Percutaneous coronary intervention (PCI) has become the standard procedure for patients with angina and acute coronary syndrome. From the perspective of technology and technique, PCI has advanced over the last four decades, resulting in considerably improved clinical outcomes in patients with coronary artery disease in the current era. In this review article, we summarize recent advances, promising technologies, and areas for research in the field of PCI.

There are high expectations regarding heart regeneration for refractory heart failure (HF). Transplantation of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) is expected to replace CMs lost due to HF, and various studies have been conducted to apply this therapy clinically. Though issues such as arrhythmias and immune rejection remain, the mass production of purified hPSC-derived CMs, their efficient transplantation, and methods to improve their engraftment pushed up the transplantation of hPSC-derived CMs to the clinical stage. In contrast, a direct cardiac reprogramming method has been developed, where cardiac fibroblasts are directly converted into CM-like cells without undergoing PSCs by overexpressing reprogramming factors. Although many challenges still remain in the clinical application of direct cardiac reprogramming, this can be a novel treatment which overcomes issues of transplantation of hPSC-derived CMs.

Asthma is characterized by chronic airway inflammation as its primary pathological condition, which leads to various respiratory symptoms due to airway narrowing, with type 2 inflammation playing a central role. Asthma treatment, primarily centered on inhaled corticosteroids, aims to suppress type 2 inflammation and improve airway narrowing. However, severe asthma that cannot be controlled with high-dose inhaled corticosteroids or other asthma medications remains a clinical issue. The availability of multiple biological agents has recently improved the management of severe asthma. In addition, the concept of clinical remission has emerged as a treatment goal, further clarifying the objectives of asthma management. However, despite these advancements, the treatment of severe asthma driven primarily by non-type 2 inflammation remains a major challenge, and new biologics are currently being developed to address this issue.

Chimeric antigen receptor-T-cell (CAR-T) therapy for hematologic malignancies has made significant advancements over the years, and it is now incorporated as a treatment algorithm. Early phase clinical trials are underway for various solid tumors, and the effectiveness of CAR-T cell therapy has been demonstrated for specific types of glioma and several solid tumors. However, its efficacy does not match that observed in hematological malignancies. Recently, a case series reported CAR-T cell therapy targeting CD19 for autoimmune diseases such as systemic lupus erythematosus, leading to a dramatic improvement in the clinical symptoms and the possibility of discontinuing immunosuppressive agents. Furthermore, CAR-T cell therapy is expected to be effective against various viruses and Aspergillus spp. Finally, attempts have been made to introduce CAR constructs into regulatory T cells to target their immunosuppressive effects. This article introduces the current progress in CAR-T cell therapy beyond the treatment of only hematologic malignancies and discusses future directions, considering the current medical situation in Japan.

In the pathophysiology of Alzheimer's disease (AD), the amyloid hypothesis, which posits that amyloid β-protein (Aβ) abnormally aggregates and damages neurons with tau, has been proposed. It was originally thought that the accumulation of insoluble amyloid fibrils in the brain leads to AD-inducing neurotoxicity; however, in recent years, the positioning of early and intermediate aggregates has also been emphasized. In particular, following the positive results of phase 3 clinical trials of lecanemab and its approval in Japan and the United States, the pathology of protofibrils, which are the target molecules of lecanemab, has attracted attention. Using high-speed atomic force microscopy, we have previously reported that lecanemab, which has a high affinity for protofibrils, binds to and surrounds them. Donanemab, a recombinant monoclonal antibody that primarily targets fibrils composed of N3pG Aβ, has also attracted attention because of its efficacy in phase 3 clinical trials in patients with early stage AD.

Migraine is a prevalent and highly disabling neurological disorder. Recent progress in neuroscientific research has contributed to the development of new therapies for migraine, including triptans, ditans, calcitonin gene-related peptide (CGRP) antagonists, and CGRP-related monoclonal antibodies. Noninvasive neuromodulation devices have also been developed. We herein review the recent advances in research and the current standard of management for migraine patients.

Phase 3 clinical trials have validated the clinical efficacy of some anti-amyloid β (Aβ) antibody therapies, such as lecanemab and donanemab. To date, several clinical trials of anti-Aβ drugs have been conducted. However, most of these methods have been unsuccessful. Various Aβ aggregates are present during Aβ aggregation. The difference in the clinical efficacy of anti-Aβ antibody therapy may be attributed to variations in the Aβ aggregates targeted. Lecanemab primarily targets protofibrils, and donanemab targets plaques. Solanezumab and bapinezumab target Aβ aggregates of monomers alone or from monomers to low molecular weight oligomers. Anti-Aβ antibody therapies with clinical cognitive efficacy are thus characterized by targeting large-molecular-weight Aβ aggregates, such as protofibrils and plaques. In addition, a positive association was observed between the reduction in amyloid deposition and the inhibition of cognitive decline.

The number of patients with cancer qualifying for treatment with immune checkpoint inhibitors (ICIs) continues to increase, and a clearer understanding of the mechanisms underlying their activity-driven side effects, or immune-related adverse events (irAEs), has become crucial. Patients receiving ICIs can develop irAEs in any organ, and numerous studies have suggested that irAE development may be associated with improved ICI efficacy. However, the robustness and magnitude of such associations are unclear, and little is known about the relationship between irAE development and ICI efficacy at the individual organ level. A precise understanding of these links could improve patient care and provide further insight into the immunological mechanisms underlying both irAE development and ICI efficacy. We herein review the prognostic implications of irAEs occurring in patients with cancer treated with ICIs and discuss outstanding issues that should be addressed in future studies.

Objective This study investigated the significance of diagnosing an endoscopic atrophic pattern of the fornix in autoimmune gastritis (AIG).

Materials Of 10,608 individuals (men/women: 6,551/4,057) who underwent an esophagogastroduodenal endoscopy (EGD) examination between April 2016 and March 2022 for a medical checkup, 80 patients (men/women: 34/46, mean age 58.7 years old) were diagnosed with AIG based on endoscopic findings and positivity for gastric autoantibodies. The mucosal atrophy pattern of the fornix shown in the endoscopic findings of AIG cases was divided into four classifications: none, patchy, wide-range, and whole.

Results The number of AIG cases classified as none, patchy, wide-range, and whole was 9, 26, 14, and 31, respectively. Whole-fornix atrophy was frequently observed in Helicobacter pylori-uninfected cases, while the atrophic pattern was correlated with the area of remnant oxyntic mucosa in the gastric body. The serum levels of pepsinogen I and pepsinogen I/II ratio decreased, while the gastrin level increased in association with the enlarged atrophic area of the fornix. The pepsinogen I/II ratio was ≥3.0, in 70.8% of the cases, with a patchy pattern. Follow-up EGD findings obtained after the AIG diagnosis showed gradual progression of mucosal atrophy of the fornix, with such progression primarily observed in H. pylori-eradicated cases.

Conclusion The degree of endoscopic atrophy of the fornix was correlated with AIG progression. Patchy atrophy pattern in the fornix may be helpful in the detection of AIG prior to oxyntic gland atrophy expansion.

Objective Proton pump inhibitors (PPIs) are ineffective in suppressing gastric acid secretion after prolonged exposure to an acidic environment in the stomach. In this study, we compared vonoprazan (VPZ) and PPI esomeprazole (EPZ) according to the rate of ulcer scarring after gastric endoscopic submucosal dissection (ESD) in the postoperative stomach, where food residues are often observed, and we investigated their effectiveness in clinical practice.

Methods We compared 56 lesions treated with VPZ (20 mg) and 52 lesions treated with EPZ (20 mg) in the postoperative stomach and retrospectively evaluated the scarring rate of post-ESD ulcers at 8 weeks. ESD was performed in our hospital between January 2011 and May 2023.

Results The post-ESD ulcer scarring rate after eight weeks was significantly higher in the VPZ group than in the EPZ group (83.9% vs. 57.7%, p<0.01). In the respective groups, the mean age was 72.8 and 70.8 years, food residual rate were 41.1% and 30.8%, the mean resection area was 770.0 and 1,282.4 mm² (p<0.05), and the postoperative bleeding rates were 5.4% and 7.7%, respectively. There were no significant differences in sex, surgical procedure, diabetes status, or use of steroids, nonsteroidal anti-inflammatory drugs, or antithrombotic medications. An analysis using propensity scores to adjust for age, sex, surgical procedure, and resection area showed a significantly higher scarring rate in the VPZ group (odds ratio 2.65, p<0.05).

Conclusion VPZ was associated with a significantly higher scarring rate for post-ESD ulcers in the postoperative stomach than EPZ.

Objective Evaluating language symptoms is challenging owing to their varied presentations. We developed a Japanese Language Screen (JLS) to assess 11 language aspects, including agrammatism, impairment of articulation and prosody (IAP), word recall, syntactic comprehension, meaning of proverbs, and writing, considering the unique features of the Japanese language.

Methods Using the JLS, we assessed the language functions in patients with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and healthy controls (HC) to identify language symptoms specific to each condition and determine whether the JLS can differentiate between diseases and HC.

Results The study included 168 participants. The total JLS score categorized the participants' language status as normal or impaired. According to the total score, PSP patients had more severe language deficits than AD patients, despite comparable cognitive scores. Substantial differences were found in the 11 assessed items for each disease. Patients with AD and PSP showed decreased performance in more than half of the items compared to HC, with the PSP group being more impaired. ALS patients showed decreases in IAP and writing, notably in the meaning of proverbs, whereas PD was closely comparable to HC.

Conclusion This study suggests that while the JLS is useful for understanding the language symptoms associated with neurodegenerative disorders, its ability to classify them remains limited.

Objective The Japanese Clinical Practice Guidelines for Behçet's Disease 2020 describe an algorithm for the diagnosis and treatment of acute neuro-Behçet's disease (ANB). However, they do not provide specific policies regarding which patients should be treated. We thus formulated severity classification criteria for ANB for use in clinical practice.

Methods The treatment intensity score (TIS) was classified into five levels based on treatment details [e.g. glucocorticoid (GC) dosage]. A retrospective analysis was conducted to determine the relationship between various endpoints and the TIS in patients with ANB. The endpoints were neurological symptoms, cerebrospinal fluid findings, brain magnetic resonance imaging (MRI) findings, GC dosage, recovery from symptoms, and recurrence of further attacks.

Patients Sixty-one patients with ANB [37 men, 24 women, 40.8±1.6 years old (mean±standard error of the mean) ] who met the international classification criteria for Behçet's disease were included.

Results A higher TIS was significantly associated with worse recovery from acute attacks, indicating that the TIS reflected the severity. Furthermore, the TIS was significantly correlated with the presence of focal brain symptoms and MRI T2 high-intensity areas (any brain region or brainstem). Thus, the severity classification criteria for ANB (stage 1-4) were established according to the presence or absence of focal brain symptoms and MRI findings. Finally, higher stages in the criteria were significantly correlated with worse recovery from acute attacks and with higher doses of GC or immunosuppressant use.

Conclusion These results indicate that the novel severity classification criteria may be useful in determining treatment strategies in clinical practice.

Objectives This study aimed to investigate the clinical features of lymphoproliferative disease (LPD) in rheumatoid arthritis (RA) patients.

Methods We examined the reasons for methotrexate (MTX) discontinuation in 829 patients with RA. In 68 patients with RA whose reason for discontinuation was suspected LPD, blood test results and patient background on the day of MTX discontinuation, pathological characteristics, and the use of biologics after the diagnosis of LPD were analyzed.

Results In 829 RA patients in whom MTX was discontinued during the course of treatment, suspected LPD was the fourth most common reason for discontinuation (n=68). Patients who discontinued MTX due to suspected LPD were significantly older and had lower lymphocyte counts, higher serum LDH levels, lower serum albumin levels, higher serum CRP levels, and higher serum soluble interleukin-2 receptor (sIL-2R) levels than patients who discontinued MTX for other reasons. In patients who discontinued MTX due to suspected LPD, the MTX dose used at the time of MTX discontinuation was significantly higher in patients whose lesions regressed spontaneously with MTX discontinuation alone than in patients whose lesions required treatment due to a lack of regression or who died. During the observation period, 16 patients received biologics after LPD regression. LPD did not relapse during the observation period.

Conclusions Biologics might be an effective choice for patients with RA after LPD regression, but their safety has not been fully evaluated. Therefore, careful follow-up is required.

Ectopic insulinomas are rare neuroendocrine tumors that present with diagnostic challenges because of their atypical location. We report the case of a 64-year-old woman with recurrent hypoglycemia caused by an insulinoma originating from the gastric pyloric antrum. The diagnosis was confirmed through clinical assessment, biochemical testing, imaging studies, and a histopathological examination. Laparoscopic distal gastrectomy with D1 lymphadenectomy was performed to resolve the hypoglycemic episodes. This case highlights the importance of considering ectopic insulinomas in the differential diagnosis of unexplained cases of hypoglycemia, and it underscores the need for a multidisciplinary approach using advanced imaging and histopathological evaluations to make an accurate diagnosis and provide effective treatment.

A 70-year-old man with idiopathic pulmonary fibrosis undergoing nintedanib treatment for 2 years experienced worsening diarrhea, which prompted colonoscopy. An examination revealed a coarse mucosal appearance and erosion extending from the rectum to the ascending colon with linear mucosal defects in the sigmoid colon. Histopathological findings from the biopsies demonstrated features resembling those of collagenous colitis (CC). The diarrheal symptoms resolved rapidly after nintedanib withdrawal. The patient was subsequently diagnosed with nintedanib-associated, drug-induced colitis with CC-like features. Although linear mucosal defects linked to proton pump inhibitors, particularly lansoprazole, have been reported in CC, they have not been previously described in nintedanib-associated colitis.

The Harmony™ transcatheter pulmonary valve (TPV) is specifically designed to treat severe pulmonary regurgitation in a native or surgically repaired right ventricular outflow tract. To date, no reports have described TPV implantation (TPVI) in patients with prior aortic valve replacement (AVR) using a mechanical valve. Therefore, the risks of technical challenges or complications, particularly coronary compression or device fracture associated with prior AVR, remain unknown.

This is the first report of successful TPVI using a Harmony™ TPV in a 52-year-old Asian man diagnosed with tetralogy of Fallot (TOF) who had previously undergone AVR following TOF repair with no associated technical difficulties or complications.

A 34-year-old pregnant woman of half-Japanese and half-European descent developed deep vein thrombosis at 23 weeks' gestation. Treatment included an initial infusion of unfractionated heparin, followed by subcutaneous injections, and oral edoxaban 60 mg after delivery. The patient's father had a history of venous thromboembolism and had been diagnosed with a Factor V Leiden mutation in Belgium. A subsequent genetic analysis revealed a heterozygous Factor V Leiden mutation, which was previously thought to be absent in Japan. In this era of globalization, the potential for genetic risk factors to cross geographical boundaries warrants careful consideration.

Central diabetes insipidus (CDI) can develop as an acquired systemic disease. However, cases of eosinophilic granulomatosis with polyangiitis (EGPA) with concurrent CDI are rare. We herein report a case of EGPA following CDI. A 68-year-old woman with a 30-year history of sinusitis and asthma developed CDI, followed by severe renal dysfunction with eosinophilia and elevated myeloperoxidase-antineutrophil cytoplasmic antibody levels. A renal biopsy confirmed EGPA. Intensive treatment resulted in dialysis discontinuation, while partial improvement in arginine vasopressin secretion suggested a potential link between EGPA and CDI. We also conducted a literature review on concurrent EGPA and CDI. Clinicians should be aware of EGPA in CDI patients with asthma or sinusitis.

A 44-year-old woman presented with bilateral kidney cysts, scattered hepatic cysts, and a family history of polycystic kidney disease initially suspected of being autosomal dominant polycystic kidney disease (ADPKD). However, her clinical course showed atypical features: a modest total kidney volume increase (436 to 643 mL over 4 years) and rapid progression to end-stage kidney disease by 48 years old. Genetic testing revealed autosomal dominant tubulointerstitial kidney disease caused by a UMOD mutation (ADTKD-UMOD). This case highlights the importance of considering genetic testing in ADPKD cases with atypical features, since the diagnosis affects treatment decisions, including kidney replacement therapy selection.

We herein report the first case of Pneumocystis pneumonia (PCP) in a 78-year-old man with unresectable pancreatic head cancer who was treated with nab-paclitaxel plus gemcitabine. The patient experienced fever during the second treatment course, and computed tomography revealed diffuse ground-glass opacities in the bilateral lungs. The β-D-glucan level was elevated. A polymerase chain reaction (PCR) assay of his bronchoalveolar lavage fluid specimen showed positivity for Pneumocystis jirovecii DNA. After treatment with corticosteroids and trimethoprim/sulfamethoxazole, the patient's general condition improved, followed by atovaquone. The administration of corticosteroids to prevent chemotherapy-induced nausea and vomiting (CINV) and lymphocytopenia due to chemotherapy may be therefore involved in the development of PCP.

A man in his 60s on methotrexate for rheumatoid arthritis developed a fever and lymph node swelling, suggesting a lymphoproliferative disorder. Methotrexate was discontinued; however, the patient was admitted for acute kidney injury (AKI) and thrombocytopenia. Blood tests showed high levels of inflammatory markers, positive plasma Epstein-Barr virus DNA, and CD10-positive abnormal T cells, indicating T-cell neoplasm. CHOP chemotherapy with continuous hemodiafiltration improved the patient's condition. A lymph node biopsy confirmed the diagnosis of angioimmunoblastic T-cell lymphoma (AITL). To our knowledge, this is the first reported case of methotrexate-associated AITL complicated by AKI with a successful treatment course.

Autosomal recessive spinocerebellar ataxia-8 (SCAR8) is a neurodegenerative disorder caused by the biallelic pathogenic variants of SYNE1. It is characterized by slowly progressive cerebellar ataxia and atrophy. We identified two SCAR8 families using exome analyses and two novel variants, c.2127delG (p.Met709Ilefs) and c.15943G>T (p.Gly5315*), in SYNE1 (NM_182961.4). Pathogenic variants of SYNE1 cause various symptoms, including cerebellar ataxia, pyramidal tract disorders, and joint disorders, and the pathogenic variants discovered in this study were located in a region prone to cerebellar ataxia.

A 46-year-old man presented with an 8-month history of rapidly progressive dementia (RPD). Diffusion-weighted brain imaging, electroencephalography, and amyloid positron emission tomography revealed no significant findings. Creutzfeldt-Jakob disease (CJD) was considered in the differential diagnosis of RPD, and further testing revealed elevated 14-3-3 protein levels in the cerebrospinal fluid and the M232R mutation in the prion protein gene, confirming a diagnosis of hereditary CJD. We herein report a case of RPD that was challenging to diagnose as hereditary CJD because of the absence of characteristic findings suggestive of CJD on imaging and other examinations.

Distinguishing between primary and metastatic tumors is critical in patients with multiple cancers. We present the case of a man in his 70s with quadruple carcinoma, squamous cell carcinoma in both lungs, invasive urothelial carcinoma of the bladder, and esophageal cancer, discovered during follow-up after sigmoid colon cancer surgery. A histopathological analysis, including immunostaining, could not confirm whether these were primary or metastatic cancer. A comprehensive oncogene mutation analysis using next-generation sequencing revealed distinct gene mutations in each tumor, confirming that all were primary cancers of heterogeneous origin. Our findings highlight the importance of advanced genomic studies on complex cancer cases.