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AIMS: To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. RESULTS: A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. CONCLUSIONS: Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period.
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Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions: Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.
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Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a conductive polymer, has gained popularity as the channel layer in organic electrochemical transistors (OECTs) due to its high conductivity and straightforward processing. However, difficulties arise in controlling its conductivity through gate voltage, presenting a challenge. To address this issue, aromatic amidine base, diazabicyclo[4.3.0]non-5-ene (DBN), is used to stabilize the doping state of the PEDOT chain through a reliable chemical de-doping process. Furthermore, the addition of the proton-penetrable material Nafion to the PEDOT:PSS channel layer induces phase separation between the substances. By utilizing a solution containing both PEDOT:PSS and Nafion as the channel layer of OECTs, the efficiency of ion movement into the channel from the electrolyte is enhanced, resulting in improved OECT performance. The inclusion of Nafion in the OECTs' channel layer modifies ion movement dynamics, allowing for the adjustment of synaptic properties such as pulse-paired facilitation, memory level, short-term plasticity, and long-term plasticity. This research aims to introduce new possibilities in the field of neuromorphic computing and contribute to biomimetic technology through the enhancement of electronic component performance.
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BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
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Atorvastatina , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Dislipidemias , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Humanos , Atorvastatina/uso terapéutico , Atorvastatina/administración & dosificación , Metformina/uso terapéutico , Metformina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Anciano , LDL-Colesterol/sangre , Resultado del Tratamiento , AdultoRESUMEN
While the shape-dependent quantum confinement (QC) effect in anisotropic semiconductor nanocrystals has been extensively studied, the QC in facet-specified polyhedral quantum dots (QDs) remains underexplored. Recently, tetrahedral nanocrystals have gained prominence in III-V nanocrystal synthesis. In our study, we successfully synthesized well-faceted tetrahedral InAs QDs with a first excitonic absorption extending up to 1700 nm. We observed an unconventional sizing curve, indicating weaker confinement than for equivalently volumed spherical QDs. The (111) surface states of InAs QDs persist at the conduction band minimum state even after ligand passivation with a significantly reduced band gap, which places tetrahedral QDs at lower energies in the sizing curve. Consequently, films composed of tetrahedral QDs demonstrate an extended photoresponse into the short-wave infrared region, compared to isovolume spherical QD films.
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BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.
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Antituberculosos , Estado Prediabético , Tuberculosis Pulmonar , Humanos , Tuberculosis Pulmonar/mortalidad , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Antituberculosos/uso terapéutico , Resultado del Tratamiento , Estudios Prospectivos , Adulto , República de Corea/epidemiología , Estado Prediabético/epidemiología , Estado Prediabético/complicaciones , Factores de Riesgo , Sistema de Registros , Diabetes Mellitus/epidemiología , Anciano , Complicaciones de la DiabetesRESUMEN
Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Fibrosis Pulmonar Idiopática , Neoplasias Pulmonares , Humanos , Femenino , Masculino , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/diagnóstico , Programas Nacionales de Salud , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
The tobacco emission condensate, henceforth referred to as "tobacco condensate," plays a critical role in assessing the toxicity of tobacco products. This condensate, derived from tobacco emissions, provides an optimized liquid concentrate for storage and concentration control. Thus, the validation of its constituents is vital for toxicity assessments. This study used tobacco condensates from 3R4F cigarettes and three heated tobacco product (HTP) variants to quantify and contrast organic compounds (OCs) therein. The hazard index (HI) for tobacco emissions and condensates was determined to ascertain the assessment validity. The total particulate matter (TPM) for 3R4F registered at 17,667 µg cig-1, with its total OC (TOC) at 3777 µg cig-1. HTPs' TPM and TOC were 9342 ± 1918 µg cig-1 and 5258 ± 593 µg stick-1, respectively. 3R4F's heightened TPM likely arises from tar, while HTPs' OC concentrations are influenced by vegetable glycerin (2236-2688 µg stick-1) and propylene glycol (589-610 µg stick-1). During the condensation process, a substantial proportion of OCs in 3R4F smoke underwent significant concentration decreases, in contrast to HTPs, where fewer than half of the examined OCs exhibited notable concentration declines. The HI for tobacco emissions exhibited a marginally higher value compared to tobacco condensate, with variations ranging from 7.92% (HTPs) to 18.6% (3R4F), denoting a minimal differential. These observations emphasize the importance of accurate OC recovery techniques to maintain the validity and reliability of toxicity assessments based on tobacco condensates. This study not only deepens the comprehension of chemical behaviors in tobacco products but also establishes a novel benchmark for their toxicity evaluation, with profound implications for public health strategies and consumer protection.
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Productos de Tabaco , Aerosoles/análisis , Material Particulado/toxicidad , Material Particulado/química , Reproducibilidad de los Resultados , Humo , Productos de Tabaco/análisisRESUMEN
BACKGROUND: Telmisartan exhibits superior efficacy in controlling 24-h blood pressure (BP) compared with other angiotensin receptor blockers (ARBs). However, data on its cardiovascular effects in patients with hypertension are limited. This study aimed to evaluate the cardiovascular outcomes in patients taking telmisartan compared to those taking other ARBs. METHODS: This multicenter retrospective study used data from the Korea University Medical Center database, built from electronic health records. A total of 19,247 patients taking two or more antihypertensive medications were identified. Patients prescribed telmisartan (telmisartan users) were compared with those prescribed an ARB other than telmisartan (other ARB users). The primary outcome was major adverse cardiac events (MACE), a composite of cardiovascular death, myocardial infarction, stroke, and hospitalizations due to heart failure. The adjusted outcomes were compared using 1:1 propensity score (PS) matching. RESULTS: Overall, 3,437 (17.9%) patients were telmisartan users. These patients were more likely to be younger and male and less likely to have a history of chronic kidney disease, dialysis, or heart failure. In the PS-matched cohort, BP control was similar in both groups; however, telmisartan users exhibited significantly lower visit-to-visit BP variability. The adjusted 3-year MACE rate was similar between telmisartan users (4.6%) and other ARB users (4.7%, log-rank Pâ =â 0.75), with comparable safety profiles. CONCLUSIONS: In real-world practice, telmisartan showed cardiovascular outcomes similar to those of other ARBs in patients with hypertension taking two or more antihypertensive drugs.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II , Registros Electrónicos de Salud , Hipertensión , Telmisartán , Humanos , Telmisartán/uso terapéutico , Masculino , Femenino , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/mortalidad , Hipertensión/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , República de Corea/epidemiología , Resultado del Tratamiento , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Factores de Tiempo , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Factores de RiesgoRESUMEN
Near-infrared (NIR) light-responsive hydrogels have emerged as a highly promising strategy for effective anticancer therapy owing to the remotely controlled release of chemotherapeutic molecules with minimal invasive manner. In this study, novel NIR-responsive hydrogels were developed from reactive oxygen species (ROS)-cleavable thioketal cross-linkers which possessed terminal tetrazine groups to undergo a bio-orthogonal inverse electron demand Diels Alder click reaction with norbornene modified carboxymethyl cellulose. The hydrogels were rapidly formed under physiological conditions and generated N2 gas as a by-product, which led to the formation of porous structures within the hydrogel networks. A NIR dye, indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) were co-encapsulated in the porous network of the hydrogels. Upon NIR-irradiation, the hydrogels showed spatiotemporal release of encapsulated DOX (>96 %) owing to the cleavage of thioketal bonds by interacting with ROS generated from ICG, whereas minimal release of encapsulated DOX (<25 %) was observed in the absence of NIR-light. The in vitro cytotoxicity results revealed that the hydrogels were highly cytocompatible and did not induce any toxic effect on the HEK-293 cells. In contrast, the DOX + ICG-encapsulated hydrogels enhanced the chemotherapeutic effect and effectively inhibited the proliferation of Hela cancer cells when irradiated with NIR-light.
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Carboximetilcelulosa de Sodio , Hidrogeles , Humanos , Hidrogeles/farmacología , Hidrogeles/química , Especies Reactivas de Oxígeno , Células HEK293 , Sistemas de Liberación de Medicamentos/métodos , Doxorrubicina/química , Liberación de FármacosRESUMEN
High-performance semiconductor materials and devices are needed to supply the growing energy and computing demand. Organic semiconductors (OSCs) are attractive options for opto-electronic devices, due to their low cost, extensive tunability, easy fabrication, and flexibility. Semiconducting single-walled carbon nanotubes (s-SWCNTs) have been extensively studied due to their high carrier mobility, stability and opto-electronic tunability. Although molecular charge transfer doping affords widely tunable carrier density and conductivity in s-SWCNTs (and OSCs in general), a pervasive challenge for such systems is reliable measurement of charge carrier density and mobility. In this work we demonstrate a direct quantification of charge carrier density, and by extension carrier mobility, in chemically doped s-SWCNTs by a nuclear magnetic resonance approach. The experimental results are verified by a phase-space filling doping model, and we suggest this approach should be broadly applicable for OSCs. Our results show that hole mobility in doped s-SWCNT networks increases with increasing charge carrier density, a finding that is contrary to that expected for mobility limited by ionized impurity scattering. We discuss the implications of this important finding for additional tunability and applicability of s-SWCNT and OSC devices.
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Inspired by traditional shaduf technology in the irrigation field, we fabricated a superhydrophobic stainless steel mesh bucket by layering polystyrene and SiO2 nanoparticles through a facile dip coating technique for effective oil-water separation. The superhydrophobic steel mesh bucket could effectively lift oil as well as microplastic pollutants from the water surface. The water contact angle of a two-layered polystyrene-silica coating was 158.5° ± 2°, while the oil contact angle was nearly 0°. The oil-water separation performance of superhydrophobic mesh was tested using several kinds of oil. The separation efficiency achieved for low viscous oil was 99.33 %, while 86.66 % efficiency was recorded for high viscous oil. The superhydrophobic mesh showed high durability against mechanical tests including bending, folding, twisting, adhesive tape tearing (25 cycles), and sandpaper abrasion (20 cycles). The mesh presented admirable thermal and chemical durability. The present superhydrophobic steel mesh bucket is a suitable candidate for large-scale application.
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Plásticos , Acero Inoxidable , Poliestirenos , Dióxido de Silicio , Acero , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.
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Fumar Cigarrillos , Enfermedades Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Ratas , Animales , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedades Pulmonares/patología , Líquido del Lavado BronquioalveolarRESUMEN
OBJECTIVE: In the growing population of older patients with hypertension, limited evidence supports an association between lowering systolic blood pressure (SBP) and decreased adverse events. We aimed to investigate cardiovascular outcomes according to on-treatment SBP in older hypertensive patients. METHODS: This multicenter, retrospective study used data from the Korea University Medical Center database built on electronic health records from 2017 to 2022. Patients initiated on at least two antihypertensive drugs in combination were followed for three years. The patients were grouped by average on-treatment SBP in 10-mmHg increments from <110 to 160âmmHg or more. The primary outcome was a composite of all-cause death, myocardial infarction, stroke, and hospitalization due to heart failure. RESULTS: A total of 6427 patients aged ≥75âyears (mean age, 80âyears) were identified. The incidence of the primary outcome was lowest in individuals with an SBP of 120-129âmmHg (14.0%, P â<â0.001), and the adjusted hazard ratio for the primary outcome showed a J-shaped relationship with on-treatment SBP. Achieving an SBP of 120-129âmmHg showed acceptable safety profiles, including electrolyte imbalance, acute kidney injury, new-onset atrial fibrillation, and new-onset dementia or Alzheimer's disease when compared to the group with SBP of 130-139âmmHg. CONCLUSIONS: An average on-treatment SBP of less than 130âmmHg was associated with improved outcomes in older hypertensive patients without raising safety concerns. These findings support the target SBP of 130âmmHg in older patients, if tolerated.
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Hipertensión , Infarto del Miocardio , Anciano , Anciano de 80 o más Años , Humanos , Antihipertensivos , Presión Sanguínea/fisiología , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/epidemiología , Estudios RetrospectivosRESUMEN
Novel chemically cross-linked hydrogels derived from carboxymethyl cellulose (CMC) and alginate (Alg) were prepared through the utilization of the norbornene (Nb)-methyl tetrazine (mTz) click reaction. The hydrogels were designed to generate reactive oxygen species (ROS) from an NIR dye, indocyanine green (ICG), for combined photothermal and photodynamic therapy (PTT/PDT). The cross-linking reaction between Nb and mTz moieties occurred via an inverse electron-demand Diels-Alder chemistry under physiological conditions avoiding the need for a catalyst. The resulting hydrogels exhibited viscoelastic properties (G' ~ 492-270 Pa) and high porosity. The hydrogels were found to be injectable with tunable mechanical characteristics. The ROS production from the ICG-encapsulated hydrogels was confirmed by DPBF assays, indicating a photodynamic effect (with NIR irradiation at 1-2 W for 5-15 min). The temperature of the ICG-loaded hydrogels also increased upon the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility assessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Furthermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells after NIR exposure.
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Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic therapy. The aim of this study was to examine the prevalence of CKD and prescription status of pirfenidone in IPF patients and to analyze its impact on mortality. Data from the Korean National Health Insurance Service (NHIS) database between October 2015 and September 2021 were used. IPF and CKD were defined based on both International Classification of Diseases 10th Revision (ICD-10) codes and Rare Intractable Disease (RID) codes. The risk of mortality was assessed based on accompanying CKD with or without antifibrotic therapy. Among 5038 patients with IPF, 8.4% had comorbid CKD and 83.3% with CKD did not receive renal replacement therapy (RRT). Patients with IPF and CKD were older, predominantly male, and had more frequent comorbidities such as cardiovascular disease and diabetes mellitus than subjects without CKD. Pirfenidone was prescribed to 105 (24.6%) of 426 CKD patients, and 89.5% of them did not receive RRT. Pirfenidone was also prescribed to 775 (16.8%) of 4612 IPF patients without CKD. Significant difference was not found in all-cause mortality between the IPF patients with or without CKD regardless of pirfenidone treatment. The use of antifibrotics in IPF patients with CKD is limited due to CKD severity; however, evidence is lacking. Mortality did not increase with accompanying CKD regardless of antifibrotic use. Further research on IPF and CKD is needed.
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Fibrosis Pulmonar Idiopática , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/epidemiología , Piridonas/farmacología , Comorbilidad , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/inducido químicamente , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: The prognostic implications of septic cardiomyopathy have not been clearly demonstrated. We evaluated serial changes in left ventricular (LV) and right ventricular (RV) function in patients with septic shock and their prognostic value on 7-day and in-hospital mortality. METHODS: Transthoracic echocardiography was performed within 48 hours of the diagnosis of septic shock and 7 days after the initial evaluation. In addition to traditional echocardiographic parameters, LV and RV function was evaluated using global longitudinal strain (GLS), and tricuspid annular plane systolic excursion (TAPSE). RESULTS: A total of 162 patients (men, 83, 51.5%; 70.7±13.4 years; Acute Physiology and Chronic Health Evaluation [APACHE] II, 30.6±9.2) were enrolled. Initial GLS and TAPSE were -14.9±5.2% and 16.9±5.5 mm, and improved in the follow-up evaluation (GLS, -17.6±4.9%; TAPSE, 19.2±5.4 mm). Seven-day and in-hospital mortality were 24 (14.9%) and 64 (39.8%). Seven-day mortality was significantly associated with initial GLS >-16% (odds ratio [OR], 14.066, 95% confidence interval [CI], 1.178-167.969, p=0.037) and APACHE II score (OR, 1.196, 95% CI, 1.047-1.365, p=0.008). The in-hospital mortality of 7-day survivors was associated with follow-up TAPSE <16 mm (OR, 10.109, 95% CI, 1.640-62.322, p=0.013) and Sequential Organ Failure Assessment score (OR, 1.340, 95% CI, 1.078-1.667, p=0.008). GLS was not associated with in-hospital mortality of 7-day survivors. CONCLUSIONS: Fluctuation of both ventricular function was common in septic shock. Seven-day mortality of patients with septic shock was related to GLS, whereas in-hospital mortality of 7-day survivors was related to TAPSE, not to GLS.
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A method of preparing heated tobacco product aerosol condensate (HTPAC) was developed to expedite HTP toxicity evaluation, and the effectiveness was assessed. To prepare HTPAC, HTP aerosol was generated and collected using a Cambridge filter (particulate phase) and Dulbecco's phosphate buffered saline (DPBS; gaseous phase). The aerosol collected on the Cambridge filter was extracted using methanol, which was thereafter removed by nitrogen purging. The HTP aerosol residue was mixed with DPBS loaded with the collected HTP vapor, ultimately yielding HTPAC. Nicotine and formaldehyde, key harmful compounds in HTP aerosol, were detected in HTPAC (901 ± 224 and 22.2 ± 3.90 µg stick-1, respectively, comparable to those in HTP aerosol (990-1350 (nicotine) and 2.33-21.9 µg stick-1 (formaldehyde)). Propylene glycol and vegetable glycerin, which influence the amount of HTP aerosol, were detected at similar levels in HTPAC and HTP aerosol (propylene glycol = 616 ± 57.1 (HTPAC) and 320-630 µg stick-1 (aerosol) and vegetable glycerin = 2418 ± 224 (HTPAC) and 1667-4000 µg stick-1 (aerosol)). Known components of HTP aerosol (hydroxyacetone, acetic acid, triacetin, and 2-furanmethanol) were also detected in HTPAC. Consequently, HTPAC offers an effective method for concentrating harmful compounds found in HTP aerosols. This, in turn, facilitates comprehensive toxicity assessments, paving the way for guidelines ensuring the safe utilization of HTP.
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Glicerol , Productos de Tabaco , Nicotina , Aerosoles , Formaldehído , Gases , PropilenglicolRESUMEN
Background: Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT. Methods: A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated. Results: Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5â g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders. Conclusions: Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.
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OBJECTIVE: Compared with placebo, olmesartan has been linked to numerical imbalances in cardiovascular mortality. There is a paucity of contemporary real-world evidence on this agent for different study populations. This study investigated the clinical outcomes of olmesartan and other antihypertensives in patients with advanced hypertension. METHODS: This multicenter retrospective study used data from the Korea University Medical Center database, built from electronic health records. Patients prescribed at least two antihypertensive medications as a combined therapy were followed-up for 3âyears. The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for heart failure. Adjusted outcomes were compared using propensity score (PS) matching. RESULTS: Among 24 806 patients, 4050 (16.3%) were olmesartan users between January 2017 and December 2018. The average patient age was 64âyears, 45% were women, and 41% had diabetes. Olmesartan users were younger and less likely to have diabetes mellitus or chronic kidney disease. In PS-matched cohort, the 3-year cumulative incidences of the primary outcome were similar between the two groups ( P â=â0.91). The cumulative incidence of MI at 3âyears was 1.4% in olmesartan users (4.8 per 1000 person-years) and 1.5% in active comparators (5.2 per 1000 person-years; P â=â0.74). Olmesartan also showed similar safety profiles, including acute kidney injury and newly started dialysis. CONCLUSIONS: In real-world practice, olmesartan use in combination therapy resulted in similar cardiovascular outcomes when compared with those of active comparators, and our findings did not show any conclusive evidence that olmesartan is harmful in patients with hypertension.