Prognostic Factors of In-hospital Mortality in Patients without Human Immunodeficiency Virus Infection with Pneumocystis Pneumonia: A Retrospective Cohort Study.

Objective This study explored the prognostic factors of in-hospital mortality in patients with Pneumocystis pneumonia (PCP) without human immunodeficiency virus (HIV) infection, using a Japanese nationwide inpatient database. Methods We extracted the data of patients with PCP without HIV infection between July 2010 and March 2022 from the Diagnosis Procedure Combination database. We performed multivariable logistic regression analyses to identify the prognostic factors of in-hospital mortality in with PCP without HIV infection. Results We identified 1,704 patients with PCP without HIV infection and 404 (23.7%) in-hospital deaths. Higher in-hospital mortality was associated with advanced age, male sex (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-2.00), a low Barthel index score, non-hematological malignancy (OR, 1.81; 95% CI, 1.22-2.70), receipt of mechanical ventilation (OR, 2.49; 95% CI, 1.47-4.21), and administration of antibiotics (OR, 1.52; 95% CI, 1.12-2.06) and antifungal drugs (OR, 1.83; 95% CI, 1.26-2.67). Lower in-hospital mortality was associated with connective tissue disease and vasculitis (OR, 0.55; 95% CI, 0.37-0.81), hematological malignancy (OR, 0.59; 95% CI, 0.38-0.93), and early trimethoprim-sulfamethoxazole treatment (OR, 0.63; 95% CI, 0.44-0.90). Conclusions These findings will help physicians identify patients who may benefit from early aggressive therapeutic interventions.

Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study.

BACKGROUND AND OBJECTIVE: Pyrazinamide (PZA) is the standard first-line treatment for tuberculosis (TB); however, its safety in elderly patients has not been thoroughly investigated. METHODS: This retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for TB between July 2010 and March 2022. Patients were categorized into HRE (isoniazid, rifampicin and ethambutol) and HREZ (isoniazid, rifampicin, ethambutol and PZA) groups. Primary outcomes included in-hospital mortality and overall adverse events (characterized by a composite of hepatotoxicity, gout attack, allergic reactions and gastrointestinal intolerance). Secondary outcomes included the length of hospital stay, 90-day readmission and use of drugs related to the primary outcome adverse events. Data were analysed using propensity score matching; we also conducted a subgroup analysis for those aged ≥75 years. RESULTS: Among 19,930 eligible patients, 8924 received HRE and 11,006 received HREZ. Propensity score matching created 3578 matched pairs with a mean age of approximately 80 years. Compared with the HRE group, the HREZ group demonstrated a higher proportion of overall adverse events (3.1% vs. 4.7%; p < 0.001), allergic reactions (1.4% vs. 2.5%; p < 0.001) and antihistamine use (21.9% vs. 27.6%; p < 0.001). No significant differences were observed regarding in-hospital mortality, hepatotoxicity or length of hospital stay between the groups. Subgroup analysis for those aged ≥75 years showed consistent results. CONCLUSION: Medical practitioners may consider adding PZA to an initial treatment regimen even in elderly patients with TB.

Factors affecting in-hospital mortality in patients with miliary tuberculosis: A retrospective cohort study.

BACKGROUND: Miliary tuberculosis (TB) is a fatal disease; thus, prompt diagnosis and immediate intervention are indispensable. However, the risk factors for in-hospital mortality in patients with miliary TB remain unclear. Therefore, this study aimed to identify the factors associated with in-hospital mortality in patients with miliary TB using a Japanese nationwide inpatient database. METHODS: Patients diagnosed with miliary TB between July 2010 and March 2022 were enrolled from the Diagnosis Procedure Combination database. Multivariate logistic regression analyses were performed to identify the factors associated with in-hospital mortality in patients with miliary TB. RESULTS: In total, 2817 patients with miliary TB and 637 (22.6%) in-hospital deaths were identified. Older age; male sex (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.04-1.64); low body weight (OR, 1.41; 95% CI, 1.14-1.76); altered consciousness; a low Barthel index score; chronic respiratory failure (OR, 3.85; 95% CI, 1.61-9.19); hematologic malignancy (OR, 2.60; 95% CI, 1.26-5.35); conditions requiring oxygenation (OR, 1.70; 95% CI, 1.37-2.10) or high-flow nasal cannula therapy (OR, 2.78; 95% CI, 1.01-7.62); or the administration of vasopressors (OR, 2.25; 95% CI, 1.39-3.63) or antibiotics (OR, 1.40; 95% CI, 1.14-1.74) were associated with higher in-hospital mortality. CONCLUSIONS: This study identified the factors affecting in-hospital mortality among patients with miliary TB. The findings of this study will aid clinicians in identifying patients who may benefit from aggressive therapeutic interventions.

Endobronchial silicone spigot in prolonged air leaks: Nationwide study on outcomes and risk factors for treatment failure.

BACKGROUND: The endobronchial silicone spigot, also known as the endobronchial Watanabe spigot, is used in bronchoscopic interventions to manage prolonged pulmonary air leakage. However, the outcomes of this procedure have not been thoroughly investigated. METHODS: Using a Japanese national inpatient database from April 2014 to March 2022, we assessed the clinical characteristics and outcomes of all eligible patients who received the endobronchial spigot. We also investigated risk factors associated with treatment failure. Treatment failure was defined as in-hospital death or the need for surgery after bronchial occlusion. RESULTS: We analyzed data of 1095 patients who underwent bronchial occlusion using the endobronchial spigot. Among them, 252 patients (23.0%) died during hospitalization, and 403 patients (36.8%) experienced treatment failure. Factors associated with treatment failure included age between 85 and 94 years (odds ratio [OR] 1.83; 95% confidence intervals [CI], 1.04-3.21); male sex (OR 2.43; 95% CI, 1.44-4.11); low Barthel index score; comorbidities of interstitial pneumonia (OR 1.71; 95% CI, 1.18-2.48); antibiotics treatment (OR 1.45; 95% CI, 1.02-2.07); steroids treatment (OR 1.59; 95% CI, 1.07-2.36); and surgery prior to bronchial occlusion (OR 2.08; 95% CI, 1.29-3.35). In contrast, pleurodesis after bronchial occlusion (OR 0.49; 95% CI, 0.32-0.75), and admission to high-volume hospitals were inversely associated with treatment failure (OR 0.58; 95% CI, 0.37-0.90). CONCLUSIONS: The endobronchial Watanabe spigot could be a nonsurgical treatment option for patients with prolonged pulmonary air leaks. Our findings will help identify patients who may benefit from such bronchial interventions.

Rigorous evaluation of genetic and epigenetic effects on clinical laboratory measurements using Japanese monozygotic twins.

The investigation of environmental effects on clinical measurements using individual samples is challenging because their genetic and environmental factors are different. However, using monozygotic twins (MZ) makes it possible to investigate the influence of environmental factors as they have the same genetic factors within pairs because the difference in the clinical traits within the MZ mostly reflect the influence of environmental factors. We hypothesized that the within-pair differences in the traits that are strongly affected by genetic factors become larger after genetic risk score (GRS) correction. Using 278 Japanese MZ pairs, we compared the change in within-pair differences in each of the 45 normalized clinical measurements before and after GRS correction, and we also attempted to correct for the effects of genetic factors to identify Cytosine-phosphodiester-Guanine (CpG) sites in DNA sequences with epigenetic effects that are regulated by genetic factors. Five traits were classified into the high heritability group, which was strongly affected by genetic factors. CpG sites could be classified into three groups: regulated only by environmental factors, regulated by environmental factors masked by genetic factors, and regulated only by genetic factors. Our method has the potential to identify trait-related methylation sites that have not yet been discovered.

The efficacy and safety of anamorelin for patients with cancer-related anorexia/cachexia syndrome: a systematic review and meta-analysis.

Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic agent for the treatment of CACS. In this systematic review, we assessed the efficacy of oral anamorelin treatment for patients with CACS. On July 6, 2022, we systematically searched the following databases for randomized controlled trials (RCTs) of adults with CACS comparing oral anamorelin versus placebo: CENTRAL, PubMed, EMBASE, and ICHUSHI. The primary outcomes were total body weight (TBW), patient-reported quality of life (QOL), and adverse events (AEs). Secondary outcomes included lean body mass (LBM), overall survival (OS), non-dominant hand grip strength (HGS), and appetite. We included seven RCTs with a total of 1944 CACS patients. Anamorelin significantly increased TBW (mean difference (MD) 1.73, 95% confidence interval (CI) 1.34-2.13, p < 0.00001), LBM (MD 1.06, 95% CI 0.30-1.81, p = 0.006), and QOL (standardized mean difference (SMD) 0.16, 95% CI 0.04-0.27, p = 0.006) compared with placebo without a significant difference in all AEs, severe AEs, OS, HGS or appetite. Anamorelin may be an effective treatment for CACS patients; however, further studies are needed to confirm the efficacy and safety of this drug.

Empyema and bacteremia caused by Parvimonas micra: A case report.

Parvimonas micra is a gram-positive anaerobic coccus (GPAC) that colonizes the oral cavity and gastrointestinal tract. Recent advances in bacterial identification have confirmed the clinical importance of Parvimonas micra. Here, we report a case of empyema with bacteremia caused by Parvimonas micra. We successfully treated the patient with the appropriate antibiotics and drainage. Parvimonas micra can cause respiratory infections, including empyema, which can progress to bacteremia if treatment is delayed. In Parvimonas micra infections, not only the oral cavity but also the entire body must be investigated to clarify the entry mechanism.

Immunogenicity and safety of influenza vaccine in patients with lung cancer receiving immune checkpoint inhibitors: A single-center prospective cohort study.

INTRODUCTION: Patients with lung cancer have a high risk of influenza complications. International guidelines recommend annual influenza vaccination for patients with cancer. Immune checkpoint inhibitors (ICIs) are progressively used to treat lung cancer. Data regarding immunogenicity and safety of influenza vaccine are limited in patients with lung cancer receiving ICIs; therefore, we conducted this single-center, prospective observational study in the Japanese population. METHODS: Patients with lung cancer receiving ICIs and influenza immunization were enrolled. Blood samples were collected from patients for serum antibody titer measurement pre- and 4 ± 1 weeks post-vaccination. The primary endpoint was seroprotection rate (sP) at 4 ± 1 weeks post-vaccination. The secondary endpoints were geometric mean titer (GMT), mean fold rise, seroresponse rate (sR), seroconversion rate (sC), and immune-related adverse events (irAEs), defined as adverse effects caused by ICI administration, 6 months post-vaccination. RESULTS: Influenza vaccination in the 23 patients included in the immunogenicity analyses significantly increased GMT for all strains, and sP, sR, and sC were 52%-91%, 26%-39%, and 26%-35%, respectively. In the 24 patients included in the safety analyses, 7 (29%) and 5 (21%) patients exhibited systemic and local reactions, respectively. Only one patient (4%) (hypothyroidism, grade 2) showed post-vaccination irAEs. CONCLUSIONS: Overall, influenza vaccination in patients with lung cancer receiving ICIs showed acceptable immunogenicity and safety, thus supporting annual influenza vaccination in this population.

Association between intrapleural urokinase monotherapy and treatment failure in patients with pleural infection: a retrospective cohort study.

BACKGROUND: Pleural infection, an infection of the pleural space, is frequently treated with antibiotics and thoracic tube drainage. In case of insufficient drainage, an intrapleural fibrinolytic agent is considered before surgical intervention. However, the effectiveness of fibrinolytic monotherapy is still controversial. Therefore, we aimed to examine the association between urokinase monotherapy and treatment failure in patients with pleural infection. METHODS: In this retrospective observational study, patients with pleural infection underwent chest tube insertion were divided into two groups including patients treated with or without intrapleural instillation of urokinase. The propensity score overlap weighting was used to balance the baseline characteristics between the groups. Treatment failure was defined by the composite primary outcome of in-hospital death and referral for surgery. RESULTS: Among the 94 patients, 67 and 27 patients were in the urokinase and non-urokinase groups, respectively. Urokinase monotherapy improved the composite outcome between the groups (19.4% vs. 48.1%, p = 0.01). After adjusting using propensity score overlap weighting, urokinase monotherapy improved the composite outcome compared to the non-urokinase group (19.0% vs. 59.5%, p = 0.003). CONCLUSIONS: Urokinase monotherapy can be an important nonsurgical treatment option for patients with pleural infection. TRIAL REGISTRATION: The participants were retrospectively registered.

Twin Study: Genetic and Epigenetic Factors Affecting Circulating Adiponectin Levels.

CONTEXT: Clarification of the association among phenotypes, genetic, and environmental factors with clinical laboratory traits can reveal the cause of diseases and assist in developing methods for the prediction and prevention of diseases. It is difficult to investigate the environmental effect on phenotypes using individual samples because their genetic and environmental factors differ, but we can easily investigate the influence of environmental factors using monozygotic (MZ) twins because they have the same genetic factors. OBJECTIVE: We aimed to examine the methylation level of CpG sites as an environmental factor affecting adiponectin levels on the basis of the same genetic background using MZ twins and to identify the epigenetic factors related to adiponectin levels and the genetic factors associated with sensitivity to acquired changes in adiponectin. METHODS: Using 2 groups built from each twin of 232 MZ twin pairs, we performed a replicated epigenome-wide association study to clarify the epigenetic factors affecting adiponectin levels adjusted by genetic risk score. Moreover, we divided twin pairs into concordant and discordant for adiponectin levels. We conducted a genome-wide association study to identify a genetic background specific for discordance. RESULTS: Methylation levels at 38 CpG sites were reproducibly associated with adjusted adiponectin levels, and some of these CpG sites were in genes related to adiponectin, including CDH13. Some genes related to adiponectin or insulin resistance were found to be genetic factors specific for discordance. CONCLUSION: We clarified specific epigenetic factors affecting adiponectin levels and genetic factors associated with sensitivity to acquired changes in adiponectin.

The relationship between chest tube position in the thoracic cavity and treatment failure in patients with pleural infection: a retrospective cohort study.

BACKGROUND: Pleural infection is an infection of the pleural space that is usually treated with antibiotics and source control. Chest tube insertion is the most popular and widely used drainage technique. We typically attempt to place the tube at the bottom of the thoracic cavity to consider the effects of gravity; however, the effectiveness of this practice is not well-defined. Therefore, we aimed to examine whether the position of the tip of the thoracic tube affects treatment failure in patients with pleural infection. METHODS: In this retrospective observational study, patients with pleural infection who underwent thoracic tube insertion were divided into two groups: those with the tip of the tube positioned below the 10th thoracic vertebra at the level of the diaphragm (lower position group) and those with the tip placed above the 9th thoracic vertebra (upper position group). We compared whether the position of the tube tip affected treatment failure. Stabilized inverse probability treatment weights (SIPTW) were used to balance the baseline characteristics between the groups. Treatment failure showed a composite outcome of hospital death, referral to surgeons for surgery, and additional chest tube insertion. RESULTS: Among the 87 patients, 41 and 46 patients were in the lower and upper groups, respectively. No significant difference was observed in the composite outcomes between the groups (46.3% vs. 54.3%, P = 0.596). There was also no significant difference in the composite outcome between both groups after adjusting for SIPTW (52.3% vs. 68.8%, P = 0.286). CONCLUSIONS: There were no significant differences in the treatment failure in this study addressing pleural infection treatment, in which the drain tip position was stratified by the 9th and 10th thoracic vertebrae. The position of the tip of the thoracic tube may not be important for pleural infection treatment providing that it is in the thoracic cavity. Trial registration The participants were registered retrospectively.

Low cut-off value of serum (1,3)-beta-D-glucan for the diagnosis of Pneumocystis pneumonia in non-HIV patients: a retrospective cohort study.

BACKGROUND: Non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP) is a fulminant disease with an increasing incidence. The serum beta-D-glucan (BDG) assay is used as an adjunct to the diagnosis of PCP; however, the cut-off value for this assay is not well-defined, especially in the non-HIV PCP population. Therefore, we aimed to identify the assay cut-off value for this population. METHODS: In this retrospective observational study, we reviewed the medical records of all patients (≥ 18 years old) with clinical suspicion of PCP who underwent evaluation of respiratory tract specimens between December 2008 and June 2014 at Kameda Medical Center. We created a receiver operating characteristic curve and calculated the area under the curve to determine the cut-off value for evaluating the inspection accuracy of the BDG assay. RESULTS: A total of 173 patients were included in the study. Fifty patients showed positive results in specimen staining, loop-mediated isothermal amplification assay, and polymerase chain reaction test, while 123 patients showed negative results. The receiver operating characteristic analyses suggested that the BDG cut-off level was 8.5 pg/mL, with a sensitivity and specificity of 76% and 76%, respectively. CONCLUSIONS: The Wako-BDG cut-off value for the diagnosis of non-HIV PCP is 8.5 pg/mL, which is lower than the classical cut-off value from previous studies. Clinicians should potentially consider this lower BDG cut-off value in the diagnosis and management of patients with non-HIV PCP. TRIAL REGISTRATION:  The participants were retrospectively registered.

Long-term survival of a patient with uterine cancer-induced pulmonary tumor thrombotic microangiopathy following treatment with platinum-based chemotherapy and bevacizumab: A case report.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal cancer-related disease. Owing to its non-specific findings, aggressive course, and lack of established treatment guidelines, only a few cases of antemortem diagnosis in long-term survivors have been reported. We aimed to report a case of uterine cervical cancer induced PTTM that was suspected based on pulmonary hypertension and successfully treated using combination chemotherapy despite of delayed diagnose. It is important to be aware that PTTM should be suspected when respiratory failure occurs in patients with unexplained pulmonary hypertension. Multidisciplinary treatments including molecular targeted therapies might be effective treatment options.

Simultaneous treatment for M ycobacterium-avium complex lung disease and allergic bronchopulmonary aspergillosis: A case report.

Recently, there are several reports of simultaneous allergic bronchopulmonary aspergillosis (ABPA) and Mycobacterium-avium complex (MAC) lung disease. However, the strategies for early diagnosis and appropriate treatment for patients with both ABPA and MAC lung disease have not been established. Here, we report a case with ABPA complicated by MAC lung disease, which was successfully diagnosed and treated by simultaneous administration of systemic steroids and antimycobacterial drugs. Bronchoscopy can be useful in the diagnosis of such cases. Furthermore, in a patient with concurrent ABPA and MAC lung disease, simultaneous treatments for both diseases could reduce both diseases.

Adrenal crisis precipitated by influenza A led to the diagnosis of Sheehan's syndrome 18 years after postpartum hemorrhage.

Physicians must recognize and treat adrenal crisis that may occur with acute viral illnesses such as influenza in women with Sheehan's syndrome that has been undiagnosed and hence untreated, sometimes for many years, after postpartum hemorrhage.

Pulmonary Sarcoidosis Presenting with Acute Respiratory Failure: A Report of a Case Diagnosed by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration on Ventilation after Intubation.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology and is pathologically characterized by non-caseating granulomas in the organs involved. We herein report a case of sarcoidosis in a Japanese woman with acute respiratory failure, diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on the ventilator after intubation. Only a few cases of previously undiagnosed sarcoidosis presenting acute respiratory failure have been reported. It is important to be aware that undiagnosed sarcoidosis may present with acute respiratory failure. Therefore, EBUS-TBNA under mechanical ventilation may be useful for the immediate diagnosis of patients.

Estimation of the effects of heavy Asian dust on respiratory function by definition type.

BACKGROUND: The adverse effects of Asian dust (AD) on health have been demonstrated in earlier studies, but there is no standardized definition for heavy-AD. This study aimed to examine which definition of heavy-AD has the most adverse effect on respiratory function. METHODS: One-hundred-and-thirty-seven adults with asthma, and 384 school children self-measured their morning peak expiratory flow (PEF). The four definitions of heavy-AD are: (1) the definition provided by the Japan Meteorological Agency (JMA), (2) daily median AD particle level ≥ 0.07 km-1, obtained through light detection and ranging (LIDAR) (3) hourly AD particle level ≥ 0.1 km-1, and (4) hourly level ≥ 0.07 km-1. Linear mixed models were used to estimate the effects of heavy-AD, by definition type, on daily PEF values. RESULTS: In adults with asthma, as per the JMA's definition, significantly reduced PEF were observed on heavy-AD days (lag 0), lag 0-1, and lag 0-3. In school children, after a heavy-AD event, as defined by the JMA, PEF significantly decreased on lag 0-1, lag 0-2, and lag 0-3. However, as per the other definitions, there was no significant decrease in the PEF in the adults and children. CONCLUSION: The associations between heavy-AD and respiratory function differed between these definitions.

Fabrication of disk droplets and evaluation of their lasing action.

Disk resonators are difficult to create with droplets, since they self-form spheres due to the surface tension. In this study, disk (cylindrical) droplets were created by enclosing a dye (rhodamine 6G) solution in silicone rubber. Lasing actions of these droplets were examined by pulsed green laser excitation. In a large droplet (2 mm diameter), the whispering gallery mode emission was difficult to attain, since it competed with the radial or axial modes that made a round trip in the droplet. A disk droplet of 150 µm diameter exhibited a comb-like spectrum of the whispering gallery mode resonant emission.

Association between Outdoor Fungal Concentrations during Winter and Pulmonary Function in Children with and without Asthma.

Outdoor fungi are important components of airborne particulate matter (PM). However, the associations between pulmonary function and outdoor fungi are less well known compared to other airborne PM constituents. The objective of this study was to investigate the association between outdoor fungi and pulmonary function in children. Morning peak expiratory flow (PEF) rates were measured daily in 339 schoolchildren (including 36 with asthma), aged 10 to 12, 2 to 27 February 2015. Airborne PM was collected on filters, using a high volume air sampler, each day during the study period. The daily concentration of outdoor fungi-associated PM was calculated using a culture-based method. A linear mixed model was used to estimate the association between PEF values and daily concentrations of outdoor fungi, and the daily levels of suspended PM (SPM) and PM ≤ 2.5 µm (PM2.5). An increase in the interquartile range (46.2 CFU/m³) for outdoor fungal concentration led to PEF changes of -1.18 L/min (95% confidence interval, -2.27 to -0.08) in all children, 1.22 L/min (-2.96 to 5.41) in children without asthma, and -1.44 L/min (-2.57 to -0.32) in children with asthma. Outdoor fungi showed a significant negative correlation with PM2.5 levels (r = -0.4, p = 0.04), but not with SPM (r = ‒0.3, p = 0.10) levels. Outdoor fungi may be associated with pulmonary dysfunction in children. Furthermore, children with asthma may show greater pulmonary dysfunction than those without asthma.