How did the COVID-19 pandemic affect inpatient care for children in Germany? An exploratory analysis based on national hospital discharge data

Background: The delivery of health services around the world faced considerable disruptions during the COVID-19 pandemic. While this has been discussed for a number of conditions in the adult population, related patterns have been studied less for children. In light of the detrimental effects of the pandemic, particularly for children and young people under the age of 18, it is pivotal to explore this issue further. Methods: Based on complete national hospital discharge data available via the German National Institute for the Reimbursement of Hospitals (InEK) data browser, we compare the top 30 diagnoses for which children were hospitalised in 2019, 2020, 2021 and 2022. We analyse the development of monthly admissions between January 2019 and December 2022 for three tracers of variable time-sensitivity: acute lymphoblastic leukaemia (ALL), appendicitis/appendectomy and tonsillectomy/adenoidectomy. Results: Compared to 2019, total admissions were approximately 20% lower in 2020 and 2021, and 13% lower in 2022. The composition of the most frequent principal diagnoses remained similar across years, although changes in rank were observed. Decreases were observed in 2020 for respiratory and gastrointestinal infections, with cases increasing again in 2021. The number of ALL admissions showed an upward trend and a periodicity prima vista unrelated to pandemic factors. Appendicitis admissions decreased by about 9% in 2020 and a further 8% in 2021 and 4% in 2022, while tonsillectomies/adenoidectomies decreased by more than 40% in 2020 and a further 32% in 2021 before increasing in 2022; for these tracers, monthly changes are in line with pandemic waves. Conclusions: Hospital care for critical and urgent conditions among patients under the age of 18 was largely upheld in Germany during the COVID-19 pandemic, potentially at the expense of elective treatments. There is an alignment between observed variations in hospitalisations and pandemic mitigation measures, possibly also reflecting changes in demand. This study highlights the need for comprehensive, intersectoral data that would be necessary to better understand changing demand, unmet need/foregone care and shifts from inpatient to outpatient care, as well as their link to patient outcomes and health care efficiency

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study.

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856

In-Hospital Glucose Monitoring: Adequacy and Resource Management

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Building capacity and identifying appropriate support: how can the EU contribute to securing resources for health systems?

European health systems face increasing challenges and demands, while striving to provide high-quality care. The European Union (‎EU)‎ offers support to complement national efforts, but accessing and utilising it can be challenging for Member States. Austria, Belgium, and Slovenia are collaborating on a multi-country project supported by the EU’s Technical Support Instrument, to create an EU Health Resources Hub. This advisory service aims to help Member States access EU funding instruments for their health needs. This article discusses the project’s goals and early learnings, offering insights that could inform future health funding opportunities and policies in Europe

Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy

Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9–mediated α-galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified α-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy.publishedVersio

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study.

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856