Clinical utility of thoracoscopy in elderly tuberculous pleurisy patients under local anesthesia.

INTRODUCTION: Diagnosing tuberculous pleurisy is important in Japan because it currently has a moderate tuberculosis prevalence. However, physicians often have difficulty making a diagnosis. It was reported that thoracoscopy under local anesthesia is useful for the diagnosis of tuberculous pleurisy, but there are no reports focusing on elderly patients. METHODS: In this study, the usefulness of thoracoscopy under local anesthesia was evaluated in elderly patients. Among 170 patients who underwent thoracoscopy under local anesthesia at our hospital during 11 years from January 2008 to December 2018, those aged 75 years or older (n = 75) were investigated retrospectively. RESULTS: A total of 55 patients underwent thoracoscopy under local anesthesia for detailed examination of pleural effusion of unknown cause. Of these, 18 were diagnosed as tuberculous pleurisy. The median age was 82 years (range: 75-92 years). The diagnosis of tuberculous pleurisy was made in 11 patients in whom Mycobacterium tuberculosis was detected and in four patients whose pathological findings indicated epithelioid granuloma accompanied by caseous necrosis. Clinical diagnosis was made in the remaining three patients based on thoracoscopic findings of the pleural cavity and a high level of adenosine deaminase in pleural fluid. No serious complications attributable to the examination were observed in any patient. CONCLUSIONS: Thoracoscopy under local anesthesia was useful for the diagnosis of tuberculous pleurisy in elderly patients, with useful information being also obtained for the treatment of tuberculosis.

A case of invasive pulmonary aspergillosis diagnosed by transbronchial lung biopsy during treatment for diabetic ketoacidosis in a type 1 diabetic patient.

Invasive pulmonary aspergillosis (IPA) patients with non-hematological malignancy are far less than with hematological malignancy patients. We encountered a very rare case of IPA in which type 1 diabetes was the only conceivable risk factor. Further, according to the diagnostic categories of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria for IPA, the frequency of proven diagnosis is very low. Here we report a proven IPA, which rapidly developed when the patient with type 1 diabetes was being treated for diabetic ketoacidosis, which was successfully treated with the combination therapy of voriconazole (VRCZ) and micafungin (MCFG), based on early diagnosis using bronchoscopy.

Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis.

BACKGROUND: Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB). METHODS: We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥ 1 based on low attenuation area < - 950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment. RESULTS: Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [interquartile range (IQR) 29.0-66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0-42.0 days) (p < 0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18-4.97; p = 0.015), cavities (HR: 2.15; 95% CI: 1.83-3.89; p = 0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64-5.31; p < 0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p = 0.015, and 84.21% vs 60.98%; p = 0.021, respectively). CONCLUSIONS: This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion.

Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors.

Background This study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of single and multiple doses of nivolumab in Japanese patients with malignant solid tumors. Subjects and Methods This was an open-label, dose-escalation study in 17 patients with advanced solid tumors with a life expectancy of ≥3 months. Patients were observed for 3 weeks after a single dose of nivolumab at 1, 3, 10 or 20 mg/kg, then received the same dose of nivolumab every 2 weeks until unacceptable toxicity or disease progression occurred. This study included a maximum dose of 20 mg/kg, which is the highest dose of nivolumab evaluated to date. The maximum dose was 10 mg/kg in previous studies. Results The commonest adverse drug reaction was lymphopenia, which occurred in 10 (58.8%) patients, including two (11.8%) with Grade ≥3 events. No dose-limiting toxicities (DLTs) were observed up to the maximum dose of 20 mg/kg. The area under the concentration-time curve from time 0 to the last measurable concentration was linear up to 20 mg/kg. The maximum concentration showed dose-dependency up to 10 mg/kg, but not between 10 and 20 mg/kg. One durable complete response and two partial responses were observed. Conclusions Nivolumab at doses of 1-20 mg/kg was not associated with DLTs, and it was generally well tolerated at doses of up to 20 mg/kg in Japanese patients with advanced solid tumors.

Pediatric-onset Chronic Nonspecific Multiple Ulcers of Small Intestine: A Nationwide Survey and Genetic Study in Japan.

We performed a Japanese nationwide survey of pediatric-onset chronic nonspecific multiple ulcers of the small intestine between January 2000 and July 2013 in 176 institutions of pediatric surgery or pediatric gastroenterology and clarified the clinical features associated with genetic abnormalities in the Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) gene. A total of 4 cases (3 girls and 1 boy) were diagnosed in this series, which had to be differentiated from Crohn disease, Behçet disease, tuberculosis, or drug-induced enteropathy. Clinical symptoms appeared in infants and accurate diagnosis required several years. Medical therapies for inflammatory bowel disease were administered in all patients; however, 2 of the 4 patients had mutation in the SLCO2A1 gene which are responsible for primary hypertrophic osteoarthopathy, and underwent strictureplasty or ileal resection after long-term follow-up. Pediatric gastroenterologists should include this new entity in the differential diagnosis of small intestinal ulcers and inflammatory bowel disease.

Pharmacotherapy for pediatric chronic intestinal pseudo-obstruction: Nationwide survey in Japan.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare disabling and life-threatening disorder characterized by severe impairment of gastrointestinal peristalsis. While a number of pharmacotherapeutics have been developed, only a few trials have been carried out for improvement of the pathological condition of CIPO patients. This report describes the results of a nationwide survey on the pharmacotherapy used in pediatric CIPO in Japan. METHODS: In 2012, a nationwide survey was conducted to identify the clinical presentation of CIPO in Japan. Information was gathered on pharmacotherapy. Four categories were created for medicines used in pharmacotherapy: "probiotics", "Japanese herbal medicines (Kampo medicines)", "laxatives", and "prokinetics". RESULTS: Ninety-two responses were collected from 47 facilities. Of the 62 patients who met the diagnostic criteria, 52 were treated with medications, while the remaining 10 were not. Thirty-four patients were given a total of 49 probiotics; 39 were treated with a total of 50 Kampo medicines; 20 were treated with a total of 28 laxatives; and 26 were given a total of 30 prokinetics, 70% of whom were treated specifically with mosapride. CONCLUSION: Traditional Japanese medicines such as Kampo medicines and mosapride are often used to treat CIPO in Japan. Two combinations, that is, probiotics and Kampo medicines; and Kampo medicines and prokinetics, were often used for pediatric CIPO in Japan.

Picoliter-Droplet Digital Polymerase Chain Reaction-Based Analysis of Cell-Free Plasma DNA to Assess EGFR Mutations in Lung Adenocarcinoma That Confer Resistance to Tyrosine-Kinase Inhibitors.

PURPOSE: The objective of this study was to evaluate the utility of analyzing cell-free plasma DNA (cfDNA) by picoliter-droplet digital polymerase chain reaction (ddPCR) to detect EGFR mutations that confer resistance to tyrosine-kinase inhibitors (TKIs) used for treatment of lung adenocarcinoma (LADC). EXPERIMENTAL DESIGN: Thirty-five LADC patients who received epidermal growth factor receptor (EGFR)-TKI therapy, including ten who received tumor rebiopsy after development of resistance, were subjected to picoliter-ddPCR-cfDNA analysis to determine the fraction of cfDNA with TKI-sensitive (L858R and inflame exon 19 deletions) and -resistant (i.e., T790M) mutations, as well as their concordance with mutation status in rebiopsied tumor tissues. RESULTS: cfDNA samples from 15 (94%) of 16 patients who acquired resistance were positive for TKI-sensitive mutations. Also, 7 (44%) were positive for the T790M mutation, with fractions of T790M (+) cfDNA ranging from 7.4% to 97%. T790M positivity in cfDNA was consistent in eight of ten patients for whom rebiopsied tumor tissues were analyzed, whereas the remaining cases were negative in cfDNA and positive in rebiopsied tumors. Prior to EGFR-TKI therapy, cfDNAs from 9 (38%) and 0 of 24 patients were positive for TKI-sensitive and T790M mutations, respectively. Next-generation sequencing of cfDNA from one patient who exhibited innate resistance to TKI despite a high fraction of TKI-sensitive mutations and the absence of the T790M mutation in his cfDNA revealed the presence of the L747P mutation, a known driver of TKI resistance. CONCLUSION: Picoliter-ddPCR examination of cfDNA, supported by next-generation sequencing analysis, enables noninvasive assessment of EGFR mutations that confer resistance to TKIs. IMPLICATIONS FOR PRACTICE: Noninvasive monitoring of the predominance of tumors harboring the secondary T790M mutation in the activating mutation in EGFR gene is necessary for precise and effective treatment of lung adenocarcinoma. Because cells harboring the T790M mutation are resistant to epidermal growth factor receptor-tyrosine-kinase inhibitors (TKIs), the predominance of tumor cells harboring the T790M mutations influences the choice of whether to use conventional or next-generation TKIs. Digital polymerase chain reaction-based examination of cfDNA is a promising method; however, its feasibility, including its consistency with examination of rebiopsied tumor tissue, has not been fully proven. Here, picoliter-droplet digital polymerase chain reaction technology is presented as a candidate method for testing cfDNA and assessing the predominance of T790M-mutant tumors.

Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis.

BACKGROUND: The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. METHODS: During 2006-2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of more than twice the upper limit of normal (ULN). We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN), moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN), and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN). We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin). RESULTS: In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97). In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046). CONCLUSION: Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

Distinguishing primary from secondary Δ(4) -3-oxosteroid 5ß-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis.

OBJECTIVE: Deficiency of Δ(4) -3-oxosteroid 5ß-reductase (5ß-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ(4) bile aciduria. The 5ß-reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5ß-reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ-glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography-mass spectroscopy (GC-MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5ß-reductase deficiency. DESIGN, PATIENTS AND MEASUREMENTS: We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ(4) bile aciduria using urinary steroid analysis by GC-MS of both cortisol and cortisone compounds, such as 5ß-tetrahydrocortisol (5ß-THF) and 5ß-tetrahydrocortisone (5ß-THE). Patients previously were diagnosed with primary 5ß-reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6). RESULTS: Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5ß-THE and elevated 5α/5ß-THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2 -weighted images. In the six patients with other secondary deficiencies, urinary 5ß-THF and 5α/5ß-THF differed from those in primary deficiency (P < 0·05). CONCLUSIONS: Urinary steroid analysis can distinguish primary and NH-related deficiencies from other secondary deficiencies.

Successful diuretics treatment of protein-losing enteropathy in Noonan syndrome.

There are few reports on successful high-dose spironolactone treatment of refractory protein-losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first-line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome.

[Challenge of gene-based personalized lung cancer medicine].

Up to the present, several genes have been identified as drivers for lung carcinogenesis, and their aberrations have been shown to be linked with differential response to therapy. Optimized treatments are, therefore, important in the situation that we have options for treatments by driver gene aberrations. Recently, comprehensive analyses of DNA and RNA from lung tumor tissues have been actively performed and have been pushing the lung cancer medicine forwards. In addition, circulating cell-free tumor DNA in plasma as a "liquid biopsy" opens a great hope for noninvasive molecular diagnosis. This article will highlight findings of recent comprehensive genome analysis to improve precision lung cancer medicine.

Safety and tolerability of AZD8055 in Japanese patients with advanced solid tumors; a dose-finding phase I study.

BACKGROUND: This is the first phase I, dose-finding study of AZD8055, a first-in-class dual mTORC1/2 inhibitor, in Japanese patients with advanced solid tumors. PATIENTS AND METHODS: Patients received a single oral dose of AZD8055, followed by twice-daily (BID) dosing. The starting dose was 10 mg with dose escalations in subsequent cohorts to a maximum of 90 mg BID or a non-tolerated dose. RESULTS: Seventeen patients were dosed: 10 mg (n=3), 40 mg (n=4), 60 mg (n=3), 90 mg (n=7). In the 90 mg cohort, one dose limiting toxicity (n=1) of increased aspartate aminotransferase and increased alanine aminotransferase was observed in the 90 mg BID cohort (n=1). Four patients, all in the 90 mg BID cohort, experienced a serious adverse event considered to be related to AZD8055: increased alanine aminotransferase (n=3), increased aspartate aminotransferase (n=3), increased gamma-glutamyltransferase (n=2). The 90 mg BID dose was considered as tolerated in Japanese patients but higher doses were not investigated as this dose was also the maximum tolerated dose in Western patients. AZD8055 was rapidly absorbed with greater-than-proportional increases in exposure with increasing dose. No responses were reported, but two patients had stable disease. Mean pAKT and p4EBP1 levels decreased in most cohorts. Conclusion The tolerability and pharmacokinetic profiles of AZD8055 in Japanese patients were similar to those reported in Western patients.

Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment.

BACKGROUND AND AIMS: In two Japanese infants with neonatal cholestasis, 3-oxo-Δ(4)-steroid 5ß-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ(4) bile acids were detected in their serum and urine by gas chromatography-mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment. PATIENTS AND METHODS: SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated. RESULTS: With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine. CONCLUSION: Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.

Pre and post-operative evaluation of gastroesophageal reflux and esophageal motility in neurologically impaired children using combined pH-multichannel intraluminal impedance measurements.

BACKGROUND: Gastroesophageal reflux disease (GERD) in patients with neurological impairment (NI) has not been fully studied before and after fundoplication procedure because their characteristics such as generalized gastrointestinal dysmotility, non-acid reflux, and the proximal reflux due to feeding of enteral nutrition via a nasogastric tube prevent their GERD from being detected by 24 h pH monitoring. The aim of this study was to elucidate whether multichannel impedance-pH measurement (pH/MII) is able to detect the subtypes of GERD and the differences in the reflux episodes of the severity of GERD, the ingestion pathway, and before and after fundoplication. The second aim was to determine whether a trial evaluation of dry swallows was able to be used to assess the esophageal motility of NI patients as an alternative examination. PATIENTS AND METHODS: The 24 h pH/MII was conducted on 20 NI children [15 were the patients before Nissen's fundoplication (BN), of whom, six were fed orally (FO) and nine were fed via nasogastric tube (NGT), and five were the patients after Nissen's fundoplication (AN)]. All reflux episodes were evaluated and compared between patients with pathological GERD (PG) and non-pathological GERD (NG) and between patients who had FO and NGT and patients between BN and AN. Dry swallows were conducted to evaluate the esophageal motility. The average bolus presence time (BPT) and total bolus transit time (TBTT) were compared between the PG and NG, FO and NGT, and the BN and AN subgroups. RESULTS: A total of 1,064 reflux episodes were detected by pH/MII. Of those, 303 (28.5 %) were non-acid-related and 477 episodes reached the proximal esophagus. Of the 12 patients (57.1 %) showing pathological GERD, two cases (16.7 %) demonstrated predominantly weakly acidic PG. More than half of the reflux episodes of PG patients reached to the proximal esophagus. The numbers of total reflux and proximal reflux episodes in the PG were significantly higher than those in NG patients. The number of proximal reflux episodes in the FO group was significantly higher than that in the NGT groups, whereas NGT patients showed more non-acidic reflux episodes than FO patients. A trial evaluation of dry swallows demonstrated no significant differences in this study. CONCLUSION: The pH/MII was useful to detect the subtype of GERD in NI patients which could not be detected by 24 h pH monitoring. It can, therefore, be considered to have first priority for testing NI patients who are suspected to be suffering from GERD.

Association between serum ferritin level and decreased diffusion capacity 3 months after the onset of COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia can have prolonged sequelae and lead to respiratory dysfunction, mainly because of impaired diffusion capacity for carbon monoxide (DLCO). The clinical factors associated with DLCO impairment, including blood biochemistry test parameters, remain unclear. METHODS: Patients with COVID-19 pneumonia who underwent inpatient treatment between April 2020 and August 2021 were included in this study. A pulmonary function test was performed 3 months after onset, and the sequelae symptoms were investigated. Clinical factors, including blood test parameters and abnormal chest shadows on computed tomography, of COVID-19 pneumonia associated with DLCO impairment were investigated. RESULTS: In total, 54 recovered patients participated in this study. Twenty-six patients (48%) and 12 patients (22%) had sequelae symptoms 2 and 3 months after, respectively. The main sequelae symptoms at 3 months were dyspnea and general malaise. Pulmonary function tests showed that 13 patients (24%) had both DLCO <80% predicted value (pred) and DLCO/alveolar volume (VA) <80% pred, and appeared to have DLCO impairment not attributable to an abnormal lung volume. Clinical factors associated with impaired DLCO were investigated in multivariable regression analysis. Ferritin level of >686.5 ng/mL (odds ratio: 11.08, 95% confidence interval [CI]: 1.84-66.59; p = 0.009) was most strongly associated with DLCO impairment. CONCLUSIONS: Decreased DLCO was the most common respiratory function impairment, and ferritin level was a significantly associated clinical factor. Serum ferritin level could be used as a predictor of DLCO impairment in cases of COVID-19 pneumonia.

Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study.

Background: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses. Objectives: We report details of the clinical portion prior to omics analyses. Design: A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed. Methods: Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results: A total of 103 patients (median age 70 years, range 42-88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654). Conclusions: As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib. Trial registration: UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688.

[Mycobacterium xenopi lung infection in a patient with multiple lung cysts that responded well to chemotherapy: a case report].

An abnormal shadow was observed on the chest radiograph of a 39-year-old man during health examination. The chest CT scan showed a consolidation around the cysts in the left upper lobe. The patient was diagnosed with Mycobacterium xenopi lung infection based on the presence of acid-fast bacilli in the sputum culture several times, which were identified as Mycobacterium xenopi by DNA-DNA hybridization. Two weeks after the initation of chemotherapy with 4 drugs (isoniazid, rifampicin, ethambutol, and clarithromycin), the patient's sputum smear and culture test results were negative; additionally, the consolidation on the chest CT scan improved after 10 months of treatment. There have been several case reports on Mycobacterium xenopi lung infection in Japan. However, few have studied Mycobacterium xenopi lung infections associated with multiple lung cysts that responded well to chemotherapy are rare.

Liquid biopsy for the detection of resistance mutations to ROS1 and RET inhibitors in non-small lung cancers: A case series study.

Liquid biopsy can identify gene alterations that are associated with resistance to fusion gene-targeted treatments. In this study, we present three cases of advanced non-small cell lung cancer (NSCLC) harboring gene fusions; cell-free DNA (cfDNA) was used to assess the resistance mutations. A patient with MET amplification underwent RET-fusion NSCLC treatment with selpercatinib. A patient with ROS1 G2032R underwent ROS1-fusion NSCLC treatment with crizotinib. A patient who underwent ROS1-fusion NSCLC treatment with crizotinib harbored no somatic mutations. This case series shows that cfDNA analysis can identify potentially actionable genomic alterations, after disease progression, in targeted therapy for fusion genes. TRIAL REGISTRATION: The study was registered in the UMIN Clinical Trial Registry (UMIN 000017581).

Impact of emphysema on the prognosis of Mycobacterium avium complex pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major comorbid disease of Mycobacterium avium complex pulmonary disease (MAC-PD). Emphysema is one of the main pathological findings in COPD, a risk factor for chronic pulmonary aspergillosis (CPA), and is associated with poor prognosis. We aimed to clarify the effect of emphysema on mortality in MAC-PD. METHODS: We retrospectively analyzed 203 patients with MAC-PD at The Jikei Daisan Hospital between January 2014 and December 2018. We investigated the mortality and CPA development rates after MAC-PD diagnosis in patients with or without emphysema. RESULTS: Multivariate Cox proportional hazards regression analysis showed the following negative prognostic factors in patients with MAC-PD: emphysema (hazard ratio [HR]: 11.46; 95% confidence interval [CI]: 1.30-100.90; P = 0.028); cavities (HR: 3.12; 95% CI: 1.22-7.94; P = 0.017); and low body mass index (<18.5 kg/m2) (HR: 4.62; 95% CI: 1.63-13.11; P = 0.004). The mortality and occurrence of CPA were higher in MAC-PD patients with than without emphysema (log-rank test, P < 0.0001 and P < 0.0001). CONCLUSION: Our study findings showed that emphysema detected by computed tomography was associated with an increased risk of CPA development and mortality in MAC-PD.