Factors Enhancing Treatment of Hepatitis C Virus-Infected Italian People Who Use Drugs: The CLEO-GRECAS Experience.

INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.

Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study.

BACKGROUND: An unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals. METHODS: According to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up. RESULTS: Nine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p < 0.0001, OR: 5.686, 95% CI 2.455-13.169). CONCLUSIONS: Our data suggest that early HCC occurrence appears more frequently related to Sofosbuvir-based therapy without Ribavirin which, indeed, seems to play a protective role on HCC onset. Therefore, a careful follow-up should be mandatory, especially in those regimens including Sofosbuvir without Ribavirin.

Rate of non-response to ursodeoxycholic acid in a large real-world cohort of primary biliary cholangitis patients in Italy.

Background and aim: Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking.Methods: Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided.Results: Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts.Conclusions: A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers.

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis.

PURPOSE: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. METHODS: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12). RESULTS: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5 g/dL (OR 2.04: 95% CI 1.0-4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3-9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2 mg/dL (OR 4.9: 95% CI 1.17-20.71, p = 0.029) as the only variable independently associated with SVR12. CONCLUSION: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

Efficacy and safety of sofosbuvir/simeprevir plus flat dose ribavirin in genotype 1 elderly cirrhotic patients: A real-life study.

BACKGROUND & AIMS: The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir (SOF) and simeprevir (SMV) plus a flat dose of 800 mg/d ribavirin (RBV) in elderly patients with cirrhosis compared to younger patients. METHODS: Retrospective observational multicentre real-life investigation study of SOF/SMV/RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis. RESULTS: Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks (SVR12) was achieved by 94.2% (129/137) of those aged <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event (AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004). CONCLUSIONS: Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis.

Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma.

UNLABELLED: BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. RESULTS: HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). CONCLUSIONS: Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.

Awake Craniotomy in Conscious Sedation: The Role of A2 Agonists.

BACKGROUND: In Awake Craniotomy (AC), α2-agonists and remifentanil (clonidine and dexmedetomidine) are used in the preoperative phase and throughout the procedure to combine monitored anesthesia care and local anesthesia. The study aims were to specify the key role of α2-agonists administered and to evaluate complication presence/absence in anesthesiologic management. METHODS: 42 patients undergoing AC in 3 different centers in the south of Italy (Foggia, San Giovanni Rotondo, and Bari) were recruited. Our protocol involves analgo-sedation by administering Dexmedetomidine and Remifentanil in continuous intravenous infusion, allowing the patient to be sedated and in comfort but contactable and spontaneously breathing. During pre-surgery, the patient is premedicated with intramuscular clonidine (2 µg/kg). In the operating setting, Dexmedetomidine in infusion and Remifentanil in Target Controlled Infusion for effect are started. At the end of the surgical procedure, the infusion of drugs was suspended. RESULTS: There were no intraoperative side effects. The mean duration of interventions was 240 ± 62 min. The average quantity of Remifentanil and Dexmedetomidine infused during interventions were 4.2 ± 1.3 mg and 1.0 ± 0.3 mg, respectively. No significant side effects were described in the post-operative phase. A total of 86% of patients and 93% of surgeons were totally satisfied. CONCLUSIONS: Synergy between opioid drugs and α2 agonists plays a fundamental role in ensuring procedure success.

Depression and Anxiety in Pediatric Patients with Beckwith-Wiedemann Syndrome: A Pilot Study.

The study's aim was to determine the prevalence of depression and anxiety in children with Beckwith-Wiedemann syndrome (BWS) and their effects on social relationships and family acceptance. The Pediatric Symptom Checklist-35 items (PSC-35), Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Vineland Adaptive Behavior Scale Second Edition (VABS-II) were administered to the children. The parental Acceptance Rejection/Control Questionnaire (PARQ/Control) and Zarit Burden Inventory (ZBI) were administered to parents. In total, 6 patients and 10 parents were included. Patients showed a significant presence of internalizing behavior in PSC-35 (mean, 7.66 ± 3.67), anxiety symptoms (SCARED: mean, 46.33 ± 17.50) and socialization difficulties (mean, 90.83 ± 10.09). Parents reported a perceived good acceptance (mean, 56.33 ± 1.03) and a moderate control (mean, 24.17 ± 1.83), but the burden level was ranked moderate to severe (mean, 59.33 ± 16.78). It was found that the severity of the burden level reported by parents was related to internalizing behavior (OR = 2.000; 95% CI = 0.479-3.521; p = 0.022) and anxiety symptoms (SCARED total score: OR = 3.000; 95% CI = 1.479-4.521; p = 0.005) of children. During psychological counseling in the context of BWS treatment, it is important to identify specific resources that can support patients and families in dealing with stress and identify any critical areas that could hinder the adaptation process.

Perioperative Management of a Pediatric Patient with Beckwith-Wiedemann Syndrome Undergoing a Partial Glossectomy According to Egyedi/Obwegeser.

Here, we report the perioperative management of a clinical case of a 6 year, 5 month old girl suffering from Beckwith-Wiedemann syndrome undergoing a partial glossectomy procedure in a patient with surgical indication for obstructive sleep apnea syndrome (OSAS), difficulty swallowing, feeding, and speech. On surgery day, Clonidine (4 µg/kg) was administered. Following this, a general anesthesia induction was performed by administering Sevoflurane, Fentanyl, continuous intravenous Remifentanil, and lidocaine to the vocal cords, and a rhinotracheal intubation with a size 4.5 tube was carried out. Before starting the procedure, a block of the Lingual Nerve was performed with Levobupivacaine. Analgosedation was maintained with 3% Sevoflurane in air and oxygen (FiO2 of 40%) and Remifentanil in continuous intravenous infusion at a rate of 0.08-0.15 µg/kg/min. The surgical procedure lasted 2 h and 32 min. At the end of the surgery, the patient was under close observation during the first 72 h. In the pediatric patient with Beckwith-Wiedemann syndrome submitted to major maxillofacial surgery, the difficulty in managing the airways in the preoperative phase during intubation and in the post-operative phase during extubation should be considered.

Anesthetic Management for Awake Craniotomy Applied to Neurosurgery.

Our anesthetic technique proposed for awake craniotomy is the monitored anesthesia care (MAC) technique, with the patient in sedation throughout the intervention. Our protocol involves analgo-sedation through the administration of dexmedetomidine and remifentanil in a continuous intravenous infusion, allowing the patient to be sedated and in comfort, but contactable and spontaneously breathing. Pre-surgery, the patient is pre-medicated with intramuscular clonidine (2 µg/kg); it acts both as an anxiolytic and as an adjuvant in pain management and improves hemodynamic stability. In the operating setting, dexmedetomidine in infusion and remifentanil in target controlled infusion (TCI) for effect are started. The purpose of the association is to exploit the pharmacodynamics of dexmedetomidine which guarantees the control of respiratory drive, and the pharmacokinetics of remifentanil characterized by insensitivity to the drug. Post-operative management: at the end of the surgical procedure, the infusion of drugs was suspended. Wake-up craniotomy is associated with reduced hospital costs compared to craniotomy performed in general anesthesia, mainly due to reduced costs in the operating room and shorter hospital stays. Greater patient satisfaction and the benefits of avoiding hospital stay have led to the evolution of outpatient intracranial neurosurgery.

Real-Time Neuropsychological Testing (RTNT) and Music Listening during Glioblastoma Excision in Awake Surgery: A Case Report.

In this case report, real-time neuropsychological testing (RTNT) and music listening were applied for resections in the left temporal-parietal lobe during awake surgery (AS). The case is based on a 66-year-old with glioblastoma and alterations in expressive language and memory deficit. Neuropsychological assessment was run at baseline (2-3 days before surgery), discharge from hospital (2-3 days after surgery), and follow-up (1 month and 3 months). RTNT was started before beginning the anesthetic approach (T0) and during tumor excision (T1 and T2). At T0, T1, and T2 (before performing neuropsychological tests), music listening was applied. Before AS and after music listening, the patient reported a decrease in depression and anxiety. During AS, an improvement was shown in all cognitive parameters collected at T0, T1, and T2. After the excision and music listening, the patient reported a further decrease in depression and anxiety. Three days post surgery, and at follow-ups of one month and three months, the patient reported a further improvement in cognitive aspects, the absence of depression, and a reduction in anxiety symptoms. In conclusion, RTNT has been useful in detecting cognitive function levels during tumor excision. Music listening during AS decreased the patient's anxiety and depression symptoms.

Epidemiology of HCV and HBV in a High Endemic Area of Southern Italy: Opportunities from the COVID-19 Pandemic-Standardized National Screening or One Tailored to Local Epidemiology?

The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930-1939 and a second peak (5.6%) for those born in 1960-1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology.

Efficacy and safety of the sofosbuvir/velpatasvir combination for the treatment of patients with early mild to moderate COVID-19.

SARS-CoV-2 is still a health problem worldwide despite the availability of vaccines. Therefore, there is a need for effective and safe antiviral. SARS-CoV-2 and HCV necessitate RNA-dependent RNA polymerase (RdRp) for replication; therefore, it has been hypothesized that RdRp inhibitors used to treat HCV may be effective treating SARS-CoV-2. Accordingly, we evaluated the effect of the sofosbuvir/velpatasvir (SOF/VEL) combination in early SARS-CoV-2 infection. A multicenter case-control study was conducted, enrolling 120 patients with mild or moderate COVID-19, of whom 30, HCV coinfected or not, received SOF/VEL tablets (400/100 mg) once daily for 9 days within a median of 6 days from the beginning of infection and 90 controls were treated with standard care. The primary endpoint was the effect on viral clearance, and the secondary endpoint was the improvement of clinical outcomes. Nasal swabs for SARS-CoV-2 by PCR were performed every 5-7 days. Between 5-14 days after starting SOF/VEL treatment, SAS-CoV-2 clearance was observed in 83% of patients, while spontaneous clearance in the control was 13% (p < 0.001). An earlier SARS-CoV-2 clearance was observed in the SOF/VEL group than in the control group (median 14 vs 22 days, respectively, p < 0.001) also when the first positivity was considered. None of the patients in the SOF/VEL group showed disease progression, while in the control group, 24% required more intensive treatment (high flow oxygen or noninvasive/invasive ventilation), and one patient died (p < 0.01). No significant side effects were observed in the SOF/VEL group. Early SOF/VEL treatment in mild/moderate COVID-19 seems to be safe and effective for faster elimination of SARS-CoV-2 and to prevent disease progression.

Fever management in critically ill COVID-19 patients: a retrospective analysis.

BACKGROUND: Fever has been reported as a common symptom in COVID-19 patients. The aim of the study was to describe the characteristics of COVID-19 critically ill patients with fever and to assess if fever management had an impact on some physiologic variables. METHODS: This is a retrospective monocentric cohort analysis of critically ill COVID-19 patients admitted to the Department of Intensive Care Unit (ICU) of Erasme Hospital, Brussels, Belgium, between March 2020 and May 2020. Fever was defined as body temperature ≥38 °C during the ICU stay. We assessed the independent predictors of fever during ICU stay. We reported the clinical and physiological variables before and after the first treated episode of fever during the ICU stay. RESULTS: A total of 72 critically ill COVID-19 patients were admitted to the ICU over the study period and were all eligible for the final analysis; 53 (74%) of them developed fever, after a median of 4 [0-13] hours since ICU admission. In the multivariable analysis, male gender (OR 5.41 [C.I. 95% 1.34-21.92]; P=0.02) and low PaO2/FiO2 ratio (OR 0.99 [C.I. 95% 0.99-1.00]; P=0.04) were independently associated with fever. After the treatment of the first febrile episode, heart rate and respiratory rate significantly decreased together with an increase in PaO2 and SaO2. CONCLUSIONS: In our study, male gender and severe impairment of oxygenation were independently associated with fever in critically ill COVID-19 patients. Fever treatment reduced heart rate and respiratory rate and improved systemic oxygenation.

The Acquisition of Multidrug-Resistant Bacteria in Patients Admitted to COVID-19 Intensive Care Units: A Monocentric Retrospective Case Control Study.

Whether the risk of multidrug-resistant bacteria (MDRB) acquisition in the intensive care unit (ICU) is modified by the COVID-19 crisis is unknown. In this single center case control study, we measured the rate of MDRB acquisition in patients admitted in COVID-19 ICU and compared it with patients admitted in the same ICU for subarachnoid hemorrhage (controls) matched 1:1 on length of ICU stay and mechanical ventilation. All patients were systematically and repeatedly screened for MDRB carriage. We compared the rate of MDRB acquisition in COVID-19 patients and in control using a competing risk analysis. Of note, although we tried to match COVID-19 patients with septic shock patients, we were unable due to the longer stay of COVID-19 patients. Among 72 patients admitted to the COVID-19 ICUs, 33% acquired 31 MDRB during ICU stay. The incidence density of MDRB acquisition was 30/1000 patient days. Antimicrobial therapy and exposure time were associated with higher rate of MDRB acquisition. Among the 72 SAH patients, 21% acquired MDRB, with an incidence density was 18/1000 patient days. The septic patients had more comorbidities and a greater number of previous hospitalizations than the COVID-19 patients. The incidence density of MDRB acquisition was 30/1000 patient days. The association between COVID-19 and MDRB acquisition (compared to control) risk did not reach statistical significance in the multivariable competing risk analysis (sHR 1.71 (CI 95% 0.93-3.21)). Thus, we conclude that, despite strong physical isolation, acquisition rate of MDRB in ICU patients was at least similar during the COVID-19 first wave compared to previous period.

Eosinopenia in COVID-19 Patients: A Retrospective Analysis.

Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm3. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic-ROC curve, 0.84 (95% CIs 0.78-0.90) and 0.84 (95% CIs 0.77-0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.

Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome. METHODS: We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present. RESULTS: Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 [349-2116] vs. 336 [195-646] pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 [95% CI 0.57-0.89]; p = 0.01). CONCLUSIONS: Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.

The Prognostic Role of Lactate Concentrations after Aneurysmal Subarachnoid Hemorrhage.

Blood lactate concentrations are often used to assess global tissue perfusion in critically ill patients; however, there are scarce data on lactate concentrations after subarachnoid hemorrhage (SAH). We aimed to assess the prognostic role of serial blood lactate measurements on hospital mortality and neurological outcomes at 3 months after SAH. We reviewed all SAH patients admitted to the intensive care unit from 2007 to 2019 and recorded the highest daily arterial lactate concentration for the first 6 days. Patients with no lactate concentration were excluded. Hyperlactatemia was defined as a blood lactate concentration >2.0 mmol/L. A total of 456 patients were included: 158 (35%) patients died in hospital and 209 (46%) had an unfavorable outcome (UO) at 3 months. The median highest lactate concentration was 2.7 (1.8-3.9) mmol/L. Non-survivors and patients with UO had significantly higher lactate concentrations compared to other patients. Hyperlactatemia increased the chance of dying (OR 4.19 (95% CI 2.38-7.39)) and of having UO in 3 months (OR 4.16 (95% CI 2.52-6.88)) after adjusting for confounding factors. Therefore, initial blood lactate concentrations have prognostic implications in patients with SAH; their role in conjunction with other prognostic indicators should be evaluated in prospective studies.

Sustained virological response in patients with HCV treated with daclatasvir plus sofosbuvir, with or without ribavirin: a large, field-practice study.

BACKGROUND: The once-daily oral combination of daclatasvir (DCV) and sofosbuvir (SOF), with or without ribavirin (RBV), is effective and well tolerated in patients with hepatitis C virus (HCV). However, further field-practice studies are necessary to investigate the effectiveness and safety of the DCV+SOF combination in diverse subpopulations of patients with HCV, including those who are more challenging to treat such as patients with a genotype 3 (G3) infection. The aim of this retrospective, multicenter, field-practice study was to investigate the therapeutic efficacy and safety of the oral combination of DCV and SOF, with or without RBV (DCV+SOF±RBV), in a large unselected cohort of patients with chronic HCV infection (CHC). PATIENTS AND METHODS: Consecutive patients received DCV+SOF±RBV for 12 or 24 weeks. The efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12). Safety factors were also considered. RESULTS: A total of 620 patients were included in this study; the predominant genotype was G3 (55.3%). Of the total sample, 248 (40%) patients were treated with DCV+SOF+RBV and 372 (60%) did not receive RBV. The majority of patients assessed at week 12 (98%, 596/608) achieved SVR12. Among G3 patients, 98.8% (335/339) achieved SVR12. The most common adverse event was elevated bilirubin (30.6%), recorded in 4.9% of cases as a grade 3-4 adverse event. CONCLUSION: This study shows the high pan-genotypic effectiveness and safety of the DCV+SOF±RBV combination in a large, unselected sample of CHC patients with G1-4, including a wide proportion of G3 CHC patients.