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BACKGROUND Recent reports of patients with coronavirus disease 2019 (COVID-19) developing pneumothorax correspond mainly to case reports describing mechanically ventilated patients. The real incidence, clinical characteristics, and outcome of spontaneous pneumothorax (SP) as a form of COVID-19 presentation remain to be defined. RESEARCH QUESTION: Do the incidence, risk factors, clinical characteristics, and outcomes of SP in patients with COVID-19 attending EDs differ compared with COVID-19 patients without SP and non-COVID-19 patients with SP? STUDY DESIGN AND METHOD: This case-control study retrospectively reviewed all patients with COVID-19 diagnosed with SP (case group) in 61 Spanish EDs (20% of Spanish EDs) and compared them with two control groups: COVID-19 patients without SP and non-COVID-19 patients with SP. The relative frequencies of SP were estimated in COVID-19 and non-COVID-19 patients in the ED, and annual standardized incidences were estimated for both populations. Comparisons between case subjects and control subjects included 52 clinical, analytical, and radiologic characteristics and four outcomes. RESULTS: We identified 40 occurrences of SP in 71,904 patients with COVID-19 attending EDs (0.56 parts per thousand; 95% CI, 0.40% 0 -0.76 parts per thousand). This relative frequency was higher than that among non-COVID-19 patients (387 of 1,358,134, 0.28 parts per thousand; 95% CI, 0.26 parts per thousand 0 -0.32 parts per thousand; OR, 1.93; 95% CI, 1.41-2.71). The standardized incidence of SP was also higher in patients with COVID-19 (34.2 vs 8.2/100,000/year; OR, 4.19; 95% CI, 3.64-4.81). Compared with COVID-19 patients without SP, COVID-19 patients developing SP more frequently had dyspnea and chest pain, low pulse oximetry readings, tachypnea, and increased leukocyte count. Compared with non-COVID-19 patients with SP, case subjects differed in 19 clinical variables, the most prominent being a higher frequency of dysgeusia/ anosmia, headache, diarrhea, fever, and lymphopenia (all with OR > 10). All the outcomes measured, including in-hospital death, were worse in case subjects than in both control groups. INTERPRETATION: SP as a form of COVID-19 presentation at the ED is unusual (< 1 parts per thousand cases) but is more frequent than in the non-COVID-19 population and could be associated with worse outcomes than SP in non-COVID-19 patients and COVID-19 patients without SP.

A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in derivation (DC) and validation cohort (VC). A multivariate analysis to detect variables related to all-cause mortality within the first 15 years from SSc diagnosis was performed, assigning points to the rounded beta values to create the score (RESCLESCORE). 1935 SSc patients were included. The variables in the final model were as follows: age at diagnosis (+2 points > 65 years-old), male gender (+1 point), lcSSc subset (-1 point), mode of onset other than Raynaud's (+1 point), cancer (+1 point) and visceral involvement, such as ILD (+1 point), PAH (+1 point), heart ( +1 point) and renal involvement ( +2 points). Autoantibodies did not achieve statistical significance in the multivariate analysis. The 3 categories of risk to predict 15-year all-cause mortality at the time of diagnosis were as follows: low risk (5% vs. 7%, p = .189), intermediate risk (26.5% vs. 25.5%, p = .911) and high risk (47.8% vs. 59%, p = .316). The AUC was 0.799 (DC) vs. 0.778 (VC) (p = .530). In conclusion, the RESCLESCORE demonstrated an excellent ability to categorize SSc patients at the time of diagnosis in separate 15-year all-cause mortality risk strata at the time of diagnosis.

Toxin-gamma (T gamma) from the Brazilian scorpion Tityus serrulatus venom caused a concentration-and time-dependent increase in the release of norepinephrine and epinephrine from bovine adrenal medullary chromaffin cells. T gamma was similar to 200-fold more potent than veratridine judged from EC50 values, although the maximal secretory efficacy of veratridine was 10-fold greater than that of T gamma (1.2 vs. 12 mu g/ml of catecholamine release). The combination of both toxins produced a synergistic effect that was particularly drastic at 5 mM extracellular Ca2+ concentration ([Ca2+](o)), when 30 mu M veratridine plus 0.45 mu M T gamma were used. T gamma (0.45 mu M) doubled the basal uptake of Ca-45(2+), whereas veratridine (100 mu M) tripled it. Again, a drastic synergism in enhancing Ca2+ entry was seen when T gamma and veratridine were combined; this was particularly pronounced at 5 mM [Ca2+](o). Veratridine induced oscillations of cytosolic Ca2+ concentration ([Ca2+](i)) in single fura 2-loaded cells without elevation of basal levels. In contrast, T gamma elevated basal [Ca2+](i) levels, causing only small oscillations. When added together, T gamma and veratridine elevated the basal levels of [Ca2+](i) without causing large oscillations. T gamma shifted the current-voltage (I-V) curve for Na+ channel current to the left. The combination of T gamma with veratridine increased the shift of the I-V curve to the left, resulting in a greater recruitment of Na+ channels at more hyperpolarizing potentials. This led to enhanced and more rapid accumulation of Na+ in the cell, causing cell depolarization, the opening of voltage-dependent Ca2+ channels, and Ca2+ entry and secretion. Inst Butantan, Farmacol Lab, BR-05503 Sao Paulo, Brazil Inst Butantan, Lab Bioquim & Biofis, BR-05503 Sao Paulo, Brazil Escola Paulista Med, Dept Farmacol, BR-04034970 Sao Paulo, Brazil Univ Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, Madrid 28029, Spain Univ Madrid, Hosp Princesa, Inst Gerontol, Serv Farmacol Clin, Madrid 28006, Spain Escola Paulista Med, Dept Farmacol, BR-04034970 Sao Paulo, Brazil Web of Science