Clinical relevance of clonal hematopoiesis in persons aged ≥80 years.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.

Mortality during the SARS-CoV-2 Pandemic: A Comparative Analysis between Lombardy in Italy and Israel.

Background: This retrospective study contrasts the impact of the SARS-CoV-2 pandemic in Lombardy (Italy) and Israel, focusing on mortality, healthcare response, public health measures, and demographics. Methods: We analyzed SARS-CoV-2 data from Lombardy and Israel covering four viral waves. Data included infection rates, hospitalizations, and mortality. In Lombardy, healthcare data were collected from the administrative database of the Lombardy Welfare Directorate; in Israel, they were collected from Clalit Health Services and the Israeli Ministry of Health's COVID-19 database. Statistical analyses compared trends in infection rates, demographics, and mortality rates across the four viral waves by using logistic and linear regression models and adjusting for age, sex, and comorbidities. Results: Lombardy exhibited significantly higher SARS-CoV-2 infections and COVID-19 hospitalization rates during the first wave than Israel, with 71,558 cases over a population sample of ~10 million versus 5741 over a population sample of ~4.7 million in Israel. The majority of cases in Israel were managed at home, with 18 cases only (0.3%) requiring intensive care unit (ICU) hospitalization during the first wave, compared to 4104 (5.7%) cases in Lombardy. Israel's vaccination campaign began earlier, so that by the fourth wave, 439,545 (42.2%) people in Israel were fully vaccinated with three doses, compared to 214,542 (22.9%) in Lombardy. Mortality decreased over time in both sites, dropping from 103 cases (1.8%) to 1550 (0.1%) in Israel and from 13,372 (18.7%) to 4388 (0.3%) in Lombardy. Conclusions: Early public health interventions and vaccination were crucial in managing the SARS-CoV-2 impact.