ABSTRACT Sodium phenylbutyrate (NaPBA) is used for nitrogen scavenging in urea cycle disorders (UCDs), but its volume, palatability, and sodium load affect adherence and ammonia control. Glycerol phenylbutyrate (GPB) offers an alternative option with demonstrated improvements in metabolic control and palatability. For a Japanese perspective, we undertook an open‐label, multicentre, prospective Phase 3 study of efficacy, pharmacokinetics (PK), and safety. In a switch‐over, 15 patients received NaPBA for 7 days, then GPB for 7 days. Primary endpoint: 24‐h blood ammonia AUC (AUC NH3,0–24 ). Secondary endpoints: blood ammonia and glutamine concentration; PK of scavenger metabolites in blood and urine; safety. Patients then received GPB for up to 12 months. For GPB and NaPBA, respectively, mean (SD) AUC NH3,0–24 was 627 (198) and 757 (307) μmol·h/L (ratio 0.849; 95% CI 0.723–0.997). Mean peak and mean blood ammonia were 37 and 26 μmol/L versus 52 and 32 μmol/L. Mean plasma AUC 0–24 for phenylbutyrate (PBA), phenylacetate (PAA), and phenylacetylglutamine (PAGN) were 470, 1420, and 836 versus 425, 984, and 741 μg·h/mL. Mean PBA metabolite fluctuation was 297% versus 366%. One adverse event (hyperammonaemia) led to discontinuation in each treatment arm. In the extension ( n = 14), mean (SD) blood ammonia at Month 12 was 21 (8) μmol/L. No new safety findings were observed. GPB demonstrated effective control of blood ammonia with a favourable safety profile. It offers a practical and clinically advantageous alternative to NaPBA, extending previous evidence to Japanese individuals with UCDs. Trial registration: jRCT2071220110.
BACKGROUND:The CJLSG1901 phase 2 study evaluated efficacy and safety of pembrolizumab plus pemetrexed in older populations. A novel first-line approach for older patients with metastatic non-squamous non-small cell lung cancer (NSCLC) was assessed. METHODS:A subgroup analysis was conducted to determine the efficacy and safety of pembrolizumab plus pemetrexed in older patients with metastatic non-squamous NSCLC according to programmed cell death-ligand 1 (PD-L1) status (<1 % vs 1 %-49 %) using data from the CJLSG1901 study. RESULTS:Forty-nine patients were enrolled between July 2020 and May 2022. The objective responserate (ORR) was 36.7 %. The median progression-free survival (PFS) was and median overall survival (OS) were 7.6 months and 19.4 months,respectively. Twenty-one patients had a PD-L1 expression of <1 %, whereas 28 had a PD-L1 expression of 1 %-49 %. The median age, sex, Eastern Clinical Oncology Group performance status, and stage were similar in both groups. ORRs were 23.8 % in the PD-L1 <1 % group and 46.4 % in the PD-L1 1 %-49 % group. Median PFS were 4.4 months in the PD-L1 <1 % group and 7.8 months in the PD-L1 1 %-49 % group. Median OS were 19.4 months and 19.1 months in these groups, respectively. Adverse events (AEs) of any grade were observed in all patients, regardless of PD-L1 status. AE severerity was comparable between the groups. Severe treatment-related AEs occurred in five patients (25 %) in the PD-L1 <1 % group and seven patients (25 %) in the PD-L1 1 %-49 % group. CONCLUSIONS:The ORR was higher in the PD-L1 1 %-49 % group; however, the PFS and OS were similar in both groups.
ABSTRACT Here, we report a rare case of severe central airway obstruction caused by mediastinal and hilar lymph node metastases with persistent bleeding from renal cell carcinoma. Hemoptysis and critical left main bronchial stenosis were initially managed with bronchial arterial embolization, which reduced the risk of bleeding during subsequent interventions. This enabled safe placement of an AERO airway stent, leading to a rapid improvement in respiratory status. The patient was able to proceed with systemic therapy without delay. This case demonstrates the value of combining bronchial arterial embolization (BAE) with airway stenting as an effective bridge strategy for the treatment of life‐threatening malignant airway stenoses.
Introduction The coexistence of VACTERL (vertebral anomalies, anorectal malformation, cardiac defects, tracheoesophageal fistula, renal, and limb anomalies) and MURCS (Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia) associations has rarely been reported. Case presentation A female infant was born at 39 weeks of gestation with a birth weight of 2430 g. She demonstrated type C esophageal atresia, an anocutaneous fistula, left renal agenesis, and vertebral anomalies, fulfilling the diagnostic criteria for VACTERL association. Primary repair of the esophageal atresia was performed during the neonatal period. Anoplasty for the anocutaneous fistula was electively performed at 1 and 11 months of age, as the patient maintained an adequate bowel function via the fistula. Although vaginal introitus could not be identified at the time of anoplasty, further evaluation of the internal genital anatomy was intentionally deferred until adolescence, when reconstructive options could be discussed with the patient. Pelvic magnetic resonance imaging at 12 years old revealed uterine and vaginal agenesis with normal ovaries, establishing the diagnosis of Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome with MURCS association. At 14 years old, sigmoid vaginoplasty was performed without complications. She performs regular self-dilation of the neovagina. Her renal function gradually declined since birth, and she was currently classified as having stage 3 chronic kidney disease. Conclusion Females with VACTERL association should undergo a thorough evaluation of their internal and external genitalia. Although rare, Mayer–Rokitansky–Küster–Hauser syndrome can occur in females with VACTERL association. Elective sigmoid vaginoplasty after puberty is a feasible reconstructive procedure.
