Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

The use of peginterferon in monotherapy or in combination with ribavirin for the treatment of acute hepatitis C.

BACKGROUND: Acute hepatitis C becomes chronic in 50% of cases. Early treatment seems to be effective in eradicating HCV infection, although no clear recommendations are available in terms of time of initiation, regimen and duration of therapy. We report a retrospective review of 48 patients with acute HCV infection between January 2006 and December 2007. PATIENTS AND METHODS: This multicenter retrospective study involved three Infectious Disease Units in Sicily and was carried out in three stages: (1) Collection of patients data; (2) Selection of patients according to: elevated ALT (at least 5 times above normal values), seroconversion from negative to positive anti-HCV status; (3) Final selection of patients with a minimum of 12 months follow-up. RESULTS: Out of 60 patients with a diagnosis of acute HCV infection, 48 were eligible for the study. In 13 subjects (52%) of the 25 who were not treated, the disease resolved spontaneously. 23 patients received pegylated interferon in monotherapy or in combination with ribavirin. 95% achieved a sustained virological response (SVR). Of the 22 sustained responders, 17 (70%) negativized HCV RNA within 8 weeks. No difference appeared between patients receiving monotherapy and those treated with combination therapy. Also, no difference was observed, in terms of SVR, between the two different pegylated interferons given for treatment. CONCLUSIONS: The rate of viral clearance was higher in the treated group versus the untreated one (95% versus 52%). The SVR found in our study population (95%) was comparable to that reported in other studies. The combination with ribavirin did not appear to impact our sustained response rate, although ribavirin appeared to induce a faster normalization of ALT levels.

Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C.

OBJECTIVES: Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients. METHODS: One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI. RESULTS: TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027). CONCLUSIONS: In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.

[Saccharomyces cerevisiae fungemia associated with multifocal pneumonia in a patient with alcohol-related hepatic cirrhosis]. / Fungemia da Saccharomyces cerevisiae con polmonite a focolai multipli in paziente con cirrosi epatica alcool correlata.

Saccharomyces cerevisiae is usually considered non-pathogenic and has rarely been reported as a cause of fungemia in immunocompromised patients, especially those admitted to an intensive care unit or those affected by acquired immune deficiency syndrome or under immunosuppressive treatment. In all described cases the use of probiotic yeast has been given as the main risk factor. We report a case of S. cerevisiae sepsis complicated by pneumonia in a patient affected by alcohol-related cirrhosis with no evidence of probiotic drug intake. In this case recovery was obtained after a treatment course with liposomal amphotericin B. S. cerevisiae should be taken into consideration when sepsis lacks to isolate any aetiological agent.

Clinical survey of Leishmania/HIV co-infection in Catania, Italy: the impact of highly active antiretroviral therapy (HAART).

The clinical and parasitological features of visceral leishmaniasis (VL) were investigated, retrospectively, in 27 HIV-infected patients who attended the out-patient clinic of Catania University's Department of Infectious Diseases between 1990 and 1998. The aim was to evaluate the epidemiological, clinical, therapeutic and prognostic characteristics of the co-infection, to determine if there were any interactions between the two infections, and to see if the use of highly active antiretroviral therapy (HAART) had any impact on the leishmaniasis. The most dramatic observation was a marked, HAART-attributable reduction in the annual incidence of VL relapses among the patients.

Visceral leishmaniasis and HIV co-infection: a rare case of pulmonary and oral localization.

Visceral leishmaniasis (VL) has increased as a complicating infection in subjects with human immunodeficiency virus (HIV) in countries bordering the Mediterranean sea. The clinical course as well as organ involvement of VL are often atypical in HIV positive subjects. In this study a case of VL with pulmonary and oral mucose localisation in a patient with acquired immune deficiency syndrome (AIDS), is reported. These findings, together with the presence of the parasite in the peripheral blood smear, confirm that in HIV positive patients the impaired immune system allows the spreading and the atypical localisation of the Leishmania amastigotes more easily than in immuno-competent individuals. In endemic areas and in HIV positive subjects a systemic and careful parasitological follow-up is necessary to ensure that any clinical form of leishmaniasis is not overlooked.

Serum cytokines as predictors of clinical outcome in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: Clinical variability in the natural course of cryptosporidiosis in patients affected by acquired immunodeficiency syndrome has been correlated to the degree of T-cell immunosuppression; however, cryptosporidiosis can occur as a self-limiting disease even in patients with very low T-lymphocyte count. AIMS: We tested the serum values of a panel of cytokines in AIDS patients with cryptosporidial enteritis in order to evaluate their role in predicting the clinical outcome of the disease. PATIENTS AND METHODS: Thirty one HIV-positive patients with cryptosporidiosis and a CD4+ count of less than 100/mm3 were studied. Interleukin-2, Interleukin-4, Interleukin-10, Interferon-gamma, Interleukin-12, Tumor Necrosis Factor alpha values were measured in serum at diagnosis. RESULTS: Interleukin-4 and Interleukin-10 concentration was significantly lower in patients with mild disease whereas serum Interleukin-2 and -12 was higher in this same group. The serum level of Interferon-gamma did not differ in relation to the severity of the disease. Patients with self-limiting diarrhoea showed significantly lower levels of Tumor Necrosis Factor-alpha than subjects who did not show any clinical improvement. CONCLUSIONS: In our study, it has been shown that cytokine levels in serum may represent early predictive markers both for the severity of symptoms and the clinical outcome of cryptosporidial enteritis in AIDS patients with a low CD4+ count.

Visceral leishmaniasis in HIV infected patients: treatment with high dose liposomal amphotericin B (AmBisome).

Visceral leishmaniasis (VL) in patients coinfected with human immunodeficiency virus (HIV) is often atypical, and characteristically relapses after treatment. We treated 10 HIV infected patients (9 men) with parasitologically confirmed VL with liposomal amphotericin B ("AmBisome': L-AMB) at a dose of 4 mg/kg/day on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38. Patients were hospitalized for the first 5 days, and were monitored during, and 1 week and 1, 3 and 6 months after, L-AMB therapy. There were no serious adverse events, and L-AMB was well tolerated. 9/10 patients completed therapy, one patient defaulted at day 24. Clinical improvement was seen in all nine patients and the bone marrow aspirate was cleared of visible/culturable parasites in 8/9 patients. During follow-up, one patient defaulted. The seven remaining patients relapsed at 2, 3, 3, 5, 5, 6 and 7 months. Re-treatment with a variety of antileishmanial drugs was unsatisfactory. The time from first diagnosis of VL to death in six patients was 5-40 months (mean 18.8 months). Only one patient remained alive 26 months after treatment. L-AMB is safe and provides a good initial clinical response. Intermittent dosing enables a short period of hospitalization. However, relapse is probably inevitable.