A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome.

Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72_73delGA, in BMPR1A. The proband's elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified.

[Dissolution and maintenance of portal vein thrombosis with antithrombin III and edoxaban in liver cirrhosis:a case report].

A male patient in his 70s was referred to our department. He was found to have alcoholic liver cirrhosis, esophageal varices, and portal vein thrombosis. Antithrombin III (ATIII) formulation was administered. The thrombus was almost completely lysed 2 days after administration. Because portal vein thrombosis could recur, edoxaban, a direct oral anticoagulant (DOAC), was introduced to prevent recurrence. After 4 months, he showed no recurrence of portal vein thrombosis. In the present case, the combination of an ATIII formulation as initial treatment and edoxaban as maintenance therapy was safe and effective. The combination of ATIII and edoxaban may be a treatment option for patients with portal vein thrombosis.

[Clinical study of pneumocystis pneumonia in patients with rheumatoid arthritis].

We reviewed case of pneumocystis pneumonia (PCP) with rheumatoid arthritis. We administered the antirheumatic drug methotrexate (MTX) at the time of to 13 patients, corticosteroids to 11 patients and a tumor necrosis factor (TNF) inhibitor to 3 patients. Treatment for PCP was started on admission in all cases. We administered adrenocorticosteroids to all 13 patients with a PaO2 level < 70 Torr. Three patients were under respiratory management, and 4 patients died. By univariate analysis, prognostic indicators of death were: presence of acute respiratory distress syndrome (ARDS), peripheral blood neutrophil/lymphocyte ratio, serum albumin value, serum beta-D-glucan value, and AaDO2 and PaO2/FiO2 ratios. Readministration of a TNF inhibitor in 2 patients and MTX in 3 patients was possible after PCP remission. Even though we began treatment for PCP on the day of admission, 25% of patients died. PCP may occur in patients who are given MTX or a TNF inhibitor or both, and the clinician should endeavor to detect its onset as early as possible. Elucidation of the prognostic indicators of recovery may require multivariate analysis of many cases.

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated. METHODS: Consecutive patients with usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (>or=2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (>or=1/3 of the area of the base of the lungs). RESULTS: Among 660 patients with UIP on HRCT, 221 showed upper-lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DL(CO), 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group. CONCLUSIONS: Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.

[Case of novel influenza A (H1N1) pneumonia with shrinkage of a pulmonary lesion].

Fever developed in a 56-year-old man with sarcoidosis and bronchial asthma, and influenza was diagnosed. He was given zanamivir on the day of diagnosis, but he suffered a bronchial asthma attack 4 days after the diagnosis of influenza, and pneumonia developed 7 days subsequently. He was then admitted to our hospital. A rapid antigen test was positive for influenza type A, and reverse-transcriptase polymerase chain reaction results were also positive for novel influenza A (H1N1). Chest computed tomography showed homogeneous ground-glass opacities in bilateral lung fields, and novel influenza A (H1N1) pneumonia was diagnosed. The patient was treated with oseltamivir and steroid therapy for the bronchial asthma attack; however, ground-glass opacities enlarged and became consolidated. The lower lobes of both lungs showed shrinkage and persistent volume loss. Improvement in the consolidation was accompanied by improvement in his respiratory condition. We report a case with an interesting radiological course.

[Autopsy case of diffuse pleural thickening presenting respiratory impairment and benign asbestos pleurisy].

A 51-year-old man presented with back pain in 1997. He had a 30-year-history of occupational asbestos exposure. His chest CT showed bilateral pleural thickening and pleural effusion. The pleural effusion of the right thorax exhibited both elevated level of adenosine deaminase and increased numbers of lymphocytes. Antituberculous chemotherapy had no effect on the exudates. Progressive bilateral pleural thickening were found on chest CT, and pulmonary function tests showed severe restrictive ventilatory impairments since 1998. Thoracoscopic pleural biopsy was conducted in 2001 to exclude pleural malignant mesothelioma. No malignancy was found in pleural samples. After 3-year observation and excluding other causes, he was given a diagnosis of benign asbestos pleurisy. In 2005, fibrotic changes were found in both lower lung fields in chest CT. He suffered from respiratory failure with carbon dioxide retention, and died in 2006. The autopsy disclosed asbestos-related lung diseases. We suspected that diffuse pleural thickening could be a major cause of fatal respiratory impairment in this case.

Clinical characteristics and prognostic factors of pneumonia in patients with and without rheumatoid arthritis.

BACKGROUND: To elucidate the characteristics of pneumonia in rheumatoid arthritis (RA) patients and to assess whether pneumonia in RA patients differs from that in non-RA patients. METHODS: We retrospectively divided pneumonia patients into two groups, those with RA and those without RA, and compared the two groups. We evaluated the risk factors for mortality with univariate and multivariate logistic regression analysis. RESULTS: Among 1549 patients, 71 had RA. The RA patients with pneumonia were 71.0±8.9 years old, 54.9% were female, 40.9% had a smoking history, and 71.8% had underlying respiratory disease. Female sex, non-smoker, and respiratory comorbidities were statistically more frequent in the RA patients than non-RA patients. The most frequent causative microbial agents of pneumonia in the RA patients were Streptococcus pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Mycoplasma pneumoniae, and influenza virus, whereas those of pneumonia in non-RA patients were S. pneumoniae, influenza virus, M. pneumoniae, Legionella spp., P. aeruginosa, H. influenzae, and Moraxella catarrhalis. Polymicrobial infection were identified as etiologies more frequently in the RA patients than non-RA patients. Although the severity of pneumonia did not differ between the two groups, mortality was statistically higher in the RA patients than non-RA patients. Multivariate analysis showed RA to be an independent risk factor for mortality. CONCLUSIONS: P. aeruginosa, H. influenzae, M. catarrhalis, and polymicrobial infection were statistically more frequent etiologies of pneumonia in the RA patients than non-RA patients. RA itself was found to be an independent risk factor for mortality from pneumonia.

Deterioration of the immune response induced by sulfamethoxazole-trimethoprim in a rheumatoid arthritis patient with Pneumocystis jirovecii pneumonia.

A 73-year-old woman with rheumatoid arthritis treated with methotrexate and prednisolone was admitted with dyspnea and ground-glass opacity on chest CT. We diagnosed her with Pneumocystis jirovecii pneumonia (PCP) based on a positive PCR analysis of Pneumocystis jirovecii and the presence of cysts in bronchoalveolar lavage fluid. The PaO2 was 74.7 Torr on room air, and treatment with sulfamethoxazole-trimethoprim only was initiated. The hypoxemia and ground-glass opacity increased on hospital day 3, and the administration of adjunctive steroid therapy resulted in an improvement in the patient's condition. Although patients with PCP with HIV infection and hypoxemia are often treated with adjunctive steroid therapy to prevent adverse immune reactions, the efficacy of additive steroid administration in case of non-HIV PCP has not been established.

An autopsy case of pulmonary aspergillosis with fungus ball formation in an artificial aortic graft.

A 38-year-old man with Marfan syndrome underwent an aortic replacement with an artificial aortic valve at 27 years of age and an aortic graft at 31 years of age. In 2011, he was diagnosed as having chronic necrotizing pulmonary aspergillosis (CNPA). He developed a fever and an increased sputum volume and was admitted to the hospital in 2012. Contrast-enhanced CT showed an irregularly shaped nonenhanced structure in the aortic graft. He died on hospital day 31. From the autopsy findings, we speculated that an infiltration by the CNPA lesion into a pulmonary vein was followed by the hematogenous formation of a fungus ball in the aortic graft.

Etiology and factors contributing to the severity and mortality of community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) remains a major cause of death. No studies have reported the use of rapid influenza diagnostic tests (RIDT) for the etiological diagnosis, and the factors contributing to severity and mortality have not yet been fully investigated. The aim of this study was to review the etiologies of CAP using RIDT and to identify risk factors related to the severity and mortality of the disease. METHODS: This retrospective study assessed these factors in hospitalized patients, with special emphasis on microbial etiology. RESULTS: A total of 1,032 patients aged 63.9±18.3 years were studied, 66.2% of whom were men. Microbial identification was obtained in 57.0% of the cases. The most frequent causative microbial agents were Streptococcus pneumoniae, Mycoplasma pneumoniae and the influenza virus, and the second most frequent pathogens in the patients with severe CAP and the non-survivors were S. pneumoniae and the influenza virus. Age (≥65 years), chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, dementia and Legionella spp. infection and polymicrobial infection were each found to be independent factors related to severity in the multivariate analysis, whereas "unidentified pathogen" was found to be an independent factor for non-severe CAP. Age (≥65 years), chronic pulmonary aspergillosis, post-lung cancer surgery and severe CAP were found to be independent factors for non-survival according to a multivariate analysis. CONCLUSION: In addition to S. pneumoniae, the influenza virus was a frequent cause of CAP overall and a frequent causative pathogen in both severe cases of CAP and non-survivors. Legionella spp. infection and polymicrobial infection were found to be an independent factor for the severity of CAP along with advanced age and certain comorbidities. An advanced age, certain respiratory comorbidities and severe CAP were found to be important independent factors for the mortality of CAP.

Prognostic factors and radiographic outcomes of nontuberculous mycobacterial lung disease in rheumatoid arthritis.

OBJECTIVE: The aims of our study were to retrospectively review patients with rheumatoid arthritis (RA) with nontuberculous mycobacterial (NTM) lung disease, to assess the prognostic factors, and to analyze the time to disease deterioration according to the antirheumatic drugs received during the NTM lung disease followup period. METHODS: We retrospectively analyzed medical records of 98 HIV-negative RA patients with NTM lung disease treated at our institution, and investigated potential risk factors of mortality with Cox regression analysis. Time to radiologic deterioration was evaluated if antirheumatic drugs were not changed during observational periods and computed tomography was performed once each year. RESULTS: Mean patient age was 67.6 years, and median followup period was 4.4 years. NTM species included Mycobacterium avium complex (83.7%), M. kansasii (6.1%), M. gordonae (6.1%), and others (4.1%). Radiographic features included nodular/bronchiectatic (NB) disease (57.1%), fibrocavitary (FC) disease (14.3%), FC+NB disease (16.3%), and other types (12.2%). Initial management included observation in 74 (75.5%) patients. Negative prognostic factors of mortality were C-reactive protein (CRP) ≥ 1.0 mg/dl and radiographic features of FC, FC+NB, or other disease types. Median time to radiologic deterioration was 3.6 years. Erythrocyte sedimentation rate (ESR) > 50 mm/h was a negative prognostic factor of radiologic deterioration. CONCLUSION: The most frequent NTM species was M. avium complex. CRP and radiographic features were prognostic factors for all-cause mortality, and ESR was a prognostic factor of radiologic deterioration. Further studies are warranted focusing on time to disease deterioration according to antirheumatic drug received during NTM followup.