[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

Increased serum adenosine and interleukin 10 levels as new laboratory markers of increased intra-abdominal pressure.

BACKGROUND: Increased intra-abdominal pressure (IAP), intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are severe complications of surgical interventions with a high rate of mortality. The technique of IAP measurement is accurate, precise, reproducible and cost-effective. However, laboratory measures for monitoring of IAH have not been defined. We investigated the linkage between the serum levels of adenosine and interleukin 10 (IL-10) with IAP. METHODS: The sera of 25 surgical patients with IAP <12 mmHg and of 45 surgical patients with IAP >12 mmHg were tested. Serum adenosine concentration was measured by HPLC. Serum IL-1ß, IL-2, IL-4, IL-10, TNFα, IFNγ and IL-10 were determined by enzyme linked immunosorbent assay (ELISA). CRP was measured by nephelometry. RESULTS: Significant correlations of IAP were found only with serum levels of adenosine and IL-10. In the sera of patients with IAP >12 mmHg, the levels of both adenosine (1.61 versus 0.06 µM, p < 0.01) and IL-10 (63.23 versus 27.27 pg/ml, p < 0.01) were significantly higher than those in patients with IAP <12 mmHg. Moreover, significant correlations were found between individual patient IAP-adenosine values (r = 0.766, p < 0.001), IAP-IL-10 values (r = 0.792, p < 0.001) and adenosine-IL-10 values (r = 0.888, p < 0.001). A direct linear correlation between IAP-adenosine and IAP-10 values was only observed with IAP >15 (Grade II-IV). CONCLUSION: We report associations between IAP and the serum adenosine and IL-10 levels providing new tools for the laboratory monitoring of IAH as well as further understanding of the pathomechanisms contributing to ACS.

Altered signal pathway in angiotensin II-stimulated neutrophils of patients with hypercholesterolaemia.

Angiotensin II (AII) in 1-10 nM concentrations has an in vivo immunostimulating effect on human neutrophils. The release of superoxide anions and leukotrienes (LTs) is significantly increased by 10 nM AII-stimulated neutrophils of patients with hypercholesterolaemia (HCH). These oxidizing agents may be involved in the damage of vessel walls, i.e., in atherosclerotic plaque formation. To clarify the receptor types and signal pathways in neutrophils of healthy controls and patients, inositol trisphosphate (IP(3)) production and Ca(2+) signalling were studied. Neutrophils were pretreated before AII stimulation with different inhibitory drugs. In control cells, the stimulation occurred predominantly through pertussis toxin-sensitive, type angiotensin 1 receptors. This induced IP(3) production and Ca(2+) signalling from intracellular pools. In neutrophils of hypercholesterolaemic patients, the enhanced release of oxidizing agents was dependent more on type angiotensin 2 than type angiotensin 1 receptors. After stimulation, there was no IP(3) production detected. The Ca(2+) signalling was lower than in control cells and was dependent on extracellular Ca(2+).