Efficacy of bezlotoxumab in preventing the recurrence of Clostridioides difficile infection: an Italian multicenter cohort study

Objectives: Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. Methods: A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). Results: rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). Conclusion: Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors

Efficacy of bezlotoxumab in preventing the recurrence of Clostridioides difficile infection: an Italian multicenter cohort study

Objectives: Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. Methods: A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). Results: rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). Conclusion: Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors

Clinical characteristics, management and health related quality of life in young to middle age adults with COVID-19

Background: The outbreak of COVID-19 has rapidly spread to Italy, including Pesaro-Urbino province. Data on young to middle age adults with COVID-19 are lacking. We report the characteristics, management and health-related quality of life (HRQoL) in patients with COVID-19 aging ≤50 years. Methods: A retrospective analysis was performed in all patients ≤50 years with a confirmed diagnosis of COVID-19 admitted to Emergency department (ED) of San Salvatore Hospital in Pesaro from February 28th to April 8th, 2020. Data were collected from electronical medical records. HRQoL was investigated after 1 month from hospital discharge using the SF-36 questionnaire. Outcomes were evaluated between hospitalized and not hospitalized patients. Results: Among 673 patients admitted to the ED and diagnosed with COVID-19, 104 (15%) were ≤ 50 years old: 74% were discharged at home within 48 h, 26% were hospitalized. Fever occurred in 90% of the cases followed by cough (56%) and dyspnoea (34%). The most frequent coexisting conditions were hypertension (11%), thyroid dysfunction (8%) and neurological and/or mental disorders [NMDs] (6%). Mean BMI was 27. Hypokalaemia and NMDs were significantly more common in patients who underwent mechanical ventilation. Regardless of hospitalization, there was an impairment in both the physical and mental functioning. Conclusions: Overweight and hypertension are frequent conditions in young to middle age adults with COVID-19. Hypokalaemia and NMDs are commonly associated with progressive disease. A significant impact on HRQoL in the early stage of post-discharge is common in this population

Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU

Background: Remdesivir is a prodrug with in vitro activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical efficacy in patients with COVID-19 under mechanical ventilation remains to be evaluated. Methods: This study includes patients under mechanical ventilation with confirmed SARS-CoV-2 infection admitted to the ICU of Pesaro hospital between 29 February and 20 March 2020. During this period, remdesivir was provided on a compassionate use basis. Clinical characteristics and outcome of patients treated with remdesivir were collected retrospectively and compared with those of patients hospitalized in the same time period. Results: A total of 51 patients were considered, of which 25 were treated with remdesivir. The median (IQR) age was 67 (59–75.5) years, 92% were men and symptom onset was 10 (8–12) days before admission to ICU. At baseline, there was no significant difference in demographic characteristics, comorbidities and laboratory values between patients treated and not treated with remdesivir. Median follow-up was 52 (46–57) days. Kaplan–Meier curves showed significantly lower mortality among patients who had been treated with remdesivir (56% versus 92%, P < 0.001). Cox regression analysis showed that the Charlson Comorbidity Index was the only factor that had a significant association with higher mortality (OR 1.184; 95% CI 1.027–1.365; P = 0.020), while the use of remdesivir was associated with better survival (OR 3.506; 95% CI 1.768–6.954; P < 0.001). Conclusions: In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. The use of remdesivir was associated with a significant beneficial effect on survival

Prevalence, incidence and clinical outcome of hepatitis B virus and hepatitis C virus hepatitis in patients undergoing allogeneic hematopoietic stem cell transplantation between 2001 and 2004.

The prevalence, incidence and clinical course of viral hepatitis were prospectively determined in consecutive recipients of T-cell depleted hematopoieic stem cell transplants (49 mismatched, 60 matched, mean age 38 years; range 11-65). The prevalence of hepatitis B virus (HBV) was 15.6% and that of hepatitis C virus was 3.7% (HCV). HBV reactivated in one patient. Another developed ex novo acute hepatitis B which progressed to chronic hepatitis. There were no new cases of hepatitis C or worsening of pre-transplant HCV infections. HBV and HBC did not affect the outcome of T-cell depleted hematopoieic stem cell transplantation. Surveillance is important given the risk of HCV and HBV infection and/or reactivation and the efficacy of the new anti-hepatitis drugs

The Effect of Switching to Maraviroc + Darunavir/Ritonavir Dual Therapy in Virologically Suppressed Patients on the Progression of Liver Fibrosis: Findings From a Randomized Study

In vitro and animal studies revealed a potential protective role of CCR5 antagonists on reducing liver fibrosis progression and protecting from developing hepatocellular carcinoma.1 Hepatocytes bear CXCR4 and CCR5, the 2 main coreceptors for HIV entry into cells and the blockade of coreceptors on hepatic stellate cells, the major producers of extracellular matrix in the liver, will slow progression of liver fibrosis, especially due to HIV-envelope gp120–mediated fibrogenesis modulation.2–5 The aim of present analysis was to compare the evolution of liver fibrosis over time evaluated by surrogated biomarker assays in HIV-1–infected patients on a virologically successful antiretroviral therapy (stable HIV-1 RNA &lt;50 copies/mL), randomized to switch to maraviroc + darunavir/r (MVC + DRV/r arm) qd or to continue the current MVC-free 3-drug antiretroviral therapy (ART) (3-drug ART arm). Patients included in the study were enrolled in the GUided Simplification with Tropism Assay (GUSTA) trial, a multicenter, open-label, randomized study (www.clinicaltrials.gov, number NCT01367210), whose main results have been published.6 Briefly, GUSTA included patients with HIV-1 RNA &lt;50 copies/mL for at least 6 months, R5 tropism and CD4 counts &gt;200 cells/μL for at least 3 months before enrollment; hepatitis B virus–coinfected patients and those with Child-Pugh B/C cirrhosis were excluded. We retrospectively evaluated Fibrosis-4 (FIB-4) Index and aspartate aminotransferase to Platelet Ratio Index (APRI) scores, at baseline and after 12, 24, 48, and 96 weeks. The cutoff points of serum marker tests of hepatic fibrosis were as follows: FIB-4 &lt;1.45 (F0-F1), 1.45–3.25 (indeterminate), and &gt;3.25 (F3-F4); APRI &lt;0.5 (F0-F1), &gt;1.5 (F2) and &gt;2 (cirrhosis). Differences between arms were assessed by χ2 and Student t test, longitudinal within-group differences by McNemar test. The FIB-4 Index and APRI scores were used as continuous variables; their predictors at baseline and their change over time were investigated by linear regression

Hepatitis C in the elderly: a multicentre cross-sectional study by the Italian Association for the Study of the Liver.

BACKGROUND: The prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population. AIM: To define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus. METHODS: We evaluated 1544 anti-hepatitis C virus positive patients aged 6565 years referred to 34 Italian outpatient specialty clinics over a two-year period. RESULTS: The study population included 1134 (73%) early elderly (65-74 years) and 410 (27%) late elderly patients ( 6575 years). Late elderly subjects were less likely to have their virus genotyped, their viral load assessed or a histological evaluation of liver disease. Overall, 30% of patients had advanced liver disease whose prevalence increased with increasing age. In both age groups, about 40% of patients had normal transaminase levels. Excluding patients with past infection, 51% had not received any antiviral treatment and only 25% were treated after the age of 65. Late elderly patients, women and patients with advanced liver diseases had been less frequently treated. The main reason for exclusion from treatment was age followed by the presence of comorbid conditions. CONCLUSIONS: Elderly hepatitis C virus patients referred to Italian specialty clinics have advanced and underestimated liver disease. Nevertheless, they are progressively understudied in parallel with increasing age

Predicting the occurrence of embolic events: An analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI)

Background: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism.Methods: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30).Results: There were 499 episodes of infective endocarditis (34%) that were complicated by 65 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size 65 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size 65 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001).Conclusions: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surger