Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity

IntroductionThe success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.MethodsWe report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.ResultsIn contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.DiscussionThese features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges

Correlação entre a síndrome antifosfolipídica e a crioglobulinemia: série de quatro casos e revisão da literatura

Resumo Introdução: A crioglobulinemia é uma vasculite de pequenos vasos mediada por imunocomplexos que normalmente envolvem a pele, os rins e os nervos periféricos. A síndrome antifosfolipídica (SAF) é um transtorno da hipercoagulabilidade autoimune que provoca trombose dos vasos sanguíneos. Pode se manifestar como um distúrbio microtrombótico que afeta múltiplos órgãos, denominado SAF catastrófica. Objetivo: Esta série de casos objetiva descrever os desafios de diagnóstico e tratamento que surgem quando esses dois graves transtornos estão presentes simultaneamente no mesmo paciente. Métodos: Foram descritos quatro pacientes internados em nosso hospital em decorrência de danos graves a múltiplos órgãos mediados pela vasculite crioglobulinêmica com SAF concomitante. Resultados: As manifestações clínicas incluíram úlceras de perna, livedo reticular, insuficiência renal e neuropatia periférica. As etiologias sugeridas para a combinação de síndromes foram a hepatite C, o lúpus eritematoso sistêmico e a doença mieloproliferativa retal associada a linfoma de zona marginal tipo células B. Todos os pacientes foram tratados com anticoagulantes, altas doses de corticosteroides, rituximabe, gamaglobulinas intravenosas e troca de plasma. Conclusão: A rara associação entre a SAF grave ou catastrófica e a crioglobulinemia deve ser considerada por médicos que atendem pacientes com isquemia ou necrose de múltiplos órgãos

Gender differences in the comprehension of care plans in an emergency department setting

Abstract Background Previous studies have shown that, in a variety of health care settings, patients often do not understand what health care professionals tell them about their diagnoses and care plans; this is particularly true among male patients. Emergency department (ED) settings present unique challenges to communication with patients due to the rapid pace of activity, substantial changes in personnel over the course of the day and the week, and the need for fast decision-making processes. The aim of our study was to investigate the extent to which patients in an Israeli ED comprehended their plan of care and whether there were gender differences in this regard. Methods We conducted a questionnaire-based prospective study, in which patients admitted to the ED at Rabin Medical Center were evaluated during the years 2014–2016. The primary outcome was patients’ comprehension of their plan of care, stratified by gender of patients. Plan of care included information related to diagnosis, treatment and discharge instructions. The secondary outcome was patients’ satisfaction with the instruction process. Results One hundred seventy seven ED patients met study criteria and were asked to participate in the study; 85% of them agreed to do so. Overall, 150 ED patients aged 18–80 were recruited [75 men (50%) and 75 women (50%)]. 80% of the respondents reported a satisfactory understanding of their plan of care. Overall, no gender-related differences were found. Differences between men and women concerning satisfaction with the instructions provided by nurses were found among non-Hebrew speakers, but not among Hebrew speakers. Conclusion Contrary to most earlier studies, patients at our ED demonstrated a high degree of self-reported adequate comprehension concerning their plan of care, and overall no gender-related differences were found. These finding may be due in part to improved training of the medical staff to better communicate with the patients and to answer their questions. In addition, patients may feel more comfortable than in the past about asking the medical staff questions regarding their plan of care and diagnosis. The main implication of this study is that physician education programs should continue to emphasize patient-physician communications skills and improving methods for providing patients with information

Is warfarin usage a risk factor for osteoporotic fractures? A cohort study in the emergency department

Background Several studies have examined the association between warfarin sodium use and risk of osteoporotic fractures with conflicting results. Our study addresses this question, for the first time regarding patients attending emergency department (ED). Aims The aim of this study was to retrospectively detect whether there is higher rate of usage of warfarin sodium in patients with osteoporotic fractures attending an ED. Methods This is a retrospective study from patients' computerized charts. All individuals >65 years old who had an osteoporotic fracture and attended an ED in a tertiary hospital were compared with a similar group of elderly individuals >65 years old without an osteoporotic fracture who attended the ED for a cause other than an osteoporotic fracture. Results This study included 328 patients who were evaluated in the years 2005–2016. Overall, 164 individuals with a typical osteoporotic fracture (hip -66 patients (40 per cent), spine- 92 patients (56 per cent), humerus -4 patients (2 per cent), radius -13 patients (8 per cent)) were identified and compared with a matched group of elderly individuals who were evaluated in the ED for other complaints. Warfarin sodium was used in 61 individuals (19 per cent) in the entire cohort, 34 in the fracture group and 27 in the non-fracture group (p=0.324). Conclusion In elderly patients, attending an ED, warfarin sodium use does not seem to be a risk factor for an osteoporotic fractur

Elevated Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 Level in Patients with Acute Coronary Syndrome (ACS): A Biomarker of Disease Severity and Outcome

Background and Aims. Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome. Methods. Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30. Results. Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (539.4±330.3 pg/ml vs. 432.5±196.4 pg/ml vs. 230.1±85.5 pg/ml, respectively; P<0.001) and positively correlated with the number of stenosed/occluded coronary arteries on angiography (P<0.001). On logistic regression analysis, higher sTREM-1 levels predicted definite ACS vs. NSCP determined on day 30 (OR 1.29, 95% CI 1.07-1.54, P=0.01) as well as with recurrent ACS (P=0.04) and stroke (P=0.02) at 6 months. Conclusions. Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome

Using external data to assess the external validity of a randomised controlled trial

Background: Few studies have addressed external validity of randomized controlled trials in infectious diseases. We aimed to assess the external validity of an investigator-initiated trial on treatment for uncomplicated urinary tract infection.Methods: In the original study, women (n = 513) with urinary tract infection were randomized to nitrofurantoin or fosfomycin treatment in three countries between 2013 and 2017. In the present study we compared women who were screened for enrolment but excluded to women who participated in the trial, both groups in Israel. The primary outcome was the rate of emergency department index visits resulting in hospitalization within 28 days.Results: We compared 127 included to 110 excluded patients. The most common reasons for exclusion were logistic difficulties in recruitment and antibiotic use in the preceding month. Included patients tended to be older [39 (IQR 29-59) vs. 35.5 (IQR 24-56.25 years)], more likely to have history of recurrent infection and had more urinary symptoms. Among excluded patients, 13.6% (15/110) had initial visits resulting in hospitalization compared to 3.1% (4/127) of included participants (p = .003). The rate of emergency department visits within 28 days was similar in both groups. Clinical and microbiological failures were significantly more common in included patients [26% (33/127) vs. 1.8% (2/110), p Conclusions: While differences were observed between included and excluded patients, the excluded group did not represent a more 'complicated' population. The present study shows the importance of collecting data on patients excluded from randomized controlled trials.</p

Risk factors for treatment failure in women with uncomplicated lower urinary tract infection

Given rising antibiotic resistance and increasing use of delayed prescription for uncomplicated lower urinary tract infections (UTI), patients at risk for treatment failure should be identified early. We assessed risk factors for clinical and microbiological failure in women with lower UTI. This case-control study nested within a randomized clinical trial included all women in the per-protocol population (PPP), those in the PPP with microbiologically confirmed UTI, and those in the PPP with UTI due to Escherichia coli. Cases were women who experienced clinical and/or microbiologic failure; controls were those who did not. Risk factors for failure were assessed using multivariate logistic regression. In the PPP, there were 152 clinical cases for 307 controls. Among 340 women with microbiologically confirmed UTI, 126 and 102 cases with clinical and microbiological failure were considered with, respectively, 214 and 220 controls. Age ≥52 years was independently associated with clinical (adjusted OR 3.01; 95%CI 1.84–4.98) and microbiologic failure (aOR 2.55; 95%CI 1.54–4.25); treatment with fosfomycin was associated with clinical failure (aOR 2.35; 95%CI 1.47–3.80). The association with age persisted among all women, and women with E. coli-related UTI. Diabetes was not an independent risk factor, nor were other comorbidities. Postmenopausal age emerged as an independent risk factor for both clinical and microbiological treatment failure in women with lower UTI and should be considered to define women at-risk for non-spontaneous remission, and thus for delayed antibiotic therapy; diabetes mellitus was not associated with failure

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial

The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI)