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Metal halide perovskite light-emitting diodes (PeLEDs) have exceptional color purity but designs that emit deep-blue color with high efficiency have not been fully achieved and become more difficult in the thin film of confined perovskite colloidal quantum dots (PeQDs) due to particle interaction. Here it is demonstrated that electronic coupling and energy transfer in PeQDs induce redshift in the emission by PeQD film, and consequently hinder deep-blue emission. To achieve deep-blue emission by avoiding electronic coupling and energy transfer, a QD-in-organic solid solution is introduced to physically separate the QDs in the film. This physical separation of QDs reduces the interaction between them yielding a blueshift of ≈7 nm in the emission spectrum. Moreover, using a hole-transporting organic molecule with a deep-lying highest occupied molecular orbital (≈6.0 eV) as the organic matrix, the formation of exciplex emission is suppressed. As a result, an unprecedently high maximum external quantum efficiency of 6.2% at 462 nm from QD-in-organic solid solution film in PeLEDs is achieved, which satisfies the deep-blue color coordinates of CIEy < 0.06. This work suggests an important material strategy to deepen blue emission without reducing the particle size to <≈4 nm.
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Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.
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Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Transdução de Sinais , Sorafenibe , Superóxido Dismutase-1 , Serina-Treonina Quinases TOR , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Animais , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos , Vírus da Hepatite B/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose/efeitos dos fármacos , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Ditiocarb/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos Nus , Proliferação de Células/efeitos dos fármacos , Transativadores , Proteínas Virais Reguladoras e AcessóriasRESUMO
PURPOSE: This study assessed whether or not the ABO blood type affects the incidence of HCC recurrence after living donor liver transplantation (LDLT). METHODS: This retrospective observational study included 856 patients with hepatocellular carcinoma (HCC) who underwent LDLT between January 2006 and December 2016 at the Asan Medical Center. RESULTS: This study included 324 patients (37.9%) with blood type A, 215 (25.1%) with blood type B, 210 (24.5%) with blood type O, and 107 (12.5%) with blood type AB. ABO-incompatible LT was performed in 136 (15.9%) patients. The independent risk factors for the disease-free survival (DFS) were maximal tumor diameter, microvascular invasion, and Milan criteria. The only independent risk factor for the overall survival (OS) was microvascular invasion. The ABO blood group did not affect the DFS (P = 0.978) or OS (P = 0.261). The DFS according to the ABO blood group did not differ significantly between the ABO-compatible (p = 0.701) and ABO-incompatible LDLT recipients (p = 0.147). The DFS according to the ABO blood group did not differ significantly between patients within the Milan criteria (p = 0.934) and beyond the Milan criteria (p = 0.525). The DFS did not differ significantly between recipients with and without type A blood (p = 0.941). CONCLUSIONS: This study demonstrated that the ABO blood group system had no prognostic impact on the oncological outcomes of patients undergoing LT for HCC.
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Backgrounds/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. Methods: We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. Results: The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). Conclusions: HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.
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INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014 to 2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR <0.7% vs. GRWR ≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients [GRWR <0.7 ( n =59) vs. GRWR ≥0.7 ( n =1946)]. In the entire cohort, 5-year RFS was significantly lower in the GRWR <0.7 than in the GRWR ≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR <0.7 was an independent risk factor for RFS [adjusted hazard ratio (aHR) 1.89, P =0.012], but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR <0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR <0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Doadores Vivos , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Tamanho do Órgão , Recidiva Local de Neoplasia/patologia , República da Coreia/epidemiologia , Fígado/patologia , Fígado/cirurgiaRESUMO
Living donor liver transplantation (LDLT) has emerged as a favorable alternative to deceased donor liver transplantation, significantly reducing waitlist mortality, particularly in Asian countries with very low deceased organ donation rates. Asan Medical Center (AMC) in South Korea has pioneered innovative LDLT surgical techniques and become established as an extremely high-volume center for LDLT. This retrospective study analyzed 6000 consecutive LDLT procedures, including 510 dual-graft procedures, performed at AMC between December 1994 and January 2021. Of these, 312 LDLT procedures were performed in children aged < 18 years. In adult recipients, liver cirrhosis (LC) related to viral hepatitis was the most common indication, occurring in 69.8% of cases. Biliary atresia (46.8%) was the most common indication for pediatric LDLT. This study demonstrated outstanding long-term outcomes, with patient survival rates at 1, 5, 10, and 20 years of 92.7%, 85.9%, 82.1%, and 70.9%, respectively, in LDLT group for adults aged 50 and under at the time of LDLT, and 92.9%, 89.0%, 88.1%, and 81.9%, respectively, in the pediatric group. The in-hospital mortality rate of adult recipients was 3.8% (n = 214/5688). This study demonstrates the importance of refined surgical techniques, selection of grafts tailored to the recipient, and comprehensive multidisciplinary perioperative patient care in expanding the scope of LDLT and improving recipient outcomes.
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Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.
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BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.
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Doença Hepática Terminal , Acidente Vascular Cerebral Hemorrágico , Aneurisma Intracraniano , Transplante de Fígado , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Acidente Vascular Cerebral Hemorrágico/complicações , Transplante de Fígado/efeitos adversos , Amônia , Doença Hepática Terminal/complicações , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/etiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Rationale: The surge of severe liver damage underscores the necessity for identifying new targets and therapeutic agents. Endoplasmic reticulum (ER) stress induces ferroptosis with Gα12 overexpression. NF-κB essential modulator (NEMO) is a regulator of inflammation and necroptosis. Nonetheless, the regulatory basis of NEMO de novo synthesis and its impact on hepatocyte ferroptosis need to be established. This study investigated whether Nrf2 transcriptionally induces IKBKG (the NEMO gene) for ferroptosis inhibition and, if so, how NEMO induction protects hepatocytes against ER stress-induced ferroptosis. Methods: Experiments were conducted using human liver tissues, hepatocytes, and injury models, incorporating NEMO overexpression and Gα12 gene modulations. RNA sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation analyses were done. Results: NEMO downregulation connects closely to ER and oxidative stress, worsening liver damage via hepatocyte ferroptosis. NEMO overexpression protects hepatocytes from ferroptosis by promoting glutathione peroxidase 4 (GPX4) expression. This protective role extends to oxidative and ER stress. Similar shifts occur in nuclear factor erythroid-2-related factor-2 (Nrf2) expression alongside NEMO changes. Nrf2 is newly identified as an IKBKG (NEMO gene) transactivator. Gα12 changes, apart from Nrf2, impact NEMO expression, pointing to post-transcriptional control. Gα12 reduction lowers miR-125a, an inhibitor of NEMO, while overexpression has the opposite effect. NEMO also counters ER stress, which triggers Gα12 overexpression. Gα12's significance in NEMO-dependent hepatocyte survival is confirmed via ROCK1 inhibition, a Gα12 downstream kinase, and miR-125a. The verified alterations or associations within the targeted entities are validated in human liver specimens and datasets originating from livers subjected to exposure to other injurious agents. Conclusions: Hepatic injury prompted by ER stress leads to the suppression of NEMO, thereby facilitating ferroptosis through the inhibition of GPX4. IKBKG is transactivated by Nrf2 against Gα12 overexpression responsible for the increase of miR-125a, an unprecedented NEMO inhibitor, resulting in GPX4 induction. Accordingly, the induction of NEMO mitigates ferroptotic liver injury.
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Ferroptose , Hepatopatias , MicroRNAs , Humanos , Estresse do Retículo Endoplasmático/genética , Ferroptose/genética , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Quinases Associadas a rhoRESUMO
BACKGROUND The effects of a low graft-to-recipient weight ratio (GRWR) on the prognosis of patients with hepatocellular carcinoma (HCC) are unclear. The present study examined whether the GRWR had an impact on the rate of HCC recurrence following living donor liver transplantation (LDLT). MATERIAL AND METHODS This retrospective observational single-center study included 856 patients who underwent LDLT for HCC between January 2006 and December 2016 at Asan Medical Center and evaluated the association between GRWR and post-transplant tumor recurrence. RESULTS Of the 856 patients who underwent LDLT for HCC, 54 (6.3%), 272 (31.8%), 274 (32.0%), and 256 (29.9%) had GRWR <0.8%, 0.8-0.99%, 1.0-1.19%, and ≥1.2%, respectively. Analysis of all patients revealed that the disease-free survival (DFS; P=0.545) and overall survival (OS; P=0.313) rates were not different in these 4 groups. Subgroups analyses also showed that GRWR did not influence survival rates in patients within (DFS: P=0.398; OS: P=0.676) and beyond (DFS: P=0.602; OS: P=0.649) the Milan criteria, or in patients with alpha-fetoprotein-des-γ-carboxyprothrombin-tumor volume scores <5log (DFS: P=0.633; OS: p=0.285) and ≥5log (DFS: P=0.674; OS: P=0.906). CONCLUSIONS GRWR less than 0.8% did not demonstrate a noteworthy prognostic influence on the oncological results among patients who had undergone LDLT for HCC. High-volume multi-center studies are necessary to validate these findings.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Doadores Vivos , Carcinoma Hepatocelular/cirurgia , Estudos Retrospectivos , Neoplasias Hepáticas/cirurgia , Prognóstico , MagrezaRESUMO
BACKGROUND: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss. METHODS: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively. RESULTS: We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m2 to 23.8 ± 3.1 kg/m2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000). CONCLUSION: Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors.
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Hepatic artery thrombosis (HAT) is a common cause of graft loss in living-donor liver transplantation, occurring in ~2.5%-8% of patients. Some right lobe grafts have 2 hepatic arteries (HAs), and the optimal reconstruction technique remains controversial. This study aimed to identify risk factors for HAT and to evaluate the efficacy of reconstructing 2 HAs in right lobe grafts. This retrospective, single-center study analyzed 1601 living-donor liver transplantation recipients with a right liver graft and divided them into 1 HA (n = 1524) and 2 HA (n = 77) groups. The reconstruction of all HAs was performed using a microscope with an interrupted suture. The primary outcome was any HAT event. Of the 1601 patients, 37.8% had a history of transcatheter arterial chemoembolization, and 130 underwent pretransplant hepatectomy. Extra-anatomical arterial reconstruction was performed in 38 cases (2.4%). HAT occurred in 1.2% of patients (20/1601) who underwent surgical revascularization. In the multivariate analysis, undergoing pretransplant hepatectomy ( p = 0.008), having a female donor ( p = 0.02), having a smaller graft-to-recipient weight ratio ( p = 0.002), and undergoing extra-anatomical reconstruction ( p = 0.001) were identified as risk factors for HAT. However, having 2 HA openings in right liver grafts was not a risk factor for HAT in our series. Kaplan-Meier survival analysis showed no significant difference in graft survival and patient survival rates between the 1 HA and 2 HA groups ( p = 0.09, p = 0.97). In our series, although the smaller HA in the 2 HA group should increase the risk of HAT, HAT did not occur in this group. Therefore, reconstructing both HAs when possible may be a reasonable approach in living-donor liver transplantation using a right liver graft with 2 HA openings.
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Sobrevivência de Enxerto , Hepatectomia , Artéria Hepática , Transplante de Fígado , Doadores Vivos , Trombose , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Artéria Hepática/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Trombose/etiologia , Trombose/epidemiologia , Trombose/cirurgia , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Resultado do Tratamento , Fígado/cirurgia , Fígado/irrigação sanguínea , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Estimativa de Kaplan-Meier , IdosoRESUMO
BACKGROUND: The COVID-19 pandemic has had a major impact on liver transplantation (LT) and living donor programs globally. PURPOSE: In this study, we aimed to present the principles and strategies of our LT program during the pandemic period and describe its achievements. BASIC PROCEDURES: We retrospectively reviewed the outcomes of 1417 LTs performed at Asan Medical Center, Seoul, Korea, from 2020 to 2022. Of these, 216 recipients who received transplants from deceased donors were excluded, and 1201 recipients who received transplants from 1268 live donors were included in the study, including 38 children <18 years old. MAIN FINDINGS: Among the 1201 living donor LT (LDLT) recipients, the most common indication for LT was unresectable hepatocellular carcinoma (315/1163, 27.1%) in adults and biliary atresia (29/38, 76.3%) in pediatric recipients. Emergency LDLT was performed in 40 patients (3.3%). The median model of end-stage liver disease and pediatric end-stage liver disease scores were 13.9 ± 7.2 and 13.8 ± 7.1, respectively. In-hospital mortality of recipients was higher than usual at 2.2%, but the cause of death was not related to COVID-19 infection. Of the 1268 live donors who underwent hepatectomy for liver donation, 660 (52.1%) underwent hepatectomy using a minimally invasive approach. Although 17 (1.3%) live donors experienced major complications, there were no serious life-threatening complications and no mortality. CONCLUSION: Even in a pandemic era, a team with well-established infection control protocols, patient-tailored surgical strategies, and thorough perioperative care can maintain LDLT at a similar quantitative and qualitative level as in a non-pandemic era.
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COVID-19 , Doença Hepática Terminal , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Criança , Humanos , Adolescente , Doadores Vivos , Transplante de Fígado/métodos , Doença Hepática Terminal/cirurgia , Pandemias , Estudos Retrospectivos , Resultado do Tratamento , COVID-19/epidemiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The prevalence of atrial fibrillation (AF) continues to increase in modern aging society. Patients with AF are at high risk for multiple adverse cardiovascular events, including heart failure, stroke, and mortality. Improved medical care is needed for patients with AF to enhance their quality of life and limit their medical resource utilization. With advances in the internet and technology, telehealth programs are now widely used in medical care. A fourth-generation telehealth program offers synchronous and continuous medical attention in response to physiological parameters measured at home. Although we have previously shown the benefits of this telehealth program for some patients with a high risk of cardiovascular disease, its benefits for patients with AF remains uncertain. OBJECTIVE: This study aims to investigate the benefits of participating in a fourth-generation telehealth program for patients with AF in relation to cardiovascular outcomes. METHODS: This was a retrospective cohort study. We retrospectively searched the medical records database of a tertiary medical center in Northern Taiwan between January 2007 and December 2017. We screened 5062 patients with cardiovascular disease and enrolled 537 patients with AF, of which 279 participated in the telehealth program and 258 did not. Bias was reduced using the inverse probability of treatment weighting adjustment based on the propensity score. Outcomes were collected and analyzed, including all-cause readmission, admission for heart failure, acute coronary syndrome, ischemic stroke, systemic embolism, bleeding events, all-cause mortality, and cardiovascular death within the follow-up period. Total medical expenses and medical costs in different departments were also compared. Subgroup analyses were conducted on ischemic stroke stratified by several subgroup variables. RESULTS: The mean follow-up period was 3.0 (SD 1.7) years for the telehealth group and 3.4 (SD 1.9) years for the control group. After inverse probability of treatment weighting adjustment, the patients in the telehealth program had significantly fewer ischemic strokes (2.0 vs 4.5 events per 100 person-years; subdistribution hazard ratio [SHR] 0.45, 95% CI 0.22-0.92) and cardiovascular deaths (2.5 vs 5.9 events per 100 person-years; SHR 0.43, 95% CI 0.18-0.99) at the follow-up. The telehealth program particularly benefited patients comorbid with vascular disease (SHR 0.11, 95% CI 0.02-0.53 vs SHR 1.16, 95% CI 0.44-3.09; P=.01 for interaction). The total medical expenses during follow-up were similar in the telehealth and control groups. CONCLUSIONS: This study demonstrated the benefits of participating in the fourth-generation telehealth program for patients with AF by significantly reducing their ischemic stroke risk while spending the same amount on medical expenses.
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Fibrilação Atrial , Insuficiência Cardíaca , AVC Isquêmico , Telemedicina , Humanos , Fibrilação Atrial/terapia , Estudos Retrospectivos , Qualidade de Vida , Insuficiência Cardíaca/terapiaRESUMO
This study evaluated how often clinically significant lung nodules were detected unexpectedly on chest radiographs (CXR) by artificial intelligence (AI)-based detection software, and whether co-existing findings can aid in differential diagnosis of lung nodules. Patients (> 18 years old) with AI-detected lung nodules at their first visit from March 2021 to February 2022, except for those in the pulmonology or thoracic surgery departments, were retrospectively included. Three radiologists categorized nodules into malignancy, active inflammation, post-inflammatory sequelae, or "other" groups. Characteristics of the nodule and abnormality scores of co-existing lung lesions were compared. Approximately 1% of patients (152/14,563) had unexpected lung nodules. Among 73 patients with follow-up exams, 69.9% had true positive nodules. Increased abnormality scores for nodules were significantly associated with malignancy (odds ratio [OR] 1.076, P = 0.001). Increased abnormality scores for consolidation (OR 1.033, P = 0.040) and pleural effusion (OR 1.025, P = 0.041) were significantly correlated with active inflammation-type nodules. Abnormality scores for fibrosis (OR 1.036, P = 0.013) and nodules (OR 0.940, P = 0.001) were significantly associated with post-inflammatory sequelae categorization. AI-based lesion-detection software of CXRs in daily practice can help identify clinically significant incidental lung nodules, and referring accompanying lung lesions may help classify the nodule.
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Neoplasias Pulmonares , Neoplasias , Humanos , Adolescente , Inteligência Artificial , Pulmão , Estudos Retrospectivos , Inflamação , Neoplasias Pulmonares/diagnóstico por imagem , Radiografia TorácicaRESUMO
We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B1 exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.
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Ceramidas , Transplante de Fígado , Humanos , Camundongos , Animais , Esfingomielinas , Cromatografia Líquida , Transplante de Pele , Espectrometria de Massas em Tandem , Hepatócitos , Células DendríticasRESUMO
PURPOSE: To compare the image quality, contrast administration, and radiation dose between single-energy CT (SECT) and dual-energy CT (DECT) in pediatric patients. METHODS: From March to December 2021, children who underwent abdominal SECT or DECT were retrospectively included in this study. The DECT group received 10-30 % less contrast than the routine dose. CT images were obtained at hepatic venous phase using a routine reconstruction method (iDose4). DECT scans were additionally reconstructed with a virtual monoenergetic image (VMI) at 40 and 65 keV. Quantitative image evaluations compared the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) of the liver, portal vein, and pancreas. Qualitative analysis assessed degree of contrast enhancement, lesion or organ conspicuity, image noise, artificiality, and overall image quality. RESULTS: Among 318 patients, 112 (median age, 16 years; 56 in each group) were included after propensity score matching. Compared with the SECT group, DECT group with iDose4 demonstrated lower CNRs and SNRs, while VMI at 40 or 65 keV showed no significant difference. In qualitative analysis, iDose4 produced higher scores on artificiality, and VMI at 40 keV demonstrated superior contrast enhancement and lesion conspicuity in the DECT group. Overall image quality was higher with VMI 65 keV among the DECT patients, and there was no significant difference compared to SECT. The volume CT dose index (CTDIvol) did not differ significantly between the two groups (median, 2.8 mGy vs. 2.9 mGy; p = 0.802). The injected contrast volume was reduced by 10 % in the DECT group. CONCLUSION: Pediatric abdominal DECT with reduced contrast administration showed no significant differences in image quality and radiation dose compared to SECT.
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Meios de Contraste , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Humanos , Criança , Adolescente , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Pontuação de Propensão , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Doses de Radiação , Razão Sinal-Ruído , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
Background: Portal vein (PV) interposition can induce various PV-related complications, making more reliable techniques necessary. The present study describes the development of a modified patch venoplasty technique, combining the native PV wall and a vein homograft conduit, called modified patch-conduit venoplasty (MPCV). Methods: The surgical technique for MPCV was optimized by simulation and applied to seven pediatric patients undergoing liver transplantation (LT) for biliary atresia combined with PV hypoplasia. Results: The simulation study revealed that inserting the whole-length native PV wall as a longitudinal rectangular patch was more effective in preventing PV conduit stenosis than the conventional technique using triangular partial insertion. These findings were used to develop the MPCV technique, in which the native PV wall was converted into a long rectangular patch, acting as a backbone for PV reconstruction. A longitudinal incision on the vein conduit converted the cylindrical vein into a large vein patch. The wall of the native PV was fully preserved as the posterior wall of the PV conduit, thus preventing longitudinal redundancy and unwanted rotation of the reconstructed PV. This technique was applied to seven patients with biliary atresia undergoing living-donor and deceased-donor split LT. None of these patients has experienced PV complications for up to 12 months after transplantation. Conclusions: This newly devised MCPV technique can replace conventional PV interposition. MCPV may be a surgical option for reliable PV reconstruction using fresh or cryopreserved vein homografts during pediatric LT.
RESUMO
OBJECTIVE: To compare graft survival after LDLT in patients receiving GRWR<0.8 versus GRWR≥0.8 grafts and identify risk factors for graft loss using GRWR<0.8 grafts. SUMMARY BACKGROUND DATA: Favorable outcomes after living donor liver transplantation (LDLT) using graft-to-recipient weight ratio (GRWR)<0.8 grafts were recently reported; however, these results have not been validated using multicenter data. METHODS: This multicentric cohort study included 3450 LDLT patients. Graft survival was compared between 1:3 propensity score-matched groups and evaluated using various Cox models in the entire population. Risk factors for graft loss with GRWR<0.8 versus GRWR≥0.8 grafts were explored within various subgroups using interaction analyses, and outcomes were stratified according to the number of risk factors. RESULTS: In total, 368 patients (10.7%) received GRWR<0.8 grafts (GRWR<0.8 group), whereas 3082 (89.3%) received GRWR≥0.8 grafts (GRWR≥0.8 group). The 5-y graft survival rate was significantly lower with GRWR<0.8 grafts than with GRWR≥0.8 grafts (85.2% vs. 90.1%, P=0.013). Adjusted hazard ratio (HR) for graft loss using GRWR<0.8 grafts in the entire population was 1.66 (95% confidence interval [CI] 1.17-2.35, P=0.004). Risk factors exhibiting significant interactions with GRWR<0.8 for graft survival were age ≥60 y, MELD score ≥15, and male donor. When ≥2 risk factors were present, GRWR<0.8 grafts showed higher risk of graft loss compared to GRWR≥0.8 graft in LDLT (HR 2.98, 95% CI 1.79-4.88, P<0.001). CONCLUSIONS: GRWR<0.8 graft showed inferior graft survival than controls (85.2% vs. 90.1%), especially when ≥2 risk factors for graft loss (among age ≥60 y, MELD score ≥15, or male donor) were present.