Kyushu University Hospital

Giant coronary artery aneurysms (CAAs), defined as dilatations exceeding 20 mm or four times the reference vessel diameter, are rare and risk rupture or thrombosis. Coronary pulmonary artery fistulas may lead to grow aneurysm formation via chronic high-flow shunting. Their coexistence is rare in elderly patients without prior Kawasaki disease. An 83-year-old woman with hypertension, dyslipidaemia, and type 2 diabetes mellitus was referred for evaluation of an abnormal mediastinal contour. Chest computed tomography showed a 43 × 33 mm left anterior descending artery aneurysm with a fistulous to the pulmonary artery, grown from 30 × 20 mm over 10 years. Right heart cardiac catheterization showed no evidence of pulmonary artery hypertension with a mild shunt flow (Qp/Qs: 1.15). Despite being asymptomatic, the aneurysm's size and growth warranted intervention. Considering her age and comorbidities, transcatheter coil embolization was selected over surgical or stent-based therapies. Coils were deployed using intravascular ultrasound (IVUS) and a balloon-assisted technique, successfully occluding the aneurysm without compromising distal flow. Follow-up angiography at 6 months and echocardiography up to 3 years confirmed sustained occlusion. This case highlights that even in asymptomatic elderly patients, large and expanding CAAs with fistulas warrant careful evaluation due to the risk of rupture. Transcatheter coil embolization provided a safe and effective treatment alternative to surgery, especially in high-risk anatomical and clinical settings. IVUS and balloon assistance were critical to procedural success, and long-term follow-up demonstrated sustained aneurysm exclusion.

Currently, there are no established treatments for esophagogastric junction outflow obstruction (EGJOO). In this study, we evaluated the efficacy and safety of acotiamide for EGJOO by targeting impaired lower esophageal sphincter (LES) function. This investigator-initiated, multicenter, randomized, double-blind, placebo-controlled phase II trial enrolled 35 patients with EGJOO between December 2021 and December 2023. Patients were randomized to receive either placebo (n = 11) or acotiamide (300mg/day, n = 12; 600mg/day, n = 12) for 4weeks (placebo-controlled period). Subsequently, all patients received 600mg/day acotiamide for an additional 4weeks (open-label period). As a primary endpoint, during the placebo-controlled period, the improvement rate of food-sticking symptoms in the chest was 12.5% and 0.0% in the acotiamide and placebo groups, respectively (p = 0.3092). In terms of secondary endpoints, the integrated relaxation pressure (IRP) normalization rate was significantly higher in the acotiamide group (41.7%) than in the placebo group (0.0%) (p = 0.0107). No other secondary endpoints showed significant differences between the groups. Regarding the exploratory endpoints, during the open-label period, among the 24 patients treated with ≥ 300mg/day of acotiamide for 8weeks, the improvement rate of food-sticking symptoms in the chest increased to 37.5%, and the IRP normalization rate rose to 54.2%. Acotiamide is effective in normalizing impaired LES relaxation in patients with EGJOO and may improve food-sticking symptoms in the chest. Japan Registry of Clinical Trials ( https://jrct.mhlw.go.jp/en-top ); registration number jRCT2071210072.

ABSTRACT Focal segmental glomerulosclerosis (FSGS) is a major cause of glucocorticoid-resistant nephrosis, yet its pathogenesis remains unclear. To define the molecular and cellular landscape of FSGS, we employed multi-omics approaches on independent human kidney biopsy cohorts. Proteomics revealed enhanced immune and complement activation. Spatial transcriptomics using a target gene panel constructed from the proteomics highlighted alternative pathway activation driven by complement factor D as a prominent feature. Complement activation emerged in glomeruli alongside altered signaling in podocytes and parietal epithelial cells (PECs): Podocytes displayed reduced PECAM1 and elevated macrophage migration inhibitory factor (MIF) signaling, and PECs display complement and collagen signaling as early events, and progressively acquired cellular activation, prompting glomerular fibrosis. These pathogenic signals propagated into adjacent interstitial regions, paralleling immune cell infiltration and fibrosis. These results uncover dynamics of dysregulated intercellular interactions originated from podocyte and PECs underlying the pathogenesis of FSGS, which provides insights into potential stage-specific interventions.

Long-term follow-up (LTFU) outpatient clinics play a primary role in screening, preventing, and addressing late effects after hematopoietic cell transplantation (HCT). Following the 2018 nationwide survey, which led to the development of standardized nationwide tools to deliver information to HCT survivors, we re-evaluated changes in the current status of LTFU clinics. We targeted 267 HCT centers certified by the Japanese society for transplantation and cellular therapy. Several questionnaire categories were retained from the 2018 survey to compare results (e.g., LTFU clinic establishment and institutional practices for late-effect screening). The response rate was high in both adult (90%) and pediatric HCT centers (88%), and the establishment rate of post-HCT LTFU clinics increased to 82% (adult, 90%; pediatric, 64%). Pediatric centers were more likely to continue follow-up of patients who received HCT beyond 5 years post-HCT. Regarding transitional medical care for long-term survivors at non-HCT institutions, only a few HCT centers conducted routine transitions to specific referral facilities. We observed significant changes in recommendations for secondary cancer screenings compared to 2018, with a substantial decrease in the proportions of "not routinely included as a screening issue." In the future, it is essential to create a sustainable follow-up system, establish networks with non-HCT facilities, and educate patients to encourage behavioral changes for lifelong health screenings.

Abstract Understanding how molecular diversity across long-range neural circuits governs brain function remains a central challenge in neuroscience. Here, we developed a projection-specific spatial proteomics approach and revealed robust presynaptic molecular divergence across six projection-defined pathways of the medial prefrontal cortex (mPFC), including efferent projections to the basolateral amygdala (BLA), nucleus accumbens (NAc), thalamus (Thal), hypothalamus (HT) and cortex (CTX), as well as the afferent projection from the BLA to the mPFC. Among these pathways, we identify BLTP2 (KIAA0100), a previously uncharacterized transmembrane protein, as highly enriched in the projection from the mPFC to the BLA. BLTP2 localizes to excitatory presynaptic terminals and is enriched at synapses that are activated during memory formation. Loss of BLTP2 impairs synaptic structure and transmission, and reduces activity-dependent remodelling, resulting in selective deficits in contextual fear memory, anxiety-related behavior, and social behavior. Mechanistically, BLTP2 promotes presynaptic assembly by recruiting Neurexin 1. These findings reveal projection-specific presynaptic molecular diversity and provide mechanistic insights into circuit-level vulnerabilities in neuropsychiatric disorders.

ABSTRACTOxaliplatin‐induced peripheral neuropathy (OIPN) causes numbness and pain in the limbs, often leading to interruption of chemotherapy and representing a significant clinical problem. Previous basic studies have suggested that the dipeptidyl peptidase‐4 (DPP‐4) inhibitor alogliptin may prevent OIPN. To evaluate whether concomitant use of DPP‐4 inhibitors could prevent the development of OIPN in clinical practice, we retrospectively analyzed data from 1180 patients who initiated oxaliplatin treatment at Kyushu University Hospital between January 1, 2009 and December 31, 2019. The primary endpoint was the occurrence of OIPN of any grade. Kaplan–Meier analysis with cumulative doses demonstrated a significantly lower incidence of OIPN in the DPP‐4 inhibitor group (p = 0.0422). After propensity score matching to adjust for patient backgrounds, the protective association remained significant (p = 0.0389). Furthermore, Cox proportional hazards analysis incorporating gender, age, regimen, and concomitant DPP‐4 inhibitor use as covariates confirmed that DPP‐4 inhibitor use was an independent protective factor for OIPN (HR = 0.690; 95% CI, 0.490–0.972; p = 0.034). These findings suggest that concomitant use of DPP‐4 inhibitors may moderate the development of OIPN in patients receiving oxaliplatin.