[Evaluation of Characteristics and Management of Influenza Patients in Relation to the STIKO Vaccination Recommendation During the 2017/2018 Season]. / Evaluation von Charakteristika und Management von Influenzapatienten in Bezug auf die STIKO Impfempfehlung während der Saison 2017/2018.

BACKGROUND: Every year a large number of patients is suffering from influenza infection with often severe outcome. The influenza season 2017/2018 was characterized by a high number of cases (in Germany>346,000 laboratory-confirmed cases), but also by a high rate of hospitalizations with sometimes severe clinical outcome - also in the group of patients under 60 years. AIM: The aim of the present study was to find out whether patients not fullfilling the STIKO vaccination recommendation in the 2017/18 season were suffering from a worse outcome. MATERIALS AND METHODS: All laboratory-confirmed influenza patients at Frankfurt University Hospital were retrospectively analyzed for disease severity with respect to the primary endpoint. Secondary endpoints were defined as demographic data, length of hospital stay, previous illnesses, intensive care therapy and its duration, drug therapy, and mortality. RESULTS: Fifty-one of 303 patients (16.8%) required intensive care treatments. Of these 51, 46 patients (90.2%) belonged to the group that should have been vaccinated according to the vaccination recommendations according to STIKO, 5 patients (9.8%) did not belong to this group (p=0.434). Of the 51 ICU patients, 16 (31.4%) died. All deceased were from the group with vaccination recommendation (p=0.120). CONCLUSIONS: Based on these data, it appears that severe disease progression occurs in both the group of patients with and without STIKO vaccination recommendation, but deaths occur only in the group of patients with recommendation.

Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.

To interrogate signaling pathways activated in mantle cell lymphoma (MCL) in vivo, we contrasted gene expression profiles of 55 tumor samples isolated from blood and lymph nodes from 43 previously untreated patients with active disease. In addition to lymph nodes, MCL often involves blood, bone marrow, and spleen and is incurable for most patients. Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL. However, the role of specific signaling pathways in the lymphomagenesis of MCL and the biologic basis for ibrutinib sensitivity of these tumors are unknown. Here, we demonstrate activation of B-cell receptor (BCR) and canonical NF-κB signaling specifically in MCL cells in the lymph node. Quantification of BCR signaling strength, reflected in the expression of BCR regulated genes, identified a subset of patients with inferior survival after cytotoxic therapy. Tumor proliferation was highest in the lymph node and correlated with the degree of BCR activation. A subset of leukemic tumors showed active BCR and NF-κB signaling apparently independent of microenvironmental support. In one of these samples, we identified a novel somatic mutation in RELA (E39Q). This sample was resistant to ibrutinib-mediated inhibition of NF-κB and apoptosis. In addition, we identified germ line variants in genes encoding regulators of the BCR and NF-κB pathway previously implicated in lymphomagenesis. In conclusion, BCR signaling, activated in the lymph node microenvironment in vivo, appears to promote tumor proliferation and survival and may explain the sensitivity of this lymphoma to BTK inhibitors.