Objective The COVID-19 pandemic has significantly impacted the lifestyle patterns in Japan. During behavioral restrictions, reduced physical activity may have increased the prevalence of reflux esophagitis (RE). We compared the prevalence of RE regardless of the presence or absence of reflux symptoms before and during the pandemic and evaluated its relationship with clinical factors.

Methods We conducted a retrospective analysis of individuals who underwent esophagogastroduodenoscopy during an annual health checkup. The study period was divided into pre-pandemic (April 2017-March 2020; 15,039 cases) and pandemic (April 2020-March 2023; 14,338 cases) phases. We compared the acid-suppressive agent use, the prevalence and severity of RE, BMI, waist circumference, and diaphragmatic hiatus size between the phases.

Results The use of acid-suppressive agents increased from 4.6% before the pandemic to 6.3% during the pandemic (p <0.001). After excluding participants who used acid-suppressive agents, the prevalence of RE increased significantly from 14.3% before the pandemic to 18.9% during the pandemic (p <0.001), and the prevalence of severe RE cases increased from 0.6% to 1.4%. The diaphragmatic hiatus size increased significantly during the pandemic. The COVID-19 pandemic period was positively associated with RE, with an odds ratio (95% confidence interval) of 1.22 (1.14-1.31) in the multiple logistic regression analysis. Among the 4,440 individuals who underwent endoscopy in both phases without acid-suppressive agents, the RE prevalence, mean BMI, proportion with BMI ≥25 kg/m², and waist circumference increased significantly.

Conclusion During the COVID-19 pandemic, the use of acid-suppressive agents and the prevalence of endoscopically diagnosed RE increased, which may be associated with an increased BMI, waist circumference, and diaphragmatic hiatus size, thus indicating the contribution of lifestyle-related factors.

A 46-year-old Japanese man with nonobstructive hypertrophic cardiomyopathy harboring a heterozygous PSEN1 c.367G>A (p.Glu123Lys) variant experienced sudden cardiac arrest due to ventricular fibrillation at 56 years of age. Although PSEN1 variants are primarily associated with early onset Alzheimer's disease, emerging evidence suggests a role in cardiomyopathy that is independent of the amyloid pathology. This case demonstrates a novel cardiac manifestation of presenilin 1 dysfunction. At the time of genetic diagnosis, the patient exhibited normal cognition, suggesting that cardiovascular manifestations may precede neurodegeneration. This report suggests an expansion of the phenotypic spectrum associated with PSEN1 variants and highlights the need for further investigation of potential cardiac manifestations in PSEN1 variant carriers.

Objective Nationwide population-based epidemiological data on intussusception in Japan are limited. This study aimed to preliminarily investigate the temporal trends, demographic characteristics, and seasonal patterns of intussusception reduction procedures using a comprehensive administrative database.

Methods We analyzed data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data (2014-2023). The procedures were categorized as nonoperative or operative. The crude and age-adjusted procedure rates were calculated per 100,000 person-years. Temporal trends were assessed using linear and Poisson regressions. Seasonal variations (April 2019-March 2024) were evaluated using a one-way analysis of variance with post-hoc comparisons, and correlations with pediatric infectious diseases and meteorological variables were examined using Pearson's correlation coefficients.

Results Over the decade, 42,173 procedures were performed, with an average annual rate of 3.4 per 100,000 person-years and an overall male-to-female ratio of 2.1:1. The age distribution was bimodal, with a major peak among children aged 0-4 years and a minor peak among adults aged ≥90 years. The annual procedure counts declined from 5,836 in 2014 to 3,735 in 2023. The age-adjusted nonoperative procedure rates decreased significantly, particularly among older adults (p <0.001). In 2023, nonoperative reductions accounted for 94.7% of all procedures, whereas operative procedures accounted for 5.3%. Nonoperative procedures demonstrated significant seasonal variation (p <0.05), particularly between spring and summer, and showed moderate positive correlations with pharyngoconjunctival fever and hand, foot, and mouth disease, as well as weak positive correlations with temperature.

Conclusion This preliminary nationwide study provides contemporary epidemiological insights into the management of intussusception in Japan.

A 77-year-old man receiving a seven-week course of systemic glucocorticoids for organizing pneumonia was referred to our hospital with persistent fever and generalized edema. During hospitalization, swelling of the left wrist became apparent and it progressively worsened. Repeated blood culture examinations were initially negative, and Corynebacterium striatum was subsequently isolated from the synovial fluid and from a single set of blood cultures obtained on the sixth attempt. However, these findings were initially regarded as contamination. A subsequent synovial biopsy identified C. striatum, thus leading to a final diagnosis of native wrist septic arthritis. The patient's symptoms improved after initiating intravenous vancomycin therapy.

Objective Neurobehavioral symptoms of dementia substantially impair the quality of life (QOL) of caregivers. However, most caregiver burden instruments are ordinal and lack empirically derived symptom-specific weighting, limiting quantitative interpretation. This study aimed to develop a utility-weighted scale to quantitatively assess caregiver QOL impairment across the dementia severity levels.

Methods Eleven dementia-related neurobehavioral symptoms were identified through a literature review and interviews with 115 dementia care professionals. Utility weights were estimated using a conjoint analysis based on the rankings of 27 hypothetical dementia profiles. The resulting Caregiver Quality of Life (CgQOL) scale was evaluated for reliability and validated in individuals with Alzheimer's disease using the Zarit Burden Interview (ZBI), Functional Assessment Staging Tool (FAST), and Mini-Mental State Examination (MMSE).

Results A conjoint analysis revealed a clear hierarchy of symptom importance, with agitation having the highest relative importance (15.5%), followed by difficulties with toileting (12.1%) and sleep disturbances (11.7%). The total CgQOL scores ranged from 0 to 36.3. The scale demonstrated excellent inter-rater reliability (weighted κ=0.86) and internal consistency (Cronbach's α=0.998). CgQOL scores increased monotonically with advancing FAST stage and were negatively correlated with the MMSE scores. Moderate convergent validity was observed with the ZBI scores, thus indicating that the two instruments captured related but distinct aspects of the caregiver burden.

Conclusion The CgQOL scale is a novel parametric utility-weighted instrument that quantitatively captures caregiver QOL impairment associated with dementia-related neurobehavioral symptoms and complements existing caregiver burden measures. This framework enables a more nuanced and quantitative evaluation of caregiver burden and may serve as a complementary tool to conventional scales in both clinical and research settings.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by asthma, chronic rhinosinusitis with nasal polyps, eosinophil-driven tissue inflammation, and necrotizing small- to medium-sized vessel vasculitis. Myeloperoxidase - Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA) is detectable in approximately 30%-40% of patients, and ANCA-positive and ANCA-negative diseases exhibit distinct yet overlapping clinical patterns. Type 2 immune responses are predominant, with interleukin-5 (IL-5) driving eosinophil differentiation and survival, and IL-4 and IL-13 promoting eosinophil recruitment and IgE-associated pathways. Activated eosinophils contribute to tissue injury through degranulation and eosinophil extracellular trap formation (EETosis). Glucocorticoids remain the foundation of therapy, but they are often insufficient to achieve a sustained remission as monotherapy. Conventional immunosuppressants are used for severe disease, and B-cell-targeted therapy may be considered for selected vasculitic presentations. Biological agents targeting the IL-5/IL-5 receptor axis have been shown to prolong remission, reduced relapse risk, and enabled glucocorticoid sparing. However, some patients remain symptomatic, and reliable biomarkers to guide individualized therapy are lacking. Ongoing research focuses on biomarker panels and cell-free DNA to clarify the role of EETosis and define molecular endotypes to support precision-medicine approaches.

Ulcerative colitis (UC) and Crohn's disease (CD) are well-known representative forms of inflammatory bowel disease (IBD) and they have long been regarded as intractable diseases of unknown etiology. Recent advances in genomic analyses, immunology, studies of the intestinal microbiota, elucidation of environmental factors, and long-term human cohort studies have greatly improved our understanding of the disease pathogenesis and accelerated the development of preventive approaches. Historically, the incidence of IBD was the highest in Western countries; however, in recent years, the number of patients in newly industrialized countries has increased rapidly. Therefore, the establishment of active strategies aimed at preventing disease onset has become extremely important, in addition to the development of new therapeutic agents. This review summarizes the most recent findings regarding the etiology of IBD obtained mainly from human cohort studies and discusses the current efforts directed toward prevention and early intervention, with particular emphasis on the importance of dietary and nutritional factors.

Chronic obstructive pulmonary disease (COPD) is a major global health burden. However, it remains widely under-recognized despite its substantial impact on morbidity and mortality rates. Most cases remain undiagnosed because the early symptoms are often subtle, thus hindering timely intervention. Globally, the World Health Organization (WHO), within its noncommunicable disease framework, advocates a multifaceted approach to COPD, including prevention, early diagnosis, and long-term management. Several countries have established national COPD strategies that emphasize early diagnosis, rehabilitation, and population-based interventions. In Japan, the Japanese Respiratory Society launched "COMORE-By2032" (Project for COPD Mortality Reduction By 2032), which phonetically corresponds to the Japanese word "Komorebi," pronounced "koh-moh-reh-bee." It employs a two-step approach. Step 1 promotes public awareness and early consultation for high-risk individuals, whereas Step 2 supports healthcare professionals in improving diagnosis and treatment. This initiative emphasizes collaboration to enhance awareness, improve the diagnostic rates, prevent exacerbations, and ultimately extend the healthy life expectancy.

Objective Physician burnout threatens healthcare quality, safety, and sustainability. Identifying individual (e.g., lifestyle) and organizational (e.g., work environment, leadership) factors is critical for developing effective interventions. This study aimed to examine the factors associated with burnout among board-certified internists in Japan.

Methods A nationwide cross-sectional survey was conducted from November 15 to December 31, 2024, among 3,320 internists on the Japanese Society of Internal Medicine mailing list; 353 responded (10.6%). Burnout was assessed using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), which covers emotional exhaustion, depersonalization, and reduced personal accomplishment. The survey also captured professional, community, and personal factors.

Results Among 316 complete responses, 17.1% (n=54) met the criteria for extreme burnout (high-risk thresholds in all domains), and 64.6% (n=204) met high-risk thresholds for emotional exhaustion and/or depersonalization. The risk factors included a high workload (OR 2.16, 95% CI 1.36-3.41), electronic health record burden (OR 1.42, 95% CI 1.11-1.83), and preoccupation with the past or future (OR 2.43, 95% CI 1.84-3.21). Protective factors included in-person social interaction (OR 0.58, 95% CI 0.39-0.87), supportive/respectful leadership from supervisors (OR 0.52, 95% CI 0.38-0.69), and perceived support from senior leadership (OR 0.60, 95% CI 0.47-0.78) and co-workers (OR 0.63, 95% CI 0.49-0.81).

Conclusion Workload, psychological stress, and leadership quality strongly influence burnout among Japanese internists. Structural interventions that promote a supportive culture and relational well-being may help mitigate burnout.

A 34-year-old woman with common variable immunodeficiency (CVID) developed pulmonary abnormalities despite adequate subcutaneous immunoglobulin replacement and long-term low-dose erythromycin therapy. Her lung lesions and hypoxemia progressed, and a surgical biopsy confirmed granulomatous-lymphocytic interstitial lung disease (GLILD). Prednisolone and cyclosporine were administered. However, her condition worsened, and she died of infectious complications. Although patients with CVID-GLILD often respond to immunoglobulin replacement therapy or immunosuppression, this case was rapidly progressive and refractory to treatment.

A 73-year-old woman experienced sudden drowsiness and sleep attacks for 10 years, as well as a loss of strength in her legs when laughing. Polysomnography (PSG) showed an apnea-hypopnea index (AHI) of 87.0, indicating severe obstructive sleep apnea (OSA). The Multiple Sleep Latency test showed three sleep-onset rapid eye movement periods, and symptoms of sleep attacks and cataplexy were observed, leading to a diagnosis of narcolepsy. After Continuous Positive Airway Pressure treatment, the AHI decreased to 21.0, and cataplexy occurred only once a month. Late-onset narcolepsy is a rare condition. We herein report a case of late-onset Type1 narcolepsy complicated by OSA.

We report a case of intravascular large B-cell lymphoma (IVLBCL) characterized by three episodes of spontaneous remission before a definitive diagnosis. A 60-year-old man presented with headache and cognitive impairment, with elevated serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor levels. Although IVLBCL was suspected, a random skin biopsy and bone marrow examination yielded nonspecific findings, and the symptoms resolved spontaneously. Similar self-limited relapses occurred twice in this patient. Ten months after onset, persistent fever, neurological deterioration, hypoxemia, and sustained LDH elevation developed, and IVLBCL was finally diagnosed by a random skin biopsy. This case illustrates the extremely rare phenomenon of the repeated spontaneous remission in IVLBCL.

Neisseria meningitidis is a Gram-negative diplococcus that rarely causes invasive diseases in Japan. We report a case of polyarticular meningococcal septic arthritis in an immunocompetent 62-year-old Japanese man. After 3 days of fever, he developed pain in the dorsum of the right hand and right shoulder. Computed tomography revealed effusions in the right wrist and acromioclavicular joint. Blood cultures grew N. meningitidis serogroup Y, sequence type 1655. A PCR assay detected the 16S rRNA gene of N. meningitidis in culture-negative wrist synovial fluid. Treatment with ceftriaxone followed by oral amoxicillin led to a complete recovery.

A 51-year-old woman presented with severe headache and severe anemia. She was diagnosed with autoimmune hemolytic anemia (AIHA) and treated with prednisolone and red blood cell transfusion. During the clinical course, the patient developed acute transient neurological symptoms. Magnetic resonance angiography revealed multifocal segmental narrowing of the cerebral arteries, which improved spontaneously on follow-up. The clinical and radiological findings were consistent with reversible cerebral vasoconstriction syndrome (RCVS). This case highlights that multiple factors, including active hemolysis, red blood cell transfusion, and corticosteroid therapy, may contribute to the development of RCVS.

Pulmonary infarction (PI) often mimics lobar pneumonia. A 23-year-old man with prostatitis presented with pleuritic pain and hemoptysis. Despite high inflammatory markers, consolidation was refractory to antibiotic treatment. Retrospectively, the initial opacities represented the hyperacute hemorrhagic phase of PI. Thoracentesis revealed bloody effusion, and contrast-enhanced computed tomography (CECT) confirmed pulmonary thromboembolism with characteristic "central lucencies." Anticoagulation therapy led to his recovery. PI should be considered in young patients with refractory pneumonia. Bloody effusion and central lucencies are critical diagnostic clues. Combined localized infection and transient stressors (dehydration/immobility) can trigger venous thromboembolism, even in the absence of hereditary thrombophilia. Early CECT can prevent unnecessary invasive procedures.

A 53-year-old man presented with recurrent, motor-predominant acute polyneuropathy that progressed to a loss of ambulation, accompanied by fever and arthralgia. Nerve conduction studies demonstrated demyelinating features, a cerebrospinal fluid analysis revealed albuminocytological dissociation, and the presence of anti-GM1/GM2 IgM antibodies suggested acute inflammatory neuropathy. Further evaluation revealed markedly elevated interleukin-6 (IL-6) levels and diffuse lymphadenopathy on FDG-PET imaging, and a subsequent lymph node biopsy confirmed idiopathic multicentric Castleman disease (iMCD). While slowly progressive sensory neuropathy is the typical manifestation of iMCD, acute, severe, motor-predominant neuropathy is extremely rare. This case highlights the mechanisms of IL-6-mediated neuropathy.

Acute autonomic and sensory neuropathy (AASN) is a rare disorder characterized by severe autonomic and sensory dysfunction without motor involvement, often occurring after a febrile illness. A 47-year-old woman had recurrent syncope episodes four days after fever onset, followed by progressive deep sensory loss. On day 14 of hospitalization at the previous hospital, she was transferred to our institution. Magnetic resonance imaging revealed hyperintensity in the posterior columns of the cervical cord spanning three vertebral levels on T2-weighted images and diffuse enhancement of the posterior roots in the cervical and lumbar spinal cord on contrast-enhanced T1-weighted images. Sensory responses were absent in nerve conduction studies, whereas motor responses in both the upper and lower extremities were preserved. Two weeks after syncope became apparent, aggressive immunotherapy was administered; however, the outcome was poor. The early recognition of autonomic and sensory neuropathy, along with contrast-enhanced MRI of the spinal cord, may be useful for the diagnosis and management of AASN.

Orbital apex syndrome (OAS) is a rare complication of odontogenic maxillary sinusitis. An 87-year-old woman with gingivitis caused by a dental implant infection developed diplopia, followed by a rapid visual deterioration and limited extraocular movement in her left eye. Imaging revealed penetration of the upper left first molar into the maxillary sinus and inflammation involving the extraocular muscles and the orbital apex. Staphylococcus lugdunensis (S. lugdunensis) was cultured from the patient's sinus. Steroid pulse therapy, antimicrobial treatment, tooth extraction, and sinus irrigation partially improved her visual acuity, while extraocular movement was fully recovered. This report presents a rare case of OAS caused by S. lugdunensis.

IgG4-related disease (IgG4-RD) is characterized primarily by elevated serum IgG4 levels and it can affect multiple organs. We herein present a case of IgG4-RD affecting the kidneys, right submandibular gland, lungs, mediastinal lymph nodes, and retroperitoneum, despite normal serum IgG4 levels. In this case, a histopathological examination of the kidneys and submandibular glands revealed marked lymphoplasmacytic infiltration and a relatively small number of IgG4-positive plasma cells. The patient was diagnosed with IgG4-RD and showed a favorable response to corticosteroid therapy. This case highlights the importance of a histopathological evaluation for diagnosing IgG4-RD, particularly in patients with normal serum IgG4 levels.

Osteoporosis is a major complication of rheumatoid arthritis (RA), caused by glucocorticoid use and chronic inflammation, leading to an increased fracture risk. We report a rare case of bilateral insufficiency calcaneal fractures presenting with talalgia and swelling in a patient with RA who was initially misdiagnosed as having a disease relapse and treated with escalated biological disease-modifying antirheumatic drugs. Subsequent foot magnetic resonance imaging (MRI) revealed bone marrow edema and bilateral fracture lines in the posterior calcaneus without synovitis. This case highlights that talalgia in patients with RA may reflect insufficiency fractures rather than disease relapse, and appropriate imaging evaluation is therefore important for an early and accurate diagnosis.

Delayed inflammatory complications after the coil embolization of intracranial aneurysms appearing years after angiographic cure are rare. We describe a patient who underwent coil embolization for a ruptured internal carotid-posterior communicating artery aneurysm at 61 years of age and developed recurrent transient neurological symptoms seven years later. A cerebrospinal fluid analysis revealed marked neutrophilic pleocytosis and hypoglycorrhachia, strongly suggesting infectious meningitis. However, extensive tests for infection and autoimmune reactions were negative. Magnetic resonance imaging revealed perianeurysmal vasogenic edema with intra-aneurysmal enhancement. Corticosteroid therapy resulted in a rapid clinical and radiological resolution of the symptoms. This case highlights a rare delayed inflammatory complication that mimics infectious meningitis.

Idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO) rarely involves the lungs. We report the case of a 50-year-old man with persistent gastrointestinal symptoms who was found to have bilateral ground-glass opacities on chest CT. Despite prominent imaging abnormalities, a bronchoscopic lung biopsy revealed no inflammatory changes in the lungs. Bone marrow and lymph node biopsies confirmed the diagnosis of iMCD-TAFRO. Treatment with tocilizumab and corticosteroids resulted in clinical remission for 3 years. Pulmonary manifestations likely reflect secondary fluid retention rather than primary lung disease. This illustrates the importance of performing comprehensive tissue evaluations beyond a lung biopsy when systemic symptoms are accompanied by pulmonary findings.

True hemothorax as an initial manifestation of prostate cancer has not yet been reported. An adult male presented with acute right-sided pleural effusion. Diagnostic thoracentesis yielded hemorrhagic pleural fluid, with a pleural fluid hematocrit ≥ 50% of the peripheral blood hematocrit, confirming hemothorax. Contrast-enhanced computed tomography revealed prostate enlargement, pulmonary nodules, and pleural masses. Transbronchial biopsies of the pulmonary nodule confirmed metastatic adenocarcinoma positive for prostate-specific antigen and negative for thyroid transcription factor-1, thus establishing the diagnosis of metastatic prostate adenocarcinoma. Androgen deprivation therapy improved the hemothorax. Bloody pleural effusion warrants hematocrit measurement and evaluation for malignancy, including metastatic prostate cancer.

We report a rare case in which CD5-positive diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS), and CD5-positive intravascular large B-cell lymphoma (IVLBCL) were identified in different samples from the same patient. A 76-year-old man presented with widespread lymphadenopathy and a prostatic mass on imaging. A prostatic biopsy revealed CD5+ DLBCL NOS. Notably, he had undergone transurethral resection of the prostate (TURP) four months prior because of urinary retention. A retrospective histological review of the TURP specimen revealed CD5-positive IVLBCL. This case suggests that DLBCL may initially manifest with an IVLBCL-like growth pattern at an extremely early stage.

Malignant lymphoma in ulcerative colitis (UC) is uncommon, and diffuse large B-cell lymphoma (DLBCL) without immunosuppressive or biologic therapy is particularly rare. We report a case of an Epstein-Barr virus-negative patient with long-standing left-sided UC in remission who developed rapidly enlarging synchronous DLBCL lesions in the ascending and sigmoid colon. The diagnosis was made endoscopically and histologically, and treatment with Pola-R-CHP followed by rituximab achieved a complete remission. A literature review showed that most UC-associated lymphomas are EBV-positive DLBCL related to immunosuppression. Although malignant lymphoma is rare in patients with UC, it can occur and therefore should be considered during surveillance colonoscopy.

Objective In cancer care, the patient burden encompasses not only physical and psychological toxicity, but also financial and time toxicity. Multiple myeloma (MM) requires ongoing therapy. However, the impact of time toxicity on treatment decision-making is unclear.

Methods We retrospectively reviewed the medical records of the patients diagnosed with MM between April 1, 2010, and March 31, 2023, at a single center. The collected data included M-protein type, age at diagnosis, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), employment status, commute time, and receipt of ixazomib, lenalidomide, and dexamethasone (IRd) therapy.

Results Of the 97 identified patients, 74 with relapsed/refractory MM were included in the main analysis. The mean commute time was 74.5 min for patients who received IRd therapy and 46.3 min for those who did not. When the patients were stratified by commute time (≥65 min, Long group), 52.9% of the long group received IRd compared with 19.3% in the not-long group. In multivariable logistic regression, the longer commute time was significantly associated with IRd use (odds ratio, 4.63; 95% CI, 1.45-15.4; p = 0.009).

Conclusion Our findings suggest that longer commute times may be associated with treatment selection, thus highlighting the time burden as an important factor in real-world decision-making for MM.

Cerebral cortical encephalitis (CCE) represents a distinct phenotype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. The most frequent presentation of CCE is acute encephalitis. We describe two cases with diverse clinical courses that posed diagnostic challenges. The cases included a 24-year-old man with a seizure-predominant smoldering course over several months, initially diagnosed with focal epilepsy, and a 27-year-old woman with nonspecific headache and fever without any neurological deficits or seizures. Brain magnetic resonance imaging (MRI) in both cases showed cortical fluid-attenuated inversion recovery hyperintensity with adjacent subcortical hypointensity. CCE may present with diverse clinical courses, and characteristic MRI findings were pivotal for making an accurate diagnosis.

A woman in her late 50s with advanced lung adenocarcinoma, initially EGFR mutation-negative on single-plex testing, received cytotoxic chemotherapy and immune checkpoint inhibitors. After 1 year and 8 months, she developed peritoneal carcinomatosis. Third-line erlotinib led to an improvement in her performance status (PS 3 to 2 in 10 days) and a marked reduction in peritoneal carcinomatosis after 4 months, with the effect lasting for 9 months. Immunohistochemistry of the ascitic fluid revealed an EGFR L858R mutation. This case highlights the possibility of false-negative results on initial testing and suggests the potential benefit of EGFR-TKIs, even in EGFR mutation-negative cases at diagnosis.

Objectives To investigate the efficacy of switching from oral to subcutaneous methotrexate (MTX) in alleviating MTX-related intolerance symptoms in Japanese patients with rheumatoid arthritis (RA).

Methods This non-randomized, prospective, observational study included Japanese patients with RA who experienced intolerance symptoms despite combination therapy with folic acid. Patients were assigned to switch to subcutaneous MTX (switching group) or continue oral MTX (continuation group). The primary endpoint was the change in patient nausea visual analog scale (VAS) from baseline to week 13. The secondary endpoints were the change in patient fatigue VAS and the change in RA activity from baseline to week 13 before and after adjusting for patient characteristics.

Results Of the 60 patients enrolled, 28 were assigned to the switching group and 32 to the continuation group. In the adjusted analysis, the switching group showed a significantly greater reduction in patient nausea VAS and a numerically greater reduction in patient fatigue VAS than that in the continuation group. Changes in the RA activity were similar between the groups. Multivariate logistic regression analyses demonstrated that switching to subcutaneous MTX significantly improved the patient-reported nausea.

Conclusions Switching from oral to subcutaneous MTX reduced intolerance symptoms compared with oral MTX in Japanese patients with RA.

Advanced-stage Parkinson's disease (PD) and myasthenia gravis (MG) share overlapping clinical features, including dysphagia, dysarthria, fatigue, and fluctuating symptoms. When PD precedes MG, these manifestations may be misinterpreted as a progression of PD, potentially leading to an underdiagnosis of MG. Although the coexistence of PD and MG is rare, it nevertheless requires careful consideration. Furthermore, the pharmacological treatments for these two disorders differ substantially, and medications used for one condition may exacerbate the other condition. We report a patient with PD complicated by MG, in whom anticholinergic treatment with biperiden led to the exacerbation of MG-related symptoms, ultimately resulting in the diagnosis of MG.

Acquired lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare cause of a marked reduction in high-density lipoprotein cholesterol (HDL-C). We report a 75-year-old Japanese woman with a progressive decline in HDL-C from 64 to <2 mg/dL over five years. Laboratory tests showed a markedly decreased LCAT activity and protein levels with anti-LCAT autoantibodies, whereas a genetic analysis revealed no LCAT mutations. Lipidomic profiling demonstrated free cholesterol accumulation, the loss of HDL subclasses, and TG-rich LDL particles. No underlying autoimmune disease was identified. This case highlights the importance of a lipid subclass analysis and the recognition of acquired LCAT deficiency in patients with a marked HDL-C deficiency.

Objective This study aimed to clarify the background of non-communicable disorders, including hypertension (HTN), liver dysfunction, obesity, and hyperuricemia, which could be related to the incidence of diabetes, using a cohort of newly enrolled students (aged 18-20 years) at a university in Gifu, Japan.

Methods We analyzed data collected over a 12-year period from April 2010 to March 2022 at a university in Gifu, Japan.

Materials From the above dataset, we selected individuals who did not have diabetes at admission and who underwent a follow-up examination four years later at the time of their progression to a master's course (n=3,242).

Results Five of these participants (0.15%) developed probable diabetes (elevated plasma glucose or HbA1c, or both) and three (0.09%) developed definite diabetes (elevated plasma glucose and HbA1c) by the time of their second visit. A logistic regression analysis of the association between preceding HTN and the risk of new-onset diabetes demonstrated a significant crude odds ratio of 53.7 for probable diabetes and 35.0 for definite diabetes. Crude odds ratios for obesity, liver dysfunction, and hyperuricemia were calculated for probable diabetes, but not for definite diabetes.

Conclusion Preceding non-communicable disorders, especially HTN, are remarkable risk factors for diabetes in young adults.

Heparin-induced thrombocytopenia (HIT) is a potentially fatal complication of heparin therapy, particularly during extracorporeal mechanical support requiring anticoagulation. We report the case of a 57-year-old woman with fulminant myocarditis complicated by acute kidney injury who was transferred while receiving extracorporeal membrane oxygenation and continuous renal replacement therapy with unfractionated heparin. After transfer, a rapid platelet decline and repeated circuit occlusions raised a strong suspicion of HIT based on the 4Ts score. Heparin was replaced with nafamostat mesilate or argatroban, and HIT antibodies were detected. Both bleeding and thrombotic complications occurred during intensive care, thus reflecting the complexity of managing critically ill patients receiving multiple extracorporeal mechanical supports.

The management of ischemic heart disease has traditionally focused on obstructive epicardial coronary artery disease. However, a substantial proportion of patients with angina and objective myocardial ischemia have no significant coronary stenosis. Vasospastic angina (VSA; also termed coronary spastic angina [CSA] ) and coronary microvascular dysfunction (CMD) are now recognized as major mechanisms underlying angina/ischemia with non-obstructive coronary arteries (ANOCA/INOCA). These evolving concepts have been progressively incorporated into the clinical practice guidelines. Japanese guidelines have played a pioneering role in establishing diagnostic criteria for VSA through coronary spasm provocation testing. More recently, international guidelines have emphasized CMD as a distinct clinical entity and recommended coronary functional assessment using both invasive and non-invasive modalities. This review summarizes the historical evolution of the guideline-based perspectives on VSA and CMD and discusses their implications for contemporary clinical practice.

Objective Changes in the left ventricular ejection fraction (LVEF) after an ST-segment elevation myocardial infarction (STEMI) are associated with subsequent ischemic events and mortality. This study aimed to investigate the determinants of a mid-term improvement and deterioration of LVEF in patients with STEMI.

Methods We included 585 patients with STEMI who had a modified Simpson EF both at index admission and mid-term (6-12 months) follow-up. We divided the patients into the EF deterioration group (≥10% decrease in EF, n=38), the EF improvement group (≥10% increase in EF, n=127), and the unchanged EF group (<10% change in EF, n=420).

Results Baseline EF was significantly associated with an EF deterioration (OR1.472 per 5.0 % increase, 95%CI:1.231-1.761, p<0.001). The hemoglobin levels were inversely associated with an EF deterioration (OR0.760 per 1.0 g/dL increase, 95%CI: 0.632-0.914, p=0.003). The peak creatine kinase levels were significantly associated with an EF deterioration (OR1.034 per 100 U/L increase, 95%CI: 1.019-1.050, p<0.001). A female sex was significantly associated with an EF improvement (OR2.118, 95%CI: 1.222-3.671, p=0.008). The pulse rate was inversely associated with an EF improvement (OR0.887 per 10 bpm increase, 95%CI: 0.791-0.995, p=0.041). Infarct-related artery with LMT-left anterior descending artery was significantly associated with an EF improvement (OR1.661, 95%CI: 1.009-2.734, p=0.046). Time interval between the Baseline EF and follow-up EF was significantly associated with an EF improvement (OR1.008, 95%CI: 1.002-1.013, p=0.006). The peak creatine kinase level (OR0.981 per 100 U/L increase, 95%CI: 0.970-0.992, p<0.001) and baseline EF (OR0.568, 95%CI: 0.500-0.645, p<0.001) was inversely associated with an EF improvement.

Conclusion A higher baseline EF, lower hemoglobin levels at admission, and higher peak creatine kinase levels were associated with a mid-term deterioration of LVEF, whereas a female sex, LM-LAD as the infarct-related artery, and the time interval between baseline and follow-up EF were associated with a mid-term improvement in LVEF. Knowledge of these determinants may help to refine the post-STEMI risk stratification and therapeutic strategies.

Objective Steatotic liver disease is increasingly prevalent, and patients with this condition who have a poor albumin-bilirubin (ALBI) score are at a high risk of liver-related complications and all-cause mortality. We evaluated the factors associated with progression to a poor ALBI score in individuals with hepatic steatosis over a 5-year follow-up in a health check-up population.

Patients and Methods In this longitudinal cohort study, 5,038 individuals with hepatic steatosis at baseline and a low ALBI score (<−2.77) were followed for 5 years. Clinical and metabolic factors associated with a high ALBI score with hepatic steatosis at the end of the follow-up were analyzed using a multivariate logistic regression analysis.

Results Of the 5,038 participants with hepatic steatosis and a low baseline ALBI score in 2018 with data of ALBI score in 2023, 682 (13.5%) were classified into the High group (ALBI score ≥−2.77) in 2023. A multivariate logistic regression analysis demonstrated that being overweight or obese at baseline was independently associated with a high ALBI score with hepatic steatosis at the 5-year follow-up (OR: 1.550, p<0.001). Changes in overweight or obese status from 2018 to 2023 were significantly associated with the prevalence of a high ALBI score with hepatic steatosis in 2023 (p<0.001). The prevalence was highest among participants who were overweight or obese at both time points (14.6%).

Conclusion Being overweight or obese with hepatic steatosis was associated with a worse ALBI score.

Neuroleptic malignant syndrome (NMS) can be complicated by rhabdomyolysis, a known cause of acute kidney injury (AKI) that typically resolves within a short period. However, some cases of NMS-associated rhabdomyolysis require hemodialysis. We report a woman in her fifties who developed AKI secondary to NMS-associated rhabdomyolysis and required prolonged renal replacement therapy (RRT). She experienced sepsis and contrast exposure, and dialysis independence was achieved only after 2 months, the longest reported duration. This case highlights that NMS-associated rhabdomyolysis-induced AKI may lead to prolonged dialysis, particularly in the presence of additional risk factors for renal injury.

Enteric-type thymic adenocarcinomas are rare histological variants with limited treatment options. We report the case of a 56-year-old woman with stage IVB enteric-type thymic adenocarcinoma who was treated with lenvatinib. The patient underwent chemoradiotherapy and subsequently received lenvatinib for local recurrence. Despite the patient receiving a low dosage owing to side effects, the size of the recurrent lesions decreased. However, 5 months later, new brain metastases and carcinomatous meningitis developed, and the patient eventually succumbed to cancer. This case suggests that lenvatinib may be an effective treatment for enteric-type adenocarcinomas. However, at low doses, its efficacy may be limited to intracranial lesions.

Acute intermittent porphyria (AIP) is a condition characterized by the neurotoxic accumulation of δ-aminolevulinic acid and porphobilinogen. However, chronic kidney disease is an under-recognized complication. A 50-year-old woman experienced recurrent abdominal pain with repeated acute kidney injury and hyponatremia, resulting in a rapid decline in renal function. Marked elevations of both metabolites, as well as her genetic mutation, confirmed AIP. The administration of hemin markedly decreased the frequency of porphyria attacks and significantly attenuated the annual estimated glomerular filtration rate decline. Although the patient eventually developed end-stage kidney disease, hemin treatment slowed the progression of renal failure.

We present the case of a 74-year-old woman with a large ovarian tumor who developed cancer-associated stroke with multiple acute cerebral infarcts and markedly elevated D-dimer levels. Unfractionated heparin was initiated. However, thrombocytopenia and rising D-dimer levels on Day 11 led to its discontinuation and a diagnosis of probable heparin-induced thrombocytopenia, supported by a strongly positive PF4/heparin antibody assay. Despite subsequent non-heparin anticoagulation, she developed recurrent ischemic stroke and systemic embolic events, and surgery for the ovarian tumor was no longer feasible. This case highlights the therapeutic dilemma posed by the coexistence of cancer-associated stroke and immune-mediated heparin-induced thrombocytopenia.

Objective Sternal wound infection (SWI) is a devastating complication following cardiac surgery. Although most SWI are bacterial and well described, Candida SWI remains poorly characterized. This study aimed to examine the clinical characteristics, management, and outcomes of Candida SWI.

Methods We retrospectively reviewed the data of patients with Candida SWI following cardiac surgery at Baylor St. Luke's Medical Center between 2013 and 2024.

Results Of the 11,108 cardiac surgeries, 55 Candida SWI were identified: superficial (10.9%), deep (21.8%), sternal osteomyelitis (40.0%), and mediastinitis (27.3%). Most occurred within 90 days postoperatively (70.9%). Candida albicans was most common (69.1%), followed by C. parapsilosis (12.7%), C. glabrata (9.1%), and C.tropicalis (7.3%). Surgical intervention was performed in 87.3% of the patients, and 60.0% received antifungal therapy for >6 weeks. The ninety-day mortality was 20.0%. In-hospital mortality was significantly associated with postoperative mechanical ventilation >48 hours [100% (in-hospital death group) vs. 63.9% (survivor group), OR: 17.38, 95% CI, 0.95-316.99; P =.008] and a lack of surgical debridement [26.4% (in-hospital death group) vs. 6.8% (survivor group), OR: 0.14, 95% CI, 0.02-0.79, P =.023]. However, it was not associated with mediastinitis [54.5% (in-hospital death group) vs. 20.5% (survivor group), OR: 4.41, 95% CI, 1.15-16.90; P =.052]. Mediastinitis was associated with a longer cardiopulmonary bypass time [213 min (mediastinitis group) vs. 142.5 min (non-mediastinitis group), P =.005] and extended postoperative hospital stays [55 days (mediastinitis group) vs. 36 days (non-mediastinitis group), P =.027].

Conclusions Candida SWI presented with variable extents and onsets. Despite aggressive surgical management and prolonged antifungal therapy, the prognosis remains challenging.

We report the case of a 53-year-old woman with type 2 diabetes and bulimia nervosa who developed prolonged paralytic ileus after self-injecting tirzepatide 7.5 mg, 10 mg, and 15 mg on three consecutive days. Tirzepatide had been prescribed for diabetes treatment. However, the excessive self-administration resulted in paralytic ileus. No mechanical obstruction was found, and the condition resolved after three weeks of conservative therapy, including gastrointestinal decompression and prokinetic agents. Because tirzepatide has a long half-life, an overdose may cause the persistent suppression of intestinal motility. Misunderstanding about drug effects may lead to an overdose, thus requiring careful instruction and medication management.

Chronic pulmonary aspergillosis typically affects individuals with normal or mildly compromised immune systems and it is categorized into several subtypes based on the lesion morphology and disease progression patterns. We present a rare case of a bacterial lung abscess developing within a pre-existing pulmonary cavity, representing a transitional phase from simple pulmonary aspergilloma to chronic cavitary pulmonary aspergillosis. The patient underwent percutaneous drainage of the purulent cavity, followed by combined antibacterial and antifungal therapy, resulting in favorable outcomes without any complications. In selected cases in which the cavitary structure remains intact, minimally invasive treatments, such as percutaneous lung abscess drainage, may offer a viable therapeutic option.

A 58-year-old man underwent left lower lobectomy for lung cancer. During the postoperative follow-up, upper-lung field pulmonary fibrosis (upper-PF) radiologically consistent with pleuroparenchymal fibroelastosis, gradually emerged in the left upper lobe. Seventeen years after surgery, the patient presented with acute dyspnea. Chest computed tomography demonstrated bilateral ground-glass opacities, predominantly in the contralateral non-fibrotic lung. After excluding other potential causes of acute respiratory failure, an acute exacerbation of unilateral upper-PF was diagnosed and successfully treated with anti-inflammatory therapy. Chest physicians should recognize that an acute exacerbation can develop even in patients with unilateral upper-PF, although it might be extremely rare.