Allelic frequency of pathogenic α-antitrypsin variants in the Japanese population: Results from a survey of open Japanese genetic variation databases.

α-antitrypsin deficiency (AATD) is a hereditary disorder with a global prevalence that differs across regions. AATD is highly prevalent in Europe and North America but rarely found in Asian countries, including Japan, possibly because of the founder effect of the pathogenic SERPINA1 variants PI*Z and PI*S. However, AATD remains underdiagnosed even in high-prevalence and low-prevalence regions, possibly because of lack of awareness.

A 53-year-old Man with Idiopathic Bilateral Chylothorax Refractory to Lymphaticovenular Anastomosis: A Case Report.

A 53-year-old man with chronic dyspnea and bilateral pleural effusion was subsequently diagnosed with idiopathic chylothorax. Lymphatic scintigraphy confirmed lymphatic fluid leakage at the left venous angle, prompting management with lymphaticovenular anastomosis (LVA). Although the left pleural effusion was controlled, the right pleural effusion continued to increase, resulting in bilateral leg lymphedema that was refractory to LVA.

Stepwise Incremental Dose Schedule of Sirolimus Is Successfully Tolerated by a Patient With Lymphangioleiomyomatosis Who Was Initially Allergic to mTOR Inhibitors.

Lymphangioleiomyomatosis (LAM) is a rare disease involving the proliferation of LAM cells in the lungs and the axial lymphatic system and mechanistic target of rapamycin (mTOR) inhibitors are the only effective medicines for treating it. Patients suffering from LAM, who are allergic to mTOR inhibitors can be treated by desensitizing them to the medicine. A 39-year-old woman presented with dyspnea caused by chylous pleural effusion, ascites, and retroperitoneal lymphangioleiomyomas.

Lymphangioleiomyomatosis as a potent lung cancer risk factor: Insights from a Japanese large cohort study.

Background And Objective: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease.

Methods: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population.

Pulmonary Erdheim-Chester Disease With BRAF-AGAP3 Fusion: Late-Onset Osteolytic Femoral Lesions Despite Long-Term Pulmonary Stabilization With Corticosteroid.

Erdheim-Chester disease (ECD) is a rare inflammatory myeloid neoplasm affecting multiple systems and organs. The patient is a 38-year-old male with ECD complicated with pulmonary and cutaneous manifestations but without bone lesions diagnosed in 2008. Initial treatment with oral and inhaled corticosteroids achieved persistent favorable disease remission.

An elderly woman with Birt-Hogg-Dubé syndrome having multiple pulmonary cysts mimicking lymphangioleiomyomatosis.

The characteristics of the pulmonary cysts on the high-resolution computed tomography (HRCT) chest images are an important diagnostic clue to distinguish among cystic lung diseases. The diagnostic accuracy of HRCT was reported to be as high as 90% by experienced pulmonologists and radiologists. Herein, we report the case of an elderly woman with Birt-Hogg-Dubé syndrome (BHDS) whose HRCT images displayed lymphangioleiomyomatosis-like features of the pulmonary cysts, rendering it difficult for us to diagnose BHDS.

Extrapleural air secondary to idiopathic pulmonary fibrosis-related pneumomediastinum.

Extrapleural air is a rare condition that may concurrently develop with pneumomediastinum and pneumothorax, especially in older patients with fragile connective tissues. Physicians should consider extrapleural air to prevent inadvertent harm. Coronal reconstruction computed tomography images help appreciate extrapleural air and recognize the track of extrapulmonary air.

Postoperative hormonal therapies reduce the recurrence of thoracic endometriosis-related pneumothorax.

Objectives: Thoracic endometriosis-related pneumothorax (TERP) frequently recurs even after surgery. Meanwhile, postoperative hormonal therapies (HTx) are believed to be effective for pelvic endometriosis. Therefore, we evaluated the relationship between postoperative TERP recurrence and postoperative HTx in a retrospective observational study.

Clinicopathological Impacts of Expression of Neuronal Markers in Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a tuberous sclerosis complex (TSC)-associated tumor, characterized by the expression of neural crest lineages including neuronal markers. Neural crest cells can differentiate into multiple cell types that contribute to tissues associated with TSC-related tumors, and TSC-related tumors could be specifically associated with distinct neural crest subtypes. This study aimed to clarify the clinicopathological effects of expression of neuronal markers in LAM.

Clinical and genetic features of 334 Asian patients with Birt-Hogg-Dubé syndrome (BHDS) who presented with pulmonary cysts with or without a history of pneumothorax, with special reference to BHDS-associated pneumothorax.

Background: The clinical pulmonary manifestations and genetic features of Birt-Hogg-Dubé syndrome (BHDS) in Asian patients remained unclear. We aimed to clarify the clinical features of BHDS-associated pneumothorax (PTX) and retrospectively investigate potential contributing factors in the largest Asian cohort to date.

Methods: We reviewed the clinical and genetic data collected in 2006-2017, from the BHDS patients who were Asian and presented with pulmonary cysts with or without a history of PTX.

Prophylactic renal artery embolization before pregnancy in patients with lymphangioleiomyomatosis and renal angiomyolipoma.

Objective: Pregnant patients with lymphangioleiomyomatosis (LAM) and renal angiomyolipomas (AMLs) require care for both renal AMLs and pulmonary dysfunction because AMLs can grow and rupture during pregnancy, potentially causing hemorrhagic shock and fetal death. This study examined whether prophylactic transcatheter arterial embolization (TAE) could prevent the pregnancy-associated growth and rupture of renal AMLs in patients with LAM.

Methods: This retrospective study included five women with 14 renal AMLs (initial diameter, ≥2 cm) first encountered between September 2010 and August 2015 who subsequently became pregnant.

Propylene glycol, a component of electronic cigarette liquid, damages epithelial cells in human small airways.

Background: Electronic cigarettes (e-cigarettes) are used worldwide as a substitute for conventional cigarettes. Although they are primarily intended to support smoking cessation, e-cigarettes have been identified as a gateway to smoking habits for young people. Multiple recent reports have described the health effects of inhaling e-cigarettes.

Long-term safety of Prolastin®-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency.

Background: Safety and pharmacokinetics (PK) of alpha-proteinase inhibitor, modified process (Alpha-1 MP), was evaluated in a clinical trial of Japanese patients with alpha-antitrypsin deficiency (AATD). The present study aimed to evaluate the long-term safety of weekly intravenous infusions of 60 mg/kg Alpha-1 MP in Japanese patients with AATD.

Methods: This was a multi-center, open-label extension (OLE) study that enrolled adult patients with AATD, who had completed the preceding safety and PK clinical trial.

Perioperative management of thoracic surgery in patients with lymphangioleiomyomatosis.

Background: General surgery for patients with lymphangioleiomyomatosis (LAM) is infrequent, however, general surgeons also occasionally experience it. Only a few reports have described the specific perioperative management appropriate for patients with LAM. Hence, in this case series, we aimed to investigate the surgical outcomes of LAM patients and their characteristics.

Antibody response and seroprevalence in healthcare workers after the BNT162b2 vaccination in a University Hospital at Tokyo.

In 2020, we reported a low seroprevalence of N-specific antibodies in 4147 health care workers (HCWs) at a frontline hospital in Tokyo, Japan. In Japan, a vaccine campaign was launched in early 2021. We re-evaluated seroprevalences of N- and S-specific antibodies in 2202 HCWs who took two doses of the BNT162b2 vaccine.

Increased delta variant SARS-CoV-2 infections in a highly vaccinated medical center in Japan.

The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta among 3,911 healthcare workers (HCWs) at a medical center of Tokyo with a high vaccination rate of 84.1%.

Vasohibin-1 and -2 in pulmonary lymphangioleiomyomatosis (LAM) cells associated with angiogenic and prognostic factors.

Lymphangioleiomyomatosis (LAM) is a rare pulmonary neoplasm, clinically associated with dyspnea and respiratory failure. Current therapeutic modalities do not necessarily reach satisfactory outcome and novel therapeutic approaches are currently warranted. Therefore, in this study, we focused on vasohibin-1 (VASH1) and -2 (VASH2); VASH1 terminated and VASH2 promoted angiogenesis.

Elevated depressive symptoms among newer and younger healthcare workers in Japan during the COVID-19 pandemic.

Aim: Depression is a frequent outcome of long-term stress, but no studies have examined depression rates among Japanese healthcare workers fighting the COVID-19 pandemic. Therefore, we conducted a web-based interview of hospital employees to assess depression prevalence and factors.

Methods: This observational cohort study was conducted from July to August, 2020, as part of a mandatory health checkup of Juntendo University Hospital employees (Tokyo, Japan).

Real-world evidence for the effectiveness and breakthrough of BNT162b2 mRNA COVID-19 vaccine at a medical center in Japan.

Evidence of BNT126b2 vaccine effectiveness and breakthrough has been primarily demonstrated in populations outside of Asia; studies in the Western Pacific region are limited. Our retrospective cohort study assessed SARS-CoV-2 cases after vaccine rollout starting from mid-March 2021 at a tertiary hospital in Tokyo. Of 8,749 staff members, no fully vaccinated staff demonstrated confirmed infection, versus 19 cases in unvaccinated or partially vaccinated staff, by the end of June.

Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers in Japan.

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021.

Folliculin haploinsufficiency causes cellular dysfunction of pleural mesothelial cells.

Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS.