Efficacy and Safety of Sarilumab in patients with COVID19 Pneumonia: A Randomized, Phase III Clinical Trial (SARTRE Study).

INTRODUCTION: SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). METHODS: We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15. RESULTS: A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48-2.20). No relevant safety issues were identified. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.

Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis.

Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism.

Risk of mortality and predisposing factors after osteoporotic hip fracture: a one-year follow-up study.

BACKGROUND AND AIMS: To determine mortality and predisposing factors in patients with fracture of the proximal femur, one year after the initial fracture, in a tertiary hospital in Castile and Leon (Spain). METHODS: Observational case-control study. Patients aged ≥65 years admitted to the orthopedic surgery department of the Rio Hortega Hospital, a tertiary care hospital with approximately 560 beds, due to non-traumatic hip fracture between September 2005 and November 2006, were included. An age-matched control group of 81 institutionalized patients with similar characteristics was recruited. A protocolized telephone interview and a review of hospital medical records was made at 12 months followup. RESULTS: Of the 170 patients recruited, the final analysis was made in 139: 121 (87.1%) women and 18 (12.9%) men. The control group was formed of 81 patients: 64 (79%) women and 17 (21%) men. Mortality was 41.7% in the study group and 2.5% in controls (p; 0.001). Mortality was 31% in month 1, 24.1% between months 2 and 6 and 29.3% between months 6 and 12 (in 15.6% the date of death was unknown). Factors associated with mortality were: age >86 years (p; 0.024); prior cognitive deterioration (p; 0.011); prior locomotor disorder (p; 0.047); male gender (p; 0.017); heart disease (p; 0.042). CONCLUSIONS: Patients with hip fracture, had substantially higher mortality than comparable healthy people, and mortality was highest in the first six months after fracture. Age and prior comorbidities were associated with excess mortality.

HIV type 1 viral encephalitis after development of viral resistance to plasma suppressive antiretroviral therapy.

HIV-1 viral encephalitis produced by antiretroviral-resistant strains in cerebrospinal fluid (CSF), despite suppression of plasma HIV-1 RNA, has been rarely described. We report two cases of symptomatic viral encephalitis demonstrated by clinical, magnetic resonance imaging (MRI), and an inflammatory CSF profile. Viral load in CSF was 24,000 and 6850 copies/ml, whereas plasma HIV RNA level was undetectable since the beginning of therapy. A resistance test in CSF showed genotypic mutations confering resistance to the drugs the patients received for more than 2 years. In the two cases, a high baseline HIV RNA level, a low nadir CD4(+) count, and suboptimal CSF levels of atazanavir were considered as the risk factors for developing encephalitis. The two cases did not resolve with a change to antiretroviral drugs with better CNS penetration, but they had complete clinical and MRI recovery after changing to therapy considering both CNS viral resistance and penetration.