Hospital-acquired infections (HAIs) are frequent complications among acute patients hospitalized in neurological units, especially among those hospitalized for stroke. This study aimed to investigate ...if enhanced hygienic measures, including the systematic use of personal protective equipment (PPE), determined a decrease in HAI during the recent COVID-19 outbreak in “COVID-free” neurological units.
Patients hospitalized in neurology and stroke units of Policlinico Umberto I Hospital in Rome from March 8, 2020 and discharged prior to May 31, 2020 were included in the study and compared with patients hospitalized during the same period in 2019.
A total of 319 patients were included in the study (n = 103 in 2020, n = 216 in 2019). Among patients hospitalized in 2019, the incidence of HAIs was 31.5% (95% confidence interval (CI): 0.25–0.38), compared with 23.3% (95% CI: 0.15–0.32) in 2020 (p = 0.12). Multivariable logistic regression showed that hospitalization during 2020 was independently associated with a lower risk of HAIs (odds ratio: 0.34, 95% CI:0.16–0.71, p = 0.004). Poisson regression models showed that hospitalization during 2020 was also independently associated with both a lower number of HAIs (relative risk RR: 0.56, 95% CI:0.38–0.81, p = 0.01) and a lower number of prescribed antibiotics per patient (RR: 0.66, 95% CI: 0.49–0.87, p = 0.02).
Our study design provides evidence regarding the impact of stricter hygienic measures, such as increased PPE use, on HAIs. Larger studies are needed to support the extension of preventive measures even after the COVID-19 outbreak in order to limit the occurrence of HAIs.
•During the COVID-19 outbreak, stricter hygienic measures were followed in hospitals.•Our study explores the impact of such measures on Hospital-Acquired Infections (HAI).•A reduced risk of HAI was observed in our units compared with the previous year.•A significant decrease in antibiotic prescription was also observed.•An extension of stricter hygienic measures beyond the pandemic could be beneficial.
CD163, a haptoglobin-hemoglobin scavenger receptor mostly expressed by monocytes and macrophages, is involved in the regulation of inflammatory processes. Following proteolytic cleavage after ...pro-inflammatory stimulation, CD163 is shed from the cell surface and its soluble form in plasma, sCD163, is a biomarker of monocyte/macrophage lineage activation.The assessment of sCD163 plasmatic levels in an early stage of the disease could have clinical utility in predicting the severity of COVID-19 pneumonia. The use of tocilizumab (monoclonal antibody anti-IL-6 receptor) in COVID-19 patients reduces lethality rate at 30 days. The aim of the study was to investigate the effect of tocilizumab on sCD163 plasmatic levels in a cohort of COVID-19 patients.
In COVID-19 patients, on hospital admission (T0), after 7 days from hospitalization (T7) and after 45 days from discharge (T45) sCD163 plasmatic levels were evaluated, along with other laboratory parameters. COVID-19 patients were stratified into tocilizumab (TCZ) and non-tocilizumab (non-TCZ) groups. TCZ group was further divided into responder (R) and non-responder (NR) groups. Patients who died or required mechanical ventilation were defined as NR. As control group, healthy donors (HD) were enrolled.
Seventy COVID-19 patients and 47 HD were enrolled. At T0, sCD163 plasmatic levels were higher in COVID-19 patients compared to HD (p<0.0001) and the longitudinal evaluation showed a reduction in sCD163 plasmatic levels at T7 compared to T0 (p=0.0211). At T0, both TCZ and non-TCZ groups showed higher sCD163 plasmatic levels compared to HD (p<0.0001 and p=0.0147, respectively). At T7, the longitudinal evaluation showed a significant reduction in sCD163 plasmatic levels (p=0.0030) only in the TCZ group, reaching levels comparable to those of HD. Conversely, not statistically significance in non-TCZ group was observed and, at T7, a statistically significance was found comparing non-TCZ group to HD (p=0.0019). At T0, R and NR groups showed not statistically significance in sCD163 plasmatic levels and both groups showed higher levels compared to HD (p=0.0001 and p=0.0340, respectively). The longitudinal evaluation showed significant reductions in both groups (R: p=0.0356; NR: p=0.0273) independently of the outcome. After 45 days of follow-up sCD163 plasmatic levels remain stable.
sCD163 plasmatic levels are increased in COVID-19 pneumonia and is efficiently down-regulated by tocilizumab treatment regardless of the clinical outcome.
Abstract
Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation ...in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment.
Violacein is a natural pigment, a pyrrolidone, and a bisindole derived from the condensation of two tryptophan molecules, which gives a blue violet color to several gram-negative violacein-producing ...bacteria. Violacein production provides a competitive advantage against antagonistic species or predators. In addition, the compound has antibacterial, antifungal, antiviral, and antioxidant activities. Several studies on colon, breast, and head and neck cancer lines have already demonstrated the anti-proliferative potential of violacein. Bladder cancer is one of the most common types of cancer in urology. The therapeutic approach is mainly based on surgery, chemotherapy, and immunotherapy. The aim of the present study was to evaluate the anti-proliferative activity of violacein against the human bladder cancer cell lines, HTB4 (T24) and HTB9 (5637), using low-grade and high-grade transitional cell carcinoma models, respectively, which has never been assayed before. For this purpose, the potential violacein anti-proliferative effect on T24 and 5637 cells was evaluated by studying the cell viability, proliferation, cell cycle, and caspase-3 activation. The results showed that violacein had anti-proliferative activity in the two cell lines, which was greater for the second-stage bladder cancer cell line (5637), and a different mode of action against the two cell lines.
Emerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic ...levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects).
On admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups.
Compared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% CI: 44.1-68.4 specificity 73.8% CI: 58.9-84.7). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492).
The increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.
Cancer patients (CPs), being immunosuppressed due to the treatment received or to the disease itself, are more susceptible to infections and their potential complications, showing therefore an ...increased risk of developing severe COVID-19 compared to the general population.
We evaluated the immune responses to anti-SARS-CoV-2 vaccination in patients with solid tumors one year after the administration of the third dose and the effect of cancer treatment on vaccine immunogenicity was assessed. Healthy donors (HDs) were enrolled. Binding and neutralizing antibody (Ab) titers were evaluated using chemiluminescence immunoassay (CLIA) and Plaque Reduction Neutralization Test (PRNT) respectively. T-cell response was analyzed using multiparametric flow cytometry.
CPs who were administered three vaccine doses showed lower Ab titers than CPs with four doses and HDs. Overall, a lower cell-mediated response was found in CPs, with a predominance of monofunctional T-cells producing TNFα. Lower Ab titers and a weaker T-cell response were observed in CPs without prior SARS-CoV-2 infection when compared to those with a previous infection. While no differences in the humoral response were found comparing immunotherapy and non-immunotherapy patients, a stronger T-cell response in CPs treated with immunotherapy was observed.
Our results emphasize the need of booster doses in cancer patients to achieve a level of protection similar to that observed in healthy donors and underlines the importance of considering the treatment received to reach a proper immune response.
To support physicians in clinical decision process on patients affected by Coronavirus Disease 2019 (COVID-19) in areas with a low vaccination rate, we devised and evaluated the performances of ...several machine learning (ML) classifiers fed with readily available clinical and laboratory data. Our observational retrospective study collected data from a cohort of 779 COVID-19 patients presenting to three hospitals of the Lazio-Abruzzo area (Italy). Based on a different selection of clinical and respiratory (ROX index and PaO2/FiO2 ratio) variables, we devised an AI-driven tool to predict safe discharge from ED, disease severity and mortality during hospitalization. To predict safe discharge our best classifier is an RF integrated with ROX index that reached AUC of 0.96. To predict disease severity the best classifier was an RF integrated with ROX index that reached an AUC of 0.91. For mortality prediction the best classifier was an RF integrated with ROX index, that reached an AUC of 0.91. The results obtained thanks to our algorithms are consistent with the scientific literature an accomplish significant performances to forecast safe discharge from ED and severe clinical course of COVID-19.
The purpose of the study was to assess biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in adolescents and young adults with human ...immunodeficiency virus (HIV) infection on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction.
Twenty-one patients aged 12-39 years with HIV, 21 normal controls of the same age and sex, and 21 patients with idiopathic nonischemic dilated cardiomyopathy (DCM) were studied with 3DSTE. All HIV patients were stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection, and were on highly active antiretroviral therapy with good immunological control. Standard echocardiographic measures of left ventricular (LV)-right ventricular (RV) function were assessed. 3D LV global longitudinal strain (GLS), circumferential strain, radial strain, and LV twist were calculated. Global area strain (GAS) was calculated by 3DSTE as percentage variation in surface area defined by the longitudinal and circumferential strain vectors. 3D RV global and free-wall longitudinal strain (FWLS) were obtained.
LV GLS and GAS were lower in HIV patients compared to normal controls (p = 0.002, and p = 0.01, respectively). There were no significant differences in LV ejection fractions between the groups. There was a weak positive correlation between LV GLS and age (r = 0.215, p = 0.034) and a weak negative correlation between LV GLS and nadir-CD4 T-cells count (r = 0.198, p = 0.043). DCM patients had more marked and widespread reduction in LV GLS and GAS compared to controls (p < 0.001), whereas in HIV patients LV strain impairment (p < 0.05) was more localized in basal and apical regions. RV FWLS was significantly reduced in HIV patients when compared with the control group (p = 0.03). No patient had pulmonary systolic pressure higher than 35 mm Hg.
3DSTE may help to identify HIV patients at high cardiovascular risk allowing early detection of biventricular dysfunction in the presence of normal LV ejection fraction and in the absence of pulmonary hypertension. LV strain impairment in HIV patients is less prominent and widespread compared to DCM patients.
To evaluate the effectiveness of Tocilizumab (with or without corticosteroids) in a real-life context among moderate-to-severe COVID-19 patients hospitalized at the Infectious Diseases ward of two ...hospitals in Lazio region, Italy, during the first wave of SARS-CoV-2 pandemic. We conducted a retrospective cohort study among moderate-to-severe COVID-19 pneumonia to assess the influence of tocilizumab (with or without corticosteroids) on: 1) primary composite outcome: risk for death/invasive mechanical ventilation/ICU-transfer at 14 days from hospital admission; 2) secondary outcome: COVID-related death only. Both outcomes were also assessed at 28 days and restricted to baseline more severe cases. We also evaluated the safety of tocilizumab. Overall, 412 patients were recruited, being affected by mild (6.8%), moderate (66.3%) or severe (26.9%) COVID-19 at baseline. The median participant' age was 63 years, 56.5% were men, the sum of comorbidities was 1.34 (±1.44), and the median time from symptom onset to hospital admission was 7 3-10 days. Patients were subdivided in 4 treatment groups: standard of care (SoC) only (n = 172), SoC plus corticosteroid (n = 65), SoC plus tocilizumab (n = 50), SoC plus tocilizumab and corticosteroid (n = 125). Twenty-six (6.3%) patients underwent intubation, and 37 (9%) COVID-related deaths were recorded. After adjusting for several factors, multivariate analysis showed that tocilizumab (with or without corticosteroids) was associated to improved primary and secondary outcomes at 14 days, and at 28-days only when tocilizumab administered without corticosteroid. Among more severe cases the protective effect of tocilizumab (± corticosteroids) was observed at both time-points. No safety concerns were recorded. Although contrasting results from randomized clinical trials to date, in our experience tocilizumab was a safe and efficacious therapeutic option for patients with moderate-to-severe COVID-19 pneumonia. Its efficacy was improved by the concomitant administration of corticosteroids in patients affected by severe-COVID-19 pneumonia at baseline.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with ...multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19).
PwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty
) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1.
Thirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD.
The evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.