Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

BACKGROUND: The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. METHOD: We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. RESULTS: The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. CONCLUSIONS: The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 37.2% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents.

Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001-2011: A case series and literature review.

BACKGROUND: Mycobacterium scrofulaceum is a well-known pathogen associated with cervical lymphadenitis in children. However, pulmonary M. scrofulaceum disease is a rare condition with unknown clinical features. The present study aimed to clarify the clinical features of pulmonary M. scrofulaceum disease described in recent cases and reports. METHODS: We reviewed the medical records of all adult patients with pulmonary M. scrofulaceum disease at Keio University Hospital and the National Center for Global Health and Medicine Center Hospital between 2001 and 2011. We also conducted a review of the PubMed database to identify additional cases of pulmonary M. scrofulaceum disease in adults. RESULTS: Our study identified 8 cases of pulmonary M. scrofulaceum disease at the 2 identified institutions during our study period. Most cases were diagnosed in middle-aged and elderly men with underlying pulmonary diseases such as chronic obstructive pulmonary disease and Mycobacterium avium complex lung disease, as well as those with a history of pulmonary tuberculosis. In contrast, most previously reported cases identified through our literature review had a history of dust inhalation or underlying silicosis. Three of 8 cases at our institutions and 20 of 23 cases from the literature were treated with combination therapies. CONCLUSIONS: We conclude that in the recent histories of our institutions, pulmonary M. scrofulaceum disease has mainly occurred in patients with chronic pulmonary diseases. We further conclude that combination therapies that include clarithromycin might yield better patient outcomes.

[CONTROLLING TUBERCULOSIS IN FOREIGN-BORN PERSONS IN JAPAN].

Controlling tuberculosis (TB) among foreign- born persons is an important issue in Japan. The number of foreign-born patients with TB has been slightly increasing yearly, whereas that of Japan-born patients with TB has been decreasing. Some foreign-born 'persons visited Japan with active TB due to the lack of useful medical checks performed before immigration. The percentage of those with TB among foreign-born persons is high (up to 43%) in the younger generation, especially those in their 20s. Currently, multidrug- resistant TB occurs at a low frequency in Japan; however, there is a danger of persons being easily immigrated into Japan from high-burden countries. Physicians need to be aware that TB is an imported infection. Additionally, a strategy for controlling TB in foreign-born persons (e.g., performing medical checkups before immigration, conducting target medical checkups of high-risk people for TB, administering chemoprophylaxis to foreigners, reconsidering the public medical insurance system for TB treatment, and offering patient support) needs discussed.

Combined identifying granuloma and biopsy culture is useful for diagnosing intestinal tuberculosis.

PURPOSES: Differential diagnosis of intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) can be difficult, but many gastroenterologists may only perform biopsy for pathology and their own experience. This study aimed to identify optimal sample collection and pathogen detection methods for diagnosing ITB. METHODS: A cohort of 182 patients (50 had ITB and 132 had IBD or other colonic diseases) who underwent colonoscopy was analyzed. Sensitivity of acid-fast bacilli (AFB), culture, polymerase chain reaction (PCR), and granuloma pathology on hematoxylin and eosin stain for diagnosing ITB were compared in relation to biopsy, endoscopic aspirated intestinal fluid, or standard stool evaluations. We also evaluated which combination offered the highest yield to diagnose intestinal tuberculosis in addition to granuloma pathology. RESULTS: Between ITB and non-ITB, no significant differences were observed in age, sex, and nationality. In biopsy analysis, sensitivity was as follows: culture (50%), AFB (38%), PCR (25%), granuloma pathology (51%), and caseous granuloma (8.2%), while specificity of granuloma pathology was low (80%), compared to other tests. In intestinal fluid analysis, sensitivity was as follows: culture (46%), AFB (42%), and PCR (35%). In standard stool analysis, sensitivity was as follows: culture (47%), AFB (37%), and PCR (23%). Granuloma pathology plus biopsy culture offered the highest combination sensitivity (77 %), significantly (P < 0.01) higher than that for granuloma pathology alone (51%). CONCLUSIONS: When encountering suspected intestinal tuberculosis or IBD on colonoscopy, biopsy culture is recommended in addition to pathological assessment of granuloma. This diagnostic strategy will lead to accurate differential diagnosis of colonic disease, facilitating appropriate treatment.

[Tenosynovitis confirmed by MRI during anti-tuberculous treatment suspected due to isoniazid--2 case reports and literature review].

The adverse effects of anti-tuberculosis agents is an important problem for treatment of tuberculosis. We report 2 possible cases of isoniazid-induced tenosynovitis. Case 1: A 49-year-old man with untreated diabetic mellitus presented with hypesthesia and difficulty grasping with his right hand 1 month after starting treatment of tuberculosis of the lung and pleuritis using isoniazid, rifampicin, ethambutol, and pyrazinamide. His symptoms were due to tenosynovitis, which was detected by magnetic resonance imaging. The clinical course and isoniazid challenge test revealed that the condition was related to isoniazid. After discontinuing isoniazid treatment, his symptoms gradually improved. Case 2: An 78-year-old man operated on for rectal cancer 3 weeks previously presented with edema and arthralgia of both hands 1 month after starting anti-tuberculosis treatment. His tuberculosis was diagnosed at preoperative screening tests for rectal cancer. Owing to a medical history of gout, pyrazinamide was discontinued. However, his symptoms did not improve. Magnetic resonance imaging revealed findings indicative of tenosynovitis. At the end of anti-tuberculosis treatment, his symptoms improved slightly within 6 months. Isoniazid-induced tenosynovitis and arthritis are rare adverse effects. However, they may be underestimated because the severity is variable. We suggest further investigations of the side effects of isoniazid using imaging techniques such as magnetic resonance imaging.

[New criteria enable shorter hospitalization of patients with continuously smear-positive pulmonary tuberculosis].

BACKGROUND: Sputum conversion defined as 3 consecutive smear-negative sputum samples collected on different days is one of standard requirements for discontinuation of isolation for patients with smear-positive pulmonary tuberculosis (SPpTB). Sputum smear conversion is usually seen prior to culture conversion. However, in some patients, sputum smear tests are continuously positive for a long time. To discontinue isolation of the patients, culture conversion is required instead of smear conversion. Culture testing requires a long incubation period, which results in longer patient stay and isolation. OBJECTIVES: To identify a more efficient definition of culture conversion, which will enable treating physicians to take the decision to discontinue isolation. METHODS: The charts of patients with SPpTB admitted from September 2007 to March 2011 were reviewed. The recent definition of culture conversion is 3 subsequent culture-negative sputum specimens incubated for 6 weeks (3 CNs for 6 weeks) in liquid media. Treatment days and admission days were calculated based on the application of the new 3 definitions (3 CNs for 4 weeks, 2 CNs for 6 weeks, 2 CNs for 4 weeks). RESULTS: Of 301 patients, 224 were discharged after smear conversion; 77 were continuously smear-positive and were discharged after culture conversion. The median hospital stay was 56 days in patients discharged due to smear conversion and 107 days in patients discharged due to culture conversion, based on the recent definition. The numbers of treatment days needed for culture conversion were identical in most patients, regardless of definitions. At the time of reporting, all patients conformed to the new definitions and all the patients' sputum specimens were 3 CNs for 6 weeks except for one patient happened to be with 2 consecutive smear-negative specimens at an early phase of chemotherapy. The most efficient definition of culture conversion in this study was 2 CNs for 4 weeks. This enabled to shorten each patient's stay by 31 days and to lessen each patient's cost of hospitalization by about 4,900 dollars. CONCLUSION: Two subsequent CNs for 4 weeks of smear-positive sputum samples is enough to enable discontinuation of patient isolation and may thus shorten hospital stay.

How Much More Efficient Are Adaptive Platform Trials Than Multiple Stand-Alone Trials? A Comprehensive Simulation Study for Streamlining Drug Development During a Pandemic.

With the coronavirus disease 2019 (COVID-19) pandemic, there is growing interest in utilizing adaptive platform clinical trials (APTs), in which multiple drugs are compared with a single common control group, such as a placebo or standard-of-care group. APTs evaluate several drugs for one disease and accept additions or exclusions of drugs as the trials progress; however, little is known about the efficiency of APTs over multiple stand-alone trials. In this study, we simulated the total development period, total sample size, and statistical operating characteristics of APTs and multiple stand-alone trials in drug development settings for hospitalized patients with COVID-19. Simulation studies using selected scenarios reconfirmed several findings regarding the efficiency of APTs. The APTs without staggered addition of drugs showed a shorter total development period than stand-alone trials, but the difference rapidly diminished if patient's enrollment was accelerated during the trials owing to the spread of infection. APTs with staggered addition of drugs still have the possibility of reducing the total development period compared with multiple stand-alone trials in some cases. Our study demonstrated that APTs could improve efficiency relative to multiple stand-alone trials regarding the total development period and total sample size without undermining statistical validity; however, this improvement varies depending on the speed of patient enrollment, sample size, presence/absence of family-wise error rate adjustment, allocation ratio between drug and placebo groups, and interval of staggered addition of drugs. Given the complexity of planning and implementing APT, the decision to implement APT during a pandemic must be made carefully.

Mpox Neutralizing Antibody Response to LC16m8 Vaccine in Healthy Adults.

BACKGROUND: Vaccination against mpox (formerly known as monkeypox), an infectious disease caused by the monkeypox virus (MPXV), is needed to prevent outbreaks and consequent public health concerns. The LC16m8 vaccine, a dried cell-cultured proliferative live attenuated vaccinia virus­based vaccine, was approved in Japan against smallpox and mpox. However, its immunogenicity and efficacy against MPXV have not been fully assessed. We assessed the safety and immunogenicity of LC16m8 against MPXV in healthy adults. METHODS: We conducted a single-arm study that included 50 participants who were followed up for 168 days postvaccination. The primary end point was the neutralizing antibody seroconversion rate against MPXVs, including the Zr599 and Liberia strains, on day 28. The secondary end points included the vaccine "take" (major cutaneous reaction) rate, neutralizing titer kinetics against MPXV and vaccinia virus (LC16m8) strains, and safety outcomes. RESULTS: Seroconversion rates on day 28 were 72% (36 of 50), 70% (35 of 50), and 88% (44 of 50) against the Zr599 strain, the Liberia strain, and LC16m8, respectively. On day 168, seroconversion rates decreased to 30% (15 of 50) against the Zr599 and Liberia strains and to 76% (38 of 50) against LC16m8. The vaccine "take" (broad definition) rate on day 14 was 94% (46 of 49). Adverse events (AEs), including common solicited cutaneous reactions, occurred in 98% (45 of 48) of participants; grade 3 severity AEs occurred in 16% (8 of 50). No deaths, serious AEs, or mpox onset incidences were observed up to day 168. CONCLUSIONS: The LC16m8 vaccine generated neutralizing antibody responses against MPXV in healthy adults. No serious safety concerns occurred with LC16m8 use. (Funded by the Ministry of Health, Labour and Welfare of Japan; Japan Registry of Clinical Trials number, jRCTs031220171.)

Combined endoscopy, aspiration, and biopsy analysis for identifying infectious colitis in patients with ileocecal ulcers.

BACKGROUND & AIMS: The ileocecal area is commonly involved in infection and inflammatory colonic diseases, but differential diagnosis can be difficult. We identified definitive endoscopic findings and a sample collection method for diagnosing infectious colitis. METHODS: In a retrospective study, we analyzed data on 128 patients with ileocecal ulcer who underwent colonoscopy from 2007-2011 at the National Center for Global Health and Medicine in Tokyo, Japan. We collected information on location, size, number, and distinctive endoscopic findings and estimated diagnostic odds ratios (ORs). The sensitivities of microscopy, culture, polymerase chain reaction, and histologic methods in identifying patients with infection were compared with those of standard stool, endoscopic aspirated intestinal fluid, or biopsy analyses. RESULTS: Of the 128 patients, 100 had infections, and 28 had Crohn's disease, Behçet's disease, or other inflammatory diseases. Predictive endoscopic findings were as follows: for amebiasis of the cecum (OR, 17.8), with exudates (OR, 13.9) and round-shaped ulcer (OR, 5.77); for tuberculosis (TB) with transverse-shaped ulcer (OR, 175), scar (OR, 34.6), linear-shaped ulcer (OR, 23.9), or ≥10 mm (OR, 14.0); for cytomegalovirus with round-shaped ulcer (OR, 4.09); and for Campylobacter with cecal valve lesion (OR, 58.3) or ≥10 mm (OR, 10.4). The sensitivity of endoscopic sample collection was significantly higher than that of standard stool sample collection for the diagnosis of amebiasis, TB, non-TB mycobacteria, and other bacteria (P < .05). The methods that detected infection with the highest levels of sensitivity were biopsy with histology for amebiasis, biopsy with culture for TB, biopsy with polymerase chain reaction for cytomegalovirus, and aspiration of intestinal fluid with culture for Campylobacter. CONCLUSIONS: Combining results from endoscopic analysis with appropriate sample collection and pathogen detection methods enables infectious colitis to be differentiated from other noninfectious colonic diseases.

Evaluating the Immunogenicity and Safety of a Smallpox Vaccine to Monkeypox in Healthy Japanese Adults: A Single-Arm Study.

Monkeypox (mpox) is an acute exanthematous disease caused by the monkeypox virus (MPXV). Since May 2022, patients with mpox have been reported worldwide, mainly in Europe and the Americas. In Japan, LC16"KMB," which is a smallpox vaccine derived from a dried cell culture, against mpox, has been approved. Although inoculation with a smallpox vaccine has been recommended to prevent MPXV infection, the immunogenicity of the smallpox vaccine against the MPXV is unclear, and information regarding postvaccination safety is scarce. We present the protocol for a single-arm open-label study to investigate the immunogenicity and safety of LC16"KMB" against the MPXV in healthy Japanese adults. The primary endpoint is the seroconversion rate of neutralizing antibodies against the MPXV on postvaccination day 28. The secondary endpoints are the seroconversion rates against the MPXV on postvaccination days 14 and 168; the seroconversion rates against the vaccinia virus on postvaccination days 14, 28, and 168; the incidence of mpox until day 168; and adverse and serious adverse events until postvaccination days 28 and 168. These results will pave the way for larger comparative studies using other smallpox vaccines to evaluate the test vaccine's safety and efficacy in preventing mpox.

Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis: A Multicenter Retrospective Study.

Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the clinical features and prognosis of NTM pleuritis. Methods: This retrospective observational study included patients with NTM pleuritis from January 2001 to June 2018 across eight hospitals in Japan. NTM pleuritis was defined by a positive NTM culture of pleural effusion samples. We matched patients with Mycobacterium avium complex (MAC) lung disease (MAC-LD) without pleuritis by sex and age to obtain comparative data and investigated the association between clinical parameters and the prognosis. Results: We identified 64 patients with NTM pleuritis (median age, 73 yr; 37 female patients). The median follow-up duration was 11 months, and 27 patients died. Patients with MAC pleuritis had a significantly lower survival rate than matched patients with MAC-LD without pleuritis. Multivariate analysis revealed that pleuritis (adjusted hazard ratio, 6.99; 95% confidence interval [CI], 2.58-19.00) and underlying pulmonary diseases (adjusted hazard ratio, 3.01; 95% CI, 1.44-6.28) were independently associated with all-cause mortality in patients with MAC-LD. Conclusions: The prognosis of MAC pleuritis is poorer than that of MAC-LD without pleuritis. Pleuritis is an independent prognostic factor in patients with MAC-LD.

[A case of dermatomyositis becoming symptomatic after recurrence of small cell lung cancer].

A 75-year-old man had been given a diagnosis of small cell lung cancer (SCLC) in March 2005. He had been treated with chemotherapy consisting of carboplatin and etoposide, and he had showed partial response to treatment. He presented with general fatigue, weakness of the muscles and extremities, skin lesions and finger erythema in April 2006. A muscle biopsy was performed and the pathological findings confirmed dermatomyositis. The findings of his chest X-ray and computed tomography showed an increase in the size of the lung cancer lesion. The tumor size decreased, and creatine kinase and lactate dehydrogenase levels also decreased after irinotecan chemotherapy. He was also given prednisolone (1 mg/kg) for prolonged muscle weakness. There are few cases which report dermatomyositis after a diagnosis of SCLC. In the present case, dermatomyositis appeared when the recurrence of SCLC became evident. We believed that the onset of dermatomyositis might be related to the activity level of SCLC.

A case of recurrent hemoptysis caused by pulmonary actinomycosis diagnosed using transbronchial lung biopsy after bronchial artery embolism and a brief review of the literature.

A 60-year-old man was admitted to our hospital because of massive hemoptysis with acute respiratory failure. Since six months ago, he noticed gradual worsening of hemoptysis and was transferred to our hospital. Chest computed tomography showed a nodular lesion with cavitation in the left upper lobe and surrounding ground-glass opacification. Initially, a hemostatic agent was administered, but we eventually performed bronchial artery embolization (BAE) by ourselves due to persistent hemoptysis. After achieving good hemostasis with BAE bronchoscopy was performed, which gave a diagnosis of pulmonary actinomycosis on histopathologic examination of the transbronchial biopsy specimen without the need for lung resection.

Impact of a Novel Smartphone App (CureApp Smoking Cessation) on Nicotine Dependence: Prospective Single-Arm Interventional Pilot Study.

BACKGROUND: Mobile apps have been considered to provide active and continuous support for smoking cessation. However, it is yet to be known whether a smoking cessation smartphone app improves long-term abstinence rates in nicotine-dependent patients. OBJECTIVE: This study aimed to evaluate the long-term abstinence effect of a novel smartphone app, CureApp Smoking Cessation (CASC), in patients with nicotine dependence. METHODS: In this prospective, interventional, multicenter, single-arm study, we provided the CASC app to all the participants, who used it daily for 24 weeks. The CASC app includes features to maximize the therapeutic effect of pharmacological therapies and counseling at outpatient clinics for smoking cessation. The primary endpoint was a continuous abstinence rate (CAR) from weeks 9 to 24, whereas secondary endpoints were CARs from weeks 9 to 12 and 9 to 52. RESULTS: Of the 56 adult smokers recruited, 1 did not download the app; therefore, 55 participants constituted the full analysis sample. The CAR from weeks 9 to 24 was 64% (35/55, 95% CI 51%-76%), whereas the CARs from weeks 9 to 12 and 9 to 52 were 76% (42/55, 95% CI 65%-88%) and 58% (32/55, 95% CI 46%-71%), respectively. These CARs were better than the results of the national survey on outpatient clinics with regard to smoking cessation under the National Health Insurance Program and that of the varenicline phase 3 trial in Japan and the United States. There was only 1 participant who dropped out during the 12 weeks of the treatment period. This treatment decreased the scores related to withdrawal and craving symptoms. CONCLUSIONS: The addition of CASC to usual smoking cessation therapies resulted in high CARs, high patient retention rates, and improvement of cessation-related symptoms. The smartphone app CASC is a feasible and useful tool to help long-term continuous abstinence that can be combined with a standard smoking cessation treatment program.

Clinico-microbiological analysis of 121 patients with pulmonary Mycobacteroides abscessus complex disease in Japan - An NTM-JRC study with RIT.

RATIONALE: No comprehensive analysis has previously been performed to evaluate the clinical aspects of and microbiological evidence associated with Mycobacteroides abscessus complex (MABC) infection in a region, such as Japan, with a low MABC incidence. OBJECTIVES: This study aimed to clarify the clinicopathological characteristics of MABC, which included clinical relatedness to erm(41) sequevar, phenotype (as colony morphology and minimum inhibitory concentration), and genotype. METHODS: A total of 121 MABC patients (68 with M. abscessus subsp. abscessus and 53 with M. abscessus subsp. massiliense) were recruited into this retrospective clinical-biological study from tertiary hospitals in Japan between 2004 and 2014. RESULTS: Approximately 30% of MABC patients had a history of previous nontuberculous mycobacterium (NTM) disease. Furthermore, 24.8% of the patients had another concomitant NTM infection after they were diagnosed with MABC. Fewer than 10% of the patients in the M. abscessus group had T28C in erm(41). While we observed a higher conversion rate for M. massiliense than for M. abscessus (72.4% and 34.8%, respectively, p = 0.002), recurrence remained relatively common for M. massiliense (31.0%). In the M. abscessus patients, the MIC of clarithromycin (CLR) was significantly lower on day 3 in patients with a better treatment response than in refractory patients (The median MIC; 0.75 µg/ml v.s 2.0 µg/ml, p = 0.03). There was no significant relation between clinical manifestations and variable number of tandem repeat genotypes. CONCLUSIONS: Because the history and simultaneous isolation of other NTM in MABC infection are relatively common, these information should be carefully translated into clinical actions. The evaluation of early CLR resistance in M. abscessus and the erm(41) functions should be important to improve the treatment strategy.

A case of spontaneous regression of small cell lung cancer with progression of paraneoplastic sensory neuropathy.

We report here a rare case of small cell lung cancer (SCLC) accompanied by a partial spontaneous regression with a progression of paraneoplastic sensory neuropathy (PSN). A 55-year-old woman was admitted to our hospital with dry cough and progressive numbness in the distal extremities over 1 month. She was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. About 1 month later, partial spontaneous regression of tumor with a progression of paraneoplastic sensory neuropathy was observed. A complete response was achieved through chemotherapy and concurrent radiotherapy. As the tumor size decreased, her neurological symptoms improved. A short interval between onset of PSN and the start of therapy may be essential for successful treatment for not only SCLC but also PSN.

Leptospirosis Cases in the Tokyo Metropolitan Area, Japan.

In Japan, 20-50 cases of leptospirosis are reported annually, typically involving farmers or returnees from tropical areas. Here, we report on 5 indigenous leptospirosis cases that occurred in the Tokyo urban area. All patients were men (mean age, 66.4 ± 4.6 [SD] years) and presented with clinical features that included high fever, acute kidney injury, and jaundice. Three patients presented with pulmonary infiltration and ground-glass opacity on admission. Two of the 5 patients were intubated and underwent continuous hemodiafiltration. The mean length of hospitalization was 38.0 ± 17.0 days, and all patients were treated successfully with antibiotics. Notably, all patients had a history of exposure to rats prior to becoming symptomatic, suggesting that exposure to rats is a risk factor for urban leptospirosis. Although rare, even in metropolitan areas, leptospirosis should be considered by physicians when patients present with severe sepsis, acute kidney injury, and a history of exposure to rats.

Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients: A Matched-Cohort Study.

Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p < 0.001]. Their major TB-AEs were fever (19%), rash (11%), and neutropenia (11%). TB-AEs were more severe in cases [Grade 3 or higher: cases (71%, 34/48) vs. controls (49%, 19/39), p < 0.001]. The time from treatment initiation to TB-AE was shorter in cases [median 18 (interquartile range 12-28) vs. 27 (15-57) days, p = 0.027], and 73% of TB-AEs in cases occurred within 4 weeks of starting anti-tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.

Re-administration of abatacept for the control of articular symptoms of rheumatoid arthritis during anti-tuberculous therapy.

This case report describes the re-administration of abatacept to successfully reduce the articularsymptoms of a patient with rheumatoid arthritisduring the intensive phase of anti-tuberculous therapy. A 75-year-old man developed active pulmonary tuberculosis during the administration of abatacept for rheumatoid arthritis. The patient experienced a paradoxical reaction and exacerbation of rheumatoid arthritis that caused us to discontinue the abatacept. Later re-administration of abatacept along with anti-tuberculosis treatment led to well-controlled rheumatoid arthritis without exacerbation of the tuberculosis. This case shows that re-administration of abatacept may be much safer than TNF inhibitor to treat patients who are infected with mycobacteria during thetreatment of immunological diseases such asrheumatoid arthritiswith biological agents.