BackgroundImmune checkpoint inhibitor (ICI)-associated aseptic meningitis is uncommon neurological immune-related adverse event that can cause substantial morbidity if appropriate immunosuppressive therapy is delayed while excluding infectious meningitis or leptomeningeal carcinomatosis is being evaluated. We report two lung adenocarcinoma cases illustrating an exclusion-based diagnostic process and stepwise immunosuppressive treatment of suspected ICI-associated aseptic meningitis.Case descriptionCase 1: A 66-year-old woman experienced fever, neck stiffness, and altered mental status 13 days after initiating adjuvant atezolizumab. Cerebrospinal fluid (CSF) analysis showed pleocytosis and marked protein elevation, whereas neuroimaging remained unremarkable. After alternative diagnoses were excluded, high-dose intravenous methylprednisolone was administered, resulting in prompt improvement in consciousness and neurological symptoms, followed by oral corticosteroid tapering without recurrence. Case 2: A 75-year-old man receiving carboplatin/nab-paclitaxel with durvalumab plus tremelimumab experienced ICI-associated colitis followed by Common Terminology Criteria for Adverse Events grade 3 meningitis with impaired consciousness. CSF multiplex polymerase chain reaction, cytological analysis, and further investigations supported early consideration that common infections and leptomeningeal carcinomatosis were unlikely, enabling timely immunosuppression for suspected ICI-associated aseptic meningitis. However, neurological deterioration continued despite high-dose corticosteroids and intravenous immunoglobulin. Consequently, tocilizumab was administered as rescue therapy, following which, both clinical outcomes and CSF parameters improved.ConclusionThese two cases illustrated a practical clinical approach to suspected ICI-associated aseptic meningitis based on rapid exclusion of alternative diagnoses and stepwise immunosuppressive treatment. High-dose corticosteroids remain the cornerstone of initial therapy, whereas additional immunomodulatory treatment might be considered in select refractory cases. CSF multiplex polymerase chain reaction might serve as an adjunctive tool in some patients by helping exclude common treatable infections during early diagnostic evaluation.

BACKGROUND:Optimal management of advanced thymoma remains uncertain. We compared the efficacy of first-line platinum-anthracycline chemotherapy with other platinum-based regimens in a large Japanese cohort. METHODS:We retrospectively analyzed 157 patients with unresectable or recurrent thymoma treated at 39 institutions (2000-2020). Regimens were categorized as platinum-anthracycline (n = 104) or non-anthracycline platinum (n = 53). Propensity score matching (PSM) balanced baseline characteristics (46 pairs). The primary endpoint was overall response rate (ORR); secondary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS). RESULTS:Median age was 58 years (24-79) and 53% were male; 62% had recurrent disease. Before PSM, ORR was higher with platinum-anthracycline than with non-anthracycline platinum (57% vs 31%; p = 0.0024), while rwPFS (median 15.0 vs 13.4 months; HR 1.07; p = 0.72) and OS (median 84.9 vs 111.9 months; HR 1.36; p = 0.24) did not differ. After PSM, ORR remained higher (58% vs 32%; p = 0.0014) with comparable rwPFS (12.1 vs 11.7 months; HR 0.98; p = 0.98) and OS (93.8 vs 113.5 months; HR 1.41; p = 0.31). Overall, 70% of patients received subsequent local therapy. Among fatal cases, paraneoplastic syndromes occurred in 50%, and infections and cardiovascular events were frequent causes of death in addition to tumour progression. CONCLUSIONS:Although platinum-anthracycline regimens achieved higher response rates, this did not translate into longer rwPFS or OS. Non-anthracycline platinum regimens may be reasonable for selected patients, particularly when treatment tolerability is a priority, within individualized multidisciplinary long-term management. TRIAL REGISTRATION:UMIN000048181.

Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma that frequently harbors KRAS mutations and exhibits low programmed death-ligand 1 (PD-L1) expression. As evidence on the use of immune checkpoint inhibitors (ICIs) for IMA is limited, the present study aimed to describe the clinical features, treatment patterns and outcomes to evaluate the effectiveness of ICIs for IMA. The present retrospective study included 15 patients with advanced or recurrent IMA who were treated at Toranomon Hospital (Tokyo, Japan) between April 2014 and March 2025. The present report focuses on 7 patients who received first-line ICI-based therapy. Patient characteristics, molecular and pathological features, treatments administered, and outcomes were summarized, and responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Among the 15 patients, KRAS mutations were identified in 6 patients (40%), PD-L1 expression was positive in 2 patients (13%), negative in 7 patients (47%) and unknown in 6 patients (40%). Of the 7 patients receiving first-line ICI-based therapy, 4 received dual ICIs and 3 received a single-agent ICI. The best overall response among these patients was partial response (PR) in 1 patient (14%), stable disease in 5 patients (71%) and progressive disease in 1 patient (14%). A total of 5 patients (71%) experienced immune-related adverse events leading to treatment discontinuation. In conclusion, first-line ICI-based therapies showed limited effectiveness overall. However, 3 patients treated with dual ICIs and chemotherapy achieved a 100% disease control rate, with 1 patient achieving a PR. Therefore, specific ICI-based combination therapies may be a viable option for the treatment of IMA.

The clinical relevance of M1UK type strains of Streptococcus pyogenes in Japan remains insufficiently defined. We investigated the molecular epidemiology of M1UK type strains and evaluated their clinical associations among adults with invasive group A Streptococcus (iGAS) infections. We conducted a nationwide multicenter surveillance study of iGAS infections from December 2023 to March 2025. Molecular typing, profiling of M1UK-associated single-nucleotide polymorphisms (SNPs) in the rofA, gldA, and pstB regions, and emm-cluster assignment were performed. Adult clinical characteristics and outcomes were compared between M1UK type and non-M1 type infections after exclusion of the single adult M1global case. Among 155 patients in the molecular epidemiology cohort, M1UK type strains accounted for 58 isolates, whereas only one M1global isolate was identified. Historical analysis showed that M1global predominated among isolates collected in the early 2010s, whereas M1UK type strains were detected mainly in recent periods. In adult clinical comparisons, M1UK type infection was associated with streptococcal toxic shock syndrome (STSS; p = 0.004) and necrotizing fasciitis (p < 0.001). In multivariable analysis, younger age, necrotizing fasciitis, and serum creatinine ≥ 2.0 mg/dL were associated with M1UK type infection. M1UK type strains were important contributors to contemporary iGAS infections in Japan and were associated with severe clinical presentations, supporting sustained molecular surveillance beyond conventional emm typing.

Streptococcus dysgalactiae subsp. equisimilis (SDSE), historically considered less virulent than Streptococcus pyogenes, has emerged as an important invasive pathogen, particularly in aging societies. Data on nationwide clinical and molecular epidemiology in super-aged populations remain limited. We aimed to identify admission abnormalities associated with the 28-day mortality for invasive SDSE (iSDSE) infections in Japanese adults and evaluate the molecular epidemiology of this emerging pathogen through a large-scale surveillance. A prospective nationwide surveillance of iSDSE was conducted between March 2024 and March 2025 in 132 hospitals across Japan. Clinical, epidemiological, and laboratory data, including emm type distribution, were collected and analyzed. Overall, 278 patients with iSDSE infections were identified (median age, 83 years); one-quarter of the patients were residents of long-term care facilities. Nearly all patients had comorbidities. The 28-day mortality was 12.2

A 75-year-old man with interstitial lung disease was admitted with an acute exacerbation and severe hypoxemic respiratory failure. During intensive care management, he developed acute myocardial infarction, required veno-venous extracorporeal membrane oxygenation and later underwent continuous haemodiafiltration for an acute kidney injury. A pulmonary embolism, gastrointestinal bleeding and intestinal perforation subsequently occurred, and the patient died of septic shock on day 40 of hospitalisation. An autopsy showed diffuse alveolar damage superimposed on a usual interstitial pneumonia pattern, intra-alveolar haemorrhage, a subacute myocardial infarction, pulmonary arterial thrombi, a terminal ileal perforation with transmural necrosis and microthrombi in the intestinal wall. This case illustrates the difficulty of balancing thrombosis and bleeding during and after extracorporeal support for an acute exacerbation of interstitial lung disease and highlights the need for early suspicion of intestinal ischaemia in patients receiving extracorporeal membrane oxygenation who exhibit unexplained anaemia, gastrointestinal bleeding, worsening sepsis, or rising lactate levels, particularly during deep sedation.

Background:Occurrences of amyloid A (AA) amyloidosis secondary to nontuberculous mycobacteria (NTM) are rare. Here, we report a fatal case of AA amyloidosis in a woman with pulmonary Mycobacterium avium infection, with autopsy confirming extensive amyloid deposition across multiple organs. Case Summary:A 59-year-old woman was diagnosed with pulmonary M. avium infection in 2018 but discontinued follow-up. In March 2022, she re-presented with disease progression and commenced standard oral therapy with daily clarithromycin, rifampicin, and ethambutol. After 12 months of therapy, her regimen was discontinued for 3 months due to persistent diarrhea. Upon resuming treatment, progressive weight loss persisted, leading to hospitalization in July 2023. On admission, she was severely underweight. Imaging revealed bilateral lung infiltrates with cavitary lesions. Laboratory evaluation showed elevated inflammatory markers, hypoalbuminemia, and sputum positive for acid-fast bacilli on smear and positive for M. avium by transcription-reverse transcription concerted reaction and culture. Gastrointestinal biopsies showed AA amyloid deposits confirmed by direct fast scarlet staining and immunohistochemistry. Despite modified antibiotic regimens, her condition deteriorated, leading to CO₂ narcosis, multiorgan failure, and ultimately death at 123 days after admission. Autopsy confirmed extensive amyloid deposition and advanced pulmonary mycobacterial disease. Conclusion:This case highlights a rare but severe presentation of systemic AA amyloidosis occurring with pulmonary M. avium infection, suggesting a possible association between uncontrolled M. avium infection and systemic AA amyloidosis development. In individuals with pulmonary NTM presenting with refractory diarrhea and weight loss, clinicians should consider AA amyloidosis and pursue appropriate biopsy investigations.

Systemic artery–to–pulmonary artery fistula (SAPAF) is a rare vascular anomaly, and involvement of the inferior phrenic artery is particularly uncommon. Acquired SAPAF may occur as a late postoperative complication; however, diagnosis is often challenging because of subtle imaging findings and complex hemodynamics. Four-dimensional CT angiography (4D-CTA) enables time-resolved assessment of blood flow and may facilitate accurate diagnosis and treatment planning. A 56-year-old woman was referred to the respiratory department after a screening chest CT performed for suspected malignancy revealed a vascular abnormality in the right lower lung field. Further evaluation confirmed a history of thoracoscopic wedge resection of the right middle lobe at the site of air leakage and partial diaphragmatic resection for catamenial pneumothorax 10 years earlier; the retrieved operative record indicated that no pleural adhesion procedure or reinforcement had been performed. She was asymptomatic at presentation. Dynamic 4D-CTA demonstrated absence of opacification of the right A9 segmental pulmonary artery during the pulmonary arterial phase, followed by retrograde filling of a tortuous vessel arising from the right inferior phrenic artery during the systemic arterial phase, suggesting an inferior phrenic artery–to–pulmonary artery fistula. Digital subtraction angiography confirmed the diagnosis, and coil embolization was successfully performed, with complete angiographic occlusion of the feeder artery. This case appears to represent a previously unreported late postoperative complication following surgery for catamenial pneumothorax and highlights the clinical utility of 4D-CTA as a noninvasive modality for hemodynamic assessment and treatment planning in SAPAF.

Acute exacerbation (AE) of interstitial lung disease (ILD) is life threatening, but data on acute respiratory deterioration fulfilling AE criteria after laboratory-confirmed influenza infection are limited. The current study investigated the incidence, clinical features, and outcomes of such events after laboratory-confirmed influenza in hospitalized patients with ILD. We retrospectively reviewed adults with pre-existing ILD who were hospitalized with influenza at Toranomon Hospital between April 2014 and April 2019. Influenza was confirmed by rapid diagnostic tests. Fulfillment of the AE criteria was confirmed by two pulmonologists and one radiologist. Baseline characteristics and outcomes were compared between patients with and without AE-criteria events. The Mann–Whitney U test or Fisher’s exact test were used for between-group comparisons, and the Kaplan–Meier method and the log-rank test were used for survival analysis. Of 927 patients hospitalized with ILD during the study period, 47 had laboratory-confirmed influenza, and 10 of these patients (21.3

Background:Diffuse parenchymal lung diseases have various conditions and CT imaging findings. Differentiating interstitial lung diseases (ILDs) and determining the presence or absence of usual interstitial pneumonia (UIP), can be challenging, even for experienced radiologists. To address this challenge, we developed a 3D-content-based image retrieval system (CBIR) and investigated its clinical usefulness. Methods:Using deep learning technology, we developed a prototype system that analyzes thin-slice whole lung HRCT images, automatically registers them in a database, and retrieves similar images. To evaluate search performance, we used a database of 2058 cases and assessed image similarity between query and retrieved cases using a 5-point visual score (5: Similar, 4: Somewhat similar, 3: Neither, 2: Somewhat dissimilar, 1: Dissimilar). To assess clinical usefulness, we evaluated the concordance of labels (ILD/non-ILD, with/without UIP) between query and retrieved cases, using a database of 301 cases across 57 diseases. Results:For search performance, the mean score of visual similarity between 70 queries and their top 5 retrieved cases was 4.37 ± 0.83. For clinical usefulness, label concordance between 25 queries and their top 5 retrieved cases was assessed across 4 labels. For ILD, the mean concordance of labels was 0.94 ± 0.15, while for non-ILD, it was 0.64 ± 0.31. For cases with UIP, the mean concordance of labels was 0.86 ± 0.17, while for cases without UIP, it was 0.83 ± 0.24. Conclusions:Our CBIR system showed high accuracy for identifying cases with/without UIP, suggesting its potential to support UIP differentiation in clinical practice.

Current standard treatments for breast cancer have the potential to induce interstitial pneumonia. The present report describes a case of acute fibrinous and organizing pneumonia (AFOP) in a 52-year-old female patient undergoing adjuvant therapy with abemaciclib following breast cancer surgery. The patient received abemaciclib after completion of radiation therapy. On the 85th day of abemaciclib administration and 157th day after radiation therapy initiation, the patient presented with dyspnea. CT findings were indicative of interstitial pneumonitis, warranting hospitalization. During hospitalization, transbronchial lung cryobiopsy (TBLC) was performed, which revealed pathological findings consistent with AFOP. Following two 3-day doses of 1 g intravenous methylprednisolone therapy, tacrolimus (2 mg/day) was administered and the patient was switched to oral prednisolone. The patient was discharged on the 25th day of hospitalization. Advances in bronchoscopic techniques, including TBLC, may aid in diagnosing lung injuries.

The incidence of invasive Group A Streptococcus (iGAS) infection and streptococcal toxic shock syndrome (STSS) is increasing. Early detection and diagnosis of cases that may progress to STSS are currently difficult. In this study, we aimed to identify biomarkers and emm type, one of the virulence factors, associated with STSS development. In this multicentre observational study including patients with iGAS infection (n = 305), we investigated the relative associations of host factors, clinical manifestations, biomarkers, and emm type with STSS. The overall mortality rate was 15.4

Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation is the standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) with a good performance status. However, there is currently no consensus on the management of recurrence after CCRT and durvalumab consolidation therapy. The present study describes the case of a 52-year-old male former smoker with stage IIIB NSCLC who experienced recurrence in the right hilar, mediastinal and bilateral supraclavicular lymph nodes after an initial response to CCRT and durvalumab. A treatment regimen involving combined durvalumab, tremelimumab, cisplatin and pemetrexed achieved stable disease and was continued as maintenance therapy. However, the patient later developed brain and bone metastases, indicating progressive disease. This case highlights the challenges of managing recurrent NSCLC after CCRT and durvalumab consolidation therapy. Combining immunotherapy and chemotherapy may offer a viable approach, underscoring the need for further research and standardized protocols.

The incidence of invasive Streptococcus dysgalactiae subsp. equisimilis (iSDSE) infections is increasing in developed countries, but studies on the risk factors for death in iSDSE infections are scant. Here, we aimed to clarify risk factors and predictors of mortality in adults with iSDSE infections. A multicentre observational study of adults with iSDSE infections was conducted to investigate the effects of host factors, disease severity, biomarkers, and antibiotic regimens, and bacterial factors on 28-day mortality. The overall mortality rate of 588 patients was 10.4

BackgroundPneumonia is common among older adults and often recurrent. Several studies have been conducted on the risk factors for pneumonia; however, little is known about the risk factors for recurrent pneumonia. This study aimed to identify the risk factors for developing recurrent pneumonia among older adults and to investigate methods of prevention.MethodsWe analysed the data of 256 patients aged 75 years or older who were admitted for pneumonia between June 2014 and May 2017. Moreover, we reviewed the medical records for the subsequent 3 years and defined the readmission caused by pneumonia as recurrent pneumonia. Risk factors for recurrent pneumonia were analysed using multivariable logistic regression analysis. Differences in the recurrence rate based on the types and use of hypnotics were also evaluated.ResultsOf the 256 patients, 90 (35.2%) experienced recurrent pneumonia. A low body mass index (OR: 0.91; 95% CI: 0.83‒0.99), history of pneumonia (OR: 2.71; 95% CI: 1.23‒6.13), lung disease as a comorbidity (OR: 4.73; 95% CI: 2.13‒11.60), taking hypnotics (OR: 2.16; 95% CI: 1.18‒4.01) and taking histamine-1 receptor antagonist (H1RA) (OR: 2.38; 95% CI: 1.07‒5.39) were risk factors. Patients taking benzodiazepine as hypnotics were more likely to experience recurrent pneumonia than patients not taking hypnotics (OR: 2.29; 95% CI: 1.25–4.18).ConclusionWe identified several risk factors for recurrent pneumonia. Among them, restricting the use of H1RA and hypnotics, in particular benzodiazepines, may be useful in preventing the recurrence of pneumonia in adults aged 75 years or older.

Purpose: In this study, we aimed to clarify the risk factors associated with unfavorable outcomes in adults with pneumococcal meningitis (PnM).Methods: Surveillance was conducted between 2006 and 2016. Adults with PnM (n = 268) were followed up for outcomes within 28 days after admission using the Glasgow Outcome Scale (GOS). After classifying the patients into the unfavorable (GOS1-4) and favorable (GOS5) outcome groups, i) the underlying diseases, ii) biomarkers at admission, and iii) serotype, genotype, and antimicrobial susceptibility for all isolates were compared between both groups. Results: Overall, 58.6% of patients with PnM survived,15.3% died, and 26.1% had sequelae. The number of living days in the GOS1 group was highly heterogeneous. Motor dysfunction, disturbance of consciousness, and hearing loss were the commonest sequelae. Of the underlying diseases identified in 68.9% of the PnM patients, liver and kidney diseases were significantly associated with unfavorable outcomes. Of the biomarkers, creatinine and blood urea nitrogen, followed by platelet and C-reactive protein had the most significant associations with un-favorable outcomes. There was a significant difference in the high protein concentrations in the cerebrospinal fluid between the groups. Serotypes 23F, 6C, 4, 23A, 22F, 10A, and 12F were associated with unfavorable outcomes. These serotypes were not penicillin-resistant isolates possessing three abnormalpbp genes (pbp1a, 2x, and 2b), except for 23F. The expected coverage rate of the pneumococcal conjugate vaccine (PCV) was 50.7% for PCV15 and 72.4% for PCV20.Conclusions: In the introduction of PCV for adults, the risk factors for underlying diseases should be prioritized over age, and serotypes with unfavorable outcomes should be considered.

•Gordonia bronchialis is an emerging pathogen causing various infectious diseases.•This is the first report of pneumonia caused by G. bronchialis with a foreign body.•Conventional cultures cannot be used to identify G. Bronchialis accurately.•16S ribosomal RNA gene sequencing provides definitive identification of Gordonia species.

Skin cryptococcosis often manifests as an umbilicated papule, and chest computed tomography findings of multiple nodules and cavities are also characteristic. The combination of characteristic cutaneous manifestations and radiological findings can help clinicians make an "at-a-glance" diagnosis of disseminated cryptococcosis.

Introduction: Risk factors for death from invasive pneumococcal disease (IPD) have not been clearly established in patients aged under 65 years. We aimed to evaluate contributions of host and bacterial factors to the risk of death from IPD in patients aged under 65 years in Japan. Methods: In this prospective, observational, multicenter cohort study, patients with IPD (n = 581) aged 6 -64 years were enrolled between 2010 and 2017. We investigated the role of host and bacterial factors in 28-day mortality. Results: The mortality rate increased from 3.4% to 6.2% in patients aged 6-44 years to 15.5%-19.5% in those aged 45-64 years. Multivariable analysis identified the following risk factors for mortality: age 45 -64 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-6.8, p = 0.001), bacteremia with unknown focus (HR, 2.0; 95% CI, 1.1-3.7, p = 0.024), meningitis (HR, 2.1; 95% CI, 1.1-4.0, p = 0.019), underlying multiple non-immunocompromising conditions (HR, 2.6; 95% CI, 1.1-7.4, p = 0.023), and immunocompromising conditions related to malignancy (HR, 2.4; 95% CI, 1.0-5.2, p = 0.039). Pneumococcal serotype was not associated with poor outcomes. Conclusions: Host factors, including age of 45-64 years and underlying multiple nonimmunocompromising conditions, are important for the prognosis of IPD. Our results will contribute to the development of targeted pneumococcal vaccination strategies in Japan. (c) 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.