Kansai Electric Power Hospital

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that primarily affects the mucosal layer. Previously, we identified autoantibodies against integrin αvβ6 in patients with UC. In this study, we established monoclonal antibodies (mAbs) from patients with UC to reveal the features and functions of these anti-integrin αvβ6 autoantibodies. We identified two shared heavy chain complementarity-determining region 3 (CDR3) amino acid sequences among different patients with UC. Notably, several mAbs contained the RGD sequence in their heavy chain CDR3 that mimicked the key recognition sequence of integrin αvβ6 ligands such as fibronectin. Almost all mAbs selectively reacted with integrin αvβ6 in the presence of divalent cations (Ca2+ and Mg2+) and blocked fibronectin-integrin αvβ6 binding. MAbs that shared the same heavy chain CDR3 amino acid sequence showed differences in reactivity to integrin αvβ6, indicating that the reactivity of these mAbs is also affected by the light chain. Some of the mAbs showed varying degrees of cross-reactivity with integrin αvβ3. The identification of shared CDR3 amino acid sequences in anti-integrin αvβ6 antibodies from several patients with UC suggests a common mechanism underlying their production, which may help elucidate the pathogenesis of UC.

A man in his 50s with an intellectual disability underwent a cystostomy for neurogenic bladder, followed by regular catheter exchange. Eighteen years later, the patient developed hematuria. Computed tomography and cystoscopy revealed a bladder tumor despite negative urinary cytology. Transurethral resection of the tumor confirmed the diagnosis of squamous cell carcinoma. Radical cystectomy was performed due to muscle invasion. Histopathological analysis revealed a pT3aN1M0 squamous cell carcinoma. No adjuvant therapy was administered, and the patient has remained recurrence-free for seven years postoperatively.

There is a paucity of data on safety of calcium channel blockers (CCB) in patients with severe aortic stenosis (AS) and hypertension. Among 2,460 patients with severe AS and hypertension receiving antihypertensive therapy in the CURRENT AS registry-2, we compared the clinical outcomes between patients taking antihypertensive therapy with CCB (CCB group) and without CCB (no CCB group). In the entire study population, CCB was prescribed in 1,763 patients (71.7%), which was the most commonly prescribed antihypertensive agents. The prescription rates of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and thiazides were 61.9%, 25.6%, and 7.3% in the CCB group, and 75.8%, 54.4%, and 6.0% in the no CCB group. In the propensity score matched cohort, the cumulative 3-year incidence of all-cause death or hospitalization for heart failure was not different between the CCB and no CCB groups (38.3% vs. 38.7%, log-rank P=0.65; HR, 0.94; 95%CI, 0.77-1.15; P=0.56). The cumulative 3-year incidence of syncope was low regardless of CCB prescription (1.1% vs. 1.0%, P=0.74). Among patients with severe AS and hypertension, CCB was the most commonly prescribed antihypertensive agents, and antihypertensive therapy with CCB was associated with comparable clinical outcomes to antihypertensive therapy without CCB. Syncope was rarely seen in patients with severe AS and hypertension receiving antihypertensive therapy regardless of CCB prescription.

Coordinated regional action is urgently needed to safeguard insulin access in Asia amid global product realignment. This editorial emphasizes the ethical imperative and policy frameworks required to balance innovation with equitable, uninterrupted diabetes care.

Eosinophilia during the induction of peritoneal dialysis (PD) is frequently caused by icodextrin, but allergic reactions to PD catheters have been rarely reported. In previous reports, PD catheter-induced systemic contact dermatitis in patients undergoing PD sometimes required catheter removal, therefore there is a need to consider alternative renal replacement therapies other than PD. Here, we report a case of systemic contact dermatitis associated with a PD catheter that was successfully treated with dupilumab, avoiding catheter removal. The 62-year-old man undergoing PD had eosinophilia and pruritic skin rash after PD catheter implantation and was diagnosed with systemic contact dermatitis triggered by silicon contained in the catheter. Even though low doses of steroids were introduced, skin symptoms and eosinophilia were not controlled. After initiation of dupilumab treatment, skin pruritus was improved, and eosinophils also decreased. Although dupilumab use is expanding for systemic contact dermatitis, no previous reports of dupilumab administration in dialysis patients have been reported. This case is the first of a patient undergoing PD and using dupilumab for systemic contact dermatitis caused by a PD catheter, in which dupilumab successfully controlled skin rash and pruritus eosinophilia. Dupilumab is, therefore, a favorable option for treating systemic contact dermatitis induced by a PD catheter as an alternative to steroids and removal of the PD catheter.

Pouchitis is the most common complication of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We previously reported the presence of anti-integrin αvβ6 antibodies in the serum of patients with UC. This study investigated the association between anti-integrin αvβ6 antibodies and the development of pouchitis in patients with UC. Serum levels of anti-integrin αvβ6 antibodies were measured by enzyme-linked immunosorbent assay in 16 patients with UC who underwent RPC with IPAA. Integrin αvβ6 expression in the colonic, terminal ileal, and pouch epithelium was examined using immunohistochemistry and western blot analysis. Anti-integrin αvβ6 antibody levels in patients with UC were significantly decreased at 3, 9, and 12 months after RPC (P < .05). However, in patients who developed pouchitis, antibody levels remained high. The antibody levels at the time of RPC were significantly higher in patients who developed pouchitis compared to those who did not. Kaplan-Meier analysis revealed a significantly higher incidence of pouchitis in patients with antibody levels above the cutoff at the time of RPC. Although integrin αvβ6 was not expressed in the terminal ileal epithelium at the time of RPC, expression became positive in the pouch epithelium of patients with pouchitis. The anti-integrin αvβ6 antibody levels in patients with UC were decreased after RPC but remained high in patients who developed pouchitis. The antibody levels at the time of RPC may serve as a potential prognostic biomarker for predicting the risk of pouchitis in patients with UC.

BackgroundLuseogliflozin, a sodium–glucose cotransporter 2 inhibitor, potentially exerts pleiotropic effects on the liver. However, the sufficient evidence is still lacking. We aimed to investigate the effects of luseogliflozin on hepatic steatosis, fibrosis, and cardiometabolic risk factors in diabetic patients by a pooled meta-analysis.MethodsIn this pooled meta-analysis, we enrolled diabetic patients who participated in phase III clinical trials of luseogliflozin (luseogliflozin group n = 302, placebo group n = 191). The primary outcomes were changes in fatty liver index (FLI) and Hepamet fibrosis score (HFS) after 24 weeks. The secondary outcomes were changes in cardiometabolic risk factors after 24 weeks. Statistical analysis was performed using propensity scoring analysis by the inverse probability of treatment weighting method.ResultsPrimary outcomes: Luseogliflozin significantly decreased FLI compared to placebo after 24 weeks (adjusted coefficient − 5.423, 95%CI − 8.760 to − 2.086, P = 0.0016). There was no significant difference in changes in HFS between the two groups. However, luseogliflozin significantly decreased HFS compared to placebo in diabetic patients with ALT > 30 U/L (adjusted coefficient − 0.039, 95%CI − 0.077 to − 0.001, P = 0.0438) and with FIB-4 index > 1.3 (adjusted coefficient − 0.0453, 95%CI − 0.075 to − 0.016, P = 0.0026). Secondary outcom8es: Luseogliflozin significantly decreased HbA1c level, HOMA-IR value, BMI, and uric acids level, and increased HDL cholesterol level compared to placebo.ConclusionsThis pooled meta-analysis demonstrated that 24-week treatment with luseogliflozin improved hepatic steatosis and fibrosis indexes in diabetic patients, especially those with liver injury. Furthermore, luseogliflozin improved various cardiometabolic risk factors. Thus, luseogliflozin may be useful for improving MASLD in diabetic patients.Graphical abstract

When patients administered 177Lu-DOTATATE are released or discharged from rooms where radiopharmaceuticals are used, the time required for release or discharge varies across patients. This study investigated whether the amount of radioactivity accumulated on 111In-somatostatine receptor scintigraphy (111In-SRS) performed prior to treatment can predict the 1cm dose-equivalent rate at a distance of 1m from the patient on the day after 177Lu-DOTATATE administration. Whole-body planar 111In-SRS images were acquired for 21 patients. Pixel values within whole-body and abdominal (35 × 25cm) regions of interest (ROIs) were converted to radioactivity dose (MBq). The 1cm dose-equivalent rate (µSv/h) at a distance of 1m from the patient 18.3 ± 0.5h after administration of 177Lu-DOTATATE was measured using an ionization survey meter. The following relationships were observed between the radioactivity on 111In-SRS and the 1cm dose-equivalent rate on the day after administration of 177Lu-DOTATATE: whole-body ROI: y = 0.16x + 5.01 (r = 0.56, p = 0.009), abdominal ROI: y = 0.27x + 5.13 (r = 0.63, p = 0.002). The regression equations indicate that patients cannot be released or discharged from the radiopharmaceutical room the day after 177Lu-DOTATATE administration if the whole-body and abdominal ROI doses are greater than 81 and 48MBq, respectively, on 111In-SRS. The amount of radioactivity accumulated on 111In-SRS may be a predictor of release criteria for patients receiving 177Lu-DOTATATE.