[Life at the Policlinico of Milan during the Spanish flu. A story of recurring cycles]. / Vita al Policlinico di Milano durante l'influenza Spagnola. Una storia di corsi e ricorsi.

In this period of Covid19 pandemic, for historians to create parallels with previous experiences in similar contexts becomes almost instantaneous. The Spanish Flu, which our grandparents still remember, was a disease that in the course of history killed millions of people: it is thought that at least 25-30 million people died from it, in Italy estimates show about 600,000 deaths for Spanish flu. The city of Milan, in particular the Policlinico Ca' Granda, was overwhelmed by this disease. From September 1918 to April 1919, a total of 5,684 people suffering from Influenza were admitted to the hospital, of whom 4,198 recovered and 1,486 died. Between 1918 and 1919, administrative and organizational measures were imple- mented to deal with the situation. Initiatives were taken on the hygiene of the hospital environment and on the disinfection of the patients' linen; numerous instruments were purchased; new spaces were opened for the Spanish patients and rules and procedures were introduced regarding visits to the sick by the public. We should not forget the central role that nurses played during 1918 and 1919. As today, several colleagues were affected and died for this cause, but they were awarded prizes, gratifications and praise for the hard and dangerous work they did on a daily basis.

Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective.

Neuroendocrine tumors (NETs) are classified based on morphology and are graded based on their proliferation rate as either well-differentiated low-grade (G1) to intermediate (G2-G3) or poorly differentiated high-grade neuroendocrine carcinomas (NEC G3). Recently, in gastroenteropancreatic (GEP) NETs, a new subgroup of well-differentiated high-grade tumors (NET G3) has been divided from NEC by WHO due to its different clinical-pathologic features. Although several mutational analyses have been performed, a molecular classification of NET is an unmet need in particular for G3, which tends to be more aggressive and have less benefit to the available therapies. Specifically, new possible prognostic and, above all, predictive factors are highly awaited, giving the basis for new treatments. Alteration of KRAS, TP53, and RB1 is mainly reported, but also druggable alterations, including BRAF and high microsatellite instability (MSI-H), have been documented in subsets of patients. In addition, PD-L1 demonstrated to be highly expressed in G3 NETs, probably becoming a new biomarker for G3 neuroendocrine neoplasm (NEN) discrimination and a predictive one for immunotherapy response. In this review, we describe the current knowledge available on a high-grade NET molecular landscape with a specific focus on those harboring potentially therapeutic targets in the advanced setting.