all subjects recognized unknown individuals from different breeds, however with greater difficulty.Conclusions/significanceOur results demonstrated that cattle have efficient individual recognition based on categorization capacities. Social familiarity improved their performance. The recognition of individuals with very different coat characteristics from the subjects was the most difficult task. These results call for studies exploring the mechanisms involved in face recognition allowing interspecies comparisons, including humans.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P =.01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction. [ABSTRACT FROM AUTHOR]