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To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O2) therapy and those with a severe infection if hospitalized and required O2 therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; < 0.01) and were younger (median age 45 years (IQR:19) vs 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94–0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54 –0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management.

As of January 2020, a new pandemic has spread from Wuhan and caused thousands of deaths worldwide. Several studies have observed a relationship between coronavirus disease (COVID-19) infection and the cardiovascular system with the appearance of myocardial damage, myocarditis, pericarditis, heart failure and various arrhythmic manifestations, as well as an increase in thromboembolic risk. Cardiovascular manifestations have been highlighted especially in older and more fragile patients and in those with multiple cardiovascular risk factors such as cancer, diabetes, obesity and hypertension. In this review, we will examine the cardiac involvement associated with SARS-CoV-2 infection, focusing on the pathophysiological mechanism underlying manifestations and their clinical implication, taking into account the main scientific papers published to date.

The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens. © 2018 Wiley Periodicals, Inc.

Background To date, there is no information on the safety and efficacy of the novel anti-sarbecoviruses monoclonal antibody sotrovimab administered, as a post-exposure prophylactic measure, during the aplastic phase of autologous stem cell transplantation (ASCT). Methods We describe the outcomes of a Multiple Myeloma (MM) patient, who was threateningly exposed to the Omicron (B.1.1.529) SARS-CoV-2 variant, two days after having received a myeloablative regimen of high-dose melphalan. The patient fulfilled all CDC criteria for prolonged close contacts with an index patient who tested positive for a molecular nasopharyngeal swab (Omicron; B.1.1.529) soon after admission to the ward. Given the high risks of morbidity and mortality in the case of COVID-19 developing during the aplastic phase of transplantation, we adopted a post-exposure prophylaxis intervention based on intravenous (i.v.) sotrovimab. Results Sotrovimab (500 mg i.v.) was administered at day + 2 from stem cells reinfusion, i.e. 4 days after myeloablative chemotherapy, and at day + 5 from the last close contact with the Omicron-positive index case. The patient was fully protected from SARS-CoV-2 infection throughout his clinical course and remained molecularly negative at the day + 30 from the transplant. We compared times to engraftment and transplant-related toxicities of the sotrovimab-treated patient with the last 15 MM patients transplanted at our Centre, evidencing no unexpected safety signals, infusion-related reactions, or alarming effects on engraftment kinetics. Conclusions We have shown here for the first time that administration of sotrovimab during the pre-engraftment phase of ASCT is effective, safe, and not associated with delays in hemopoietic recovery. As compared to MM patients who received the same myeloablative conditioning regimen, the patient given sotrovimab during the aplastic phase did not show any significant differences in engraftment kinetics and toxicity outcomes. Post-exposure prophylaxis with sotrovimab may represent a valuable approach in the stem cell transplantation setting for patients with high-risk exposure to a confirmed COVID-19 case sustained by highly infectious SARS-CoV-2 variants escaping the vaccine-derived immunity due to antigenic shifts in the spike proteins.

Background: Second generation direct acting antivirals (DAAs) drastically changed the landscape of chronic HCV (CHCV). Aim of this paper was to assess the effectiveness of DAAs, also looking at the demographic characteristics of subjects enrolled. Research design and methods: Ambispective multi-center real-life study conducted among patients with CHCV treated with DAAs in Campania Region (Southern Italy). Patient were enrolled in two cohorts according to time of enrolment. Results: 1,479 patients were enrolled. Patients aged ≥60 years were 74.7% in the historic cohort (953 patients) and 70.2% in the prospective cohort (526 patients. Patients aged ≥ 60 years showed a higher prevalence of genotype 1b (p

The actual Coronavirus Disease (COVID 19) pandemic is due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the coronavirus family. Besides the respiratory involvement, COVID 19 patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation. It is common to observe diffuse microvascular thrombi in multiple organs, mostly in pulmonary microvessels. Thrombotic risk seems to be directly related to disease severity and worsens patients’ prognosis. Therefore, the correct understanding of the mechanisms underlying COVID-19 induced prothrombotic state can lead to a thorough assessment of the possible management strategies. Hence, we review the pathogenesis and therapy of COVID 19-related thrombosis disease, focusing on the available evidence on the possible treatment strategies and proposing an algorithm for the anticoagulation strategy based on disease severity.

Background Health workers (HWs) are at increased risk for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and a possible source of nosocomial transmission clusters. Despite the increased risk, the best surveillance strategy and management of exposed HWs are not yet well known. The aim of this review was to summarize and critically analyze the existing evidence related to this topic in order to support public health strategies aimed at protecting HWs in the hospital setting. Main text A comprehensive computerized literature research from 1 January 2020 up to 22 May 2020 was made to identify studies analyzing the burden of infection, risk assessment, surveillance and management of HWs exposed to SARS-CoV-2. Among 1623 citation identified using MEDLINE, Embase, Google Scholar and manual search, we included 43 studies, 14 webpages and 5 ongoing trials. Health workers have a high risk of acquiring infection while caring for coronavirus disease 2019 (COVID-19) patients. In particular, some types exposures and their duration, as well as the inadequate or non-use of personal protective equipment (PPE) are associated with increased infection risk. Strict infection prevention and control procedures (IPC), adequate training programs on the appropriate use of PPE and close monitoring of HWs with symptom surveillance and testing are essential to significantly reduce the risk. At the moment there is not enough evidence to provide precise indications regarding pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). Conclusions During the spread of COVID-19 outbreak, numerous published papers investigated the epidemiology, risk assessment and prevention and control of SARS-CoV-2. However, more high-quality studies are needed to provide valid recommendations for better management and for the clinical and microbiological surveillance of healthcare personnel.

The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection is ascertained. However, some authors raised the issue of an increased incidence of de novo hepatocellular carcinoma (HCC) in patients treated with DAAs. Aim of the study was to evaluate the rate of HCC occurrence in a real-life cohort of patients who received anti-HCV treatment with DAAs.A prospective multicentre study was conducted. All adult patients with HCV infection who received treatment between March 2015 and December 2017 in 4 hospital of Campania region (South Italy) with at least 6 months of follow-up were enrolled.A total of 323 patients were included in the study. Most patients had HCV genotype 1b (61.8%). The overall SVR12 rate was 95.5%. Median time of observation was 10 months. The incidence rate of HCC was 0.2 per 100 person-months (crude incidence rate 3.4%, 95 confidence interval: 1.5%-5.3%). The median time for HCC occurrence was 11 months. HCC occurrence rate was significantly higher among patients who did not achieve SVR12 compared with patients who did (28.6% vs 2.8%, P

Background and aim: The impact of directly acting antiviral agent (DAA) regimens on renal function is not well defined and quite controversial. We evaluated the effect of DAAs on kidney function and the factors associated with an improvement or worsening. Patients and methods: The changes in estimated glomerular filtration rate (eGFR) in a cohort of 403 patients treated with a DAA regimen were evaluated. Results: The overall sustained virological response (SVR12) rate was 98%. The median eGFR progressively increased throughout treatment from 84.54ml/min/1.73m2 (IQR 70.8–97.3) to 88.12ml/min/1.73m2. Conversely, rates of patients with a eGFR more than 60ml/min/1.73m2 progressively increased from 83.1% at baseline to 87.8% at 12weeks post-treatment (p < 0.05). Considering the change in eGFR according to the different factors, a significant improvement in eGFR was observed in the patients without diabetes (p < 0.001), in those with cirrhosis (p < 0.05), in those receiving a Sof-based regimen (p < 0.01) or not receiving RBV (p < 0.05), in those with a baseline eGFR less than 60ml/min/1.73m2 (p < 0.001) and in those with SVR (p < 0.05). An improvement in eGFR (defined as an increase in baseline eGFR of at least 10ml/min/1.73m2) was observed in 148 patients (36.7%). At multivariate analysis, age (aHR 0.96; 95 CI 0.93–0.99, p < 0.01) and a diagnosis of diabetes (aHR 0.02; 95 CI 0.20–0.87, p < 0.05) were inversely and independently associated with improvement in renal function, while the presence of Child–Pugh B cirrhosis at baseline was associated with an improvement in renal function (aHR 3.07; 95 CI 1.49–6.30, p < 0.01). Conclusions: DAAs correlate with an improvement in renal function, underlining the importance of hepatitis C virus eradication to achieve also an improvement in extra-hepatic disorders.

Background: Direct-acting antivirals (DAAs) are safe and effective for the treatment of HCV infection. However, data regarding their efficacy in patients with Child–Pugh B cirrhosis are scarce and their capability in improving liver function is debated. The aim of our study was to assess the clinical benefits of treatment with DAA in subjects with Child–Pugh B cirrhosis. Methods: We conducted a prospective multicentre study among patients with Child–Pugh B cirrhosis of an Italian real-life HCV cohort (LINA cohort) who received treatment with DAAs. Results: Among 89 patients enrolled, the rate of sustained virologic response 12 was 95.5%. No discontinuation occurred, no patient died during treatment. Most patients had Genotype 1 (1b 61.8%, 1a 11.2%). Conversely, 22.5%, 1.1% and 3.4% of patients had Genotype 2, 3 and 4, respectively. At last observation, 61.8% of patients switched to a Class A cirrhosis, 33.7% remained in Class B and 4.5 worsened to Child C (p < 0.001). Liver parameters significantly improved from baseline to 12weeks after the end of treatment. Previous anti-HCV treatments and the presence of decompensated cirrhosis at 1month of treatment were significantly associated with a decompensated cirrhosis at the last observation. Conclusions: Treatment with DAA in patients with Child–Pugh B cirrhosis is safe and leads to a very high rate of viral clearance, a significant rate of re-compensation and an improvement in liver function. Further studies are needed to assess the impact of treatment on survival and quality of life in long-term follow-up.

Aim: The aim of the present study was to identify, among the patients with failure to DAA regimen, those with a late relapse (after the achievement of a sustained virological response at week 12) and to characterize the clinical, epidemiological and virological features of these patients. Material and methods: A total of 129 HCV patients with non-response to an IFN-free regimen were enrolled. Sanger sequencing of NS3, NS5A and NS5B was performed at failure by home-made protocols. Results: Of the 129 patients enrolled, 8 (6.2%) experienced a breakthrough, 15 (11.7%) non-response, 99 (76.7%) a relapse by week 12 after the end of DAA therapy, and 7 (5.4%) a late relapse (after week 12; median 24weeks, range 24-72). For two of the seven patients with a late relapse, a serum sample collected before the start of the DAA regimen was available; phylogenetic analysis showed no change in sequences of NS3, NS5A and NS5B regions, suggesting a reactivation of the initial HCV strain; for the remaining five patients, no serum collected before the DAA regimen was available, and thus, a re-infection cannot be excluded. Conclusions: Although a late relapse is infrequent, the study suggests a post-treatment follow-up of 72weeks.

Background To investigate the association between inosine triphosphatase (ITPase) activity and the degree of anaemia occurring during direct-acting antiviral (DAA)/ribavirin (RBV)-based therapy in patients with cirrhosis. Methods In a multicentre, prospective study 227 patients with HCV-related cirrhosis treated with DAA and RBV were enrolled. All patients were screened for the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using direct sequencing. Results 150 (66.1%) patients had normal (100%) ITPase activity, 48 (21.1%) had moderate (60%) activity and 29 (12.8%) minimal (≤30%) activity. The ITPase activity significantly influenced the haemoglobin concentration: at day 15 it was -1.248 (sd ±0.978) in the 150 patients with an ITPase activity of 100% and -0.616 (±0.862) in the 77 patients with an ITPase activity less than 100% ( P Conclusions This study suggests that the polymorphisms in the ITPA gene influence the severity of anaemia during the first month of a DAA/RBV-based treatment in HCV-related cirrhosis.

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus (HBV) and 1000000 to hepatitis C virus (HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.

"OBJECTIVES: To define differences in liver histology between HIV\/HCV coinfection . and HCV monoinfection, and to investigate possible causative factors.. METHODS: Liver biopsies (LBs) from 440 consecutive HIV\/HCV-coinfected patients. (Group HIV\/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were. evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of . the clinical and laboratory data. All patients were HBsAg-negative, with no. history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of. patients in Group HIV\/HCV were on an antiretroviral regimen.. RESULTS: HIV\/HCV-coinfected patients compared to the HCV-monoinfected patients. were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV. genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell. count: 518 ± 166 cells\/mm(3)). Patients in Group HIV\/HCV more frequently showed a. fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9. (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4. was significantly higher in older age classes in both Group HIV\/HCV (p < 0.005). and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher. in older age classes only in Group HIV\/HCV (p < 0.05). A multivariate analysis. for Group HIV\/HCV revealed that the patient age and nadir of CD4+ cell count were. independently associated to higher degrees of fibrosis, the patient age and. antiretroviral treatment were associated to higher degrees of necroinflammation, . and HCV genotype 3 was associated to higher degrees of steatosis.. CONCLUSION: The data suggest a need for early anti-HCV treatment in both. HCV-monoinfected and HIV\/HCV-coinfected patients."

Summary. We evaluated tolerability and virological and clinical impact of anti-Hepatitis B Virus (HBV) nucleos(t)ide analogues in cirrhotic patients with HBV/Hepatitis C Virus (HCV) coinfection. The virological and clinical course of 24 consecutive HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis was compared with that of 24 HBsAg/HBV-DNA-positive, anti-HCV-negative cirrhotic patients, pair-matched for age (±5 years), sex, HBeAg/anti-HBe status and Child-Pugh class. Patients in both groups were previously untreated with oral antiviral agents at enrolment and were treated for at least 24 months (range 24-54). At the 12th and 18th month of treatment, HBV-DNA was negative in 21 (87.5%) and 23 (95.8%) patients with hepatitis B and C and in 20 (83.3%) and 22 (91.6%) in patients with isolated HBV; all patients in both groups were HBV-DNA-negative at month 24 and at subsequent observations. Treatment was well tolerated by all patients in both groups. At the last observation (for co-infected patients, median 44 months and range 24-54; for mono-infected patients, median 40 months and range 24-54), a deterioration in Child class was observed in eight (47%) of 17 patients in patients with both HBV and HCV who were HCV-RNA-positive at baseline, but in none of seven HCV-RNA-negative patients in the same group, and in one patient (4.2%) in the mono-infected patients. Reactivation of HCV infection was relatively infrequent (12.5% of cases) and never associated with a clinical deterioration. Treatment with nucleotides in HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis showed a favourable virological effect in all cases, but a favourable clinical result only in the HCV-RNA-negative at baseline. © 2012 Blackwell Publishing Ltd.

An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.

SummaryMean platelet volume (MPV) is increased in patients with coronary heart disease or at risk for stroke. However, MPV determinants have never been assessed in a population study. The present investigation is a cross-sectional study involving 366 non-selected subjects (both sexes, mean age 72.9 ± 5.5 [1 SD] years). The main cardiovascular risk factors, several indexes of adiposity (including percent body fat as estimated by skinfold measurement, and ultrasound detection of hepatic steatosis and thickness of abdominal subcutaneous and visceral fat) and ischaemic electrocardiographic (ECG) changes were assessed in all subjects. Platelet parameters were determined by a Bayer ADVIA 120 counter. In addition to being associated directly with platelet distribution width (PDW) and inversely with platelet count (p