Yokosuka Kyosai Hospital

The dose of bendamustine used to treat previously untreated follicular lymphoma (FL) is sometimes reduced based on various clinical considerations, but the impact of such dose reductions on outcomes is unclear. We retrospectively analyzed 92 untreated FL patients treated with bendamustine at seven institutions in Japan. Dose reduction was defined as receiving less than 90% of the planned total dose of 1080 mg/m2 over six cycles. Patients with disease progression observed at ≤ 180 days of treatment initiation were defined as primary bendamustine-refractory (PBR). The 3-year overall survival (OS) and progression-free survival (PFS) were 87.1% and 71.8%, respectively. Seven patients were classified as PBR, six of whom received bendamustine at full dose without dose reduction, and they had significantly worse OS with 3-year OS of 38.1%. We excluded the PBR cases from subsequent analyses of the dose intensity's prognostic significance. The dose-reduction group had a significantly lower CR rate (93.0% vs. 74.4%, p = 0.032). Similarly, the 3-year PFS was significantly worse in the dose-reduction group (86.8% vs. 68.1%, p = 0.005). In univariate and multivariate analyses, dose reduction was associated with inferior PFS. In an analysis limited to patients who completed all six courses, the CR rate was comparable between the two groups, but 3-year PFS was significantly worse in the dose-reduction group (86.8% vs. 68.7%, p = 0.041). Furthermore, even among patients who achieved CR, the 3-year PFS tended to be poorer in the dose-reduction group (85.7% vs. 72.7%, p = 0.062). These findings suggest that PBR cases are resistant to bendamustine itself regardless of the dose intensity. In contrast, among responders including those who achieved CR, dose reduction was associated with poorer PFS, indicating that maintaining treatment intensity is important for improving prognosis in the treatment of bendamustine-responsive FL patients.

To investigate the safety and efficacy of mini-endoscopic combined intrarenal surgery (ECIRS) in older patients with renal and ureteral stones. Consecutive patients with renal or ureteral stones who underwent mini-ECIRS were retrospectively analyzed at three Japanese tertiary care institutions between 2015 and 2021. Data on patient backgrounds, stone characteristics, and postoperative indications were collected and evaluated. After matching preoperative and intraoperative factors in older patients and other groups, postoperative factors were assessed using univariate analysis. The final analysis included data from 1303 single-session mini-ECIRS of 1432 cases collected. The patients were divided into two groups: those aged > 75 and those aged < 75 years, with 121 and 1182 patients. From each group, 112 cases matched for eight factors, performance status, body mass index, sex, hydronephrosis, percutaneous nephrostomy, pyuria, preoperative urinary tract infection, and preoperative ureteral stenting, were selected. The univariate analysis was performed on postoperative factors between the groups of matched older and matched non-older patients, and there was no significant difference in any factor, including postoperative hospitalization duration, complications, and stone-free rate (SFR). To the best of our knowledge, this multicenter cohort study is the first to compare the efficacy and safety of the mini-ECIRS between older patients and other groups. It was discovered that surgery could be performed with a similar quality even in patients aged 75 and older compared to that in other groups.

Cough reflex and vagal reflex-induced bradycardia are important to predict and prevent prior to PFA to ensure procedural safety and efficacy. However, no studies have yet investigated differences in their incidence among the various PFA systems. We aimed to evaluate the incidence, predictors, and system-specific differences of cough reflex and vagal response during PFA in a large multicenter cohort. Data from 1715 patients undergoing PFA using either PulseSelect, Farapulse, or Varipulse systems at 13 centers were analyzed. Cough reflex was defined as any episode requiring procedure interruption or physical restraint, while a vagal response was defined as sinus arrest or atrioventricular block lasting ≥ 5s. Pulmonary vein isolation was achieved in all patients except for one case. Complications were rare and did not differ significantly among the PFA systems. Cough reflex occurred in 49.3% of patients, most frequently in the left superior pulmonary vein. Compared with Farapulse, the risk of cough reflex was higher with PulseSelect (odds ratio [OR] 1.648, 95% confidence interval [CI] 1.321-2.057) and Varipulse (OR 1.645, 95% CI 1.019-2.657). Patient-related factors such as male sex, asthma, heart failure, and hypertension increased the risk, whereas general anesthesia significantly reduced it (OR 0.236, 95% CI 0.174-0.318). Vagal response occurred in 15.2% of patients, with no significant differences among the PFA systems, and the sequence of pulmonary vein isolation did not affect its occurrence. Prophylactic atropine reduced the risk of vagal response. Cough reflex may vary across PFA systems, while vagal response may remain consistent.

BackgroundAcute oxalate nephropathy is a progressive kidney condition characterized by the accumulation of oxalate crystals, causing interstitial nephritis and tubular damage. Excessive intake of vitamin C, obesity, chronic inflammatory bowel disease, and gastric bypass surgery are risk factors that can cause oxalate nephropathy. However, the risks associated with this condition and its management deserve further investigation.Case presentationA 76-year-old woman had undergone Roux-en-Y gastric bypass surgery seven years prior following a diagnosis of gastric cancer. Four years previously, the patient was diagnosed with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and was prescribed 5 mg of prednisolone and an active vitamin D supplement. There was no incidence of vitamin C overdose, nor did she use ethylene glycol lotion. Her initial creatinine level was 0.72 mg/dL, which increased to 6.17 mg/dL six months later. Renal biopsy revealed deposits of oxalate crystals in the renal tubules. She was diagnosed with acute oxalate nephropathy and treated with prednisolone 35 mg/day. However, her renal function continued to deteriorate, and she had to undergo hemodialysis one month later. After two months, she developed thrombocytopenia and hemolytic anemia, and her blood pressure decreased during hemodialysis. She was diagnosed with thrombotic microangiopathy (TMA) and treated medically but unfortunately did not survive.ConclusionsOur findings indicate that oxalate nephropathy can occur even several years after Roux-en-Y gastric bypass. In addition, the use of prednisolone for treating oxalate nephropathy could also have contributed to the exacerbation of renal failure. Early detection and prevention of this condition is currently the best option.

Background This study aimed to identify tumor lesion-related factors associated with possible missed gastric cancer (PMGC) during screening endoscopy, with particular focus on cases following Helicobacter pylori (HP) eradication. Methods We analyzed consecutive gastric cancer (GC) cases detected at 11 health check-up institutions in Akita prefecture, Japan. The study focused on 171 GC cases with at least one negative endoscopy within the preceding 2 years. Based on histological assessment, GCs with pT1b or deeper invasion were classified as PMGCs. Their clinical characteristics were compared with those of the remaining pT1a GCs. A backward stepwise logistic regression analysis was performed to identify tumor lesion-related factors associated with PMGC. Results Among 171 GC cases, 39 (22.8%) were classified as PMGC, while the remaining 132 served as controls. Overall, 108 cases (63.2%) occurred in individuals with prior HP eradication, and eradication status was not statistically associated with PMGC. Multivariable regression analysis limited to post-eradication cases revealed that upper third location and undifferentiated histology were significantly associated with PMGC, with odds ratios (95% confidence intervals) of 5.65 (1.88–16.90) and 8.35 (2.22–31.40), respectively. Conclusions Undifferentiated histology and upper third location were associated with missed diagnoses of GC during screening endoscopy in individuals with prior HP eradication. These findings are clinically relevant for improving the quality of endoscopic examinations in health check-up settings, especially given the increasing prevalence of post-eradication GC.

One of the challenges in clinical genetics for rare diseases and personalized medicine is evaluating isoform alterations arising from heterozygous putative splicing variants at the allele level. Our aim was to analyze these variants by dividing cDNA or direct RNA nanopore long reads into two alleles, referencing whole-genome sequencing data containing allele-informative single nucleotide variants and then comparing the allele-separated reads using Full-Length Alternative Isoform analysis of RNA (FLAIR), a previously published bioinformatics tool for isoform analysis. In this study, we developed an allele-separative bioinformatics pipeline and described its performance. We applied our pipeline to previously published nanopore direct RNA sequencing data, as well as 5’ cap-trapping full-length cDNA nanopore sequencing (CTR-seq) data from blood samples of three individuals. We successfully identified heterozygous splicing variants associated with significant isoform differences between alleles. Furthermore, we uncovered the effects of a novel pathogenic splicing variant in PYGM on isoforms in a compound-heterozygous case of McArdle disease using nanopore cDNA amplicon and targeted genomic sequencing. This study demonstrates the utility of nanopore long-read sequencing for isoform analysis at the allele level, providing a valuable approach to evaluating the direct consequences of heterozygous splicing variants in individuals.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-14566-z.

The significance of “L” score in the radius (R), exophytic/endophytic (E), nearness (N), anterior/posterior (A), location (L); RENAL nephrometry scoring system remains unestablished compared to other subscores. This study assessed the influence of the “L” score on surgical and functional outcomes of RAPN, dividing renal tumors into medial and lateral relative to the kidney’s central line, to explore its impact on “L” score utility. A retrospective analysis was conducted on 668 RAPN patients, with 405 having medial and 263 lateral renal tumors. Patients who underwent RAPN were retrospectively analyzed, including 405 with medial renal tumors and 263 with lateral renal tumors. In medial tumors, the “L” score independently predicted non-achievement of trifecta (P = 0.011) and pentafecta (P = 0.032). In lateral tumors, the “L” score did not predict non-achievement of these outcomes. In conclusion, significance of the “L” score on surgical outcomes differs between medial and lateral tumors and it is strongly associated with outcomes in medial tumors, whereas its predictive value in lateral tumors is less marked. The RENAL nephrometry score lacks differentiation between medial and lateral tumors; therefore, surgeons should interpret “L” scores with caution.

Objective: To assess the safety of mini-endoscopic combined intrarenal surgery (mini-ECIRS) in patients with a poor performance status (PS). Methods: A retrospective analysis was conducted on 1132 patients who underwent mini-ECIRS at 3 hospitals between January 2015 and December 2021. Patients were classified according to their PS (PS0-1 and PS2-4 groups) and compared between the groups in terms of preoperative drainage status, such as ureteral stent or percutaneous nephrostomy (PNS), stone characteristics, surgical outcomes, and postoperative fever. Multivariate logistic regression models were used to identify the predictive factors for postoperative fever in each PS group. Results: Patients in the PS2-4 group were older and had a higher stone burden than those in the PS0-1 group. The stone-free rates and surgical success rate were similar between the PS groups, but PS2-4 patients had higher rates of postoperative fever without preoperative drainage. Stone composition analysis revealed a higher prevalence of infectious stones in the PS2-4 group. In the PS0-1 group, PNS reduced postoperative fever risk (odds ratio (OR): 0.65, 95% CI: 0.48-0.89, P = .01), and history of febrile urinary tract infection, stone burden ! 30 mm, number of involved calyces ! 4, and female sex were independent risk factors. Notably, in the PS2-4 group, PNS remained effective against postoperative fever (OR: 0.24, 95% CI: 0.07-0.80, P = .02), while no other factors were significant. Conclusion: The mini-ECIRS was effective even in PS-poor patients, and they may benefit more from preoperative PNS placement than normal PS cases.