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BACKGROUND AND AIMS: No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. APPROACH AND RESULTS: Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70-0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60-0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79-0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72-0.89, all p <0.05) across various sensitivity analyses. CONCLUSIONS: Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.
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The global threat posed by the COVID-19 pandemic has catalyzed the development of point-of-care (POC) molecular diagnostics. While loop-mediated isothermal amplification (LAMP) stands out as a promising technique among FDA-approved methods, it is occasionally susceptible to a high risk of false positives due to nonspecific amplification of a primer dimer. In this work, we report an enhancing LAMP technique in terms of assay sensitivity and reliability through streamlined integration with a nonpowered nanoelectric preconcentration (NPP). The NPP, serving as a sample preparation tool, enriched the virus concentration in samples prior to the subsequent LAMP assay. This enrichment enabled not only to achieve more sensitive assay but also to shorten the assay time for all tested clinical samples by â¼10 min compared to the conventional LAMP. The shortened assay time suppresses the occurrence of nonspecific amplification by not providing the necessary incubation time, effectively suppressing misidentification by false positives. Utilizing this technique, we also developed a prototype of the POC NPP-LAMP kit. This kit offers a streamlined diagnostic process for nontrained individuals, from the sample enrichment, transfer of the enriched sample to LAMP assays, which facilitates on-site/on-demand diagnosis of SARS-CoV-2. This development holds the potential to contribute toward preventing not only the current outbreak but also future occurrences of pandemic viruses.
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COVID-19 , Pandemias , Humanos , Reproducibilidad de los Resultados , Técnicas de Diagnóstico Molecular/métodos , COVID-19/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos , Sensibilidad y Especificidad , ARN ViralRESUMEN
BACKGROUND AND AIMS: NAFLD and chronic hepatitis B (CHB) infection are common etiologies of HCC. The impact of hepatic steatosis on HCC in CHB, as well as its relationship with the development of cirrhosis, fibrosis, and HBsAg seroclearance, remains controversial. APPROACH AND RESULTS: Data from observational studies were collected through PubMed, EMBASE, and the Cochrane Library from inception to February 1, 2022. Outcomes of interest included the association of hepatic steatosis with HCC, cirrhosis, advanced fibrosis, and HBsAg seroclearance, expressed in terms of pooled ORs. Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A total of 34 studies with 68,268 patients with CHB were included. Hepatic steatosis was associated with higher odds of HCC (OR, 1.59; 95% CI, 1.12-2.26; I2 = 72.5%), with the association remaining consistent in Asia (OR, 1.56; 95% CI, 1.08-2.25), studies with a median follow-up duration of ≥5 years (OR, 2.82; 95% CI, 1.57-5.08), exclusion of alcohol use (OR, 1.71; 95% CI, 1.01-2.91), and biopsy-proven steatosis (OR, 2.86; 95% CI, 1.61-5.06), although no significant association was noted among nucleos(t)ide analogue-treated patients (OR, 1.05; 95% CI, 0.62-1.77). Steatosis was associated with the development of cirrhosis (OR, 1.52; 95% CI, 1.07-2.16; I2 = 0%) and HBsAg seroclearance (OR, 2.22; 95% CI, 1.58-3.10; I2 = 49.0%). CONCLUSIONS: Hepatic steatosis was associated with an increased risk of HCC and cirrhosis among patients with CHB but with a higher chance of achieving a functional cure, highlighting the importance of identifying concomitant steatosis in CHB.
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Carcinoma Hepatocelular , Hígado Graso , Hepatitis B Crónica , Cirrosis Hepática , Neoplasias Hepáticas , Hepatitis B Crónica/complicaciones , Virus de la Hepatitis BRESUMEN
Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.
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Antivirales , Enfermedades Cardiovasculares , Hepatitis B Crónica , Tenofovir , Humanos , Masculino , Hepatitis B Crónica/tratamiento farmacológico , Femenino , Antivirales/uso terapéutico , Antivirales/efectos adversos , Tenofovir/uso terapéutico , Tenofovir/efectos adversos , Tenofovir/análogos & derivados , Persona de Mediana Edad , Adulto , República de Corea/epidemiología , Dislipidemias/inducido químicamente , Dislipidemias/epidemiología , Estudios de Cohortes , Guanina/análogos & derivados , Guanina/uso terapéutico , Guanina/efectos adversos , AlaninaRESUMEN
BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.
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BACKGROUND AND AIMS: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection. Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. METHODS: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. Of these patients, 112 without any information about Helicobacter pylori infection status, 164 who underwent APC for salvage therapy, 5 with high-grade dysplasia, and 12 with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. RESULTS: A total of 618 patients with LGD (median age, 64 years) were followed up for a median of 30 months, and local recurrence has happened in 21 (3.4%) patients. Multivariate analysis showed that lesion size (hazard ratio, 1.06; 95% confidential interval, 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 (2.6%) cases, and local recurrence was found in 7 (9.5%) cases of 109 tumors larger than 10 mm (P < .004). CONCLUSIONS: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of endoscopic resection. However, when a lesion is larger, APC should be selected carefully with close monitoring.
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Coagulación con Plasma de Argón , Recurrencia Local de Neoplasia , Neoplasias Gástricas , Humanos , Coagulación con Plasma de Argón/métodos , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estudios Retrospectivos , Anciano , Adulto , Resultado del Tratamiento , Carga Tumoral , Gastroscopía/métodos , Anciano de 80 o más Años , Clasificación del TumorRESUMEN
BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes. METHODS: This nationwide cohort study included 9 298 497 patients who participated in a health-screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese-MAFLD and lean-MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all-cause and extrahepatic malignancy-related mortality. RESULTS: In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow-up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM-MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11-1.14; p < .001) and the lean-MAFLD (aSHR = 1.12; 95% CI = 1.10-1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non-MAFLD group. However, the overweight/obese-MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non-MAFLD group (aSHR = 1.00; 95% CI = .99-1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM-MAFLD was an independent risk factor for all-cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40-1.43; p < .001) and extrahepatic malignancy-related mortality (aHR = 1.20; 95% CI = 1.17-1.23; p < .001). CONCLUSION: The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non-MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.
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Neoplasias , Enfermedad del Hígado Graso no Alcohólico , Humanos , Estudios de Cohortes , Sobrepeso , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
AIM: Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high-quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence. METHODS: Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time-varying effect of NA use on HCC recurrence was analyzed using various statistical methods. RESULTS: Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68-1.47; p = 1.00) by time-varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67-1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51-2.33; p = 0.82 for ETV). Kaplan-Meier analysis showed comparable HCC recurrence-free survival between patients who switched to TAF and those who continued with their NA (p = 0.08). Time-varying Cox analyses in various subgroups confirmed the primary findings. CONCLUSIONS: TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.
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BACKGROUND: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia. METHODS: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm3, and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis. RESULTS: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001). CONCLUSIONS: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor.
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Electrocoagulación , Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Neoplasias Esofágicas/cirugía , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Electrocoagulación/efectos adversos , Electrocoagulación/métodos , Anciano , Síndrome , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , IncidenciaRESUMEN
BACKGROUND: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas. METHODS: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection. RESULTS: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2-4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2-91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma. CONCLUSIONS: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial.
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Leiomioma , Neoplasias Gástricas , Humanos , Leiomioma/patología , Leiomioma/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Masculino , Adulto , Anciano , Gastroscopía , Estudios de Seguimiento , Progresión de la Enfermedad , GastrectomíaRESUMEN
We herein report a fundamental mechanistic investigation into photochemical metal-nitrenoid generation and inner-sphere transposition reactivity using organometallic photoprecursors. By designing Cp*Ir(hydroxamate)(Ar) complexes, we induced photo-initiated ligand activation, allowing us to explore the amidative σ(Ir-aryl) migration reactivity. A combination of experimental mechanistic studies, femtosecond transient absorption spectroscopy, and density functional theory (DFT) calculations revealed that the metal-to-ligand charge transfer enables the σ(N-O) cleavage, followed by Ir-acylnitrenoid generation. The final inner-sphere σ(Ir-aryl) group migration results in a net amidative group transposition.
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BACKGROUND & AIMS: Loss-of-function HSD17ß13 mutations protect against the development of chronic liver disease. HSD17ß13 inhibition represents a potential approach to treat liver diseases, such as non-alcoholic steatohepatitis (NASH). ARO-HSD is an RNA interference (RNAi) therapeutic designed to selectively reduce expression of HSD17ß13 mRNA in hepatocytes. In this study, we evaluated the effects of ARO-HSD in normal healthy volunteers (NHVs) and patients with confirmed or clinically suspected NASH. METHODS: The safety, tolerability, and pharmacodynamics of ARO-HSD were evaluated in 32 NHVs and 18 patients with confirmed/clinically suspected NASH. Double-blind NHV cohorts received single escalating doses of ARO-HSD (25, 50, 100, or 200 mg) or placebo subcutaneously on Day 1. Open-label patient cohorts received ARO-HSD (25, 100, or 200 mg) subcutaneously on Days 1 and 29. Liver biopsy was performed pre-dose and on Day 71 to evaluate expression levels of HSD17ß13 mRNA and protein. RESULTS: ARO-HSD treatment was well tolerated with no treatment-related serious adverse events or drug discontinuations. The most frequently reported treatment-emergent adverse events were mild injection site reactions, which were short in duration. Mean changes in hepatic HSD17ß13 mRNA from baseline to Day 71 were: -56.9% (25 mg), -85.5% (100 mg), and -93.4% (200 mg). The mean HSD17ß13 mRNA reduction was 78.6% (p <0.0001) across pooled cohorts. Hepatic HSD17ß13 protein levels were similarly reduced across doses. In patients, mean changes in alanine aminotransferase from baseline to Day 71 were -7.7% (25 mg), -39.3% (100 mg), and -42.3% (200 mg) (p <0.001 for pooled cohorts). CONCLUSIONS: ARO-HSD was well tolerated at doses ≤200 mg. This proof-of-concept study demonstrated that short-term treatment with ARO-HSD reduces hepatic HSD17ß13 mRNA and protein expression, which is accompanied by reductions in alanine aminotransferase. GOV NUMBER: NCT04202354. IMPACTS AND IMPLICATIONS: There is an unmet medical need for new therapies to treat alcohol-related and non-alcoholic liver disease. ARO-HSD is a small-interfering RNA designed to silence HSD17ß13 expression and hence to phenocopy the protective effect seen in individuals with HSD17ß13 loss-of-function. The reductions in HSD17ß13 expression and in transaminases seen with ARO-HSD administration represent an initial step towards clinical validation of HSD17ß13, a drug target with substantial genetic validation, as an important modulator of human liver disease.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Interferencia de ARN , Alanina Transaminasa , Hígado/patología , Pruebas de Función Hepática , Método Doble Ciego , Resultado del TratamientoRESUMEN
INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Masculino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/complicaciones , Inteligencia Artificial , Neoplasias Hepáticas/complicaciones , Resultado del Tratamiento , Tenofovir/uso terapéutico , Aprendizaje Automático , Virus de la Hepatitis B , Estudios RetrospectivosRESUMEN
Background US is a standard surveillance tool of hepatocellular carcinoma (HCC), but its effectiveness varies depending on the degree of fibrosis or steatosis and the etiologies of liver disease. Purpose To evaluate the detection power of US and the occurrence of HCC according to the US Liver Imaging Reporting and Data System (LI-RADS) visualization score in chronic hepatitis B (CHB). Materials and Methods Consecutive patients with CHB undergoing regular US surveillance of HCC at a tertiary referral hospital were retrospectively included in this study. During the follow-up, all patients underwent regular HCC surveillance mainly with US and, in some cases, alternative CT or MRI. Outcomes of interest included cumulative incidence of HCC and false-negative rate of US in the optimal (LI-RADS visualization A) versus suboptimal groups (visualization B or C). Cox regression analysis was conducted to calculate the hazard ratio (HR) of HCC occurrence. Results A total of 2002 patients (median age, 54 years [IQR, 46-60 years]; 1192 men) were included: 972 and 1030 in the optimal and suboptimal groups, respectively. Causes of suboptimal visualization included parenchymal heterogeneity from advanced cirrhosis (n = 489), limited penetration from fatty liver (n = 200), and limited window from overlying organ shadow (n = 341). During a median follow-up of 75 months (IQR, 69-77 months), 163 patients developed HCC. Compared with the optimal group, the suboptimal group had a higher risk of HCC (2.38% per year vs 0.48% per year: hazard ratio, 4.93; 95% CI: 3.28, 7.41; P < .001) and higher odds of a false-negative rate of US (43.9% vs 16.7%: odds ratio, 3.90; 95% CI: 1.02, 15.00; P = .04). Conclusion Among patients with CHB, those with suboptimal US LI-RADS visualization of B or C had a higher risk of HCC and higher odds of false-negative rates of US for detecting HCC than those with optimal visualization of A. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barr and Scoutt in this issue.
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Carcinoma Hepatocelular , Hígado Graso , Hepatitis B Crónica , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/epidemiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética , Medios de ContrasteRESUMEN
BACKGROUND AND AIMS: Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver-associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis. APPROACH AND RESULTS: We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver-associated mortality, and major bleeding were estimated in a propensity-score-matched cohort (19,003 pairs), accounting for competing risks. With a median follow-up of 6.7 years, 10-year cumulative incidence of HCC was 9.5% in the aspirin-treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78-0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85-1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (pinteraction , n = 0.04). Aspirin use was also associated with lower liver-associated mortality (aSHR, 0.80; 95% CI, 0.71-0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99-1.21). CONCLUSIONS: Aspirin use was associated with reduced risks of HCC and liver-associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Adulto , Antivirales/uso terapéutico , Aspirina/efectos adversos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Humanos , Incidencia , Cirrosis Hepática/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: We constructed and validated a machine learning-based malignancy risk estimation model using predefined clinicoradiological features, and evaluated its clinical utility for the management of thyroid nodules. METHODS: In total, 5708 benign (n = 4597) and malignant (n = 1111) thyroid nodules were collected from 5081 consecutive patients treated in 26 institutions. Seventeen experienced radiologists evaluated nodule characteristics on ultrasonographic images. Eight predictive models were used to stratify the thyroid nodules according to malignancy risk; model performance was assessed via nested 10-fold cross-validation. The best-performing algorithm was externally validated using data for 454 thyroid nodules from a tertiary hospital, then compared to the Thyroid Imaging Reporting and Data System (TIRADS)-based interpretations of radiologists (American College of Radiology, European and Korean TIRADS, and AACE/ACE/AME guidelines). RESULTS: The area under the receiver operating characteristic (AUROC) curves of the algorithms ranged from 0.773 to 0.862. The sensitivities, specificities, positive predictive values, and negative predictive values of the best-performing models were 74.1-76.6%, 80.9-83.4%, 49.2-51.9%, and 93.0-93.5%, respectively. For the external validation set, the ElasticNet values were 83.2%, 89.2%, 81.8%, and 90.1%, respectively. The corresponding TIRADS values were 66.5-85.0%, 61.3-80.8%, 45.9-72.1%, and 81.5-90.3%, respectively. The new model exhibited a significantly higher AUROC and specificity than did the TIRADS risk stratification, although its sensitivity was similar. CONCLUSION: We developed a reliable machine learning-based predictive model that demonstrated enhanced specificity when stratifying thyroid nodules according to malignancy risk. This system will contribute to improved personalized management of thyroid nodules. KEY POINTS: ⢠The area under the receiver operating characteristic (AUROC) curve, sensitivity, and specificity of our model were 0.914, 83.2%, and 89.2%, respectively (derived using the validation dataset). ⢠Compared to the TIRADS values, the AUROC and specificity are significantly higher, while the sensitivity is similar. ⢠An interactive version of our AI algorithm is at http://tirads.cdss.co.kr .
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Ultrasonografía/métodos , Estudios Retrospectivos , Medición de RiesgoRESUMEN
Lateral flow assays (LFAs) have emerged as indispensable tools for point-of-care testing during the pandemic era. However, the interpretation of results through unassisted visual inspection by untrained individuals poses inherent limitations. In our study, we propose a novel approach that combines computer vision (CV) and lightweight machine learning (ML) to overcome these limitations and significantly enhance the performance of LFAs. By incorporating CV-assisted analysis into the LFA assay, we achieved a remarkable three-fold improvement in analytical sensitivity for detecting Influenza A and for SARS-CoV-2 detection. The obtained R2 values reached approximately 0.95, respectively, demonstrating the effectiveness of our approach. Moreover, the integration of CV techniques with LFAs resulted in a substantial amplification of the colorimetric signal specifically for COVID-19 positive patient samples. Our proposed approach, which incorporates a simple machine learning algorithm, provides substantial enhancements in assay sensitivity, improving diagnostic efficacy and accessibility of point-of-care testing without requiring significant additional resources. Moreover, the simplicity of the machine learning algorithm enables its standalone use on a mobile phone, further enhancing its practicality for point-of-care testing.
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COVID-19 , Gripe Humana , Humanos , SARS-CoV-2 , Gripe Humana/diagnóstico , COVID-19/diagnóstico , Algoritmos , Bioensayo , Prueba de COVID-19RESUMEN
BACKGROUND AND AIM: Although Dieulafoy's lesion (DL) is an important cause of nonvariceal upper gastrointestinal (GI) bleeding, few studies have investigated the clinico-epidemiological outcomes due to its rarity. Here, we investigated clinical features of upper GI bleeding caused by peptic ulcer (PU) or DL and compared endoscopic treatment outcomes. METHODS: Patients with upper GI bleeding resulting from PU or DL who visited emergency room between January 2013 and December 2017 were eligible. Clinical features and treatment outcomes were retrospectively investigated. RESULTS: Overall, 728 patients with upper GI bleeding due to PU (n = 669) and DL (n = 59) were enrolled. The median age was 64 years (interquartile range [IQR], 56-75 years), and 74.3% were male. Endoscopic intervention was performed in 53.7% (n = 359) and 98.3% (n = 58) of the PU and DL groups, respectively (P < 0.0001). Patients were matched by sex, age, body mass index, comorbidity, and past medical history, and 190 PU and 52 DL were finally selected. The rebleeding rates within 7 (7.37% vs 17.31%, P = 0.037) and 30 (7.37% vs 26.92%, P < 0.001) days after initial endoscopy were significantly lower in the PU than in the DL group after propensity score matching. During the median follow-up period of 52 months (IQR, 34-70 months), there was no difference in overall survival rate (67.9% vs 82.7%, P = 0.518). CONCLUSIONS: Although DL is a rare cause of upper GI bleeding, it requires endoscopic hemostasis more frequently and has a higher rate of rebleeding than PU even after therapeutic endoscopy. Endoscopists should pay attention and perform active endoscopic hemostasis for DL bleeding.
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Hemostasis Endoscópica , Úlcera Péptica , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Úlcera Péptica/complicaciones , Hemostasis Endoscópica/efectos adversos , Endoscopía Gastrointestinal/efectos adversosRESUMEN
BACKGROUND: Left gastric artery (LGA) pseudoaneurysm presenting with upper gastrointestinal (UGI) bleeding is rare but fatal, unless treated. AIMS: We aimed to describe the clinical and endoscopic features of patients with UGI bleeding due to LGA pseudoaneurysms. METHODS: We performed a computerized search of our hospital's de-identified clinical data warehouse to identify patients with UGI bleeding due to an LGA pseudoaneurysm between 2000 and 2020. Patients' electronic medical records and data on esophagogastroduodenoscopy and digital subtraction angiography were reviewed retrospectively. RESULTS: Of 26 patients with an LGA pseudoaneurysm, six patients had UGI bleeding related to an LGA pseudoaneurysm. No patients had previous vascular diseases or pancreatitis. One patient had liver cirrhosis and a history of radiofrequency ablation for hepatocellular carcinoma, one had colon cancer, two had undergone abdominal surgeries, one had received chemoradiotherapy for renal cell carcinoma, and one had no intraabdominal diseases. Symptoms were hematemesis in two, hematochezia in the other two, and melena in the remaining two patients. Esophagogastroduodenoscopy showed a pulsating bulge in the ulcer in two and a large Dieulafoy's lesion-like structure in four patients. All patients achieved hemostasis by angioembolization. CONCLUSION: LGA pseudoaneurysm should be suspected in UGI bleeding if a large Dieulafoy's lesion-like structure or a pulsating bulge in the ulcer is found at the lesser curvature of the gastric body on endoscopy and if the patient has any intra-abdominal inflammatory disease.
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Aneurisma Falso , Enfermedades Gastrointestinales , Humanos , Aneurisma Falso/complicaciones , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/terapia , Artería Gástrica/diagnóstico por imagen , Estudios Retrospectivos , Úlcera , Hemorragia Gastrointestinal/diagnóstico , Endoscopía GastrointestinalRESUMEN
BACKGROUND AND AIMS: As the incidence of duodenal neuroendocrine tumors (DNET) is steadily increasing, the role of endoscopic treatment for appropriate lesions is becoming more significant. We aimed to compare the outcomes according to lesion size and endoscopic mucosal resection (EMR) techniques for DNET treatment. PATIENTS AND METHODS: Patients who underwent endoscopic treatment for DNET between June 2000 and December 2019 were included. The clinicopathologic features and treatment outcomes were investigated by reviewing medical records. RESULTS: Overall, 104 cases underwent endoscopic resection for nonampullary DNET, including conventional EMR (n = 57), cap-assisted EMR (EMR-C, n = 19), and precut EMR (EMR-P, n = 28). The en bloc resection rates (100% vs. 94.7% vs. 96.4%) and histologic complete resection rates (45.6% vs. 52.6% vs. 57.1%) were not significantly different between the EMR, EMR-C, and EMR-P groups. The histologic complete resection rates were significantly higher in lesions < 10 mm than in lesions ≥ 10 mm (69.8% vs. 38.9%, P = 0.013). In lesions < 10 mm, perforation occurred more frequently in the modified EMR group than in the conventional EMR group (13.2% vs. 0.0%, P = 0.007). During the median follow-up period of 88.0 months, the recurrence-free survival (92.2% vs. 94.4% vs. 92.1%) and overall survival (98.0% vs. 88.1% vs. 100.0%) rates did not show significant differences between the EMR, EMR-C, and EMR-P groups. CONCLUSION: Conventional EMR and modified EMR are feasible and effective for the treatment of nonampullary DNET sized < 10 mm and limited to mucosal and submucosal layer. Additionally, endoscopists should be aware of the high risk of perforation in modified EMR.