Long-term exposure to air pollution and precocious puberty in South Korea.

BACKGROUND AND AIM: The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between long-term air pollution exposure and PP has been relatively limited. We thus investigated the association between long-term air pollution exposure and the onset of PP in South Korea. METHODS: We investigated a retrospective cohort using the Korea National Health Insurance Database. Six-year-old children born from 2007 to 2009 were examined (2013-2015). We included boys ≤10 years and girls aged ≤9 years who visited hospitals for early pubertal development, were diagnosed with PP per the ICD-10 (E228, E301, and E309), and received gonadotropin-releasing hormone agonist treatment. We analyzed data for boys up until 10 years old (60-month follow-up) and for girls up to 9 years old (48-month follow-up). We assessed the association between long-term air pollution exposure and the onset of PP using a Cox proportional hazard model. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 µg/m3 increase in fine particulate matter (PM2.5) and particulate matter (PM10) and per 1 ppb increase in sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3). RESULTS: This study included 1,205,784 children aged six years old between 2013 and 2015. A positive association was found between the 48-month moving average PM2.5 (HR: 1.019; 95% CI: 1.012, 1.027), PM10 (HR: 1.009; 95% CI: 1.006, 1.013), SO2 (HR: 1.037; 95% CI: 1.018, 1.055), and O3 (HR: 1.006; 95% CI: 1.001, 1.010) exposure and PP in girls but not boys. CONCLUSIONS: This study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a risk factor that should be managed and reduced.

Effects of a Rice-Farming Simulation Video Game on Nature Relatedness, Nutritional Status, and Psychological State in Urban-Dwelling Adults During the COVID-19 Pandemic: Randomized Waitlist Controlled Trial.

BACKGROUND: During the COVID-19 pandemic, urban inhabitants faced significant challenges in maintaining connections with nature, adhering to nutritional guidelines, and managing mental well-being. OBJECTIVE: Recognizing the urgent need for innovative approaches, this study was designed to explore the potential benefits of a specific digital intervention, the rice-farming simulation game Sakuna: Of Rice and Ruin, for nature relatedness, nutritional behaviors, and psychological well-being. METHODS: A total of 66 adults without any prior major psychiatric disorders residing in an urban area were recruited for the study. They were randomly assigned to 2 groups through block randomization: the immediate intervention group (IIG; 34/66, 52%) and the waitlist group (32/66, 48%). Participants in the IIG were instructed to play the game for at least 4 days per week for 3 weeks, with each session lasting from 30 minutes to 3 hours. Assessments were performed at baseline, week 1, and week 3. The Nature Relatedness Scale (NR) and Nutrition Quotient Scale were used to evaluate nature relatedness and nutritional state, respectively. Furthermore, psychological state was assessed using the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF), Brief Fear of Negative Evaluation Scale, Social Avoidance and Distress Scale, Toronto Alexithymia Scale, State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression Scale Revised, and Korean Resilience Quotient. RESULTS: This study's results revealed significant time interactions between the IIG and waitlist group for both the total NR score (P=.001) and the score of the self subdomain of NR (P<.001), indicating an impact of the game on nature relatedness. No group×time interactions were found for the total Nutrition Quotient Scale and subdomain scores, although both groups showed increases from baseline. For psychological state, a significant group×time interaction was observed in the total WHOQOL-BREF score (P=.049), suggesting an impact of the game on quality of life. The psychological (P=.01), social (P=.003), and environmental (P=.04) subdomains of the WHOQOL-BREF showed only a significant time effect. Other psychological scales did not display any significant changes (all P>.05). CONCLUSIONS: Our findings suggest that the rice-farming game intervention might have positive effects on nature relatedness, nature-friendly dietary behaviors, quality of life, anxiety, depression, interpersonal relationships, and resilience among urban adults during the COVID-19 pandemic. The impact of pronature games in confined urban environments provides valuable evidence of how digital technologies can be used to enhance urban residents' affinity for nature and psychological well-being. This understanding can be extended in the future to other digital platforms, such as metaverses. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0007657; http://tinyurl.com/yck7zxp7.

Impact of molecular diagnostic tests on diagnostic and treatment delays in tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB). METHODS: We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays. RESULTS: A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI - 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54-4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82-53.37) and treatment initiation delay by 45.32 days (95% CI 30.27-60.37) in comparison to any culture DST methods. CONCLUSIONS: Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.

Who Dies after ICU Discharge? Retrospective Analysis of Prognostic Factors for In-Hospital Mortality of ICU Survivors.

We investigated the causes of inpatient death after intensive care unit (ICU) discharge and determined predictors of in-hospital mortality in Korea. Using medical ICU registry data of Seoul National University Hospital, we performed a retrospective cohort study involving patients who were discharged alive from their first ICU admission with at least 24 hours of ICU length of stay (LOS). From January 2011 to August 2013, 723 patients were admitted to ICU and 383 patients were included. The estimated in-hospital mortality rate was 11.7% (45/383). The most common cause of death was respiratory failure (n = 25, 56%) followed by sepsis and cancer progression; the causes of hospital death and ICU admission were the same in 64% of all deaths; sudden unexpected deaths comprised about one-fifth of all deaths. In order to predict in-hospital mortality among ICU survivors, multivariate analysis identified presence of solid tumor (odds ratio [OR], 4.06; 95% confidence interval [CI], 2.01-8.2; P < 0.001), hematologic disease (OR, 4.75; 95% CI, 1.51-14.96; P = 0.013), Sequential Organ Failure Assessment (SOFA) score upon ICU admission (OR, 1.08; 95% CI, 0.99-1.17; P = 0.075), and hemoglobin (Hb) level (OR, 0.67; 95% CI, 0.52-0.86; P = 0.001) and platelet count (Plt) (OR, 0.99; 95% CI, 0.99-1.00; P = 0.033) upon ICU discharge as significant factors. In conclusion, a significant proportion of in-hospital mortality is predictable and those who die in hospital after ICU discharge tend to be severely-ill, with comorbidities of hematologic disease and solid tumor, and anemic and thrombocytopenic upon ICU discharge.

Graphic analysis of flow-volume curves: a pilot study.

BACKGROUND: Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD). While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve. In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD. METHODS: Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25% peak expiratory flow (PEF) (0.25/0.75 V). For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts. RESULTS: Of all parameters, only RV/TLC significantly correlated with scores from St. George's Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037). Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = -0.618, p = 0.005) and Ao/PEF (r = -0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD. CONCLUSIONS: Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients.

Timely accessibility to healthcare resources and heatwave-related mortality in 7 major cities of South Korea: a two-stage approach with principal component analysis.

Background: Due to the ongoing effects of climate change, the incidence of heatwave-related mortality is rising globally. Improved allocation and utilization of healthcare resources could help alleviate this issue. This study aimed to identify healthcare resource factors associated with heatwave-related mortality in seven major cities of South Korea. Methods: We analyzed daily time-series data on mean temperature and all-cause mortality from 2011 to 2019. Using principal component analysis (PCA), we clustered district-level healthcare resource indicators into three principal components (PCs). To estimate district-specific heatwave-mortality risk, we used a distributed lag model with a quasi-Poisson distribution. Furthermore, a meta-regression was performed to examine the association between healthcare resources and heatwave-mortality risk. Findings: A total of 310,363 deaths were analyzed in 74 districts. The lag-cumulative heatwave-related mortality (RRs) ranged from 1.12 (95% confidence interval [CI]: 1.07, 1.17) to 1.21 (95% CI 1.05, 1.38), depending on the definitions used for heatwaves. Of the three PCs for healthcare resources (PC1: pre-hospital emergency medical service, PC2: hospital resources, PC3: timely access), timely access was associated with reduced risk of heatwave-related mortality, particularly among the elderly. Specifically, timely access to any emergency room (ER) exhibited the strongest association with lower heatwave-related mortality. Interpretation: Our findings suggest that timely access to any ER is more effective in reducing heatwave-related mortality risk than access to higher-level healthcare facilities, especially among the elderly. Therefore, healthcare resource factors and ER accessibility should be prioritized when identifying vulnerable populations for heatwaves, along with known individual and socio-demographic factors. Funding: This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (2022-12-303), the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C2092353) and the MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea.

Successfully treated Escherichia coli-induced emphysematous cyst infection with combination of intravenous antibiotics and intracystic antibiotics irrigation in a patient with autosomal dominant polycystic kidney disease.

A 62-yr-old woman with an autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital for further evaluation of intermittent fever, nausea and left flank discomfort. The computed tomography (CT) scan revealed a gas-forming, infectious cyst of approximately 8.1 cm in size in left kidney lower pole. Escherichia coli was identified from the cyst fluid culture examination. Her symptoms improved only after the concomitant use of intravenous ciprofloxacin and an intracystic irrigation of ciprofloxacin through a percutaneous cystostomy drainage. Our case presents the successfully treated emphysematous cyst infection with combination of intravenous antibiotics and intracystic antibiotic therapy instead of surgical management.

Proteasome Inhibitor-Induced IκB/NF-κB Activation is Mediated by Nrf2-Dependent Light Chain 3B Induction in Lung Cancer Cells.

IκB, a cytoplasmic inhibitor of nuclear factor-κB (NF-κB), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces IκBα degradation via an alternative pathway, lysosome, which results in NF-κB activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced IκBα degradation is necessary. Here, we demonstrated that PI upregulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for IκBα degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced IκBα degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent IκBα degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the IκB/NF-κB pathway, which attenuates the anti-tumor efficacy of PIs.

What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is reported that it was also effective in reducing intubation in AECOPD with hypercapnic respiratory failure. Despite the apparent need for more supporting evidence, efforts to improve efficacy of NIV have continued unabated. It is anticipated that these efforts will, over time, serve toprogressively decrease the risk of intubation and invasive mechanical ventilation in cases of AECOPD with acute respiratory failure.

Efficacy of Treatment for Latent Tuberculosis in Patients Undergoing Treatment with a Tumor Necrosis Factor Antagonist.

RATIONALE: Current guidelines recommend that all patients undergoing treatment with a tumor necrosis factor-α antagonist should receive screening for latent tuberculosis and appropriate treatment before initiating the inhibitor. However, no well-designed study has shown the efficacy of treating these patients for latent tuberculosis. OBJECTIVES: To compare the risk of active tuberculosis between tumor necrosis factor antagonist users who have received treatment for latent tuberculosis with those who have not. METHODS: We performed a national-level retrospective cohort study in South Korea, a country with an intermediate tuberculosis burden, by analyzing claims recorded between January 1, 2011, and December 31, 2013, in an obligatory national health insurance claims database. The primary outcome, the incidence of active tuberculosis, was measured as the occurrence of an International Statistical Classification of Diseases and Related Health Problems, 10th edition, diagnosis of tuberculosis and prescription of at least two antituberculosis drugs at least twice within 90 days. RESULTS: Among 10,863 eligible new tumor necrosis factor antagonist users, 2,461 (22.7%) received treatment for latent tuberculosis. The incidence rate of tuberculosis per 1,000 person-years was lower for the treated group (4.07; 95% confidence interval [CI], 1.55-6.60) than for the untreated group (12.34; 95% CI, 9.96-14.72). The risk for tuberculosis was significantly reduced by preventive chemotherapy (incidence rate ratio, 0.33; 95% CI, 0.17-0.63). CONCLUSIONS: Treatment for latent tuberculosis was highly effective in preventing the development of tuberculosis among tumor necrosis factor antagonist users.

Pulmonary Lymphoma Misdiagnosed as Pneumonia.

Pulmonary lymphoma is a very rare cause of lung tumors which occurs in less than one percent of primary malignant lung tumors. When seemingly pneumonia does not respond to treatment, the possibility of malignant lymphoma should always be considered. Here, we report two cases of pulmonary lymphoma misdiagnosed as pneumonia.

Acute Respiratory Failure Caused by Hepatopulmonary Fistula in a Patient with Hepatocellular Carcinoma.

A 59-year-old man presented with acute dyspnea following sudden productive cough and expectoration of a full cup of "blood-tinged" sputum. He had been diagnosed with hepatitis B virus-related hepatocellular carcinoma and had received transarterial chemoembolization 5 years ago for a 20-cm hepatic mass; he denied any history of hematemesis and the last esophagogastroduodenoscopy from a year ago showed absence of varix. Chest computed tomography (CT) with angiography showed new appearance of right basal lung consolidation but no bleeding focus. Despite the use of systemic antibiotics, the patient developed respiratory failure on day 7 of hospitalization. After intubation, a massive amount of brown sputum with anchovy-paste-like consistency was suctioned via the endotracheal tube. Bronchoscopic toileting was performed and the patient was extubated. In the ward, he continued to expectorate the brown sputum. On day 25 of hospitalization, a repeat CT scan showed simultaneous disappearance of the pneumonic consolidation and the necrotic fluid within the hepatic mass, suggesting the presence of a fistula. He has continued to receive systemic antibiotics, sorafenib, and entecavir, and follow up by respiratory and hepato-oncology specialists.

Conversion of aspergilloma to chronic necrotizing pulmonary aspergillosis following treatment with sunitinib: A case report.

Semi-invasive or invasive aspergillosis occurring following chemotherapy with sunitinib is a rare condition with unknown incidence and prognosis. Here, we report a case involving a 59-year-old male who had a history of underlying stable aspergilloma and was newly diagnosed with metastatic renal cell carcinoma. Following surgical resection for renal cell carcinoma and adjuvant chemotherapy with sunitinib for 8 months, the patient presented with hemoptysis. Chest computed tomography revealed an increased soft tissue mass and air crescent sign of the underlying aspergilloma, combined with consolidation and bronchial artery hypertrophy around the lesion. The patient underwent bronchoscopy with a biopsy of the lesion and was eventually diagnosed with chronic necrotizing pulmonary aspergillosis, which had progressed from the underlying stable aspergilloma. This case highlights the fact that clinicians should be aware of the risk of opportunistic conversion from stable aspergilloma to invasive fungal infections in patients undergoing sunitinib treatment.

Metastatic testicular tumor presenting as a scrotal hydrocele: An initial manifestation of pancreatic adenocarcinoma.

Metastatic pancreatic adenocarcinoma involving the testis is a rare condition with a poor prognosis. The current study describes the case of a 69-year-old male who presented with a painful swelling of the left scrotum. Scrotal ultrasonography revealed hydroceles in the scrotal sacs, with the left one being larger in size. The patient underwent left hydrocelectomy and was eventually diagnosed with metastatic adenocarcinoma. Abdominal computed tomography, which was performed to detect the primary cancer, showed a pancreatic tail carcinoma with liver and multiple lymph node metastases, and peritoneal carcinomatosis. The patient received gemcitabine-based chemotherapy but resulted in progressive disease. This case shows that in a patient in whom a primary testicular tumor is unusual due to their age, a testicular mass or hydrocele should be a suspect for possible metastatic disease.