Internal Medicine最新文献

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.

Objective The number of patients using direct oral anticoagulants (DOACs) has recently increased. However, the association between DOAC use and bronchoscopy (BS) safety has not been elucidated. This study examined the association between BS and DOAC use and safety. Methods Using data from the Japanese Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2022, patients taking DOACs who underwent BS (n=603, DOAC group) and those who did not (n=187,827, non-DOAC group) were identified. Then, 1:4 matched-pair cohort analyses were performed based on the institution, sex, age, and treatment year. The primary outcome was all-cause in-hospital mortality. The secondary outcomes were 28-day mortality, mechanical ventilation use, pneumothorax, bleeding, and thromboembolism after BS. Results A total of 603 and 2,320 patients taking and not taking DOAC, respectively, were identified via matching. The all-cause in-hospital mortality rates in the DOAC and non-DOAC groups were 12.1% and 5.8%, respectively. In a multivariable logistic regression analysis, the DOAC group had a significantly higher all-cause in-hospital mortality rate than the non-DOAC group (odds ratio = 2.84, 95% confidence interval = 1.77-4.55). Secondary and composite outcomes (mechanical ventilation, pneumothorax, bleeding, and thromboembolism after BS combined) were more frequent in the DOAC group than in the non-DOAC group. Conclusion DOACs were associated with mortality and complications in patients undergoing BS. Further studies comparing BS outcomes between patients with and without DOAC treatment are necessary.

A 60-year-old woman with a history of malignant lymphoma was referred to us with fever, sore throat, right-sided neck pain, and swelling while she was currently undergoing chemotherapy. Imaging studies, including computed tomography and ultrasonography of the neck, revealed significant perivascular wall thickening of the right carotid artery, which was suggestive of giant cell arteritis. However, fever, neck pain, and swelling resolved spontaneously and rapidly. Transient perivascular inflammation of the carotid artery (TIPIC) syndrome was most likely. However, these symptoms developed shortly after the administration of granulocyte colony-stimulating factor (G-CSF). Accordingly, the patient was diagnosed with G-CSF-induced aortitis mimicking TIPIC syndrome.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disease of the central nervous system, and many details, including pathological findings, are still unclear. We herein report a man in his 70s who had been diagnosed with CLIPPERS 4.5 years ago. He was treated with corticosteroids, and his symptoms were managed; however, he eventually died of coronavirus disease 2019. A postmortem autopsy revealed perivascular lymphocyte aggregation and demyelination centered in the brainstem and cerebellum. This is the world's first autopsied case of CLIPPERS with more than four years of follow-up.

A 56-year-old woman with high-grade or invasive intraductal papillary mucinous neoplasm (IPMN) underwent 3 pancreatic surgeries for initial and recurrent IPMN lesions. Immunostaining and genetic analyses of all lesions revealed a consistent mutation in KRAS and loss of serine/threonine kinase 11 (STK11), indicating the same origin of these lesions and the possibility of intraductal dissemination. Other immunostaining findings, such as mucin expression and a high Ki-67 labeling index, were consistent among all the lesions and supported their malignant potential. IPMNs with loss of STK11 may benefit from tailored follow-up of the remnant pancreas due to their high likelihood of recurrence through intraductal spread.

Exophiala spp. cause dematiaceous mycoses, but rarely infect human lungs. A 61-year-old man presented with bloody black sputum. Chest computed tomography showed consolidation in the truncus intermedius and peripheral bronchus, and a mass shadow in the S₇ region of the right lung. Bronchoscopy revealed a protruding black lesion in the bronchial orifice of the truncus intermedius, and Exophiala phaeomuriformis was isolated. The consolidation resolved spontaneously, and the residual tumor was diagnosed as a carcinoid tumor. This case highlights the fact that pulmonary chromomycosis may occur in immunocompetent individuals without any preexisting structural changes in the airways.