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BackgroundHyperuricemia is common during tuberculosis (TB) treatment, especially in association with pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment.MethodsWe conducted a single-center retrospective cohort study. From January 2010 through June 2017, we assessed all consecutive TB patients at Chonnam National University Hospital in South Korea. Hyperuricemia was defined as serum uric acid levels exceeding 7.0 mg/dL (men) and 6.0 mg/dL (women).ResultsOf the 1,143 patients included, PZA was administered to 1,081 (94.6%), and hyperuricemia was detected in 941 (82.3%). Eight patients experienced MACEs. Multivariate analysis using logistic regression indicated that prior ischemic heart disease was associated with MACE development (OR,14.087; 95% CI,3.304-60.061; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184-12.299; P = 0.703). For patients without drug-resistant TB, the absence of hyperuricemia was associated with higher mortality (OR, 2.609; 95% CI, 1.066-6.389; P = 0.036), whereas hyperuricemia was associated with less worse outcomes (OR,0.316; 95% CI,0.173-0.576; P < 0.000).ConclusionsAlthough most patients treated with PZA developed hyperuricemia, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to consistent adherence to TB treatment.

ObjectiveIn-hospital tuberculosis (TB) transmission remains a concern. Airborne infection isolation (AII) can be discontinued in hospitalized patients with suspected active pulmonary TB when the results of three consecutive sputum acid-fast bacilli (AFB) smears are negative. However, fiberoptic bronchoscopy can be performed in patients who may have difficulty in producing sputum samples. This study aimed to investigate the usefulness of Mycobacterium tuberculosis-polymerase chain reaction (MTB-PCR) with bronchial washing specimens in predicting AII discontinuation in hospitalized patients with suspected active pulmonary TB.MethodsWe reviewed the medical charts of patients admitted to a tertiary hospital who were isolated and underwent fiberoptic bronchoscopy for suspicious pulmonary TB from January 2016 to December 2019. Patients with positive MTB-PCR results in the initial sputum examination were excluded. Criteria for discontinuing AII were defined as negative results for three consecutive AFB smears from respiratory specimens, or cases diagnosed other than TB. The study patients were divided into two groups: TB group and non-TB group.ResultsIn total, 166 patients were enrolled in the study. Of them, 35 patients were diagnosed with TB. There was no significant difference between the number of males in the TB (81; 61.8%) and non-TB (21; 60.0%) group. Though 139 patients had negative results on MTB-PCR using washing specimens, eight showed positive AFB culture. Of the 139 patients with negative MTB-PCR results, 138 had negative results for three consecutive AFB smears or were established to not have pulmonary TB. Therefore, the predictive accuracy of MTB-PCR with bronchial washing samples for discontinuing AII was 99.2%.ConclusionAlthough a negative result from MTB-PCR with bronchial washing samples cannot exclude pulmonary TB, it can predict AII discontinuation in hospitalized patients with suspected active pulmonary TB.

ObjectivePulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs.MethodsWe retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital.ResultsFifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038).ConclusionOlder age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.

ObjectivePneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.MethodsWe retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).ResultsThe IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).ConclusionsPatients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

ObjectiveThis study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs.MethodsWe retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs).ResultsTwenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543).ConclusionsMultiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

The sensitivity of interferon-gamma release assays (IGRAs) in the detection of Mycobacterium tuberculosis infection could be affected by conditions of immune dysregulation. For this reason, diabetes mellitus (DM) may increase the frequency of indeterminate results of IGRAs. However, there have been inconsistent reports of role of DM on indeterminate IGRA results.We retrospectively reviewed all patients who underwent QuantiFERON-TB Gold In-Tube testing (QFT-GIT) at Chonnam National University Hospital. We collected the clinical and laboratory data of these patients.Of all 3,391 subjects, 1,265 (37.3%) had a positive QFT-GIT result, 266 (7.8%) had an indeterminate result, and 1,860 (54.9%) had a negative result. The mean age was 54.8 ± 18.1 years and 55.0% of the patients were male. There were 512 (15.1%) patients with DM. Multivariable analysis revealed that systemic corticosteroid use, tuberculosis, lymphocytopenia, low serum albumin, and high serum C-reactive protein (CRP) levels were significantly associated with indeterminate QFT-GIT results. However, DM was not associated with indeterminate QFT-GIT results (adjusted odds ratio, 0.98; 95% confidence interval, 0.69-1.41; P = 0.939). After propensity score matching, DM was not associated with indeterminate results of QFT-GIT.In this large cohort study, DM does not affect the incidence of indeterminate results of QFT-GIT.

Identification and understanding of the pathogens responsible for pleural infection is critical for appropriate antibiotic treatment. This study sought to determine the microbiological characteristics of pleural infection and to identify potential predictive factors associated with mortality.In this retrospective study, we analyzed patient data from 421 cases of parapneumonic effusion. A total of 184 microorganisms were isolated from 164 patients, using two culture systems: a standard method and a method using pairs of aerobic and anaerobic blood culture bottles.The most frequently isolated microorganisms were streptococci (31.5%), followed by staphylococci (23.4%), gram-negative bacteria (18.5%) and anaerobes (10.3%). Streptococci were the main microorganisms found in standard culture (41.9%) and community-acquired infections (52.2%), and were susceptible to all antimicrobial agents in drug sensitivity testing. Staphylococci were the most frequently isolated pathogens in blood cultures (30.8%) and hospital-acquired infections (38.3%), and were primarily multidrug-resistant (61.8%). In multivariate analysis, the following were significant predictive factors for 30-day mortality among the total population: CURB-65 ≥ 2 (aOR 5.549, 95% CI 2.296-13.407, p

Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD) resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS)-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh) RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.