Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Increased CD38 expression on T lymphocytes as a marker of HIV dissemination into the central nervous system.

Cross-sectional analysis on 20 HIV-1 patients with neurological symptoms admitted to two infectious disease units. Cut-off of HIV-RNA (VL) was 20 copies/ml for plasma and cerebral spinal fluid (CSF). Flow cytometry was used to analyze the phenotype of circulating and CSF T lymphocytes. CD38 mean fluorescence intensity (MFI) was higher on circulating CD4+T lymphocytes from patients with VL>20 copies/ml in plasma (P=0.001) or CSF (P=0.001). The frequency of circulating CD8+CD38+T cells and CD38 MFI on these cells were higher in patients with VL>20 copies/ml than in those with undetectable plasma VL (P=0.030 and P=0.023). The frequency of CSF CD4+CD38+T, as well as their CD38 and CD95 MFI, were increased in patients with detectable than non-detectable plasma VL (P=0.01, P=0.03, and P=0.05). The % CD38+CD8+T in CSF correlated with time of virological suppression (ρ=-0.462, P=0.040) and the CNS penetration-effectiveness (CPE) score (ρ=-0.467, P=0.038). In conclusion, (a) the expression of CD38+ on both CD4+, CD8+T lymphocytes from peripheral blood and CSF discriminated between viremic and non-viremic patients and (b) T cell activation/apoptosis markers inversely correlated with CPE to remark the importance for therapy to restore immunological functions.

Breast implant infections after surgical reconstruction in patients with breast cancer: assessment of risk factors and pathogens over extended post-operative observation.

BACKGROUND: Infection is a severe potential complication of breast implant positioning in women with cancer. There still is some degree of uncertainty regarding optimal antibiotic prophylaxis regimens, infecting pathogens, and risk factors associated with infection during long-term followup of these patients. METHODS: We performed a systematic clinical review to assess infecting microorganisms and risk factors among patients undergoing reconstructive procedures for breast cancer between January 2005 and February 2007. A randomly selected group of infection-free patients treated over the same time span was considered as a control. RESULTS: Among 240 women undergoing implant procedures performed and followed up as outpatients, 16 patients with prosthetic infections were observed (infection rate 6.7%). Infection was recorded within six months from surgery in 94% of the cases, with an overall mean time to infection of 95 days. The time interval between surgery and infection did not support a diagnosis of hospital-acquired infection in most cases. Gram-negative microorganisms were identified in seven cases. A higher proportion of patients with implant infection underwent radiotherapy or chemotherapy after surgery for advanced tumors compared with the control patients without infection. CONCLUSIONS: Extended post-operative surveillance is indicated, at least for the first six months after breast implant placement, particularly for women who need radiotherapy or chemotherapy after implant surgery. Gram-negative bacilli may be involved more often in late infections than otherwise expected. This finding may influence initial empiric antibiotic treatment.

Simplification to monotherapy with lopinavir/ritonavir in adolescents with vertically acquired HIV-1 infection.

In recent years, the use of boosted protease inhibitors monotherapy has become increasingly important, especially considering the advantages in terms of costs, tolerability, and simplification. Despite that, knowledge about the efficacy and safety of this approach in HIV-1-infected adolescents who have acquired HIV-1 infection through perinatal transmission is still limited. We report here our experience with two adolescents who have been successfully treated with lopinavir/ritonavir monotherapy.

Measles outbreak in adults in Italy.

Several outbreaks of measles have been reported since 2007 both in Italy and elsewhere in Europe. The objective of this study was to analyze the characteristics of the cases of measles that were hospitalized at San Martino Hospital from January 2008 to April 2009. All suspected cases of measles from January 2008 to April 2009 were analyzed. Laboratory confirmation was attained by determination of measles-specific IgM antibodies with enzyme immunoassay and/or detection of the measles virus genome in throat swab or urine by nested polymerase chain reaction (PCR). In all, 114 patients with clinically suspected measles were observed and laboratory confirmation was obtained in 83 cases: 34 (34/83; 41%) by specific genome PCR; five (5/83; 6%) only by IgM antibodies and 44 (44/83; 53%) by both methods. The median age was 25 years (range 15-66). The vaccination status was known for 80/83 patients, amongst whom the proportion of unvaccinated was 90% (72/80). No severe complications were observed. The most common complications were nausea/vomiting in 28/83 (34%) and radiologically documented interstitial pneumonia in 22/83 (26%) cases. The median length of hospitalization was five days (range 1-9 days). Almost 90% of patients were aged 20 years and older and hence measles cannot be regarded solely as a childhood disease. Thus widespread high vaccination coverage would be required to prevent new outbreaks and hospitalizations in the adult population.