HBsAg kinetics after 7 years of therapy with tenofovir disoproxil fumarate in a cohort of naïve patients affected by chronic hepatitis B with different genotypes.

The role of different genotypes in nucleos(t)ide analogs (NAs) treatment is still debated. Previous studies conducted on special populations evidenced that the E genotype had the lower virological and serological response. This descriptive study aims to recognize the hepatitis B "s" antigen (HBsAg) decline during tenofovir disoproxil fumarate (TDF) treatment in a cohort of patient affected by chronic hepatitis B (CHB). We retrospectively included all patients with CHB treated with TDF between April 2007 and March 2012 with a duration of treatment of 7 years. Kinetics of HBsAg was determined as serological response in this cohort. We include 110 subjects; virological response was observed in all subjects with genotypes A, B, and D; in 17 patients with C genotype (94.4%) and 24 with E genotype (96%). HBeAg loss was observed in 2 patients with genotype A (50%), 3 with B (100%), 0 with C (0%), 1 with D (20%), and 1 with E genotype (25%). In multivariate analysis we observed as predictive factors of HBsAg decline the baseline level of HBsAg (OR = 1.467; 95%CI: 1.221-5.113; p = 0.017) and viral genotypes (OR = 11.218; 95%CI: 5.441-41.138; p < 0.001). This study confirmed higher HBsAg decline after 7 years of treatment in A and B genotypes, and lower in C, E, and D genotypes. However, no evidence is enough to choose a single NAs, but in special populations, as well as in genotype E, the use of TDF should be preferred to entecavir.

Predictors of mortality in patients with COVID-19 infection in different health-care settings: A retrospective analysis from a CORACLE study group.

BACKGROUND: Despite the large number of hospitalized patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, few data are available about risk factors and mortality in subjects with nosocomially acquired respiratory infection of Coronavirus Disease 2019 (COVID-19). METHODS: We retrospectively evaluated in a multicentric study -during the pre-vaccination era-all patients admitted with confirmed diagnosis of nosocomial COVID-19 (NC). Patients were classified according to provenance: hospital-acquired NC or long-term care (LTC) facilities. RESULTS: Among overall 1047 patients evaluated with COVID-19, 137 had a confirmed diagnosis of NC (13%). 78 (56.9%) patients had hospital-acquired NC and 59 (43%) had LTC NC. Overall mortality was 35.8%, in hospital-acquired NC 24.4%, in LTC NC 50.8% (p < 0.001) (Log Rank test: p = 0.001). Timing of diagnosis was significantly different between hospital acquired and LTC NC (3.5 vs 10 days, p < 0.001). In multivariate analysis age, intensive-care unit admission, LTC provenance and sepsis were significant predictors of mortality in patients with NC infection. CONCLUSION: Patients with NC are at higher risk of mortality (especially for LTC NC) and required preventive strategies, early diagnosis, and treatment to avoid COVID-19 cluster.

Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry.

Real-life experience of molnupiravir treatment is lacking, especially in people hospitalized for underlying diseases not related to COVID-19. We conducted a retrospective analysis regarding molnupiravir therapy in patients with SARS-CoV-2 infection admitted for underlying diseases not associated with COVID-19. Forty-four patients were included. The median age was 79 years (interquartile range [IQR]: 51-93 years), and most males were 57,4%. The median Charlson Comorbidity Index and 4C score were, respectively, 5 (IQR: 3-10) and 9.9 (IQR: 4-12). Moreover, 77.5% of the patients had at least two doses of the anti-SARS-CoV-2 vaccine, although 10.6% had not received any SARS-CoV-2 vaccine. Frequent comorbidities were cardiovascular diseases (68.1%), and diabetes (31.9%), and most admissions were for the acute chronic heart (20.4%) or liver (8.5%) failure. After molnupiravir started, 8 (18.1%) patients developed acute respiratory failure, and five (11.4%) patients died during hospitalisation. Moreover, molnupiravir treatment does not result in a statistically significant change in laboratory markers except for an increase in the monocyte count (p = 0.048, Z = 1.978). Molnupiravir treatment in our analysis was safe and well tolerated. In addition, no patients' characteristics were found significantly related to hospital mortality or an increase in oxygen support. The efficacy of the molecule remains controversial in large clinical studies, and further studies, including larger populations, are required to fill the gap in this issue.

Impact of socioeconomic status on the clinical outcomes in hospitalised patients with SARS-CoV-2 infection: a retrospective analysis.

Aim: A disadvantaged socioeconomic status (SES) was previously associated with higher incidence and poor outcomes both of non-communicable diseases (NCDs) and infectious diseases. Inequalities in health services also have a negative effect on the coronavirus disease 2019 (COVID-19) morbidity and mortality. Subject and methods: The study analysed the role of SES measured by the educational level (EL) in hospitalised patients with COVID-19 between 9 March 2020 and 20 September 2021 at our centre of infectious diseases. Clinical outcomes were: length of hospitalisation, in-hospital mortality and the need of intensive-care-unit (ICU) support. Results: There were 566 patients included in this retrospective analysis. Baseline EL was: illiterate (5, 0.9%), primary school (99, 17.5%), secondary school (228, 40.3%), high school (211, 37.3%), degree (23, 4.1%); median age was higher in low EL (72.5 years vs 61 years, p = 0.003), comorbidity (56% in low EL, 34.6% in high EL, p < 0.001), time from the symptoms and PCR diagnosis (8.5 days in low EL, 6.5 days in high EL, p < 0.001), hospitalisation length (11.5 days in low EL, 9.5 days in high EL, p = 0.011), mortality rate (24.7% in low EL, 13.2% in high EL, p < 0.001). In the multivariate analysis there were predictors of mortality: age (OR = 4.981; 95%CI 2.172-11.427; p < 0.001), comorbidities (OR = 3.227; 95%CI 2.515-11.919; p = 0.007), ICU admission (OR = 6.997; 95%CI 2.334-31.404; p = 0.011), high vs low EL (OR = 0.761; 95%CI 0.213-0.990; p = 0.021). In survival analysis, higher EL was associated with a decreased risk of mortality up to 23.9%. Conclusion: Even though the EL is mainly related to the age of patients, in our analysis, it resulted as an independent predictor of in-hospital mortality and hospitalisation time. Unfortunately, this is a study focused only on hospitalised patients, and we did not examine the possible effect of EL in outpatients. Further analyses are required to confirm this suggestion and provide novel information.

Role of plasmatic and urinary concentration of tenofovir disoproxil fumarate in a cohort of patients affected by chronic hepatitis B.

The aim of this study was to evaluate plasmatic and urinary therapeutic drug monitoring (TDM) of tenofovir disoproxil fumarate (TDF) in a cohort of patients with chronic hepatitis B (CHB). In 68 enrolled patients, the estimated glomerular filtration rate (eGFR) was 68 mL/min in naive subjects, while in adefovir dipivoxil (ADV)-pretreated patients, it was 55.5 mL/min (p < 0.001). The HBV E genotype was associated with lower TDF levels (ß = -0.698, p < 0.001). The urinary TDF concentration was associated with ADV pretreatment (ß = 0.829, p < 0.001). Determination of urinary concentrations of TDF may be useful in the clinical management of older CHB patients and those with previous treatment with ADV.

Remdesivir treatment in hospitalized patients affected by COVID-19 pneumonia: A case-control study.

To date the optimal antiviral treatment against severe coronavirus disease 2019 (COVID-19) has not been proven; remdesivir is a promising drug with in vitro activity against several viruses, but in COVID-19 the clinical results are currently not definitive. In this retrospective observational study, we analyzed the clinical outcomes (survival analysis, efficacy, and safety) in a group of hospitalized patients with COVID-19 treated with remdesivir in comparison with a control group of patients treated with other antiviral or supportive therapies. We included 163 patients treated with remdesivir and 403 subjects in the control group; the baseline characteristics were similar in the two groups; the mortality rate was higher in the control group (24.8% vs. 2.4%, p < 0.001), the risk of intensive care unit (ICU) admission was higher in the control group (17.8% vs. 9.8%, p = 0.008); hospitalization time was significantly lower in patients treated with remdesivir (9.5 vs. 12.5 days, p < 0.001). The safety of remdesivir was good and no significant adverse events were reported. In multivariate analysis, the remdesivir treatment was independently associated with a 34% lower mortality rate (odds ratio = 0.669; p = 0.014). In this analysis, the treatment with remdesivir was associated with lower mortality, lower rate of ICU admission, and shorter time of hospitalization. No adverse events were observed. This promising antiviral treatment should also be confirmed by other studies.

Liver involvement and mortality in COVID-19: A retrospective analysis from the CORACLE study group.

Introduction: liver abnormalities are common in COVID-19 patients and associated with higher morbidity and mortality. We aimed to investigate clinical significance and effect on the mortality of abnormal liver function tests (ALFTs) in COVID-19 patients. Methods: we retrospectively evaluated in a multicentre study all patients admitted with confirmed diagnosis of COVID-19. Results: 434 patients were included in this analysis. Among overall patients, 311 (71.6%) had normal baseline ALT levels. 123 patients showed overall abnormal liver function tests (ALFTs) at baseline [101 ALFTs <2x UNL and 22 ≥2 UNL]. Overall in-hospital mortality was 14% and mean duration of hospitalization was 10.5 days. Hypertension (50.5%), cardiovascular diseases (39.6%), diabetes (23%) were frequent comorbidities and 53.7% of patients had ARDS. At multivariate analysis, the presence of ARDS at baseline (OR=6.11; 95% CI: 3.03-12.32; p<0.000); cardiovascular diseases (OR=4; 95% CI: 2.05-7.81; p<0.000); dementia (OR=3.93; 95%CI:1.87-8.26; p<0.000) and no smoking (OR=4.6; 95% CI: 1.45-14.61; p=0.010) resulted significantly predictive of in-hospital mortality. The presence of ALFTs at baseline was not significantly associated with mortality (OR=3.44; 95% CI=0.81-14.58; p=0.094). Conclusion: ALFTs was frequently observed in COVID-19 patients, but the overall in-hospital mortality was mainly determined by the severity of illness, comorbidities and presence of ARDS.

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy.

Sofosbuvir (SOF) is an HCV NS5B polymerase inhibitor, and GS-331007 is its major metabolite. The aim of this study was to investigate whether clinical and pharmacological factors could influence GS-331007 intracellular (IC) concentrations in peripheral blood mononuclear cells (PBMCs) associated with a sustained virological response in patients treated with SOF and ribavirin (RBV). Drug levels were analyzed using liquid chromatography at different days of therapy, whereas variants in genes encoding transporters and nuclear factors were investigated using real-time PCR. This study enrolled 245 patients treated with SOF; 245 samples were analyzed for pharmacogenetics and 50 were analyzed for IC pharmacokinetics. The GS-331007 IC concentration at 30 days was associated with its plasma concentration determinate at 30, 60 and 90 days of SOF-therapy and with daclatasvir concentrations at 7 days of therapy. No genetic polymorphism affected IC exposure. In linear multivariate analysis, ledipasvir treatment, baseline albumin and estimated glomerular filtration rate were significant predictors of IC exposure. This study presents data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. These results could be useful for regions where SOF-RBV treatment is considered the standard of care; moreover, they could further deepen the knowledge of IC exposure for similar drugs in the future.

Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry.

BACKGROUND: CORACLE is a retrospective and prospective, regional multicenter registry, developed to evaluate risk factors for mortality in a cohort of patients admitted with SARS-CoV-2 infection within non-intensive wards. METHODS: The primary objective was to estimate the role of several prognostic factors on hospital mortality in terms of adjusted Odds Ratios (aOR) with multivariable logistic regression models. RESULTS: A total of 1538 patients were enrolled; 42% were female, and 58% were >70 years old. Deceased patients were 422 (27%), with a median age of 83 years (IQR (Inter Quartile Range) 76-87). Older age at admission (aOR 1.07 per year, 95%CI 1.06-1.09), diabetes (1.41, 1.02-1.94), cardiovascular disease (1.79, 1.31-2.44), immunosuppression (1.65, 1.04-2.62), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (3.53, 2.26-5.51), higher C-reactive protein values and a decreased PaO2/FiO2 ratio at admission were associated with a higher risk of hospital mortality. Amongst patients still alive on day 7, only hydroxychloroquine (HCQ) treatment was associated with reduced mortality (0.57, 0.36-0.90). CONCLUSIONS: Several risk factors were associated with mortality in SARS-CoV-2 positive patients. Although HCQ seems to be the only factor significantly associated with reduced mortality, this result is in contrast with evidence from randomized studies. These results should be interpreted in light of the study limitations.

Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis.

PURPOSE: Severe coronavirus disease 2019 (COVID-19) is strongly related to interstitial pneumonia with frequent development of acute respiratory distress syndrome (ARDS). The role of corticosteroids (CS) treatment in these patients is still controversial. Some studies evidenced a possible role of an early short-term course of CS treatment in the treatment of severe pneumonia. PATIENTS AND METHODS: This is a single-center, retrospective study considering the patients with confirmed COVID-19 pneumonia admitted to our hospital between 9th March and 15th June 2020. Two groups were considered: early high-dose of methyl-prednisolone (eHDM; n â€‹= â€‹31) and the control group (n â€‹= â€‹52). Patients in the eHDM group received the dose of 5-8 â€‹mg/kg/day of methyl-prednisolone for 2 consecutive days. Primary outcome was the mortality evaluation; secondary outcomes were clinical improvement, side-effects and laboratory/radiographic changes. RESULTS: Significant differences between the two groups were: length of hospitalization (21.5 vs 28.4 days, p â€‹= â€‹0.026), length of non-invasive ventilation (NIV) or mechanical ventilation (11.5 vs 14.5 days, p â€‹= â€‹0.031), death (5 vs 12, p â€‹= â€‹0.006) and clinical improvement (16 vs 11, p=0.018). The following factors were related to in-hospital mortality in the multivariate analysis: comorbidities (OR â€‹= â€‹2.919; 95%CI â€‹= â€‹1.515-16.705; p<0.001), days from the onset of symptoms and the hospital admission (OR â€‹= â€‹1.404; 95%CI â€‹= â€‹1.069-12.492; p â€‹= â€‹0.011), PaO2/FiO2 (P/F) ratio (OR â€‹= â€‹3.111; 95%CI â€‹= â€‹2.334-16.991; p â€‹= â€‹0.009) and eHDM treatment (OR â€‹= â€‹0.741; 95%CI â€‹= â€‹0.129-0.917; p â€‹= â€‹0.007). CONCLUSION: The eHDM is an interesting and promising approach in the ARDS related to COVID-19 pneumonia, which reduces mortality, length of hospitalization and the need for mechanical ventilation.

Simple Parameters from Complete Blood Count Predict In-Hospital Mortality in COVID-19.

INTRODUCTION: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. MATERIALS AND METHODS: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients (F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. RESULTS: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) (χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio (χ 2 7.6; p = 0.006), and platelet count (χ 2 5.39; p = 0.02), along with age (χ 2 87.6; p < 0.001) and gender (χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/µL was, conversely, protective (OR: 0.45 (0.32-0.63)). CONCLUSION: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Trend of 25-hydroxycholesterol and 27-hydroxycholesterol plasma levels in patients affected by active chronic hepatitis B virus infection and inactive carriers.

Hepatitis B virus (HBV) infection is a global health problem with different immunological phases and therapeutic approaches. The serological condition of inactive carrier (IC) was recently well defined as a clinical and virological stable status, in which specific treatment is usually deferred, while the active chronic hepatitis B (CHB) condition requires an immediate treatment strategy. Recently, a possible broad antiviral effect of oxysterols, in particular 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC), was observed, as most likely linked to the positive modulation of innate immunity, but no clear evidence is available about their possible role in chronic HBV infection. Thus, we examined the relationship between the plasma levels of oxysterols and the disease condition of 40 HBV patients, without treatment at the start of the study. Of these, 33 were ICs and 7 were active CHB subjects. A marked reduction of 25OHC and 27OHC plasma levels was detectable in all active CHB recruited patients, while the plasma values observed in ICs all remained within the physiological range. No difference was observed between the two groups of patients with regard to the plasma levels of 24-hydroxycholesterol (24OHC). Further, the plasma level of 27OHC ≥ 140 µg/L was shown to be predictive of an inactive carrier status. This cohort study points to 27OHC as a good candidate biomarker to differentiate active and inactive CHB status. An increasing bulk of research reports is supporting the very likely contribution of this oxysterol to the immunological control of chronic hepatitis B.

Ceftobiprole Perspective: Current and Potential Future Indications.

Ceftobiprole combines an excellent spectrum for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) pathogens, with a low/medium MDR risk, and the ß-lactams' safety in frail patients admitted to the hospital in internal medicine wards which may be at high risk of adverse events by anti-MRSA coverage as oxazolidinones or glycopeptides. We aimed to report the available evidence regarding ceftobiprole use in pneumonia and invasive bacterial infections, shedding light on ceftobiprole stewardship. The clinical application and real-life experiences of using ceftobiprole for bloodstream infections, including infective endocarditis, are limited but nevertheless promising. In addition, extended-spectrum ceftobiprole activity, including Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa, has theoretical advantages for use as empirical therapy in bacteremia potentially caused by a broad spectrum of microorganisms, such as catheter-related bacteremia. In the future, the desirable approach to sepsis and severe infections will be administered to patients according to their clinical situation, the intrinsic host characteristics, the susceptibility profile, and local epidemiology, while the "universal antibiotic strategy" will no longer be adequate.

Serological and virological response in patients with hepatitis B virus genotype E treated with entecavir or tenofovir: a prospective study.

European clinical practice guidelines (EASL) on chronic hepatitis B (CHB) recently recognized the importance of migration flows in the changing hepatitis B virus (HBV) epidemiology in low-endemic European countries. The role of different genotypes in nucleos(t)ide analogue (NA) treatment is still unknown. In the case of genotype E, which is mainly circulating in West Africa, a quantitative decrease in the level of HBsAg (qHBsAg) during treatment with entecavir (ETV) predicts a longer time to HBsAg loss when compared to genotypes A and D. We prospectively evaluated qHBsAg decline in HBeAg-negative CHB patients infected with HBV genotype E who were treated with tenofovir 245 mg (TDF) or ETV 0.5 mg from 2008 to 2014. Sixty-five West African patients (58; 89.2% males) were enrolled. The median age was 29 years, and the most prevalent route of transmission was familial (25; 38.5%). Median liver stiffness was 7.4 kPa, HBV-DNA was 4.7 Log IU/ml, and qHBsAg was 3.4 Log UI/ml. According to clinical evaluation, 40 patients (61.5%) started ETV treatment, whereas 25 patients (38.5%) started TDF treatment. The decline of qHBsAg in ETV patients was significantly lower than in TDF patients after 5 years of treatment (0.31 vs. 0.68 LogIU/mL, p < 0.001). At the same time points, a significantly higher virological non-response rate was observed in ETV patients (p < 0.001). Despite the partial and non-response rates observed in the ETV group, no mutations associated with drug resistance were detected in these subjects. In genotype E infections, ETV treatment results in a significantly lower decline in qHBsAg and higher rates of virological non-response after 5 years. TDF could represent the optimal choice.

Risk for SARS-CoV-2 Infection in Healthcare Workers, Turin, Italy.

We measured severe acute respiratory syndrome coronavirus 2 spike protein subunits S1/S2 antibodies by using capillary electrophoresis and a chemiluminescence immunoassay for 5,444 active healthcare workers in Italy. Seroprevalence was 6.9% and higher among participants having contact with patients. Seroconversion was not observed in 37/213 previously infected participants.