Septicemia due to Capnocytophaga canimorsus following dog bite in an elderly male

A previously healthy, 67-year-old, man with past medical history of myocardial infarction and hypertension was rushed to the emergency room after sudden onset of fever, chills, severe rigors, hypotension, tachycardia and vomiting. The patient was diagnosed as being in septic shock, and investigations revealed intracellular gram-negative bacilli in polymorphonuclear leukocytes in the peripheral smear. A history of dog contact was elicited after this very unusual and rare finding. Cultures confirmed septicemia due to Capnocytophaga canimorsus, a normal oral and nasal flora inhabitant of cats and dogs that can cause severe and sometimes fatal septicemia in humans. We report this very interesting case because of the common prevalence of dog homeownership and the rarity of C. canimorsus inducing sepsis

Gender disparity in critical care publications: a novel Female First Author Index

Abstract Background Bibliometric analyses show gender bias against women in scientific publications and citations. We hypothesized that a metric of an individual senior author’s inclusivity of women as first authors in critical care publications would predict gender inequality. Methods Using PubMed and Web of Science, we conducted a bibliometric analysis of original research publications in critical care from 2008 to 2018 in 11 specialty and general journals. Gender for first and senior authors was assigned by a gender determination application, and manually if needed. For all senior authors we defined the novel Female First Author Index (FFA-index) = #Female first authors in publications by an individual senior author/Total # publications by that senior author. We produced a novel interactive web-based application using the R package Shiny to increase potential utilization of the FFA-index. Results Of 7370 publications, 30.4% had female first authors and 15.5% had female senior authors. After adjustment for impact factor, journal, year of publication, number of authors, country, and gender determination accuracy, female senior authorship was associated with a 1.9-fold increase in female first authorship [OR = 1.85 (95% CI 1.62, 2.11); p < 0.001] compared with male senior authorship. The mean (SD) FFA-index for all individual senior authors was 30.5 (42.9); with a significant difference in FFA-index between male and female senior authors (27.6 versus 42.5, respectively; p < 0.001). The interactive web-based application (FFA-index App) produces the same FFA-index output as our study results. Conclusions Female representation at prominent authorship positions in critical care publications is still far from achieving gender parity. By creating an authorship index score, we propose a frame of reference for the advancement of female first authorship

Eosinopenia and post-hospital outcomes in critically ill non-cardiac vascular surgery patients

Background and aims: Eosinopenia is a marker for acute inflammation. We hypothesized that eosinopenia at Intensive Care Unit (ICU) admission in vascular surgery patients who receive critical care, would be associated with increased mortality following hospital discharge. Methods and results: We performed a two-center observational cohort study of critically ill, non-cardiac adult vascular surgery patients who received treatment in Boston between 1997 and 2012 and survived hospital admission. The consecutive sample included 5083 patients (male 57%, white 82%, mean age [SD] 61.6 [17.4] years). The exposure was Absolute eosinophil count measured within 24 h of admission to the ICU and categorized as 350 cells/mu L. The primary outcome was all-cause mortality within 90 days of hospital discharge. The secondary outcome was discharge to home following hospitalization. 90-day post-discharge mortality was 6.7%, and 12.9% of patients were readmitted within 30 days. After multivariable adjustment, patients with eosinopenia ( Conclusion: Eosinopenia at ICU admission is a robust predictor of increased mortality and lower likelihood of discharge to home in vascular surgery patients treated with critical care who survive hospitalization. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved

Design of a randomized, placebo-controlled, phase 3 trial of tofersen initiated in clinically presymptomatic SOD1 variant carriers : the Atlas study

Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of ALS, with biomarker data from the Pre-Symptomatic Familial ALS (Pre-fALS) study showing that an elevation in blood neurofilament light chain (NfL) precedes phenoconversion to clinically manifest disease. Tofersen is an investigational antisense oligonucleotide designed to reduce synthesis of superoxide dismutase 1 (SOD1) protein through degradation of SOD1 mRNA. Informed by Pre-fALS and the tofersen clinical development program, the ATLAS study (NCT04856982) is designed to evaluate the impact of initiating tofersen in presymptomatic carriers of SOD1 variants associated with high or complete penetrance and rapid disease progression who also have biomarker evidence of disease activity (elevated plasma NfL). The ATLAS study will investigate whether tofersen can delay the emergence of clinically manifest ALS. To our knowledge, ATLAS is the first interventional trial in presymptomatic ALS and has the potential to yield important insights into the design and conduct of presymptomatic trials, identification, and monitoring of at-risk individuals, and future treatment paradigms in ALS.Errata: Benatar, M., Wuu, J., Andersen, P.M. et al. Correction to: Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01286-9</p

Trial of Antisense Oligonucleotide Tofersen for

The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations inIn this phase 3 trial, we randomly assigned adults withA total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons wit

Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

BackgroundThe intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).MethodsIn this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort).ResultsA total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P=0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.ConclusionsIn persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, and ; EudraCT numbers, 2015-004098-33 and 2016-003225-41.