Nationwide Study of Real-World Treatment Patterns and Clinical Outcomes in Patients with Metastatic Urothelial Carcinoma in Hungary.

INTRODUCTION: Data describing real-world treatment patterns in patients with metastatic urothelial carcinoma (mUC) in Central-Eastern Europe are scarce, and data from Hungary have not been published. This retrospective, nationwide, real-world study investigated patient characteristics, treatment patterns, comorbidities, and clinical outcomes in patients with mUC in Hungary. METHODS: Adults diagnosed with mUC from January 2016 through June 2021 were identified using the National Health Insurance Fund Administration database. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: In total, 2523 patients with mUC were identified. Median follow-up was 7.1 months. Overall, 50% of patients received an identified systemic anticancer treatment; within this subgroup, first-line treatment was platinum-based chemotherapy (PBC) in 86%, non-PBC in 8%, and immune checkpoint inhibitor (ICI) in 6%. The proportion of patients receiving treatment increased from 41% in 2016 to 59% in 2020, driven by increased use of first-line PBC or first-line ICI treatment. Comorbidities were more common in patients receiving first-line ICI treatment vs PBC or non-PBC and in patients receiving carboplatin + gemcitabine vs cisplatin + gemcitabine. Overall, only 24% received a second-line treatment. Unadjusted median OS from the start of first-line treatment in the PBC, non-PBC, and ICI subgroups was 12.8, 7.5, and 6.3 months, respectively. Median OS from date of diagnosis in untreated patients was 7.8 months. OS comparisons adjusted for differences in baseline characteristics between subgroups could not be performed. CONCLUSION: To our knowledge, this is the first study to assess treatment patterns in patients with mUC in clinical practice in Hungary, using the national health insurance database. Rates of first- and second-line treatment were consistent with those observed in other countries. Avelumab first-line maintenance treatment became available for reimbursement in Hungary in late 2022, after the study period. Given the evolving landscape of reimbursed treatments in Hungary, further analyses are warranted.

Hypothermia down-regulates the LPS-induced norepinephrine (NE) release in ischaemic human heart cells.

Hypothermia has been widely acknowledged as the fundamental component of myocardial protection during cardiac operations. In this work, we studied in human atrial tissue the effect of the common hypothermic protection used in cardiac surgery, and we assessed this effect by comparing catecholamine release among normoxic, ischaemic, and inflammatory conditions. Our results provide the first evidence that lipopolysaccharide treatment results in an extremely dramatic and significant increase in the resting norepinephrine release under ischaemic conditions that can be normalised by hypothermia. These findings demonstrate that inflammatory conditions increase the temperature sensitivity of the norepinephrine transporter in human cardiac tissue. When the possible pharmacological interventions are taken into consideration, the results presented here provide new insight into the protection against ischaemia/reperfusion injury during cardiac surgery.