Successful treatment of tuberculous meningitis in an Indian female under hemodialysis therapy.

Hemodialysis is a well-known risk factor for severe infection by putting patients under an immunocompromised state. Such patients are prone to opportunistic pathogen and present with atypical manifestations during infection. Tuberculous meningitis is a central nervous system infection of Mycobacterium tuberculosis, accounting for the highest mortality of all forms of tuberculosis. In fact, the mortality rate of tuberculous meningitis in hemodialysis patients is extremely poor because early clinical diagnosis is difficult. Here, we report a case of tuberculous meningitis in a 61-year-old Indian hemodialysis patient, who presented with fever of unknown origin and was successfully treated with empiric treatment with standard four-drug regimen against tuberculosis. Comprehensive screening of the origin of fever revealed only the positive results of interferon-gamma release assay, which led us to initiate an empiric therapy for tuberculosis, before making a definitive diagnosis by cerebrospinal fluid nested PCR. Soon after the initiation of the treatment, the fever immediately abated. Although the patient experienced a single episode of paradoxical worsening and severe liver injury, she recovered well without any complications. This report provides a clinical course of the disease in a hemodialysis patient, highlighting the importance of early clinical diagnosis and rapid initiation of empirical tuberculosis treatment.

Squamous Cell Carcinoma of the Lung Presenting Unilateral Thoracic Hyperhidrosis: A Case Report and Review of Literature.

Unilateral hyperhidrosis is an uncommon manifestation, and the majority of cases have been attributed to neurological diseases. There are few cases of unilateral hyperhidrosis associated with thoracic malignant tumors. We herein report a 74-year-old Japanese man with squamous cell carcinoma of the lung who presented with unilateral hyperhidrosis in the right thoracic area as one of the first clinical manifestations. We should consider the possibility of pleural diseases, including metastatic lung cancer, when encountering patients presenting with unilateral thoracic hyperhidrosis.

Diagnosis of pulmonary leiomyosarcoma extending into the main bronchus using repeated transbronchial cryobiopsy.

The diagnosis of pulmonary leiomyosarcoma using bronchoscopy is difficult, and surgical resection is often performed for definitive diagnosis and curative therapy. We report a case of pulmonary leiomyosarcoma, successfully diagnosed using repeated transbronchial cryobiopsy (TBCB). A 69-year-old-woman was found to have an oval mass in the left hilar region extending into the left main bronchus on computed tomography (CT). All transbronchial biopsy specimens were necrotic, but repeated TBCB removed the necrotic tissue from the tumour and finally led to the diagnosis of pulmonary leiomyosarcoma. Proton therapy was administered, which caused shrinkage of the tumour. Thus, TBCB is useful for definitive diagnosis of leiomyosarcoma without surgical biopsy. Repeated TBCB can reduce tumour volume, eliminate atelectasis, and reduce the extent of radiotherapy exposure.

Relationship Between Episodic Nocturnal Hypercapnia and History of Exacerbations in Patients with Advanced Chronic Obstructive Pulmonary Disease.

Purpose: An episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH. Patients and Methods: We enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) <55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH. Results: Twenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16-6.00] and 11.1 [95% CI: 1.39-87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04-2.64] and 6.6 [95% CI: 1.06-39.4], respectively. Conclusion: In patients with advanced COPD and a daytime PaCO2 <55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.

Antimelanoma Differentiation-Associated Gene 5 Antibody-Positive Interstitial Lung Disease After Vaccination With COVID-19 mRNA Vaccines.

OBJECTIVE: Melanoma differentiation-associated gene 5 (MDA5) is a viral RNA sensor induced by SARS-CoV-2. Similarities have been reported between the clinical presentations of coronavirus disease 2019 (COVID-19) pneumonia and anti-MDA5 antibody-positive interstitial lung disease (anti-MDA5-ILD). However, it is unknown whether COVID-19 mRNA vaccines are associated with anti-MDA5-ILD. METHODS: We retrospectively reviewed consecutive patients with anti-MDA5-ILD admitted to our hospital between April 2017 and March 2022. In addition, we investigated the clinical presentations of patients who developed anti-MDA5-ILD after vaccination with COVID-19 mRNA vaccines. We also examined the annual number of anti-MDA5-ILD cases before and after the COVID-19 vaccination campaign. RESULTS: Nine patients with anti-MDA5-ILD were seen during the study period, of whom 4 developed anti-MDA5-ILD between August and October 2021, approximately 6 to 12 weeks after vaccination with a COVID-19 mRNA vaccine and a few months after the rapid mRNA COVID-19 vaccination campaign in Japan. None of the 4 patients had evidence of SARS-CoV-2 infection. The difference in the annual number of anti-MDA5-ILD cases before vs after the COVID-19 vaccination campaign (1.25 ± 0.96 cases/yr vs 4.0 cases/yr) was not statistically significant (P = 0.08). CONCLUSION: We encountered 4 cases of anti-MDA5-ILD after COVID-19 vaccination. Further large population studies are needed to clarify the relationship between anti-MDA5-ILD and vaccination with COVID-19 mRNA vaccines.

Adult T Cell Leukemia/Lymphoma Becoming Apparent during Treatment of Pulmonary Abscess and Empyema Caused by Nocardia asiatica: A Case Report and Review of the Literature.

Nocardia is a Gram-positive bacterium that causes opportunistic infections. Nocardia asiatica was newly isolated in 2004, and there have been no case reports describing the empyema caused by N. asiatica. Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). We herein report a case in which immunosuppression attributable to ATL may have led to pulmonary abscess and empyema caused by N. asiatica. Our case demonstrates the need to investigate causes of immunosuppression, including ATL, in patients showing nocardiosis.

Durvalumab-associated Late-onset Myocarditis Successfully Treated with Corticosteroid Therapy.

We herein report a 66-year-old man with locally advanced non-small-cell lung cancer (NSCLC) who developed durvalumab-associated myocarditis. The patient underwent durvalumab administration every two weeks following concurrent chemoradiotherapy, without any adverse events or apparent disease progression. He presented with fatigue and dyspnea on exertion seven months after the first administration. Myocarditis was suspected based on laboratory data, an electrocardiogram, echocardiography, and magnetic resonance imaging findings. The definitive diagnosis was confirmed by a myocardial biopsy. Myocarditis was alleviated by cessation of durvalumab and corticosteroid therapy. This is a noteworthy case to describe late-onset myocarditis following the administration of durvalumab for NSCLC.

SARS-CoV-2-related Progressive Brain White Matter Lesion Associated with an Increased Cerebrospinal Fluid Level of IL-6.

We herein report a 49-year-old man with a fever, diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After two weeks of hospitalization, he suddenly mentioned visual field impairment. Computed tomography and magnetic resonance imaging revealed white matter damage and vasogenic edema. Cerebrospinal fluid showed increased levels of interleukin (IL)-6. His symptoms and white matter lesion deteriorated. After treatment with intravenous methylprednisolone therapy and plasmapheresis, his symptoms and white matter lesion improved gradually. We suspect that our patient was affected by a secondary hyperinflammatory syndrome related to cytokines, alone or in combination with direct viral injury through endothelial cell damage. The IL-6 levels were elevated only in the cerebrospinal fluid, suggesting focal central nervous system inflammation.

Sequential occurrence of microscopic polyangiitis and anti-glomerular basement membrane disease in a patient with small cell lung cancer: a case report.

BACKGROUND: The association between a preceding malignancy and the onset of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in several studies. While the co-existence of ANCA and anti-glomerular basement membrane (GBM) antibodies in an individual patient is not a common occurrence, this double-positive disease currently has no optimal treatment method. Herein, we report a case of a double-positive disease involving the sequential development of acute kidney injury (AKI) and diffuse alveolar hemorrhage (DAH) in a patient with small cell lung cancer (SCLC). CASE PRESENTATION: A 75-year-old Japanese woman was diagnosed with small cell lung cancer (cT3N2M1b cStage IV) and received chemotherapy. After one cycle of chemotherapy, she experienced fever and malaise. Her serum creatinine level rapidly increased, and she tested positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibody. She was diagnosed with AKI due to microscopic polyangiitis (MPA) based on renal biopsy. Corticosteroid therapy was initiated, which improved her renal dysfunction. Eight days after she was discharged from the hospital, she complained of dyspnea and bloody sputum, and her condition rapidly progressed to respiratory failure. Upon chest imaging, ground-glass opacities were seen in her bilateral lower lungs. Laboratory examinations after admission revealed a lower MPO-ANCA titer and an elevated anti-GBM antibody titer compared to her previous admission. We diagnosed her with DAH due to an anti-GBM disease. After corticosteroid pulse therapy, plasma exchange was performed five times; her oxygen saturation and chest radiologic findings improved gradually. Following five cycles of plasma exchange, her oxygen saturation recovered to 95% in room air. CONCLUSIONS: To our knowledge, this is the first reported case of vasculitis caused by MPA and anti-GBM disease leading to the development of AKI and DAH during treatment of SCLC. SCLC, MPA, and anti-GBM disease may occur sequentially. A double-positive disease might have a worse prognosis; therefore, intensive therapy is more likely to achieve a better outcome.

Legionnaire's disease presenting as bilateral central scotomata: a case report.

BACKGROUND: Legionnaire's disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire's disease are limited. CASE PRESENTATION: We report the case of a patient with Legionnaire's disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire's disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire's disease. CONCLUSIONS: This case demonstrates that Legionnaire's disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire's disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.

In vitro efficacy of combinations of eight antimicrobial agents against Mycobacteroides abscessus complex.

OBJECTIVES: A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections. METHODS: We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method. RESULTS: We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively. CONCLUSIONS: These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massiliense infections.

Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial.

BACKGROUND: Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP. METHODS: In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP. RESULTS: We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0). CONCLUSIONS: Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.

The utility of serial procalcitonin measurements in addition to pneumonia severity scores in hospitalised community-acquired pneumonia: A multicentre, prospective study.

OBJECTIVES: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. METHODS: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48-72 h after admission (PCT D3 and CRP D3), and within 144-192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. RESULTS: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46-12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07-5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. CONCLUSIONS: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP.

Mycobacterium triplex pulmonary disease in an immunocompetent host: A case report and literature review.

Mycobacterium triplex (M. triplex) is a bacterial species that can cause severe pulmonary diseases. Despite its clinical importance, only a few cases of M. triplex infection have been reported. Here, we present a rare case of pulmonary disease due to M. triplex in an immunocompetent patient who showed abnormal findings on chest X-ray and computed tomography scans. In this patient, the bacterium was identified by DNA sequencing analysis of the 16S rRNA and hsp65 genes. The patient was successfully treated with the appropriate antimicrobial agents. To put this case into the context of the current literature, we also reviewed other case reports of M. triplex infection.

Secondary pulmonary alveolar proteinosis during corticosteroid therapy for organising pneumonia associated with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is frequently complicated by pulmonary disease. Here, we describe secondary pulmonary alveolar proteinosis (sPAP) that developed during corticosteroid therapy for organising pneumonia (OP) associated with MDS. A 75-year-old woman with MDS complained of cough for 2 weeks. Chest CT showed bilateral patchy consolidations with reversed halo sign. Bronchoalveolar lavage (BAL) examination showed remarkably increased cell density with an increased lymphocyte proportion. Abnormal radiological findings improved rapidly on administration of systemic corticosteroid under the diagnosis of OP; however, they relapsed a few weeks later. Transbronchial lung biopsy showed periodic acid-Schiff stain-positive amorphous materials. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum and BAL fluid (BALF) were both negative, while GM-CSF level in BALF was elevated. The patient was diagnosed with sPAP. When chest radiological findings show exacerbation during corticosteroid therapy for OP in a patient with MDS, physicians should consider sPAP complication as a differential diagnosis.

Case of summer-type hypersensitivity pneumonitis complicated with IgA nephropathy.

Association between pulmonary disease and IgA nephropathy (IgAN) has been previously reported. However, no association has been reported between hypersensitivity pneumonitis (HP) and IgAN. Here, we report about a patient with no particular medical history, who experienced worsening dyspnoea in the course of 1 month, with ground-glass opacity on chest CT and no improvement after antibiotic therapy. The patient was diagnosed as having HP based on the history of antigen exposure, detection of Trichosporon asahii-specific antibodies and bronchoscopy findings. Concomitantly, findings of renal biopsy revealed the IgAN diagnosis. The patient underwent corticosteroid therapy, with good outcomes for both HP and IgAN. This is the first report in the literature to describe summer-type HP complicated with IgAN.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Effects of vessel interruption sequence during thoracoscopic lobectomy for non-small cell lung cancer.

OBJECTIVE: This study aimed to determine if the vessel interruption sequence during thoracoscopic lobectomy affects disease recurrence. METHODS: We retrospectively analyzed 187 consecutive patients who underwent video-assisted thoracoscopic surgery lobectomy with curative intent for non-small cell lung cancer between January 2007 and December 2013. Their clinicopathological, operative, and postoperative data were compared. Patients with minimally invasive adenocarcinoma were excluded. RESULTS: A total of 104 patients underwent total venous interruption before interruption of any artery branch (V-first), while 83 patients underwent some artery interruption first (non-V-first). Clinicopathological characteristic distributions were similar between both groups except for the resected lobe. Seven of 104 patients in the V-first group and 15 of 83 patients in the non-V-first group experienced disease recurrences. Among the 187 patients who underwent thoracoscopic lobectomy, overall survival tended to be longer in the V-first group than in the non-V-first group (P = 0.080). Furthermore, disease-free survival was significantly longer in the V-first group than in the non-V-first group (P = 0.019), particularly in stage I patients (P = 0.047). Multivariate analysis showed that vessel interruption sequence was a significant prognostic factor for poor disease-free survival, after adjusting for pathological stage and histology (hazard ratio 2.127; 95% confidence interval 1.009-4.481). There was no significant difference in intraoperative blood loss between both groups. CONCLUSIONS: Interrupting the pulmonary vein first may be associated with improved disease-free survival in patients undergoing thoracoscopic lobectomy for non-small cell lung cancer.