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

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

Ultrasound localization of central vein catheter tip by contrast-enhanced transthoracic ultrasonography: a comparison study with trans-esophageal echocardiography

Abstract Background To assess the usefulness of pre-operative contrast-enhanced transthoracic echocardiography (CE-TTE) and post-operative chest-x-ray (CXR) for evaluating central venous catheter (CVC) tip placements, with trans-esophageal echocardiography (TEE) as gold standard. Methods A prospective single-center, observational study was performed in 111 patients requiring CVC positioning into the internal jugular vein for elective cardiac surgery. At the end of CVC insertion by landmark technique, a contrast-enhanced TTE was performed by both the apical four-chambers and epigastric bicaval acoustic view to assess catheter tip position; then, a TEE was performed and considered as a reference technique. A postoperative CXR was obtained for all patients. Results As per TEE, 74 (67%) catheter tips were correctly placed and 37 (33%) misplaced. Considering intravascular and intracardiac misplacements together, they were detected in 8 patients by CE-TTE via apical four-chamber view, 36 patients by CE-TTE via epigastric bicaval acoustic view, and 12 patients by CXR. For the detection of catheter tip misplacement, CE-TTE via epigastric bicaval acoustic view was the most accurate method providing 97% sensitivity, 90% specificity, and 92% diagnostic accuracy if compared with either CE-TTE via apical four-chamber view or CXR. Concordance with TEE was 79% (p &lt; 0.001) for CE-TTE via epigastric bicaval acoustic view. Conclusions The concordance between CE-TTE via epigastric bicaval acoustic view and TEE suggests the use of the former as a standard technique to ensure the correct positioning of catheter tip after central venous cannulation to optimize the use of hospital resources and minimize radiation exposure. </jats:sec

Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study

AbstractBackgroundThis study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.MethodsThis is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4–April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable.ResultsAmong 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21–0.6; P &amp;lt; .001) and composite endpoint (HR, 0.61; 95% CI, 0.39–0.95; P = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint.ConclusionsThis study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.</jats:sec

Ultrasound localization of central vein catheter tip by contrast-enhanced transthoracic ultrasonography: a comparison study with trans-esophageal echocardiography

Background To assess the usefulness of pre-operative contrast-enhanced transthoracic echocardiography (CE-TTE) and post-operative chest-x-ray (CXR) for evaluating central venous catheter (CVC) tip placements, with trans-esophageal echocardiography (TEE) as gold standard. Methods A prospective single-center, observational study was performed in 111 patients requiring CVC positioning into the internal jugular vein for elective cardiac surgery. At the end of CVC insertion by landmark technique, a contrast-enhanced TTE was performed by both the apical four-chambers and epigastric bicaval acoustic view to assess catheter tip position; then, a TEE was performed and considered as a reference technique. A postoperative CXR was obtained for all patients. Results As per TEE, 74 (67%) catheter tips were correctly placed and 37 (33%) misplaced. Considering intravascular and intracardiac misplacements together, they were detected in 8 patients by CE-TTE via apical four-chamber view, 36 patients by CE-TTE via epigastric bicaval acoustic view, and 12 patients by CXR. For the detection of catheter tip misplacement, CE-TTE via epigastric bicaval acoustic view was the most accurate method providing 97% sensitivity, 90% specificity, and 92% diagnostic accuracy if compared with either CE-TTE via apical four-chamber view or CXR. Concordance with TEE was 79% (p &lt; 0.001) for CE-TTE via epigastric bicaval acoustic view. Conclusions The concordance between CE-TTE via epigastric bicaval acoustic view and TEE suggests the use of the former as a standard technique to ensure the correct positioning of catheter tip after central venous cannulation to optimize the use of hospital resources and minimize radiation exposure

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

AbstractHigh 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.</jats:p

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 = 271) were subdivided based on at-admission glycemic status: 1) glucose levels &amp;lt;7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38–6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67–12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 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. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27–3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92–3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P = 0.079) vs. Q1. CONCLUSIONS Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19. </jats:sec

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

Abstract 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. A multivariate 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 &amp;lt; 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P &amp;lt; 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P &amp;lt; 0.001); C-reactive protein on admission &amp;gt;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 &amp;lt; 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. </jats:sec

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 &lt;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