Abstract Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
Abstract Aim To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). Methods Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio Results The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO 2 )/fraction of inspired O 2 (FIO 2 ) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p : 0.019) and PaO 2 /FIO 2 (HR: 0.988; 95%CI 0.988–0.998; p : 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. Conclusions COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO 2 /FIO 2 in ARDS on COVID-19.
BackgroundDespite vaccinations are scientifically proven to be safe and effective public controversies limit their application in many countries. AimsAim of this review is to provide an overview of biological effects of vaccination and a picture of the ethical dilemmas about compulsory vaccination. MethodsWe conducted a review on the literature about the subject.Recent news were also included. ResultsVaccines are the best weapon against many infectious diseases.The spread of false beliefs among people have led the government authorities to increase compulsory vaccination in order to embank new outbreaks of preventable infectious diseases. ConclusionEven if compulsory is quite drastic approach it could be the on only way to reach an adequate coverage and protect immunoexpressed subjects.
Purpose of review describing the current role of carbapenems and carbapenem-sparing strategies in the setting of antimicrobial stewardship programs. Recent findings sparing carbapenems with other drugs appears to be an interesting perspective for a variety of reasons in the current context of the multidrug-resistant (MDR) pandemic. Specific algorithms should also be precisely investigated to define better how to spare carbapenems within empiric and targeted regimens, with combination treatment or monotherapies, aiming at the best use of the new drugs and improving de-escalation as soon as possible for most of the patients. Summary stewardship programs may be useful in reducing probable misuse and overuse of antibiotics, which has probably contributed to the emergence of carbapenem-resistant bacteria worldwide. The proposal of carbapenem-sparing strategies has then generated substantial scientific debate and, overall, the concept of sparing these drugs is well advocated together with judicious use of novel drugs, appropriate measures of infection control and prevention as well as in stewardship programs to curb the spread of MDR and XDR-strains in healthcare facilities.
Abstract: Fungal infections of the liver, most commonly caused by Candida spp., often occur in patients with hematologic malignancies treated with chemotherapy. Colonization of the gastrointestinal tract is thought to be the main origin of dissemination of Candida ; mucositis and neutropenia facilitate the spread of Candida from the gastrointestinal tract to the liver. Hepatic involvement due to other fungi is a less common infectious complication in this setting. Fungal infections represent a less common cause of hepatic abscesses in non-oncohematologic population and the trend appears to be decreasing in recent years. Understanding of the etiology and epidemiology of fungal infections of the liver is indicated for an appropriate antimicrobial therapy and an overall optimal management of fungal liver infections. Keywords : fungal liver infections, antifungal agents, hepatosplenic candidiasis, acute disseminated candidiasis, life-threatening infections
Therapeutic options for patients with HCV-related liver disease have increased over the last two decades. In fact, the old standard of care based on the combination of pegylated interferon and ribavirin did not result in satisfactory eradication rates, particularly in patients with liver cirrhosis. With the advent of direct-acting antivirals (DAAs), higher rates of viral clearance became possible and, patients with contraindications to interferon obtained access to treatment. However, several concerns have been raised regarding first-generation DAAs, namely their high costs, and the emergence of resistant-associated variants with low susceptibility to these drugs.In this review, the authors discuss the data about the efficacy and safety of the main anti-HCV direct-acting antivirals currently in the pipeline. Furthermore, they evaluate the impact of these drugs on the therapeutic options currently available for HCV patients.The results of trials evaluating the effectiveness of new DAAs are encouraging. These new antivirals lead to high rates of viral eradication without relevant adverse reactions and seem to be effective regardless of viral genotypes, presence of resistant-associated variants or advanced liver disease. Consequently, with the advent of this new family of drugs, chronic HCV-related hepatitis may become a curable disease.
Background
Very few cases of Pneumocystis jirovecii pneumonia (PCP) have been reported in COVID-19 so far, mostly in patients with concomitant HIV infection or in solid organ transplant recipients. Despite COVID-19 is associated with lymphopenia and use of steroids, there are no studies specifically aimed to investigate risk factors for PCP in COVID-19
Methods
retrospective case-control study in a cohort of patients with confirmed COVID-19. Direct immunofluorescence assay on respiratory samples was used to diagnose PCP.
Results
We enrolled 54 patients. Patients with PCP had significant lower median lymphocyte values (p=0.033), longer COVID-19 disease duration (p=0.014), higher cumulative dose of steroid received (p=0.026), higher CRP values (p=0.005) and lower SARS-CoV-2 vaccination rate than controls (p=0.029). Cumulative steroid dose (p=0.042) and the highest CRP value during the stay (p=0.012) were identified as risk factor for PCP, while SARS-CoV-2 vaccination with one (p=0.029) and two doses (p=0.049) as a protective factor for PCP, although not independently associated.
Conclusions
PCP develops in COVID-19 patients regardless of immunosuppressive conditions. However, a higher rate of PCP is significantly associated with the cumulative steroidal dose, high CRP values and lack of vaccination.
We describe the case of a 56-year-old man who had high aminotransferase levels and anti-hepatitis C virus (HCV) antibodies. He underwent liver biopsy and biochemical screening to evaluate whether he would benefit from interferon (IFN) treatment. The patient was discharged with a diagnosis of HCV-related active chronic hepatitis, skin porphyria, and type 2 diabetes. On December 5, 1995, he began therapy with recombinant IFN-alpha at a dose of 3 MIU three times a week. He stopped this therapy in February 1996 because of asthenia, diplopia, headache, and anxiety. During IFN therapy, he had normal aminotransferase levels and no detectable HCV RNA, a condition that persists to the present. Between March and May 1996, the patient was admitted several times to a neurology clinic, where myasthenia gravis was diagnosed and treatment with pyridostigmine and cyclosporine was initiated. This case and others indicate that caution should be exercised in administering IFN because low doses can be correlated with myasthenia gravis in patients without malignancies.
