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Common variable immunodeficiency (CVID) causes granulomatous-lymphocytic interstitial lung disease (GLILD) and has a poor prognosis. We herein report a case of GLILD in a 49-year-old woman with CTLA-4 deficiency-associated CVID. The patient presented with dyspnea that had worsened over the past two years. A laboratory examination revealed hypoglobulinemia and pancytopenia. Chest computed tomography showed diffuse infiltrative and granular shadows in the bilateral interstitium. A flow cytometric analysis of blood cells and genetic testing confirmed CTLA-4 deficiency. We performed video-assisted thoracoscopic surgery for the pathological diagnosis of GLILD and to exclude infection and malignancy. Corticosteroid treatment successfully improved the condition of the patient.

A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

We investigated epidemiological findings regarding the route of coronavirus disease 2019 (COVID-19) and infection prevention and control (IPC) measures among returnees in the emergent evacuation from Wuhan, China to Japan under the COVID-19 outbreak in 2020. A total of 12 of 14 returnees (median age [range]: 49.5 years [29-65 years]; 9 men [75%]) were confirmed COVID-19. The proportions of returnees with COVID-19 were 12/566 (2.1%) in the 1-3 flights and 2/263 (0.8%) in the 4-5 flights. Six patients were asymptomatic on admission, while three patients developed symptoms thereafter. None reported a specific history of contact with animals, going to seafood markets, or visiting medical facilities. Two patients contacted with an individual confirmed or suspected to have COVID-19, respectively. Most patients resided in hotels in the center of Wuhan city, taking taxis and trains to work and supermarkets. Patients relatively adhered to IPC measures such as wearing a mask and hand hygiene. However, emphasis on IPC measures such as universal masking and more rigorous avoidance of exposure risk may have been necessary to prevent infection. In addition, forced social distancing due to lockdown might contribute to the lower infection rates in Flights 4 and 5, compared to Flights 1-3.

BackgroundDiffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.MethodsWe conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.ResultsTwenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22–56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted )) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted ConclusionsIDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Of the strains isolated from blood cultures, 49 were identified asPOT is a simple and suitable method for molecular epidemiological monitoring and can show the introduction, outbreak, and subsequent transition of an epidemic clone of

Hepatitis A virus (HAV) commonly causes acute hepatitis in humans and is transmitted through the fecal-oral route or by ingestion of contaminated food or water. HAV infection generally follows a self-limiting course; it can seldom cause fulminant hepatitis that increases the risk of mortality. To the best of our knowledge, this is the first reported fatal case of fulminant hepatitis caused by HAV in a 40-year-old male with human immunodeficiency virus (HIV) infection. The HAV genotype in this case was IA, which has recently become common globally among people living with HIV (PLWHIV), intravenous drug users, and homeless people especially in developed countries. His HIV infection was stabilized by antiretroviral drugs and his CD4 values were stable. He developed acute hepatic encephalopathy, did not respond to repeated plasma exchange therapy, and died rapidly. It is known that HIV co-infection sometimes leads to fulminant non-HAV hepatitis, although evidence supporting a correlation between fulminant hepatitis A risk and HIV infection is still lacking. This case demonstrated the fatal risk of HAV infection in PLWHIV; it was suggested that education about appropriate preventive measures and vaccination are important for preventing HAV infections among PLWHIV.

The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan.We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality.Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality.The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Objective: Acinetobacter baumannii is a causative agent of healthcare-associated infections, and the introduction and spread of A. baumannii that has acquired drug resistance within a hospital are serious healthcare problems. We investigated the transition of epidemic clones and the occurrence of outbreaks by molecular epidemiological analysis to understand the long-term behavior of A. baumannii within a single facility. Methods: A. baumannii isolates collected from blood-culture–positive patients between January 2009 and December 2020 were subjected to PCR-based open reading frame typing (POT) for species identification, clonal typing, and homology searches. Results: Of the strains isolated from blood cultures, 49 were identified as A. baumannii and analyzed with POT. The POT#1=122 clones had different antimicrobial resistance profiles to the other POT clones, and strains belonging to this clone were dominant during outbreaks of multidrug-resistant Acinetobacter. Although the clonal diversity of A. baumannii decreased and its antimicrobial resistance increased during the outbreaks, clonal diversity and the in-hospital antibiogram improved at the end of the outbreaks. The POT#1=122 clone was not eliminated from the hospital during the study period. Conclusions: POT is a simple and suitable method for molecular epidemiological monitoring and can show the introduction, outbreak, and subsequent transition of an epidemic clone of A. baumannii.

Background SARS-CoV-2 Delta variant caused a large number of COVID-19 cases in many countries, including Vietnam. Understanding mortality risk factors is crucial for the clinical management of severe COVID-19. Methods We conducted a retrospective study at an intensive care center in Ho Chi Minh City that urgently built by Bach Mai Hospital during the COVID-19 outbreak in Vietnam, when the Delta variant predominated. Participants were laboratory-confirmed patients with SARS-CoV-2 infection, admitted in August 2021. Data on patients’ demographic and clinical characteristics, radiographic and laboratory findings, treatment, and clinical time course were compared between survivors and non-survivors. Risk factors to mortality were assessed using logistic regression. Results Among 504 eligible COVID-19 patients, case fatality was 52.2%. Unvaccinated patients accounted for 61.2% of non-survivors and 43.6% of survivors (p < 0.001). The time from onset to hospital admission was 8 days in non-survivors and 7 days in survivors (p = 0.004). Among non-survivors, 90.2% developed acute respiratory distress syndrome (ARDS). Oxygen therapy was administered for all patients, but antiviral agent was given to 51.7% of non-survivors. 54.2% of non-survivors tested positive for the bacterial infection using blood culture. The risk factors for mortality were diabetes mellitus, respiration rate, oxygen saturation, vaccination status, time from onset to admission, and older age. Conclusions Critical patients with COVID-19 owing to the Delta variant in Vietnam had delayed hospital admission, leading to ARDS and death. Early availability of vaccines and preventing bacterial infections are crucial for reducing mortality of COVID-19, especially in low- and middle-income countries.

Introduction The prevalence of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with COVID-19 varies, as well as their risks of mortality. The present study aimed to assess the prevalence of asthma, COPD, and ACO as comorbidities, and to determine their risks of mortality in patients with COVID-19 using a systematic review and meta-analysis. Methods We systematically reviewed clinical studies that reported the comorbidities of asthma, COPD, and ACO in patients with COVID-19. We searched various databases including PubMed (from inception to 27 September 2021) for eligible studies written in English. A meta-analysis was performed using the random-effect model for measuring the prevalence of asthma, COPD, and ACO as comorbidities, and the mortality risk of asthma, COPD, and ACO in patients with COVID-19 was estimated. A stratified analysis was conducted according to country. Results One hundred one studies were eligible, and 1,229,434 patients with COVID-19 were identified. Among them, the estimated prevalence of asthma, COPD, and ACO using a meta-analysis was 10.04% (95% confidence interval [CI], 8.79–11.30), 8.18% (95% CI, 7.01–9.35), and 3.70% (95% CI, 2.40–5.00), respectively. The odds ratio for mortality of pre-existing asthma in COVID-19 patients was 0.89 (95% CI, 0.55–1.4; p = 0.630), while that in pre-existing COPD in COVID-19 patients was 3.79 (95% CI, 2.74–5.24; p Conclusion Pre-existing asthma and COPD are associated with the incidence of COVID-19. Having COPD significantly increases the risk of mortality in patients with COVID-19. These differences appear to be influenced by the difference of locations of disease pathophysiology and by the daily diagnosis and treatment policy of each country.

A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

Dasatinib-related chylothorax is a rare adverse event, and the mechanism underlying its occurrence is still not fully understood. We herein report the case of a 73-year-old woman with chronic myeloid leukemia (CML) who developed dasatinib-related chylothorax refractory to conventional treatments, except for steroids. To the best of our knowledge, this is the first case of dasatinib-related chylothorax which was successfully controlled by combining diuretics with the Japanese herbal medicine “Goreisan.” “Goreisan” is known to inhibit aquaporin channels and regulate the water flow. Our findings showed that “Goreisan” is an effective treatment option for uncontrollable dasatinib-related chylothorax.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 49.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 9.2% and 0.4%, respectively.

The push and slide method is a method of endoscopic bronchial occlusion using an endobronchial Watanabe spigot that facilitates occlusion of the target bronchus rapidly and accurately using a guidewire. We herein report the case of a man who was diagnosed with empyema forming bronchopulmonary fistulae that was successfully treated by endoscopic bronchial occlusion. Because of the multiple fistulae, balloon occlusion was not a favorable therapeutic approach. Instead, the push and slide method was used in order to detect the fistulae. Endoscopic occlusion, particularly that using the push and slide method, may be a valid treatment option for empyema with multiple bronchopulmonary fistulae.

Background Zosteriform skin metastasis (ZSM) is rare, and its etiology is not well understood. ZSM is possibly derived from the retrograde movement of cancer cells through the lymphatic vessels during disease development. However, it has been difficult to demonstrate it, as no specific findings have been observed. Case presentation A 68-year-old man presented to our department with neck lymphadenopathy. After detailed examinations, squamous cell lung carcinoma (cT2aN3M1c) was diagnosed. Although cisplatin combined with gemcitabine was administered, his cancerous lymphangiopathy was exacerbated, and ZSM was observed on his right chest. Pembrolizumab was initiated as a second-line chemotherapy; however, the patient died 7 months after the initial presentation. In this case, fluorodeoxyglucose-positron emission tomography indicated the presence of skin metastasis and cancerous lymphangiopathy. Similarly, after performing an autopsy, tumor-cell filled lymph ducts were observed in the right subclavian and the cutaneous lymphatic vessel from the right hilar lymph nodes. Conclusions To the best of our knowledge, this is the first study to demonstrate that the localization of ZSM in the cutaneous lymphatics was caused by the retrograde movement of cancer cells through the lymphatic vessels, using radiographical and pathological analysis. In addition, fluorodeoxyglucose-positron emission tomography may help predict skin metastasis induced by cancerous lymphangiopathy.

The coronavirus disease 2019 (COVID-19) pandemic has affected infection control and prevention measures. We investigated the impact of the COVID-19 pandemic on postoperative infections and infection control measures in patients underwent gastrointestinal surgery for malignancies. We retrospectively evaluated changes in clinicopathological features, frequency of alcohol-based hand sanitizer use, frequency of postoperative complications, and microbial findings among our patients in February–May in 2019 (Control group) and 2020 (Pandemic group), respectively. Surgical resection in pathological stage III or IV patients was more frequently performed in the Pandemic group than in the Control group (P = 0.02). The total length of hospitalization and preoperative hospitalization was significantly shorter in the Pandemic group (P = 0.01 and P = 0.008, respectively). During the pandemic, hand sanitizer was used by a patients for an average of 14.9±3.0 times/day during the pandemic as opposed to 9.6±3.0 times/day in 2019 (p

Pulmonary complications associated with influenza, particularly pneumonia, are well recognized and are referred to as influenza (associated) pneumonia. Influenza-associated pneumonia can be classified into several subtypes, including viral pneumonia and superimposed or sequential bacterial pneumonia. Pure influenza viral pneumonia manifests in widespread diffuse lung inflammation, resulting in severe respiratory conditions. Secondary bacterial pneumonia is often seen as a post-influenza complication arising as a consequence of epithelial damage during viral infection. Viral and bacterial pneumonia can co-occur and each can promote the other. Because influenza pneumonia comprises several distinct subtypes with different clinical courses and pathophysiology, it is difficult to uniformly assess pneumonia severity. However, mortality may be slightly higher than expected, based on conventional severity indicators of community-acquired pneumonia.

The mechanisms underlying interstitial lung disease (ILD) are characterized by variable inflammation or fibrosis of the pulmonary interstitium. A negative heart sign (NHS) on 67Ga scintigrams of patients with ILD is due to considerably increased inflammatory activity in the lungs. We retrospectively analyzed relationships between NHS and established biomarkers of disease severity in patients with ILD. Among 81 consecutive non-smoking patients with ILD (mean age, 63 years) who had been hospitalized between April 2009 and October 2011, we selected 52 who had been assessed by 67Ga scintigraphy. We then evaluated relationships between NHS and blood biomarkers, pulmonary function and high-resolution computed tomography (HRCT). Among these 52 patients, 10 showed idiopathic pulmonary fibrosis and 42 had other ILD. Multivariate analysis with stepwise variable selection, serum surfactant protein (SP)-A (OR (odds ratio), 1.026; 95%CI (confidence interval), 1.003–1.050; P = 0.024) and inflammation index calculated from HRCT findings (OR, 1.358; 95%CI, 1.079–1.709; P = 0.009) were significant predictors of an NHS. Serum SP-A offered 85% sensitivity and 75% specificity for predicting NHS at an optimal cut-off of 45.8 ng/mL. Serum SP-A concentrations correlated positively with inflammation index (r = 0.344, P = 0.015). In conclusion, serum SP-A might serve as a surrogate biomarker for predicting an NHS in patients with ILD.

The occurrence of endotracheal/endobronchial metastasis (EEM) after complete resection of a primary lung cancer is rare. Here, we report the case of an 86‐year‐old woman in whom EEM occurred twice over a 20‐year period following complete resection of a primary adenocarcinoma localized to the left main bronchus and trachea. The presence of EEM was confirmed by establishing immunohistochemical homology of the metastases with the primary tumor. To the best of our knowledge, this is the first reported case of repetitive EEM of primary lung adenocarcinoma. Lymphatic invasion in the primary lesion suggested that a possible route for EEM was the peripheral lymphatic tract, explaining the slow recurrence rate. We conclude that observation of the trachea/bronchus over a long period post operation could be important in monitoring for EEM, particularly if lymphatic invasion is confirmed in the primary tumor., This is the first reported case of repetitive localized endotracheal/endobronchial metastasis of primary lung adenocarcinoma with mild lymphatic invasion that occurred twice over a 20‐year period after complete resection. Observation of the trachea/bronchus over a long period post operation could be important in monitoring for endotracheal/endobronchial metastasis, particularly if lymphatic invasion is confirmed in the primary tumor.

Background Severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2) was found to be the causative microorganism of coronavirus disease 2019 (COVID-19), which started to spread in Wuhan, China. This study was to evaluate the effectiveness of questionnaire, symptoms-based screening, and polymerase chain reaction (PCR) screening of returnees from COVID-19-endemic areas on a chartered flight, to examine the proportion of infected persons and the proportion of asymptomatic persons among infected persons who returned from Wuhan. Methods A retrospective cohort study was done in 7 tertiary medical institutions in Japan. A total of 566 Japanese who returned from Wuhan participated in the study. Results Overall, 11 of the 566 passengers had a positive SARS-CoV-2 PCR result for pharyngeal swabs and 6 were asymptomatic. Only fever differed between SARS-CoV-2-positive and -negative individuals (P < .043). Six of the 11 PCR-positive individuals were asymptomatic; 4 remained positive on day 10, and 1 asymptomatic person tested positive up to day 27. Two of the 11 were negative on the first PCR test and positive on the second. Conclusions Our results will be important insights on screening returnees from locked-down cities, as well as providing important data on the proportion of asymptomatic individuals infected with SARS-CoV-2. A 13-day observation period and a second round of PCR may be effective to screen patients, including asymptomatic infections.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 41.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.5% and 0.6%, respectively.

Approximately 250,000 immigrants from Latin America live in Japan and it is estimated that 1500–3000 of them are potentially infected with Trypanosoma cruzi, the cause of Chagas disease. Therefore, the establishment of a standardized diagnostic method for Chagas disease in Japan is urgently needed. In this study, we optimized and evaluated the ARCHITECT Chagas assay and in-house ELISA for Chagas disease in clinical settings. In particular, we evaluated the performance of ARCHITECT Chagas as well as ELISA with whole-cell lysates and three recombinant proteins (TcF, TcBCDE, and CP1 + CP3) using 93 Chagas disease-positive serum samples and 108 Chagas disease-positive samples. The sensitivities of ARCHITECT Chagas, whole-cell lysate, TcF, TcBCDE, and CP1 + CP3 ELISA were respectively 100%, 100%, 98.9%, 98.9%, and 89.2% and the corresponding specificities were 100%, 99.1%, 99.1%, 100%, and 99.1%. False-positive results were obtained for whole-cell lysate, TcF, and CP1 ± CP3 ELISA. This is the first evidence that OD cut-off values optimized for in-house ELISA are similar in terms of sensitivity and specificity to those of the ARCHITECT Chagas test, supporting the use of these in-house assays as diagnostic tests for Chagas disease in the clinical setting in Japan.

Extremely low post-settlement survival is one of the largest barriers for artificial rehabilitation of Acropora corals. However, little data have been found for interspecific difference of the post-settlement survival probably because the observation of coral juvenile is difficult in the field. Here, we analyzed the survival of three dominant species of Acropora corals (A. digitifera, A. tenuis, A. yongei), with different colony morphologies and habitat preferences, for 2 years after settlement under the same environmental conditions. The post-settlement survival was significantly higher for A. tenuis than for A. digitifera 3 months after settlement. Two years later, the survival rate of A. tenuis was approximately 15 times higher than A. digitifera. In a separate analysis of three bottle-brush species (A. awi, A. echinata, A. subglabra) and A. tenuis, post-settlement survival was always higher for A. awi than for other two bottle-brush species, suggesting that the initial survival was different among morphologically sister species. Low survival was possibly associated with slow growth rates during the first 7 months. Thus, species selection is important for successful artificial coral rehabilitation, with A. tenuis being the most viable option. Alternatively, new techniques are required to improve post-settlement survival of slow growing coral species.

Introduction The clinical benefits of adjunctive corticosteroids for Pneumocystis jirovecii pneumonia in patients not infected with the human immunodeficiency virus (HIV) has not been evaluated by meta-analysis. Methods We conducted a systematic review of published studies describing the effects of adjunctive corticosteroids on outcome in non-HIV P. jirovecii pneumonia patients. Two investigators independently searched the PubMed and Cochrane databases for eligible articles written in English. A meta-analysis was performed using a random-effects model for measuring mortality as the primary outcome, and the need for intubation or mechanical ventilation as the secondary outcome. Results Seven observational studies were eligible. In these studies, adjunctive corticosteroids did not affect mortality in non-HIV patients (odds ratio [OR] 1.26; 95% CI 0.60–2.67) and there was no beneficial effect in patients with severe hypoxemia (PaO2 Conclusions Although the studies were observational, meta-analysis showed that adjunctive corticosteroids did not improve the outcome of P. jirovecii pneumonia in non-HIV patients. The results warrant a randomized controlled trial.

Resumen Introduccion Los beneficios clinicos del tratamiento complementario con corticoides de la neumonia por Pneumocystis jirovecii (P. jirovecii) en pacientes no infectados por el virus de la inmunodeficiencia humana (VIH) no se han evaluado mediante metanalisis. Metodos Realizamos una revision sistematica de los estudios publicados que describen los efectos del tratamiento complementario con corticoides sobre la evolucion de pacientes con neumonia por P. jirovecii no infectados por VIH. Dos investigadores hicieron busquedas independientes de articulos elegibles escritos en ingles en las bases de datos PubMed y Cochrane. Se efectuo un metanalisis con un modelo de efectos aleatorios para determinar la mortalidad como variable principal, y la necesidad de intubacion o ventilacion mecanica como variable secundaria. Resultados Siete estudios observacionales resultaron elegibles. En ellos el tratamiento complementario con corticoides no afecto a la mortalidad en los pacientes no infectados por VIH ( odss ratio [OR] 1,26; IC 95% 0,60–2,67) y no tuvo ningun efecto beneficioso para los pacientes con hipoxemia intensa (PaO 2 Conclusiones Aunque los estudios eran observacionales, el metanalisis mostro que el tratamiento complementario con corticoides no mejoraba la evolucion de los pacientes con neumonia por P. jirovecii no infectados por VIH. Estos resultados justifican la realizacion de un ensayo controlado aleatorizado.

Acinetobacter baumannii is regarded as one of the most important pathogens in hospital outbreaks. To obtain an efficient and simple epidemiologic method of surveillance during outbreaks, we assessed the applicability of the polymerase chain reaction–based open reading frames typing (POT) method and compared it with pulsed-field gel electrophoresis. The POT method was found to have sufficient discriminatory power to identify the strains and would be widely applicable to epidemiologic surveillance during hospital outbreaks.

Background There are no reports on the prevalence of Chagas disease in Japan. Furthermore, screening programs and access to diagnosis and treatment have not been established. This study aimed to clarify the prevalence of Chagas disease among suspected cases in Japan and provide the reference data required for disease control. Methods Seventeen patients with suspected Chagas disease in Japan between 2012 and 2017 were included in the study. Patients were diagnosed with Chagas disease based on the two different serological tests for antibodies to Trypanosoma cruzi. Real-time polymerase chain reaction assay and blood culture techniques were performed to confirm T. cruzi parasitemia. Results Of the 17 patients, 11 (64.7%) were immigrants from Latin America. Ultimately, 6 patients (35.3%) were diagnosed with Chagas disease. Of these 6 patients, median age was 53.5 years, 5 patients were immigrants from Latin American, and 1 was Japanese who had a congenital infection. T. cruzi parasitemia was confirmed in 4 patients (66.7%), and 5 (83.3%) were in the chronic phase (Chagas cardiomyopathy, 4; megacolon, 1). Two patients (33.3%) commenced benznidazole treatment. Conclusion Our study showed that some patients of Chagas disease living in Japan are already in the chronic phase at diagnosis because of substantial diagnostic delays. Further epidemiological studies on the prevalence of Chagas disease and systematic screening programs for the Latin American population are needed.

Summary Background Outbreaks of vancomycin-resistant enterococcus (VRE) are a serious problem in hospitals. Inferring the transmission route is an important factor to institute appropriate infection control measures; however, the methodology has not been fully established. Aim To reconstruct and evaluate the transmission model using sequence variants extracted from whole genome sequencing (WGS) data and epidemiological information from patients involved in a VRE outbreak. Methods During a VRE outbreak in our hospital, 23 samples were collected from patients and environmental surfaces and analysed using WGS. By combining genome alignment information with patient epidemiological data, the VRE transmission route was reconstructed using a Bayesian approach. With the transmission model, evaluation and further analyses were performed to identify risk factors that contributed to the outbreak. Findings All VREs were identified as Enterococcus faecium belonging to sequence type 17, which consisted of two VRE genotypes: vanA (N = 8, including one environmental sample) and vanB (N = 15). The reconstruction model using the Bayesian approach showed the transmission direction with posterior probability and revealed transmission through an environmental surface. In addition, some cases acting as VRE spreaders were identified, which can interfere with appropriate infection control. Vancomycin administration was identified as a significant risk factor for spreaders. Conclusion A Bayesian approach for transmission route reconstruction using epidemiologic data and genomic variants from WGS can be applied in actual VRE outbreaks. This may contribute to the design and implementation of effective infection control measures.

Acinetobacter calcoaceticus-Acinetobacter baumannii complex, especially A. baumannii, Acinetobacter pittii and Acinetobacter nosocomialis, constitutes an important group of nosocomial pathogens; however, epidemiological or clinical characteristics and prognosis is limited in Japan. From 2009 to 2013, 47 blood stream infection cases resulting from A. baumannii group were reviewed at the National Defense Medical College, an 800-bed tertiary hospital. To determine the genospecies, further comparative nucleotide sequence analyses of the RNA polymerase b-subunit (rpoB) gene were performed. Sequence analysis of rpoB gene showed that 25 (49.0%), 17 (33.3%) and 5 (9.8%) cases were caused by A. baumannii, A. pittii and A. nosocomialis, respectively. The 30-day and in-hospital mortality rates of A. baumannii were 8.5% and 25.5%, respectively, and there were no significant differences between Acinetobacter species. Clinical characteristics were statistically insignificant. Multidrug-resistant Acinetobacter species were detected in 3 cases (5.9%) with same pulsed-field gel electrophoresis (PFGE) pattern and A. baumannii was less susceptible to amikacin and levofloxacin. In this study, the mortality and clinical characteristics were similar among A. baumannii group isolate cases despite some showing drug resistance. However, identification of Acinetobacter species helps to initiate appropriate antibiotic therapy in earlier treatment phase, because A. baumannii shows some drug resistance.

Pazopanib, a multityrosine kinase inhibitor used for treating malignant soft tissue tumors, rarely causes adverse events associated with the respiratory system. We report a case of a 73-year-old male with leiomyosarcoma treated with pazopanib. Four months after treatment initiation, chest computed tomography showed bilateral patchy consolidation and ground-glass opacities. Bronchoscopy revealed increased lymphocytes in the bronchoalveolar lavage fluid. Histological analysis of lung tissue demonstrated intraluminal fibrotic changes in alveolar spaces. According to these findings, we diagnosed the patient with pazopanib-induced organizing pneumonia. To best of our knowledge, this is the first report of such a case., Highlights • Pazopanib is a multityrosine kinase inhibitor used for treating soft tissue tumors. • Pazopanib rarely causes adverse events associated with the respiratory system. • This is the first report of a patient with pazopanib-induced organizing pneumonia.

BackgroundPneumonia is a serious disease associated with mortality among patients with dementia. However, the reported frequency of pneumonia as a cause of death in patients with dementia varies, the reason for which has not been fully elucidated.MethodsWe conducted a systematic search in PubMed and the Cochrane Database of Systematic Reviews (inception to December 2016). Two authors independently determined the suitability of studies and potential bias and extracted the data. The primary outcome was frequency of pneumonia-associated death in patients with dementia. Stratified subgroup analysis was conducted among studies grouped according to type of mortality cause (immediate or underlying), information source of mortality cause (autopsy or death certificate), and study setting (clinic, hospital, or nursing home).ResultsWe included 7 studies reporting the cause of death among patients with dementia and 12 studies comparing the cause of death among patients with and without dementia. The frequency of pneumonia-associated death among 19 eligible studies was 29.69% (95% confidence interval [CI], 25.86-33.53). Those frequencies differed according to whether the source for information about cause of death was an autopsy confirmation (49.98%; 95% CI, 43.75-56.71) or death certificate (19.65%; 95% CI, 15.48-23.83) and according to whether the type of mortality cause was an indirect cause of death (13.96%; 95% CI, 9.42-18.51) or direct cause of death (44.45%; 95% CI, 29.81-50.10). The risk of pneumonia-associated death in patients with dementia was twice as high as among those without dementia (odds ratio, 2.15; 95% CI, 1.63-2.83; p < 0.001).ConclusionThe various frequencies of pneumonia-associated death in patients with dementia were associated with the information source, type of mortality cause, and study setting. Patients with dementia in the terminal stages urgently require careful clinical management of pneumonia, to maximize patient life expectancy and quality.

Background The advent of well-tolerated and effective anti-retroviral drugs against human immunodeficiency virus-1 (HIV-1) infection has been a major step forward that has achieved long-term survival in recent years. The number of HIV-1 infected patients who experience difficulty in swallowing tablets is expected to increase as the HIV-infected population advances in age or develops comorbidities or treatment sequelae affecting the central nervous system. Case presentation Here, we describe two HIV-1-infected patients who experienced progressive dysphagia leading to inability to swallow the antiretroviral tablets included in the standard regimen. Both patients had a plasma viral load

Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus-8. Most cases are co-infected with Epstein-Barr virus (EBV). The prognosis of PEL is extremely poor and no optimal treatment regimen has been established. We report a case of EBV-negative PEL in a 49-year-old human immunodeficiency virus-positive man, presenting with massive bilateral pleural effusion.

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 (67Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

Background Influenza-related pneumonia, referred to as influenza pneumonia, was reported relatively more frequently during a recent influenza pandemic in 2009. The validity of adapting routine pneumonia severity prediction models for various types of pneumonia is unclear. Methods We conducted a nationwide survey to evaluate influenza pneumonia among adult patients in Japan. Questionnaires were sent to physicians working in departments of respiratory medicine at 2491 hospitals. Both the outcome and pneumonia severity, using invasive positive pressure ventilation (IPPV) as an indicator, were evaluated by routine pneumonia severity index (PSI), CURB-65 (confusion, urea, respiratory rate, blood pressure, and age≥65 years), and A-DROP (age, dehydration, respiration, disorientation, and blood pressure). Results Data collected from 320 patients with influenza pneumonia, including 25 cases (7.8%) of death and 43 (13.4%) of IPPV, were analyzed. Although all routine prediction models showed that higher mortality tended to be associated with a higher risk class/grade, the actual mortality rates were higher than predicted. The risk class of mortality calculated by the PSI was influenced by pneumonia patterns. Although pneumonia severity was similarly predicted, the types of pneumonia also affected severity in all prediction models. A-DROP showed the highest accuracy on receiver operating characteristic analysis for both mortality and severity. Conclusions CURB-65 and A-DROP are fair predictors of mortality regardless of pneumonia patterns. However, the current pneumonia prediction models may underestimate the severity and appropriate site of care for patients with influenza pneumonia.

We herein report the case of a 31-year-old woman who presented with bilateral upper lobe volume loss and pleural irregularities with hilar retraction. She had undergone allogeneic bone marrow transplantation (BMT) for the treatment of acute lymphoblastic leukemia nine years earlier. A surgical lung biopsy showed pleural thickening and subpleural alveolar collapse and fibrosis, consistent with a diagnosis of pleuroparenchymal fibroelastosis (PPFE). Antecedent sicca syndrome and the absence of other causes of fibroelastosis suggested that these abnormalities were associated with chronic graft-versus-host disease (cGVHD). PPFE as a late, noninfectious complication is rare; however, the present case suggests a new class of BMT-related pulmonary complications associated with cGVHD.

BackgroundThe clinical epidemiology and disease prognosis in patients with acute respiratory distress syndrome (ARDS) have not yet been fully elucidated in Vietnam.MethodsWe conducted a retrospective observational study at a national tertiary hospital in Hanoi, Vietnam. Participants were adult patients (age ≥18 years) who were admitted and diagnosed with ARDS during 2015-2017. Data on patients' general and clinical conditions, radiographic findings, ventilator settings, gas exchange, and treatment methods were collected and compared between survivors and non-survivors. Risk factors for mortality were assessed using logistic regression analysis.ResultsAmong 126 eligible patients with ARDS admitted to the central tertiary hospital in Vietnam, we observed high mortality (57.1%). Of the total patients, 91.3% were transferred from local hospitals with a diagnosis of severe pneumonia and then diagnosed with ARDS at the central hospital. At the time of admission, 53.2% of patients had severe ARDS, 37.3% had moderate ARDS, and 9.5% had mild ARDS. The mean (standard deviation) sequential organ failure assessment (SOFA) score was 9.5 (3.4) in non-survivors and 7.4 (3.4) in survivors (p = 0.002). Although there was no significant difference in PaO2/FiO2 on admission between non-survivors and survivors, that on day 3 after admission was significantly different (p = 0.002). Logistic regression revealed that PaO2/FiO2 on day 3 [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.003-1.017], length of stay in a local hospital before admission to the central hospital (OR, 1.122; 95% CI, 1.042-1.210) due to stable condition, and SOFA score on Day 1 (OR, 0.842; 95% CI, 0.708-1.002) were independent factors in patient survival.ConclusionsPatients with ARDS admitted the central tertiary hospital had severe illness and high mortality. Most patients were transferred from local hospitals. Improvements in human, medical, and sociological resources in local will contribute to reducing the mortality of ARDS in Vietnam.

We report a case of human herpes virus-8-associated multicentric Castleman’s disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman’s disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman’s disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load.

We herein describe a case of progressive human immunodeficiency virus (HIV)-associated cholangiopathy despite normalization of laboratory parameters, which had indicated liver dysfunction, after the initiation of combined anti-retroviral therapy (cART). HIV-associated cholangiopathy remains important as a differential diagnosis of bile duct disorders, although it is considered to be a rare disease in the era of cART. Magnetic resonance cholangiopancreatography could thus be a powerful tool for the diagnosis and follow-up of this disease.

Background: The clinical impacts of de-escalation antibiotic therapy on hospital-acquired (HAP), ventilator-associated (VAP), and healthcare-associated pneumonia (HCAP) have not been fully evaluated using a systematic review and meta-analysis. Methods: We conducted a systematic review of studies examining de-escalation therapy in patients with HAP, VAP, or HCAP using PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A meta-analysis was conducted using a random-effects model (DerSimonian–Laird method) to measure mortality as the primary outcome and the lengths of hospital stay, intensive care unit stay, and antibiotic therapy as the secondary outcomes. Results: Among eligible eleven studies (2,621 patients), six were cohort studies, and the remaining five studies were “before-and-after” investigations implementing guideline-oriented de-escalation therapy. In all eligible studies, de-escalation had no effect on hospital mortality (odds ratio [OR], 0.85; 95% confidence interval [95%CI], 0.58–1.25). In subgroup analysis, studies that examined de-escalation vs. non-de-escalation showed a possible but statistically insignificant effect on mortality (OR, 0.61; 95%CI, 0.34–1.11), while “before-and-after” investigations tended to reveal an increased mortality risk (OR, 1.18; 95%CI, 0.73–1.91). Studies with APACHE II scores of≤20 tended to show a reduced mortality risk (OR, 0.86; 95%CI, 0.35–2.11). Conclusions: De-escalation antibiotic therapy had a possible effect on HAP/VAP/HCAP in terms of reducing mortality, especially cases of less severe disease.

Background Primary effusion lymphoma is a rare distinct large B-cell neoplasm that is associated with Kaposi’s sarcoma–associated herpesvirus (KSHV) infection. Over recent years, 9 KSHV-positive/Epstein-Barr virus (EBV)-negative PEL cell lines have been established. Methods Tumor cells were collected from the pleural effusion of a 49-year-old male with AIDS. Cells were grown in RPMI1640 culture medium supplemented with 10 % fetus bovine serum. Single cell cloning was performed successfully by a limiting dilution method in a 96-well plate. The cell line obtained was designated SPEL. Results SPEL cells showed gourd-shaped morphology with a polarized nucleus, expressing CD38, CD138, and Blimp-1, but not B cell markers such as CD19 and CD20. Polymerase chain reaction analysis revealed that SPEL cells were positive for KSHV but negative for EBV. Tetradecanoylphorbol acetate induced expression of KSHV lytic proteins and the production of KSHV particles in SPEL cells. Subcutaneous inoculation of SPEL cells into severe combined immunodeficiency mice resulted in the formation of solid tumors. Next-generation sequencing revealed the 138 kbp genome sequence of KSHV in SPEL cells. Suberic bishydroxamate, a histone deacetylase inhibitor, induced the expression of KSHV-encoded lytic proteins and cell death in SPEL cells. Conclusions A new KSHV-positive and EBV-negative PEL cell line, SPEL was established. This cell line may contribute to furthering our understanding of the pathogenesis of PEL and KSHV infection.

We report a patient with HIV-associated multicentric Castleman's disease who had recurrent human herpesvirus-8 viremia associated with intermittent febrile exanthema and lymphadenopathy. Although the patient relapsed after single-agent treatment with liposomal doxorubicin, weekly infusions of rituximab led to complete remission even though the reactivation of the Kaposi's sarcoma was unfortunately observed. Rituximab could not only eliminate the accumulation of HHV-8 load but also play a part in the modulation of dysregulated CD20-positive B cells in HIV-associated multicentric Castleman's disease.