Objectives To describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality. Methods This retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020. Results Overall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An ‘atypical’ presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04–1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07–6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004–1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality. Conclusions COVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.

Background The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. Methods We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. Results Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21–2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). Conclusion Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.

c-erbB-2 and ras expression was measured on tumor extracts from 132 human primary breast carcinomas, by immunoblotting analysis. Expression of the c-erbB-2-encoded p185 protein was observed in 39% of the samples and found to correlate with c-erbB-2 gene amplification, detected by Southern analysis in 19 of the 77 available tumor DNAs. p185 expression was linked to the absence of progesterone receptors, but it was not related to lymph-node status or to other clinico-pathological parameters. Levels of the ras-encoded p21 proteins higher than in normal breast tissues were found in 71% of the samples. No significant correlation was seen between p21 level and the available clinical parameters. Conversely, there was a strong positive correlation between p21 and p185 levels. Analysis of follow-up data revealed that p185 expression was associated with a shorter time to relapse and death. Most notably, the contemporaneous expression of p185 and of high p21 levels was more effective than p185 expression alone in identifying cases with poor prognosis. The prognostic value of p185/p21 co-expression was particularly significant in progesterone-receptor-positive tumors. Our data suggest that c-erbB-2 and ras may act synergistically to endow breast-tumor cells with a highly aggressive phenotype.

In Italy, from January 2021, the Ministry of Health indicated a vaccination plan against COVID for frail patients and physicians based on a three-dose scheme. However, conflicting results have been reported on which biomarkers permit immunization assessment. We used several laboratory approaches (i.e., antibodies serum levels, flow cytometry analysis, and cytokines release by stimulated cells) to investigate the immune response in a cohort of 53 family pediatricians (FPs) at different times after the vaccine. We observed that the BNT162b2-mRNA vaccine induced a significant increase of specific antibodies after the third (booster) dose; however, the antibody titer was not predictive of the risk of developing the infection in the six months following the booster dose. The antigen stimulation of PBMC cells from subjects vaccinated with the third booster jab induced the increase of the activated T cells (i.e., CD4+ CD154+); the frequency of CD4+ CD154+ TNF-α+ cells, as well as the TNF-α secretion, was not modified, while we observed a trend of increase of IFN-γ secretion. Interestingly, the level of CD8+ IFN-γ+ (independently from antibody titer) was significantly increased after the third dose and predicts the risk of developing the infection in the six months following the booster jab. Such results may impact also other virus vaccinations.

SummaryThe frequencies of 13 different Ha-ras proto-oncogene alleles have been estimated in 92 breast cancer patients and 60 unaffected individuals. The Ha-ras alleles can be identified using a DNA restriction fragment length polymorphism (RFLP) closely linked to the 3' end of the gene, and are characterized by a different length due to a region of sequences repeated a variable number of times (variable tandem repeats, VTR).The statistica] analysis of the data obtained shows that the frequency of alleles ranging between specific length limits is significantly higher in breast cancer patients than in controls. The same applies to specific genotypes bearing the aforementioned alleles. This suggests that the inheritance of these alleles may be associated with an increased risk of developing breast cancer.