Evaluating the effect of COVID-19 incidence on Emergency Departments admissions. Results from a retrospective study in Central Italy during the first year of pandemic.

Introduction: The COVID-19 pandemic has had a major impact on the Healthcare System, changing the patterns of Emergency Department access. In fact, accesses for trauma and less severe cases decreased significantly. This decline has generally been attributed to both the effects of the lockdown, imposed by the government, and the fear of being infected by SARS-CoV-2 in the hospital. However, the correlation between these elements is not yet clear, since the accesses to the Emergency Department did not increase either at the end of the lockdown or in the summer when the epidemiological situation was more favorable. Aim: To evaluate the association between trends of Emergency Department accesses and COVID-19 incidence in 2020. Methods: Data on Emergency Department accesses, by month and severity triage code, from 14 hospitals in southeastern Tuscany (Italy) were obtained from hospitals' data warehouse. Official data on new cases of COVID-19 infection were used to calculate incidence. Hospitals were classified into 4 categories. Differences in Emergency Department access by month, triage code, and hospital type were investigated using Kruskal-Wallis analysis. Association between Emergency Department accesses and COVID-19 incidence was evaluated using a random-effect panel data analysis, adjusting for hospital type and triage code. Results: The trend of 268,072 Emergency Department accesses decreases substantially at the first pandemic peak; thereafter, it increased and decreased again until the minimum peak in November 2020. COVID-19 incidence appeared to be overlapping with an inverse direction. Monthly differences were significant (p<0.01) except for most severe codes. There was a significant inverse association between Emergency Department accesses and COVID-19 incidence (Coef. =-0.074, p<0.001) except for most severe cases (triage code 1: Coef. =-0.028, p=0.154). Conclusion: Emergency Department admissions trend followed the COVID-19 incidence, except for the most severe cases. Fear of infection seems to discourage patients from accessing Emergency Department for illnesses perceived as not serious.

Detection of Borrelia and Babesia species in Haemaphysalis punctata ticks sampled in Southern England.

The distribution and population size of the red sheep tick (Haemaphysalis punctata) are increasing in Northern Europe, and in the United Kingdom reports of human biting by this species have increased in recent years. To assess the risk of tick-borne disease (TBD) transmission to humans and livestock by H. punctata, ticks sampled from sites in Southern England were screened using PCR for either Borrelia species or piroplasms over a three year period, 2018-2020. A total of 302 H. punctata were collected from eight locations. From these, two Babesia species associated with TBD infections in livestock, Babesia major and Babesia motasi, and the human pathogen Borrelia miyamotoi were detected, predominantly from a single location in Sussex. Consequently, the range expansion of this tick across Southern England may impact public and livestock health.

A dose-dependent tug of war involving the NPM1 leukaemic mutant, nucleophosmin, and ARF.

In acute myeloid leukaemia (AML), nucleophosmin-1 (NPM1) mutations create a nuclear export signal (NES) motif and disrupt tryptophans at NPM1 C-terminus, leading to nucleophosmin accumulation in leukaemic cell cytoplasm. We investigated how nucleophosmin NES motifs (two physiological and one created by the mutation) regulate traffic and interaction of mutated NPM1, NPM1wt and p14(ARF). Nucleophosmin export into cytoplasm was maximum when the protein contained all three NES motifs, as naturally occurs in NPM1-mutated AML. The two physiological NES motifs mediated NPM1 homo/heterodimerization, influencing subcellular distribution of NPM1wt, mutated NPM1 and p14(ARF) in a 'dose-dependent tug of war' fashion. In transfected cells, excess doses of mutant NPM1 relocated completely NPM1wt (and p14(ARF)) from the nucleoli to the cytoplasm. This distribution pattern was also observed in a proportion of NPM1-mutated AML patients. In transfected cells, excess of NPM1wt (and p14(ARF)) relocated NPM1 mutant from the cytoplasm to the nucleoli. Notably, this distribution pattern was not observed in AML patients where the mutant was consistently cytoplasmic restricted. These findings reinforce the concept that NPM1 mutants are naturally selected for most efficient cytoplasmic export, pointing to this event as critical for leukaemogenesis. Moreover, they provide a rationale basis for designing small molecules acting at the interface between mutated NPM1 and other interacting proteins.

Comorbidity and colorectal cancer according to subsite and stage: a population-based study.

In developed countries the growing proportion of elderly colorectal cancer patients with comorbidity will probably complicate clinical management. The aim of this study was to investigate the prevalence of prognostically relevant comorbidity in unselected colorectal cancer patients diagnosed in the Eindhoven Cancer Registry, according to age, gender and subsite and the association with stage of disease, treatment and short-term survival. Comorbid conditions were recorded, according to Charlson's index. The most common concomitant illnesses were cardiovascular diseases, previous cancers and hypertension. The prevalence of comorbidity, especially of cardiovascular disease, previous cancer and diabetes, was highest in the ascending colon. It was slightly higher in patients with Dukes' stage A, probably due to early detection because of regular monitoring for the comorbid condition. Comorbidity was not associated with the resection rate, but was negatively associated with short-term survival. Elder male colorectal cancer patients particularly suffer from substantial comorbidity, influencing the prognosis.

Prediction of mortality for congestive heart failure patients: results from different wards of an Italian teaching hospital.

Congestive heart failure (CHF) constitutes an important public health problem in Italy, evidenced by the high number of hospital admissions each year. Significant inter-hospital as well as interward differences in mortality rates for CHF patients that have been described may, in part, be explained by the differences in the severity of the illness of admitted patients. The goal of this study was to predict 30-day severity-adjusted mortality risk in patients with CHF admitted to wards of a teaching hospital in Siena, Italy, in 1997. A 30-day mortality was determined by linking hospital discharge files with the Tuscany Mortality Registry database. The 3M all patient refined diagnosis related group (APR-DRG) software was used as a risk assessment method. The relationships between death and the following variables were studied by univariate analyses: APR-severity risk, APR-mortality risk, age, sex, length of stay and, discharge ward. Multivariate analysis was also performed to verify the associations between death and those parameters found to be significant by univariate analysis. Unadjusted mortality proportions ranged from 4.3 to 44.0%. Logistic regression analysis demonstrated that APR-mortality risk, length of stay, and discharge ward were significantly and independently associated with 30-day mortality risk in patients with CHF. In summary, 30-day mortality risk varied significantly according to the ward of discharge in an Italian teaching hospital, even after adjustment for severity of illness.

Does tauroursodeoxycholic acid (TUDCA) treatment increase hepatocyte proliferation in patients with chronic liver disease?

Despite numerous studies on the effects of bile salts therapy in chronic liver disease, there are no reports on the influence such therapy has on hepatocyte proliferation. The aim of this preliminary study was to evaluate the effect of TUDCA on hepatocyte proliferation in 5 patients with HCV-correlated chronic liver disease. All patients were treated with TUDCA (10-13 mg/day) for three months and the determination of PCNA (Proliferating Cell Nuclear Antigen) expression was used to assess the proliferative activity of hepatocytes at the beginning and at the end of treatment. TUDCA reduced both ALT and Knodell's score in the 5 patients in whom a significant increase of PCNA-LI (p < 0.05) was observed after treatment. TUDCA administration seems to stimulate hepatocyte proliferation in man.