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We demonstrate autosomal-recessive Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in a patient with relapsing C. albicans meningoencephalitis. We identified a novel, hypomorphic mutation with intact Th17 responses, but impaired GM-CSF responses. We report complete clinical remission with adjunctive GM-CSF therapy, suggesting that a CARD9/GM-CSF axis contributes to susceptibility to candidiasis.

and the Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group IMPORTANCE Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).OBJECTIVE To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and(3) CVST unrelated to SARS-CoV-2 vaccination.EXPOSURES Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES Clinical characteristics and mortality rate.RESULTS Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 ( 14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCEIn this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Hypomorphic CARD9 deficiency caused by p.Y91H results in adult-onset disease with variable penetrance and expressivity. Our findings establish the CARD9/RASGRF1/ERK/GM-CSF axis as critical to the pathophysiology of sCNSc.

Gait asymmetry is an important marker of mobility impairment post stroke. This study proposes a new gait symmetry index (GSI) to quantify gait symmetry with one 3D accelerometer at L3 (GSIL3). GSIL3 was evaluated with 16 post stroke patients and nine healthy controls in the Six-Minute-Walk-Test (6-MWT). Discriminative power was evaluated with Wilcoxon test and the effect size (ES) was computed with Cliff’s Delta. GSIL3 estimated during the entire 6-MWT and during a short segment straight walk (GSIL3straight) have comparable effect size to one another (ES = 0.89, p < 0.001) and to the symmetry indices derived from feet sensors (|ES| = [0.22, 0.89]). Furthermore, while none of the indices derived from feet sensors showed significant differences between post stroke patients walking with a cane compared to those able to walk without, GSIL3 was able to discriminate between these two groups with a significantly lower value in the group using a cane (ES = 0.70, p = 0.02). In addition, GSIL3 was strongly associated with several symmetry indices measured by feet sensors during the straight walking cycles (Spearman correlation: |ρ| = [0.82, 0.88], p < 0.05). The proposed index can be a reliable and cost-efficient post stroke gait symmetry assessment with implications for research and clinical practice.