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Hiroaki Ogata, Kachi Sha, Yasuaki Kotetsu, Aimi Enokizu-Ogawa, Katsuyuki Katahira, Akiko Ishimatsu, Kazuhito Taguchi, Atsushi Moriwaki, Makoto Yoshida Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, Fukuoka, JapanCorrespondence: Hiroaki Ogata, Department of Respiratory Medicine, National Hospital Organization Fukuoka National Hospital, 4-39-1 Yakatabaru, Minami-ku, Fukuoka, 811-1394, Japan, Tel +81-92-565-5534, Fax +81-92-566-0702, Email md105020@gmail.comPurpose: Similar to chronic obstructive pulmonary disease (COPD), the diffusing capacity of the lung (DLCO) might be decreased and associated with poor prognosis in preserved ratio impaired spirometry (PRISm), a clinical entity as a prodromal phase of COPD. The aims of the present study were to evaluate the distributions of DLCO and to assess the association between DLCO and mortality among subjects with PRISm.Patients and Methods: We conducted an observational cohort study at the National Hospital Organization Fukuoka National Hospital. We classified the 899 patients ≥ 40 years of age with an assessment of DLCO into five groups based on spirometry: preserved spirometry, PRISm, mild COPD, moderate COPD, and severe/very severe COPD. The prevalence of low DLCO (< 80% per predicted) was compared among the five groups. Using PRISm patients with follow-up data, we further investigated the association of low DLCO with all-cause mortality.Results: The prevalence of low DLCO in the PRISm group (58.8%) was significantly higher than that in the preserved-spirometry group (21.8%), the mild-COPD group (23.5%), and the moderate-COPD group (36.0%) (all P < 0.01), and it was comparable to that in the severe/very severe-COPD group (63.2%). The results remained unchanged after adjusting for potential confounders. Among the PRISm subjects, the overall survival rate was significantly lower in the low-DLCO group than in the preserved-DLCO group (P < 0.01). The multivariable-adjusted hazard ratio (HR) for all-cause mortality was significantly higher in the low-DLCO group than in the preserved-DLCO group (HR = 10.10 (95% confidence interval 2.33– 43.89)).Conclusion: Diffusing capacity was more impaired in PRISm subjects than in those with preserved spirometry or mild to moderate COPD. Regarding PRISm, low DLCO was a significant risk factor for all-cause mortality. Clinicians should assess DLCO in the management of PRISm to predict the future risk of overall death.Keywords: preserved ratio impaired spirometry, chronic obstructive pulmonary disease, diffusing capacity of the lungs, all-cause mortality

Background Clarification of the risk factors for coronavirus disease 2019 (COVID-19) severity is strongly warranted for global health. Recent studies have indicated that elevated body mass index (BMI) is associated with unfavorable progression of COVID-19. This is assumed to be due to excessive deposition of visceral adipose tissue (VAT); however, the evidence investigating the association between intra-abdominal fat and COVID-19 prognosis is sparse. We therefore investigated whether measuring the amount of intra-abdominal fat is useful to predict the prognosis of COVID-19. Methods The present study enrolled 53 consecutive cases of COVID-19 patients aged ≥ 20 years with chest computed tomography (CT) scans. The VAT area, total adipose tissue (TAT) area, and VAT/TAT ratio were estimated using axial CT images at the level of the upper pole of the right kidney. Severe COVID-19 was defined as death or acute respiratory failure demanding oxygen at ≥ 6 L per minute, a high-flow nasal cannula, or mechanical ventilation. The association of VAT/TAT with the incidence of progression to a severe state was estimated as a hazard ratio (HR) using Cox regression analysis. To compare the prediction ability for COVID-19 disease progression between BMI and VAT/TAT, the area under the receiver operating characteristic curve (AUC) of each was assessed. Results A total of 15 cases (28.3% of the whole study subjects) progressed to severe stages. The incidence of developing severe COVID-19 increased significantly with VAT/TAT (HR per 1% increase = 1.040 (95% CI 1.008–1.074), P = 0.01). After adjustment for potential confounders, the positive association of VAT/TAT with COVID-19 aggravation remained significant (multivariable-adjusted HR = 1.055 (95% CI 1.000–1.112) per 1% increase, P = 0.049). The predictive ability of VAT/TAT for COVID-19 becoming severe was significantly better than that of BMI (AUC of 0.73 for VAT/TAT and 0.50 for BMI; P = 0.0495 for the difference). Conclusions A higher ratio of VAT/TAT was an independent risk factor for disease progression among COVID-19 patients. VAT/TAT was superior to BMI in predicting COVID-19 morbidity. COVID-19 patients with high VAT/TAT levels should be carefully observed as high-risk individuals for morbidity and mortality.

We report the complete genome sequence of Mycobacterium heckeshornense strain JMUB5695, which was isolated from necrotizing granulomatous lesions in a lung cancer patient. The complete genome consists of a 4,865,109-bp chromosome with a GC content of 65.9% and contains no plasmids.

A 63-year-old woman visited our hospital for a further evaluation of progressive dyspnea. She had developed a progressive airflow obstruction after 3 years' remission of non-Hodgkin's lymphoma (follicular mixed cell type), which had been treated with chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The patient's primary care physician had diagnosed her as having COPD and bronchial asthma and had treated her with medications including inhaled corticosteroids, tiotropium, and oral erythromycin. Her dyspnea had gradually worsened, however, and she had a score of 4 on the modified Medical Research Council dyspnea scale at the time of admission to our hospital.

Bacteria are highly diverse, even within a species; thus, there have been many studies which classify a single species into multiple types and analyze the genetic differences between them. Recently, the use of whole-genome sequencing (WGS) has been popular for these analyses, and the identification of single-nucleotide polymorphisms (SNPs) between isolates is the most basic analysis performed following WGS. The performance of SNP-calling methods therefore has a significant effect on the accuracy of downstream analyses, such as phylogenetic tree inference. In particular, when closely related isolates are analyzed, e.g. in outbreak investigations, some SNP callers tend to detect a high number of false-positive SNPs compared with the limited number of true SNPs among isolates. However, the performances of various SNP callers in such a situation have not been validated sufficiently. Here, we show the results of realistic benchmarks of commonly used SNP callers, revealing that some of them exhibit markedly low accuracy when target isolates are closely related. As an alternative, we developed a novel pipeline BactSNP, which utilizes both assembly and mapping information and is capable of highly accurate and sensitive SNP calling in a single step. BactSNP is also able to call SNPs among isolates when the reference genome is a draft one or even when the user does not input the reference genome. BactSNP is available at https://github.com/IEkAdN/BactSNP.

We report here the draft genome sequences of five rapidly growing Mycobacterium (RGM) species potentially pathogenic to humans, M. thermoresistibile , M. fortuitum subsp. acetamidolyticum , M. canariasense , M. brisbanense , and M. novocastrense . As the clinical importance of RGMs is increasingly being recognized worldwide, these sequences would contribute to further advances in RGM research.

Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare occasion it can lead a patient with diminished lung function and poor general condition to death. A 60-year-old man with history of left upper lobe resection from tuberculosis was referred to our hospital due to the recurrence of tuberculosis. Sputum examination showed a positive smear with a Gaffky score of 10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) were administered, but his high fever persisted, and the infiltrate on the chest X-ray deteriorated. While the positive sputum smear persisted, the culture became negative after one month. The tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro. Though we performed examinations and trial treatments for non-tuberculous conditions such as pneumonia and drug-induced pneumonia, the patient died after 6 months. A necropsy specimen taken from the worsening lesion (the right upper lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It is supposed that although antituberculosis drugs were effective, a large quantity of killed organisms was continuously excreted from many cavities in the left lung toward the right lung. Lesions in the right lung thus newly produced in this paradoxical reaction seemed to reduce the remaining lung function. In addition, poorly controlled diabetes caused deteriorated heart function. These multiple factors contributed to the poor prognosis of the patient and his ultimate death.

With the progress of anti-tuberculous therapy, tuberculous peritonitis (TBP) has become a rare manifestation of active tuberculosis. Its early diagnosis is difficult due to lack of pathognomonic findings and specific symptoms. However, early diagnosis is important for effective treatment and for reducing fatality.We retrospectively reviewed medical records of eight patients who were hospitalized with TBP in National Hospital Organization Omuta National Hospital during the periods between 2001 and 2009.Three patients were males and five were females. The age of the patients ranged between 28 and 80 years old (average 67.3 years). The most common presenting findings were abdominal distention seen in four patients and loss of appetite in five patients. Blood examination suggested that most patients were in poor nutrition. Three patients were diagnosed based on bacteriological examination, two based on histopathological findings of caseating granulomas, two based on the elevation of adenosine deaminase activity in ascitic fluid and one based on clinical diagnosis. The most common CT findings were thin lines along mesenteric vessels representing thickened mesenteric leaves and smooth uniform peritoneal thickening. Most patients were treated with isoniazid, rifampicin and ethambutol for 9 months with/without pyrazinamide initially. Seven patients completed anti-tuberculous therapy successfully and were cured. However, one patient died of the deterioration of tuberculosis.TBP should be considered for diagnosis, in patients with non-specific abdominal symptoms. Adenosine deaminase activity in ascitic fluid and CT images are considered to be useful for the diagnosis of TBP in patients in whom bacteriological and histopathological examinations are difficult to perform.

A 76-year-old woman was admitted because of respiratory failure with bilateral multiple interstitial shadows and mediastinal adenopathy on chest CT images. Blood examination revealed eosinophilia without leukocytosis and elevated C-reactive protein levels. Corticosteroids were administered before diagnosis because of rapid respiratory failure. Although her symptoms and pulmonary lesions disappeared with steroid therapy, they recurred 4 days later. A definitive diagnosis was not obtained until bronchofiberoptic examination. At the time of recurrence 6 months later, angioimmunoblastic T-cell lymphoma (AITL) was diagnosed with axillary lymph node biopsy. AITL is rare, and shows rapid deterioration of respiratory failure with poor prognosis. Lymph node biopsy is necessary to establish a definitive diagnosis.