Kure Kyosai Hospital

Glucocorticoids (GC) comprise a cornerstone in the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, prolonged GC exposure leads to substantial toxicity and immune system-related complications. Hence, identifying treatment strategies that enable early GC withdrawal while maintaining disease control is of clinical importance. To investigate the proportion and characteristics of patients achieving GC-free clinical remission (GFCR) 48 weeks after treatment initiation in patients with newly diagnosed microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) and examine their long-term clinical outcomes (up to week 96). We conducted a retrospective cohort study using clinical data from a multicenter, nationwide registry in Japan comprising patients with newly diagnosed MPA or GPA and at least 48 weeks of follow-up. GFCR was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 with complete GC withdrawal. Univariable and multivariable logistic regression analyses were used to identify independent predictors of GFCR at week 48, and a sensitivity analysis using a matched cohort was performed to validate robustness. A total of 728 patients were enrolled in the registry, of whom 544 were followed for ≥ 48 weeks; among them, 29 (5.3%) achieved GFCR at week 48. Use of rituximab (RTX) for induction therapy and avacopan within 48 weeks were independently associated with achieving GFCR (multivariable analysis, model 1: RTX: odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.5–10.0; avacopan: OR: 24.3, 95% CI: 5.8–101.9; both p < 0.01). Conversely, methylprednisolone pulse therapy was associated with a lower likelihood of achieving GFCR (multivariable analysis, model 1: OR: 0.08, 95% CI: 0.02–0.44; p < 0.01). Patient’s demographic and baseline disease characteristics were not predictive of GFCR. In the long-term (weeks 48 through 96), the rates of death, relapse, and serious infection were similar regardless of GFCR status at week 48. The use of RTX for induction therapy and avacopan within 48 weeks is independently associated with achieving GFCR at week 48 in patients with MPA and GPA, supporting their potential as key components of GC-sparing strategies in AAV. Prospective studies are needed to confirm these results and optimize treatment algorithms to ensure disease control and minimize GC-related toxicity.

Some ALK-positive lung cancers show early resistance to alectinib. This study found brain metastases and elevated NLR associated with early resistance. Spatial transcriptomics and functional analysis suggested involvement of ANXA1. These results reveal clinical and molecular biomarkers that may guide treatment strategies for early resistance to alectinib.

Elevated serum IgG4 is a key diagnostic marker for type 1 autoimmune pancreatitis (AIP), but some patients lack IgG4 elevation, complicating diagnosis. This study investigated the clinicopathological features of AIP without elevated serum IgG4 levels. A total of 323 patients diagnosed with AIP at Hiroshima University Hospital and affiliated institutions were analyzed. Patients were categorized into IgG4-positive (≥ 135 mg/dL), IgG4-negative (< 135 mg/dL with “definite” or “probable” diagnosis), and possible (with “possible” diagnosis) groups. Comparative analysis was performed between the IgG4-positive (n = 281) and IgG4-negative (n = 20) groups. Segmental or focal narrowing of the main pancreatic duct (MPD) and retroperitoneal fibrosis were significantly more common in the IgG4-negative group (90.0% vs. 58.7%, P = 0.011; and 35.0% vs. 12.5%, P = 0.012, respectively). Although the number of pathological findings was comparable, the rate of surgical intervention was significantly higher in the IgG4-negative group (P < 0.001). No significant differences were observed in relapse rates or relapse sites between the two groups. These findings suggest that MPD narrowing and retroperitoneal fibrosis may be characteristic of AIP without elevated IgG4. Vigilant monitoring for relapse is warranted, regardless of serum IgG4 levels.

We aimed to compare the incidence of severe infections between mycophenolate mofetil (MMF) and other immunosuppressants in patients with systemic lupus erythematosus (SLE) on maintenance therapy using data from the Lupus Registry of Nationwide Institutions in Japan. This study employed a prospective cohort design, including patients with SLE undergoing maintenance therapy. Exposure was defined as MMF treatment, and the control group included individuals who received other immunosuppressants (non-MMF) treatments. Severe infections requiring hospitalisation were the primary outcomes, whereas secondary outcomes included all-cause hospitalisation, changes in prednisolone dosage, disease activity and organ damage. Statistical analyses employed marginal structural models with stabilised inverse probability of treatment weighting to adjust for confounders. The analysis included 1004 patients; the incidence of severe infections was 6.5% in the MMF group and 7.5% in the non-MMF group, with no significant difference (OR 0.69, 95% CI 0.34 to 1.39). Similarly, all-cause hospitalisation rates were comparable between the groups (OR 0.72, 95% CI 0.47 to 1.09). Prednisolone dosage was significantly reduced in the MMF group (-0.66 mg/day, 95% CI -1.09 to -0.23). The organ damage score was modestly reduced in the MMF group (-0.19 points, 95% CI -0.37 to -0.01), whereas the change of disease activity score was comparable between the groups (-0.10 points, 95% CI -0.74 to 0.55). MMF does not significantly increase the risk of severe infections compared with other immunosuppressants in SLE maintenance therapy. MMF may contribute to reducing the dose of prednisolone.

Background There is limited research on the factors influencing frailty improvement and on whether exercise therapy is effective in the general population with heart failure. We aimed to examine the factors and interventions that affect the improvement of frailty in older patients with heart failure during hospitalization. Methods This multicentre prospective cohort study included patients with heart failure admitted and treated in the participating hospitals. Cox regression analysis was done to determine factors and interventions that affect improvement of frailty. After the Cox regression analysis, the receiver operating characteristic (ROC) curve was calculated for significant predictors to assess the cut-off point. Results The factors that affect improvement of frailty were the high short physical performance battery (SPPB) chair-stand test and hand grip strength values. The results of the ROC analysis revealed that the cut-off values of the SPPB chair-stand test and hand grip strength were 2 points and 13.7 kg, respectively. Interventions that affect frailty improvement were use of dobutamine, low resting heart rate, early days to start until aerobic exercise, and light intensity or higher of aerobic exercise. Moreover, the cut-off values of the resting heart rate, number of days to start until aerobic exercise, and intensity of aerobic exercise were 80 beats per minute, 7 days, and 31.6%, respectively. Conclusions Our results suggest that pharmacotherapy and exercise will be effective to improve frailty in patients with heart failure. In particular, early exercise therapy, including aerobic exercise, started within 7 days, may be effective to improve frailty in older patients with heart failure with low resting heart rate, depending on their condition on admission.

Spontaneous and refractory hypoglycemia in malignancy poses diagnostic challenges, since its exact underlying mechanisms remain unclear. A 62-year-old female patient with a 10-year type 2 diabetes mellitus history presented with abdominal pain and spontaneous hypoglycemia despite discontinuation of her diabetic treatments. An initial computed tomography (CT) scan revealed a large perinephric tumor, and a second CT, performed a week later, demonstrated significant tumor growth. On admission, she had no neuroglycopenic symptoms despite a serum glucose level of 25 mg/dL (1.39 mmol/L). She showed suppressed insulin and insulin-like growth factor (IGF)-1 levels, elevated lactate levels, a pH of 7.434 with an anion gap of 24.1, and a negative test for anti-insulin antibody. A percutaneous CT-guided tumor biopsy revealed diffuse large B-cell lymphoma. She received continuous dextrose supplementation and prednisolone to alleviate the severe hypoglycemia, but she died from the tumor burden on the sixth day of hospitalization. Postmortem serum immunoblotting revealed the absence of partially processed IGF-2 precursors. The patient's refractory hypoglycemia and hyperlactatemia were consistent with tumor-associated aerobic glycolytic lactate production, known as the Warburg effect. This case illustrates the importance of increased awareness of this underrecognized oncologic emergency in the differential diagnosis of profound spontaneous hypoglycemia in malignancy.

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ObjectivesThis study aimed to clarify the impact of cachexia on physical function recovery during hospitalization among patients with heart failure using the new Asian Working Group for Cachexia criteria and to identify the characteristics of heart failure patients with cachexia.MethodsCachexia at discharge was defined by low body mass index combined with one or more of the following: low handgrip strength, elevated C-reactive protein, or anorexia. Physical function was assessed at admission and discharge. Two-way analysis of variance (ANOVA) was performed to examine the interaction and main effects of the presence of cachexia and duration factors (admission and discharge) on physical function. Hierarchical logistic regression analysis was performed to explore factors associated with the presence of cachexia.ResultsOf the 96 patients analyzed, 26 were heart failure patients with cachexia, and 70 were heart failure patients without cachexia. The results of the 2-way ANOVA indicated that heart failure patients without cachexia exhibited improved physical function at discharge compared to that at admission. In contrast, heart failure patients with cachexia showed no improvement in physical function during hospitalization. Hierarchical logistic regression analysis revealed that a low geriatric nutritional risk index (GNRI) and low muscle power were associated with the presence of cachexia in patients with heart failure.ConclusionsOur results suggest that heart failure patients with cachexia experience poor recovery of physical function during hospitalization, and that reduced muscle power and deterioration in nutritional status, as indicated by a low GNRI, were associated with the presence of cachexia.

Background:Dysmenorrhea is chronic and cyclic pain during menstruation and is a common gynecological problem worldwide. Although there are several reported risk factors for dysmenorrhea, the findings of previous studies are inconsistent. This study aimed to identify lifestyle factors associated with dysmenorrhea.Methods:The study population comprised 36,665 premenopausal female nurses aged 20–49 years who completed the Japan Nurses’ Health Study (JNHS) baseline survey. Out of grades 0–4 of menstrual pain, dysmenorrhea was defined as grades 2–4. Multivariable modified Poisson regression analysis was used to examine the associations between dysmenorrhea and possible risk factors, namely age, current menstrual cycle, marital status, parity, current body mass index (BMI), smoking status, alcohol consumption, work shift, physical activity, sleep duration, and soybean isoflavone intake.Results:There was a significant negative association between age and the prevalence ratio (PR) of dysmenorrhea (p < 0.0001). Older age and parity were significantly associated with decreased multivariable-adjusted PRs. The factors significantly associated with increased PRs were an irregular menstrual cycle, being underweight (BMI < 18.5 kg/m2), smoking, consuming alcohol, short sleep duration, and night shift work. Although the age-adjusted PRs of total isoflavone aglycone equivalents, tofu intake, and miso soup intake showed a significant linear trend toward decreased PRs, there was a significant decrease in multivariable-adjusted PRs only in the “almost every day” tofu-intake group.Conclusion:The JNHS baseline survey revealed that the factors associated with dysmenorrhea in Japanese women were age, parity, menstrual cycle, being underweight, and lifestyle factors, including soybean food intake.