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1.
Lung Cancer ; 190: 107509, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38432025

RESUMEN

OBJECTIVE: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS). RESULTS: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively. CONCLUSION: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Exantema , Neoplasias Pulmonares , Morfolinas , Pirazoles , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Estudios de Seguimiento , Parestesia/inducido químicamente , Parestesia/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Receptores ErbB/genética , Diarrea/inducido químicamente , Exantema/inducido químicamente , Prurito/tratamiento farmacológico , Mutación
2.
Cell Rep ; 42(5): 112409, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37074911

RESUMEN

Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. Dysregulations of glycoproteins have been shown to associate with ccRCC. However, the molecular mechanism has not been well characterized. Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. Additionally, inter-tumor heterogeneity and cross-correlation between glycosylation and phosphorylation are observed. The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community.


Asunto(s)
Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Proteómica , Neoplasias Renales/metabolismo , Genómica , Fosforilación
3.
Cancer Cell ; 41(1): 139-163.e17, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36563681

RESUMEN

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Proteogenómica , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Resultado del Tratamiento , Pronóstico , Biomarcadores de Tumor/genética
4.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-968584

RESUMEN

Purpose@#This study explored the potential feasibility of cell-free DNA (cfDNA) in monitoring treatment response through the measurement of chromosomal instabilities using I-scores in the context of radiation therapy (RT) for other solid tumors. @*Materials and Methods@#This study enrolled 23 patients treated with RT for lung, esophageal, and head and neck cancer. Serial cfDNA monitoring was performed before RT, 1 week after RT, and 1 month after RT. Low-depth whole-genome sequencing was done using Nano kit and NextSeq 500 (Illumina Inc.). To measure the extent of genome-wide copy number instability, I-score was calculated. @*Results@#Pretreatment I-score was elevated to more than 5.09 in 17 patients (73.9%). There was a significant positive correlation between the gross tumor volume and the baseline I-score (Spearman rho = 0.419, p = 0.047). The median I-scores at baseline, post-RT 1 week (P1W), and post-RT 1 month (P1M) were 5.27, 5.13, and 4.79, respectively. The I-score at P1M was significantly lower than that at baseline (p = 0.002), while the difference between baseline and P1W was not significant (p = 0.244). @*Conclusion@#We have shown the feasibility of cfDNA I-score to detect minimal residual disease after RT in patients with lung cancer, esophageal cancer, and head and neck cancer. Additional studies are ongoing to optimize the measurement and analysis of I-scores to predict the radiation response in cancer patients.

5.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1003034

RESUMEN

Background/Aims@#Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. Further studies on factors other than Helicobacter pylori infection are needed. This systematic review and meta-analysis aimed to evaluate risk factors for metachronous recurrence of endoscopically resected gastric cancer. @*Methods@#We searched medical literature published by February 2023 and identified patients with MGC after endoscopic resection for gastric cancer. The occurrence of MGC and the presence of intestinal metaplasia (IM), severe atrophic gastritis (AG), and H. pylori infection were quantitatively analyzed. @*Results@#We identified 2,755 patients from nine cohort studies who underwent endoscopic resection for gastric cancer by 2018. Those with severe AG or presence of IM had a significantly higher incidence of MGC than those without (RR 2.00, 95% CI 1.35–2.98, I2 = 52% for severe atrophy on antrum; RR 7.08, 95% CI 3.63–13.80, I2 = 0% for antral IM). Absolute risk difference of MGC occurrence was 7.1% in those with severe AG and 9.2% in those with IM. The difference in incidence rate per 1,000 person-years was 17.5 person-years for those with severe AG and 24.7 person-years for those with IM. However, H. pylori eradication did not significantly affect the occurrence of MGC (RR 1.18, 95% CI 0.88–1.59, I2 = 10%). @*Conclusions@#Gastric cancer patients with severe AG or presence of IM had a 2.0-fold or 7.0-fold higher risk of MGC occurrence after endoscopic resection than those without, respectively. They need more stringent follow-up to monitor MGC occurrences (CRD42023410940).

6.
Artículo en Coreano | WPRIM (Pacífico Occidental) | ID: wpr-1003024

RESUMEN

Owing to their superior pharmacokinetic and pharmacodynamic profiles, potassium-competitive acid blockers (P-CABs) score over proton pump inhibitors (PPIs) in the treatment of gastric acid-related disorders and may provide clinical benefit in the management of these conditions. Previous studies have compared P-CABs with PPIs for treatment of gastric acid-related disorders, and current data show that P-CABs are non-inferior to PPIs in the treatment of erosive esophagitis and as maintenance therapy. P-CABs are useful for effective healing and as maintenance medications in patients with severe esophagitis. These drugs also aid with healing of peptic ulcers and artificial ulcers secondary to gastric endoscopic submucosal dissection (ESD). Few studies have discussed prevention of delayed ulcer bleeding after gastric ESD and ulcers associated with long-term nonsteroidal anti-inflammatory drug administration. Well-controlled, large-scale prospective studies are warranted in future to compare P-CABs with PPIs.

7.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1002994

RESUMEN

Objectives@#Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) and CD133 are recognized stem cell markers of gastric cancer. Extensive research has examined the significance of these markers in different types of cancers and their impact on prognoses, linking them to unfavorable clinical outcomes in various tumors. However, the prognostic value of these markers for gastric cancer remains unclear. We investigated the expression of ABCG2 and CD133 and their relationship with clinical outcomes in gastric cancer. @*Methods@#ABCG2 and CD133 expression levels were analyzed, using immunohistochemistry and tissue microarrays, in tumor samples from 459 patients who underwent surgical resections due to gastric cancer. ABCG2 and CD133 expression levels were defined by intensity and dichotomized as medians. The associations among the expression levels of these markers, disease severity, and patient survival were also determined. @*Results@#In the 411 patients for whom we analyzed the expression levels of these markers, 74.9% and 80.5% were found to have high levels of ABCG2 and CD133, respectively. High expression levels of ABCG2 and CD133 were more commonly observed in well-differentiated (p<0.001 and p=0.004, respectively) and intestinal lesions (p<0.001 and p=0.002, respectively). High ABCG2 expression correlated with improved survival outcomes, whereas high CD133 expression was associated with poorer outcomes. Cox regression analysis confirmed that stage, high ABCG2 (overall survival [OS]: hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41–0.91; p=0.015; recurrencefree survival [RFS]: HR, 0.55; 95% CI, 0.34–0.88; p=0.012), and CD133 expression (OS: HR, 1.59; 95% CI, 1.00–2.51; p=0.049; RFS: HR, 2.29; 95% CI, 1.21–4.34; p=0.011) were predictors of survival. A subgroup analysis indicated that ABCG2 expression was also associated with an improved RFS rate in patients who received systemic chemotherapy. @*Conclusions@#High ABCG2 expression and low CD133 expression in tumors correlated with improved survival outcomes in post-resection patients with gastric cancer, suggesting their potential utility as prognostic biomarkers.

8.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1002920

RESUMEN

Benign mediastinal cysts are challenging to diagnose. Although Endoscopic Ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) can accurately diagnose mediastinal foregut cysts, little is known about their complications. This paper reports a rare case in which EUS-FNA performed on mediastinal hemangioma resulted in an aortic hematoma. A 29-year-old female patient was commissioned for EUS of an asymptomatic accidental mediastinal lesion. Chest CT revealed a 4.9×2.9×10.1 cm thin-walled cystic mass in the posterior mediastinum. EUS revealed a large, anechoic cystic lesion with a regular thin wall with negative Doppler. EUS-guided FNA was performed using a single-use 19-gauge aspiration needle (EZ Shot 3; Olympus, Tokyo, Japan), and approximately 70 cc of serous pinkish fluid was aspirated. The patient was in a stable condition with no signs of acute complication. One day after EUS-FNA, thoracoscopic resection for mediastinal mass was conducted. The purple and multi-loculated large cyst was removed. Upon removal, however, an aortic hematoma caused by a focal descending aortic wall injury was observed. After a few days of close observation, the patient was discharged upon stable 3D aorta angio CT findings. This paper reports a rare and severe complication of EUS-FNA, in which an aspiration needle caused a direct injury to the aorta. The injection must be performed carefully to avoid damaging the adjacent organs or digestive tract walls.

9.
Artículo en Coreano | WPRIM (Pacífico Occidental) | ID: wpr-1001800

RESUMEN

Purpose@#To introduce an intuitive method for measuring conjunctival microvascular blood flow velocity by imaging bulbar conjunctival microvessels using a slit-lamp biomicroscope equipped with a zoom lens and an ultra-high-speed camera. @*Methods@#After obtaining consent from 10 patients (1 male, 9 females) who visited Yeouido St. Mary’s Hospital from August 21, 2020, to June 12, 2021, the patients were examined under a slit lamp microscope equipped with an ultra-high-speed camera and zoom lens. The blood flow in the conjunctival microvessels was photographed. The captured images were analyzed with ImageJ software to measure the blood flow velocity in the conjunctival microvessels, and we investigated whether the blood flow velocity correlated with the vessel diameter and age. @*Results@#The median age of the subjects was 49.0 years. The mean conjunctival blood flow velocity in 53 microvessels was 0.786 ± 0.468 mm/s. The median conjunctival microvascular diameter was 7.06 μm (interquartile range 5.84 to 9.23 μm). The conjunctival microvascular diameter and blood flow velocity were not significantly correlated (Spearman’s p = 0.177), and the subjects’ age and conjunctival microvascular blood flow velocity were also not correlated (Spearman’s p = 0.669). @*Conclusions@#In this study, the blood flow velocity in the bulbar conjunctival microvessels could be measured easily by means of image analysis using a slit-lamp microscope equipped with an ultra-high-speed camera with a zoom lens.

10.
Artículo en Coreano | WPRIM (Pacífico Occidental) | ID: wpr-1001762

RESUMEN

Purpose@#This study introduces a new machine learning-based auto-merge program (HydraVersion) that automatically combines multiple ocular photographs into single nine-directional ocular photographs. We compared the accuracy and time required to generate ocular photographs between HydraVersion and PowerPoint. @*Methods@#This was a retrospective study of 2,524 sets of 250 nine-directional ocular photographs (134 patients) between March 2016 and June 2022. The test dataset comprised 74 sets of 728 photographs (38 patients). We measured the time taken to generate nine-directional ocular photographs using HydraVersion and PowerPoint, and compared their accuracy. @*Results@#HydraVersion correctly combined 71 (95.95%) of the 74 sets of nine-directional ocular photographs. The average working time for HydraVersion and PowerPoint was 2.40 ± 0.43 and 255.9 ± 26.7 seconds, respectively; HydraVersion was significantly faster than PowerPoint (p < 0.001). @*Conclusions@#Strabismus and neuro-ophthalmology centers are often unable to combine and store photographs, except those of clinically significant cases, because of a lack of time and manpower. This study demonstrated that HydraVersion may facilitate treatment and research because it can quickly and conveniently generate nine-directional ocular photographs.

11.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1001539

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse organ system disabilities, predominantly affecting young females. The clinical manifestations of SLE encompass various organs, including the kidney, cardiovascular system, and central nervous system. Young females with SLE experience higher mortality rates than the general population, making it imperative to gain insights into the disease patterns and associated factors. The current review examines the epidemiological studies to analyze the prevalence, incidence, and mortality trends of SLE in Korea and compares them with the findings from other countries. We aim to identify potential similarities, differences, and factors contributing to the burden of SLE in different populations by exploring the comparative epidemiological aspects. The knowledge derived from this comparison would aid in advancing the overall management of SLE in Korea.

12.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1001439

RESUMEN

Background/Aims@#It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD).We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. @*Methods@#Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals.Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. @*Results@#A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the noninferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. @*Conclusions@#Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

13.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1001412

RESUMEN

Background/Aims@#Hypercontractile esophagus (HE) is a heterogeneous disorder with variable clinical presentations and a natural course, leading to management challenges. This study aims to investigate the characteristics of HE and evaluate its treatment outcomes. @*Methods@#Four Korean referral centers recruited subjects with at least 1 hypercontractile swallow (distal contraction integral > 8000 mmHg·s·cm) in this retrospective observational study. Subjects were classified according to the Chicago classification version 2.0 (CC v2.0), CC v3.0, and CC v4.0. criteria. The clinical and manometric features were also investigated. The treatment modalities and outcomes of subjects with CC v4.0 were evaluated. @*Results@#In total, 59 subjects with at least 1 hypercontractile swallow were analyzed. Among them, 30 (50.8%) had increased integrated relaxation pressure values without meeting the criteria for achalasia. Among the remaining 29 patients, 6 (20.7%) had only 1 hypercontractile swallowing symptom (CC v2.0) and 23 (79.3%) met both the CC v3.0 and v4.0 criteria for HE. Dysphagia (91.3%) was the most prevalent symptom, followed by chest pain (56.5%), regurgitation (52.2%), globus (34.8%), heartburn (21.7%), and belching (8.7%). Twenty (87.0%) patients received medical treatment, and 8 (47.1%) and 5 (29.4%) showed moderate and significant improvements, respectively. Proton pump inhibitors were the most common option (n = 15, 65.2%), followed by calcium channel blockers (n = 6, 26.1%). One patient received peroral endoscopic myotomy and showed significant symptom improvement. @*Conclusions@#Sixty-one percent of patients who meet the diagnostic criteria for the high-resolution manometry are diagnosed with symptomatic HE based CC v4.0. Chest pain and regurgitation were also observed in over half of them. The overall medical treatment efficacy was moderate.

14.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1001311

RESUMEN

Glucagon-like peptide-1 (GLP-1) receptor agonists have been used extensively in the clinic and have an established safety profile in cardiovascular disease settings. For the treatment of peptide-secreting enteroendocrine cells, most research has focused on developing peptide multi-agonists as most of these cells are multihormonal. Among the various peptides secreted by enteroendocrine cells, the combination of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) is an attractive strategy for treating type 2 diabetes mellitus (T2DM) because both of these hormones have glucose-lowering actions. Tirzepatide, a synthetic peptide composed of 39 amino acids, functions as a dual receptor agonist of both the GIP and GLP-1 receptors. This unique mechanism of action has earned tirzepatide the nickname “twincretin.”Tirzepatide’s dual agonist activity may be the mechanism by which tirzepatide significantly reduces glycated hemoglobin levels and body weight in patients with T2DM as observed in phase 3 clinical trials. Besides its glucose-lowering and anti-obesity effects, tirzepatide has been reported to have potential cardiovascular benefits. In this review, we discuss the cardiovascular effects of tirzepatide based on the available preclinical and clinical data.

15.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1001145

RESUMEN

Background@#Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. @*Methods@#Individuals with influenza during four consecutive influenza seasons (2013–2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. @*Results@#Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63–4.48), and 5.6% (95% CI, 4.5–6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40–17.55) and PAF (20.7%; 95% CI, 13.2– 27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6–10.7%) for liver disease, 5.8% (95% CI, 2.9–8.5%) for respiratory disease, and 3.8% (95% CI, 1.4–6.1%) for cancer. @*Conclusion@#Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.

16.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1000305

RESUMEN

Background@#Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study. @*Methods@#In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver. @*Results@#Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis. @*Conclusion@#Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

17.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1000271

RESUMEN

With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.

18.
Clinical Endoscopy ; : 744-753, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1000061

RESUMEN

Background/Aims@#This study aimed to evaluate the prevalence and natural progression of subepithelial lesions (SELs) in the upper gastrointestinal (UGI) tract. @*Methods@#The medical records of patients with UGI SELs who underwent endoscopic screening at eight university hospitals between January and December 2010 were retrospectively investigated. The follow-up evaluations were performed until December 2016. @*Results@#UGI SELs were found in 1,044 of the 65,233 participants screened (endoscopic prevalence, 1.60%; the total number of lesions, 1,062; mean age, 55.1±11.2 years; men, 53.6%). The median follow-up period was 48 (range, 8–74) months. SELs were most frequently found in the stomach (63.8%) and had a mean size of 9.9±6.1 mm. Endoscopic ultrasonography (EUS) was performed in 293 patients (28.1%). The most common lesions were leiomyomas, followed by gastrointestinal stromal tumors (GISTs), and ectopic pancreas. The proportions of SELs with malignant potential according to size were 3% (<1 cm), 22% (1–2 cm), 27% (2–3 cm), and 38% (≥3 cm). In gastric SELs larger than 1 cm, resections were performed in 20 patients because of an increase in size, of which 12 were found to be GISTs. @*Conclusions@#The prevalence of UGI SELs was 1.60%. Further, 23% of gastric SELs ≥1 cm were precancerous lesions, most followed by EUS and clinical decisions without initial pathological confirmation.

19.
Clinical Endoscopy ; : 325-332, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1000049

RESUMEN

Background/Aims@#Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas. @*Methods@#Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen. @*Results@#Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in the analysis. Among them, 2,831 and 1,078 patients were allocated to the adenoma and non-adenoma groups, respectively. Regarding the overall diagnosis of gastric adenoma with ICD-10 codes, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.7%, 88.5%, 95.2%, and 96.8%, respectively. There were no significant differences in these parameters between the tertiary and secondary centers. @*Conclusions@#Administrative codes of gastric adenoma, according to ICD-10 codes, showed good accuracy and can serve as a useful tool to study prognosis of these patients in real-world data studies in the future.

20.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1000013

RESUMEN

Background/Aims@#To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. @*Methods@#This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. @*Results@#Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. @*Conclusions@#In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

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