Risk factors for thromboembolic events in individuals with dialysis-dependent chronic kidney disease

A recent study has shown that it is reasonable to avoid sudden fluctuations in hemoglobin levels and maintain transferrin saturation (TSAT) levels at or above 30%, rather than escalating the dosage of roxadustat. The findings of the study were published in the journal Advances in Therapy.

Thromboembolic events in patients receiving roxadustat were investigated through a combined analysis of four phase 3 trials, including PYRENEES, HIMALAYAS, SIERRAS, and ROCKIES, both prior to and following the twelfth week. Cox regression analyses were used to explore the baseline risk factors for thromboembolic events. The association between thromboembolic events and laboratory parameters that were last known before the event was explored through nested case-control studies using matched case-control pairs.

Among the 2354 patients studied, 1026 thromboembolic events were observed in 568 patients. Baseline risk factors identified included hemodialysis versus peritoneal dialysis, race, high high-sensitivity C-reactive protein, advanced age ≥ 65 years, a history of thromboembolism, cardiovascular disease, or diabetes. Univariate case-control analyses indicated that a high hemoglobin rate of rise (≥ 0.5 g/dL/week; OR 2.09; 95% CI 0.98-4.46) showed a potential increase in the risk of thromboembolic events before week twelve, while a high rate of hemoglobin decline was linked to events after week 12 (< - 0.5 g/dL/week; OR 3.73; 95% CI 1.68-8.27) in comparison to steady levels of hemoglobin (ranging from ≥ - 0.1– < 0.1 g/dL/week).

Multivariate case-control analyses demonstrated that a low last known hemoglobin level (< 10 g/dL: adjusted OR 1.91; 95% CI 1.04-3.50; versus ≥ 12 g/dL) and low last known transferrin saturation (TSAT < 10%: adjusted OR 3.78; 95% CI 1.71-8.39; versus ≥ 30%) before event onset were associated with events after week twelve. An increased dose of roxadustat was correlated with thromboembolic events in patients whose last known transferrin saturation was less than 30%, while no correlation was observed in patients with transferrin saturation of 30% or higher.

The above study demonstrated that among several risk factors associated with thromboembolic events, it is suitable to avoid abrupt changes in hemoglobin levels and keep TSAT levels at or above 30% instead of increasing the dosage of roxadustat.

Supine percutaneous nephrolithotomy vs prone percutaneous nephrolithotomy in the treatment of pediatric kidney stones

According to a recent study, supine percutaneous nephrolithotomy (PCNL) is a safe and effective method for treating pediatric kidney stones, with fewer postoperative complications observed. Additionally, the operation time and hospital stay were shorter in supine PCNL when compared to prone PCNL. This study’s findings were published in the Urolithiasis journal.

This randomized study included patients with lower pole stones larger than 1 cm, stones larger than 1.5 cm in the pelvis, midpole, upper pole, or multiple locations, and those who did not respond to ESWL or whose family preferred mini-PCNL as the primary treatment. A total of 144 patients underwent PCNL (68 patients had supine PCNL and 76 had prone PCNL).

After surgery, Clavien grade 1 complications occurred in seven patients in the prone position, while only one patient experienced such a complication in the supine position. The mean duration of the prone PCNL procedure was 119.88 ± 28.32 minutes, whereas the mean duration for supine PCNL was 98.12 ± 14.97 minutes. In terms of hospitalization, patients who underwent prone PCNL stayed for an average of 3.56 ± 1.12 days, while those who had supine PCNL stayed for an average of 3.00 ± 0.85 days.

From the above study, it can be concluded that supine PCNL is a safe and effective method, presenting fewer postoperative complications, a shorter operation time, and a shorter hospitalization period when compared to prone PCNL.

Efficacy of enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer

A recent study found that treatment involving enfortumab vedotin and pembrolizumab produced significantly better outcomes than chemotherapy for patients with untreated locally advanced or metastatic urothelial carcinoma. The results of this study were published in the New England Journal of Medicine.

In this randomized, global, open-label phase 3 trial, a total of 886 patients were assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (administered intravenously at a dose of 1.25 mg per kilogram of body weight on days 1 and 8) and pembrolizumab (administered intravenously at a dose of 200 mg on day 1) in the enfortumab vedotin-pembrolizumab group (N=442), or gemcitabine and either cisplatin or carboplatin in the chemotherapy group (N=444). Progression-free survival and overall survival were the primary endpoints of the study.

The enfortumab vedotin-pembrolizumab group exhibited a longer progression-free survival compared to the chemotherapy group, with a median of 12.5 months versus 6.3 months, respectively. Similarly, the overall survival was also prolonged in the enfortumab vedotin-pembrolizumab group, with a median of 31.5 months compared to 16.1 months in the chemotherapy group. In terms of treatment cycles, the enfortumab vedotin-pembrolizumab group had a median of 12 cycles (range, 1-46), while the chemotherapy group had a median of 6 cycles (range, 1-6). Notably, treatment-related adverse events of grade 3 or higher were observed in 55.9% of patients in the enfortumab vedotin-pembrolizumab group and in 69.5% of patients in the chemotherapy group.

Based on the above results, it can be concluded that treatment with enfortumab vedotin and pembrolizumab in patients with untreated locally advanced or metastatic urothelial carcinoma resulted in improved outcomes compared to chemotherapy.

Maralixibat improves health-related quality of life in pediatric patients with Alagille Syndrome

A recent study demonstrated that the ileal bile acid transporter inhibitor maralixibat improves health-related quality of life (HRQoL) in children with Alagille syndrome. This study was published in The Journal of Pediatrics.

The ICONIC trial was a phase 2 study, having a 4-week double-blind, placebo-controlled, randomized drug withdrawal period. The study included 27 children having Alagille syndrome with moderate-to-severe pruritus. From baseline to week 48, the treatment response to maralixibat was noted using Itch-Reported Outcome (Observer) score. The HRQoL was assessed based on the certain scale scores that included Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores.

At week 48, twenty patients attained an Itch-Reported Outcome (Observer) treatment score response. The mean (SD) change in Multidimensional Fatigue score was higher was higher for responders over non-responders. The Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores showed smaller and non-statistically significant point estimates.

Based on the results of the study, it can be concluded that maralixibat shows significant improvement in pruritis, thereby enhancing the quality of life in the affected children.