Utilizzo di immunoglobuline arricchite nella componente M nel paziente settico

Nonostante progressi notevoli per quanto riguarda la comprensione dell’immuno-fisiopatologia, l’applicazione dei bundle della SSC e la vasta gamma di antibiotici disponibili, il tasso di mortalità a lungo termine nella sepsi rimane compreso tra il 20% ed il 50%. Inoltre, la sempre più diffusa resistenza dei microrganismi patogeni nei confronti degli antibiotici ha evidenziato la necessità di trattamenti alternativi, spostando l’attenzione sulla risposta sistemica sviluppata dall’ospite. Pentaglobin® è attualmente l’unico prodotto in commercio IgM-arricchito. Questo conferisce un titolo antibatterico e anti-tossinico maggiore dei preparati a base di sole IgG. Possiede attività antibatterica, anti-tossinica, modulatrice della risposta flogistica, effetti sulla trascrizione genica ed anti-apoptotici sulle cellule immunitarie. Il target dei pazienti ed il timing di somministrazione non sono determinati in letteratura. Scopo dello studio è stata la valutazione dell’efficacia clinica della soluzione infusionale arricchita di IgM e del possibile supporto del monitoraggio immunologico nei pazienti con shock settico

Low diaphragm muscle mass predicts adverse outcome in patients hospitalized for COVID-19 pneumonia: An exploratory pilot study

BACKGROUND: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. METHODS: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P<0.10 were entered into a multivariate logistic regression model. cumulative probability for lack of adverse outcomes in patients with or without low baseline diaphragm muscle mass was calculated with the Kaplan-Meier product-limit estimator. RESULTS: The main findings of this study are that: 1) patients who developed adverse outcomes had thinner diaphragm than those who did not (2.0 vs. 2.2 mm, P=0.001); and 2) DT and lymphocyte count were independent significant predictors of adverse outcomes, with end-expiratory DT being the strongest (8=-708; oR=0.492; P=0.018). coNcLUSioNS: Diaphragmatic ultrasound may be a valid tool to evaluate the risk of respiratory failure. Evaluating the need of mechanical ventilation treatment should be based not only on Pao2/Fio2, but on a more comprehensive assess¬ ment including DT because if the lungs become less compliant a thinner diaphragm, albeit free of intrinsic abnormality, may become exhausted, thus contributing to severe respiratory failure

The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals

Hyperglycemia at hospital admission is associated with severity of the prognosis in patients hospitalized for COVID-19: The pisa COVID-19 study

OBJECTIVE To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS Hospitalized COVID-19 patients (N 5 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N 5 149 [55.0%]; median glucose5.99mmol/L[range5.38–6.72]),2)known diabetesmellitus (DM)(N5 56[20.7%]; 9.18 mmol/L [7.67–12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N 5 66 [24.3%]; 8.57 mmol/L [8.18–10.47]). RESULTS Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients.DMandHG patients hadhigherD-dimer andworseinflammatoryprofile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI1.27–3.81,P50.005)thaninNG(16.8%)andmarginallysoinDM(28.6%;1.73,0.92– 3.25, P 5 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P 5 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P 5 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P 5 0.079) vs. Q1. CONCLUSIONS Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19

Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study

Background: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives: To identify predictors of superinfections in COVID-19. Methods: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred 48 h after hospital admission. Amultivariate analysis was performed to identify factors independently associated with superinfections. Results: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). Conclusions: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced