Monocytes predict prognosis and successful treatment in older patients with miliary tuberculosis.

Background: The increasing number of patients with miliary tuberculosis (MTB) is a concern in an aging society because of its high mortality rate. Several prognostic biomarkers for MTB have been identified; however, the predictive ability of monocytes as biomarkers remains unknown. This study demonstrates the usefulness of monocytes as prognostic biomarkers for MTB. Materials and methods: We retrospectively compared the clinical findings of 52 patients with MTB hospitalized between April 2013 and October 2021. The predictive ability of biomarkers for 3-month prognosis and their cutoff values were calculated. Survival times and longitudinal changes in monocytes after initiating treatment were compared. Results: A smaller number of monocytes (#M), higher lymphocyte-monocyte ratio (LMR), higher neutrophil-monocyte ratio, and poorer performance status were associated with death within 3 months. #M was an independent prognostic factor. #M and LMR exhibited the highest predictive performance compared to others using receiver operating characteristic curve analysis (area under the curve = 0.86 and 0.85, respectively). Survival time was shorter in patients with #M ≤ 200 cells/µL and LMR > 2.5. Rapidly increasing #M after treatment was related to better prognosis in patients with #M ≤ 200 cells/µL at diagnosis. Conclusions: #M at diagnosis and longitudinal changes in monocytes are related to MTB prognosis.

Clinical Impact of Pre-Existing Autoantibodies in Patients With SCLC Treated With Immune Checkpoint Inhibitor: A Multicenter Prospective Observational Study.

Introduction: Although pretreatment autoantibodies have been associated with immune-related adverse events (irAEs) and immune checkpoint inhibitor treatment efficacy in some types of cancer, their importance has not been evaluated in patients with SCLC. Methods: A multicenter prospective observational study was conducted on a total of 52 patients with extensive-disease SCLC who received immune checkpoint inhibitors in combination with chemotherapy as the first-line treatment at either of the six participating centers in Japan. Pretreatment serum samples were collected and analyzed for autoantibodies (rheumatoid factor, antinuclear antibodies, and antithyroid). Moreover, 12 antineuronal antibodies (AMPH, CV2, PNMA2, Ri, Yo, Hu, Recoverin, SOX1, Titin, Zic4, GAD65, and Tr) were analyzed using immunoblot assays. The primary end point was the incidence of irAEs with or without autoantibodies. The secondary end points were progression-free survival (PFS) and overall survival (OS) on the basis of the presence or absence of autoantibodies. Results: PFS and OS were 4.4 and 25.3 months, respectively. Autoantibodies (rheumatoid factor, antinuclear antibodies, and antithyroid antibodies) were detected in 29 patients (56%). In total, irAEs were observed in 18 patients (35%); irAE incidence was 48% in the autoantibody-positive group and 17% in the autoantibody-negative group (p = 0.039). There was no difference in PFS or OS between patients with and without autoantibodies (4.4 mo versus 4.6 mo, p = 0.36; 15.3 mo versus 18.2 mo, p = 0.36). Antineuronal antibodies were detected in 16 patients (31%). However, the development of neurologic irAEs was not observed in both groups. Conclusions: Vigilance is required against the development of irAEs in pretreatment antibody-positive patients.

Combined pulmonary fibrosis and emphysema: effect of pulmonary rehabilitation in comparison with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effectiveness of short-term comprehensive inpatient pulmonary rehabilitation for patients with combined pulmonary fibrosis and emphysema (CPFE), and to compare responses with those of patients with chronic obstructive pulmonary disease (COPD) who underwent an identical programme. DESIGN: Retrospective analysis of several outcome measures. SETTING: Pulmonary ward at a 358-bed community teaching hospital. METHODS: 3-week inpatient pulmonary rehabilitation programme assessed by pulmonary function tests, 6 min walk test and health-related quality of life (HRQL) using the Short Form-36 (SF-36). RESULTS: 17 patients with CPFE and 49 patients with COPD were referred to and completed the programme between March 2007 and February 2015. Age, sex, smoking status, body mass index and the Medical Research Council dyspnoea grade were comparable between groups. In the CPFE group, improvement from the start of the programme to the programme end was observed in forced expiratory volume in 1 s (FEV1) (from 1.7±0.4 to 1.8±0.4, p=0.034); however, there was no significant improvement in the 6 min walk test (distance, SpO2 nadir and Borg scale on exercise). With regard to HRQL, improvement was observed in physical function (p=0.015) whereas deterioration was observed in social functioning (p=0.044). In the COPD group, significant improvement was observed after the programme in the FEV1, 6 min walk test and 4 of the 8 SF-36 subscales. There was a significant difference in changes in the 6 min walk distance: -16.6±58.4 in CPFE versus 30.2±55.6 in COPD (p=0.009). In 2 domains, there was a significant difference in SF-36 scores between groups: Δvitality, -6.3±22.4 in CPFE versus 11.3±21.1 in COPD, p=0.009; and Δsocial functioning, -18.8±34.2 in CPFE versus 5.3±35.9 in COPD, p=0.027. CONCLUSION: Patients with COPD derived greater benefits than those with CPFE, from the relatively short periods of inpatient pulmonary rehabilitation.

Association of hyperglycemia on admission and during hospitalization with mortality in diabetic patients admitted for pneumonia.

OBJECTIVE: Information available on the clinical features and outcomes of pneumonia in diabetic patients is limited. There are no data on the association between glycemic control during hospitalization and mortality in this population. The objective of this study is to examine whether the presence of hyperglycemia on admission and during hospitalization is associated with mortality in diabetic patients admitted to the hospital for pneumonia. METHODS: This study is a retrospective observational cohort study of diabetic adults hospitalized for the first time for pneumonia between 2005 and 2011 in a 358-bed community hospital. Univariate and multivariate analyses were performed for 30-day all-cause hospital mortality adjusted for sex, age, type of pneumonia (community-acquired pneumonia or nursing and health care-associated pneumonia), severity of pneumonia according to the A-DROP score and various comorbidities in consideration of the serum glucose and hemoglobin A1c levels on admission and the mean plasma glucose level during hospitalization. RESULTS: Of the 1,499 pneumonia patients evaluated, 185 (12.3%) (mean age 75 years) had diabetes mellitus. Fourteen (7.6%) of the 185 diabetic patients died within 30 days after admission. According to the univariate analysis, 30-day mortality was significantly associated with the A-DROP score (p<0.0001), the admission glucose level (p=0.01) and the mean plasma glucose level during hospitalization (p<0.0001). Even after adjusting for factors related to the severity of pneumonia, the mean plasma glucose level during hospitalization remained significantly associated with 30-day mortality (p=0.004). CONCLUSION: Hyperglycemia determined according to the mean plasma glucose level during hospitalization is independently associated with 30-day all-cause hospital mortality in diabetic patients admitted for pneumonia.

AP-VAS 2012 case report: anti-glomerular basement membrane disease with high titer of myeloperoxidase anti-neutrophil cytoplasmic antibody-an autopsy case report.

It has been reported that patients who are positive for both myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane (GBM) antibody have a poor prognosis. We present an autopsy case of anti-GBM disease with a high titer of MPO-ANCA. The patient was a 77-year-old woman with a medical history of idiopathic interstitial pneumonia. After being treated for bacterial pneumonia, she was referred to our hospital for evaluation of non-nephrotic range proteinuria, hematuria, and a course of rapidly progressive glomerulonephritis. Results of urinalysis were 2+ for protein and 3+ for blood, with many dysmorphic red blood cells observed in the urinary sediment. A sample of a 24-h urine collection contained 0.3 g protein. The serum creatinine concentration was 5.0 mg/dl on admission. The patient tested positive for MPO-ANCA at a titer of >640 EU and for anti-GBM antibody at a titer of 14 EU. Renal biopsy revealed glomerulonephritis with crescent formation, and immunofluorescence studies showed that the glomeruli had a generalized linear fluorescence and anti-immunoglobulin G (IgG) and C3 along the peripheral glomerular capillaries. She was diagnosed with anti-GBM disease. Treatment was started with intravenous prednisolone and oral cyclophosphamide, followed by plasma exchange. Despite improved renal function, she died of pulmonary hemorrhage. Autopsy revealed deposits of IgG and C3 in the basement membranes of lung alveoli.

[Three autopsy cases of chronic necrotizing pulmonary aspergillosis].

Chronic necrotizing pulmonary aspergillosis (CNPA), also called semi-invasive pulmonary aspergillosis, was first described in the early 1980s as a distinct type of pulmonary aspergillosis. CNPA was an indolent, cavitary, infectious process of the lung parenchyma secondary to local invasion by Aspergillus species. Diagnosis is confirmed by pathological evidence of lung tissue invasion by the fungus. Clinical diagnosis by combined clinical, radiological and laboratory findings is needed because histopathological confirmation cannot always be obtained in the clinical setting. CNPA is recognized as a clinical syndrome in Japan, and has been poorly defined histologically. We report three autopsy cases of CNPA evaluated histopathologically. Subjects were middle-aged to older men with a medical history of pulmonary mycobacterial infection who presented with pulmonary or systemic symptoms. Radiologically, progressive upper lobe cavitary infiltrates were seen with mycetomas and infiltration in lower lung fields. Clinically, CNPA was diagnosed based on 2007 Japanese guidelines for the diagnosis and treatment of deep fungal infection. Subjects died of respiratory failure within one month to three years of diagnosis despite antifungal therapy including micafungin, voriconazole, or itraconazole combined with broad spectrum antibiotics. Autopsy findings showed cavities containing the fungus but no fungal invasion of viable lung tissue. The area of progressive infiltration revealed bacterial pneumonia, organizing pneumonia or organizing diffuse alveolar damage without Aspergillus. In conclusion, CNPA is a chronic progressive clinical form of pulmonary aspergillosis with significant morbidity and mortality.

Gefitinib for a poor performance status patient with squamous cell carcinoma of the lung harboring EGFR mutation.

Recent reports have shown gefitinib, epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) induced marked improvement in ECOG performance status (PS) as first-line therapy in EGFR mutation-positive patients with extremely poor PS. EGFR mutations frequently occur in east-Asian, female, non-smoking, adenocarcinoma patients, however they are occasionally detected in patients with non-adenocarcinomas or with a heavy smoking history. We describe a case in which EGFR mutation was detected in a male, current smoker, squamous cell carcinoma (SCC) patient with PS 4, who showed a marked response to the first-line gefitinib therapy. EGFR mutational analysis is recommended even for SCC patients especially in east-Asian populations.

Therapeutic effect of direct hemoperfusion with a polymyxin B-immobilized fiber column in the treatment of HIV-negative severe pneumocystis pneumonia.

BACKGROUND: Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been shown to improve oxygenation in cases of diffuse alveolar damage, but little is known about its effectiveness in treating pneumocystis pneumonia (PCP) in HIV-negative immunosuppressed patients. OBJECTIVES: This study was aimed at investigating the effect of PMX-DHP in treating non-HIV-related PCP. METHODS: Between October 2005 and September 2008, 6 patients with non-HIV-related PCP were treated with 2 sessions of PMX-DHP at an attending physician's discretion when severe hypoxemia developed despite conventional treatments including high-dose corticosteroid, whereas 9 patients in a similar condition were treated without PMX-DHP. Changes in oxygenation and radiographic findings in the PMX-DHP group and adverse events associated with PMX-DHP were investigated retrospectively, as were the outcomes for both treatment groups. RESULTS: There was an improvement in PaO(2)/FiO(2) during each PMX-DHP session, from 148.8 ± 52.5 to 188.2 ± 79.3 mm Hg (p = 0.02). After 2 sessions of PMX-DHP, an improvement in PaO(2)/FiO(2), from 131.8 ± 37.4 to 213.3 ± 87.3 mm Hg, was observed (p = 0.04), but no significantly different improvement was detected on the following day. The radiographic findings improved in 4 patients during PMX-DHP. The in-hospital mortality was similarly high in both groups (50% in the PMX-DHP group vs. 67% in the non-PMX-DHP group). No significant adverse events associated with PMX-DHP were observed except for advanced thrombocytopenia in 1 patient. CONCLUSION: PMX-DHP may serve as an adjunct in the treatment of non-HIV-related PCP, temporarily alleviating severe hypoxemia even in cases refractory to conventional treatments.

Amrubicin at a lower-dose with routine prophylactic use of granulocyte-colony stimulating factor for relapsed small-cell lung cancer.

BACKGROUND: Recent reports have suggested the efficacy of amrubicin (AMR) for relapsed small-cell lung cancer (SCLC). However, doses of AMR in these reports were 40 mg/m(2) or 45 mg/m(2), and severe and frequent myelosuppression were observed. Such side effects are occasionally intolerable, as serious myelosuppression may induce fatal infections. To overcome this clinical problem, we investigated whether 35 mg/m(2) of AMR administration with routine prophylactic use of granulocyte-colony stimulating factor (G-CSF) can reduce myelosuppression, while maintaining efficacy. METHODS: Between July 2003 and November 2008, 30 relapsed SCLC patients receiving 35 mg/m(2)/day of AMR were evaluated. Amrubicin was administered on days 1-3 every 3 or 4 weeks. Routine prophylactic use of G-CSF was performed beginning on day 8 and continuing for at least 5 consecutive days or until neutrophils recovered to the normal level. RESULTS: The median number of treatment cycles was four (range 1-9). No complete responses and 13 partial responses were observed, with response rates of: overall 43% (95% confidence interval [CI]: 26-63%); sensitive cases 33% (95% CI: 10-65%); and refractory cases 50% (95% CI: 26-74%) (p=0.4651). The disease control rate (partial response and stable disease) was 80% (95% CI: 61-92%). The progression-free survival times were: overall 4.2 months (95% CI: 3.2-5.2 months); sensitive cases 4.7 months (95% CI: 2.6-5.4 months); and refractory cases 3.5 months (95% CI: 2.6-5.2 months) (p=0.7124). The median OS times were: overall 9.6 months (95% CI: 7.2-12.5 months); sensitive cases 8.4 months (95% CI: 4.6-13.4 months); and refractory cases 11.0 months (95% CI: 6.5-12.6 months) (p=0.9315). The 1-year survival rate was 33%. Regarding grade 3/4 hematological toxicities: leukopenia (47%); neutropenia (50%); anemia (30%); and thrombocytopenia (33%) were observed. Febrile neutropenia occurred in three patients (10%). Transfusions of red blood cells and platelets were performed for eight (27%) and one (3%) patients, respectively. Treatment-related deaths and grade 3/4 non-hematological toxicities were not observed at all. CONCLUSIONS: Considering both safety and efficacy, AMR at a dose of 35 mg/m(2) with routine prophylactic use of G-CSF may be more desirable for the treatment of relapsed SCLC in clinical practice.

[An open, noncomparative multicenter study of the efficacy and safety of itraconazole injections and high dose capsules in chronic pulmonary aspergillosis].

BACKGROUND: Itraconazole (ITCZ) is a novel triazole antifungal with a broad spectrum including Aspergillus species. We conducted a three-month open, noncomparative multicenter study of the efficacy and safety of ITCZ injections and high dose capsules in chronic pulmonary aspergillosis. METHODS: Patients with chronic pulmonary aspergillosis received intravenous injection of ITCZ (200mg) (twice a day for the first two days, then once a day for the following 3-12 days) prior to the oral administration of ITCZ capsules (200mg) twice a day. Radiologic findings by chest CT and clinical symptoms were evaluated at baseline and 12 weeks later. We also measured ITCZ plasma trough concentrations after two weeks and four weeks of the study. RESULTS: Twenty patients were included in the study, among which 14 patients presented with chronic necrotizing pulmonary aspergillosis (CNPA) and 6 presented with pulmonary aspergilloma. The efficacy evaluation was available in 17 patients (CNPA, 12 patients; aspergilloma, 5 patients). Radiological improvement was observed in nine (52.9%, 95%CI: 31.0%-73.8%) patients (CNPA, 7 patients; aspergilloma, 2 patients). One patient with aspergilloma showed deterioration. The clinical symptoms showed significant improvement on expectoration, bloody sputum, and pyrexia. Two patients had to stop treatment with ITCZ because of congestive heart failure. Other adverse effects were reported but did not lead to the discontinuation of treatment, as follows: hepatic dysfunction, two patients; hypokalemia, nine patients. In two patients who combined pulmonary Mycobacterium avium complex disease coadministration of ITCZ and rifampicin was done. Their ITCZ plasma concentrations were extremely low, and one of them was the only deterioration case in the primarily radiologic evaluation. CONCLUSION: Itraconazole injections and high dose capsules maintenance therapy is effective in treating chronic pulmonary aspergillosis.

[Case of rapidly progressing primary pulmonary rhabdomyosarcoma with bloody pleural effusion].

A 64-year-old man, complaining of dyspnea from the beginning of May 2006, was admitted to a local hospital because of bloody pleural effusion. After a drainage procedure of the right thoracic cavity was performed, he was referred to our hospital on May 15. Approximately one liter of bloody pleural effusion was drained every day. Computed tomography (CT) on admission showed right pleural effusion, a collapsed right lung and a large marginally enhanced low-density mass in the right lung field. We could not make a specific diagnosis even with a cytological examination of the pleural effusion and thoracoscopic pleural biopsy. Accordingly, open thoracotomy was performed and rhabdomyosarcoma was finally diagnosed. The tumor grew rapidly in a short period, and the patient died only one month after the onset of his complaint. Autopsy revealed primary pulmonary rhabdomyosarcoma occupying most of the right thoracic cavity, but no metastasis. Initially we could not identify the tumor by CT scan, mainly because it had the same density as muscle, nearly the same density as the pleural effusion and lower density than other lung cancers. Primary pulmonary rhabdomyosarcoma is rare. As this tumor could show unexpectedly fast growth, rapid diagnosis is essential. Therefore, we should include thoracic sarcoma in the list of differential diagnosis of rapidly growing lung tumors and bloody pleural effusion.

[A case of cavitating pneumococcal pneumonia developed during the treatment with etanercept for rheumatoid arthritis].

A 54-year-old woman who had been treated for rheumatoid arthritis (RA) with the anti-TNF-alpha drug, etanercept, was referred to our department on 27 April 2006 because of dyspnea and shock. Chest X-ray and computed tomography on admission indicated bilateral pneumonia which was proved to be caused by Streptococcus pneumoniae with positive blood culture results. The patient had recovered from multiple organ failure with intensive treatments such as NIPPV and cardiovascular support with cathecolamines, however, the left upper lobe of her lung had developed a large cavity that had been producing viable pneumococci on sputum culture for more than one month. As the development of lung necrosis and subsequent formation of a cavity is rare in patients with pneumococcal pneumonia, this case should be noted in terms of the relevance of both the fulminating pathogenecity of Streptococcus pneumoniae and the anti TNF-alpha drug treatment.

[Two cases of effective S-1 monotherapy for patients with metastatic adenocarcinoma of the lung after multiple previous chemotherapies].

Case one was a 76-year-old woman. She was diagnosed as having lung adenocarcinoma with multiple metastases (cT4N0M1, stage IV, mucinous BAC)in June, 2004. Starting in July, 2004, she received various modalities of chemotherapy( cisplatin+vinorelbine, gefitinib, pemetrexed, gemcitabine, docetaxel, paclitaxel). S-1 monotherapy given to her starting April, 2006 achieved a partial response(PR)as a seventh-line treatment. Case two was a 60-year-old woman. She was diagnosed as having lung adenocarcinoma with multiple metastases(cT4N3M1, stage IV)in October, 2004. That month, her chemotherapy began. After various treatments(cisplatin+vinorelbine, docetaxel, gefitinib), S-1 monotherapy was initiated in February, 2007 as the fourth-line treatment; as a result, PR was achieved. Even though chemotherapies were performed in succession, in the condition of good general status, salvage chemotherapy can be affected by the rotation of drugs. In such cases, S-1 monotherapy can be a reasonable choice from the standpoint of feasibility and effectiveness.