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1.
Liver Transpl ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38775570

RESUMEN

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

2.
Diabetes Res Clin Pract ; 211: 111650, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38604447

RESUMEN

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Hígado Graso/fisiopatología
3.
Sci Rep ; 14(1): 6518, 2024 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-38499693

RESUMEN

Family with sequence similarity 20, member A (FAM20A) is a pseudo-kinase in the secretory pathway and is essential for enamel formation in humans. Here we examine if FAM20A is a membrane-associated protein. We show that the full-length FAM20A can be purified from HEK293 cells transfected with a FAM20A-expresing construct. Further, it is only found in the membrane fraction, but not in the soluble fraction, of cell lysate. Consistently, it is not secreted out of the expressing cells. Moreover, it is co-localized with GM130, a cis-Golgi network marker, and membrane topology analysis indicates that it has its C-terminus oriented towards the lumen of the organelle. Our results support that FAM20A is a Type II transmembrane protein within the secretory compartments.


Asunto(s)
Proteínas del Esmalte Dental , Proteínas de la Membrana , Humanos , Células HEK293 , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Fosfotransferasas/metabolismo , Aparato de Golgi/metabolismo , Proteínas del Esmalte Dental/metabolismo
4.
Dig Dis Sci ; 69(5): 1844-1851, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38499735

RESUMEN

INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.


Asunto(s)
Algoritmos , Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Trasplante de Hígado , Vibración , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Trasplante de Hígado/efectos adversos , Persona de Mediana Edad , Femenino , Masculino , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Adulto , Biopsia , Anciano , Hígado/patología , Hígado/diagnóstico por imagen , Estudios Retrospectivos
5.
Curr Cardiol Rep ; 26(4): 199-210, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38376745

RESUMEN

PURPOSE OF REVIEW: The objective of this manuscript is to examine the current literature on the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD), its correlation with cardiovascular disease (CVD) outcomes, as well as to evaluate the update in nomenclature from non-alcoholic liver disease (NAFLD). RECENT FINDINGS: The update of diagnostic criteria from NAFLD to MASLD reduces the stigma associated with alcohol consumption and poor health choices. It also shines a light on the crucial role of cardiometabolic risk factors in disease pathophysiology. The incidence and prevalence of MASLD are projected to increase significantly in the future as the population burden of cardiometabolic risk factors rises. MASLD is also a potent risk factor for developing CVD that should be tackled by using a multi-disciplinary team with a holistic approach. As the new nomenclature for metabolic liver disease is adopted on a global scale, more research is needed to investigate the applicability of findings from previous trials focusing on NAFLD. It is anticipated that the epidemic of MASLD will continue to increase globally, hence the urgent need for therapeutic approaches to reverse this trend.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Factores de Riesgo , Consumo de Bebidas Alcohólicas , Enfermedades Cardiovasculares/epidemiología
7.
J Cataract Refract Surg ; 50(2): 140-145, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38259133

RESUMEN

PURPOSE: To compare the rate of intraoperative complications and visual outcomes in patients with neovascular age-related macular degeneration (NvAMD) and control eyes without NvAMD undergoing phacoemulsification. SETTING: Multicenter study. DESIGN: Retrospective, nonrandomized comparative study. METHODS: Eyes were classified based on the presence or absence of an NvAMD diagnosis. The main outcomes were (1) the rate of intraoperative complications, (2) the logMAR visual acuity (VA) at 4 to 12 weeks postoperatively in both groups, and (3) the reinjection rate of intravitreal antivascular endothelial growth factor after phacoemulsification. RESULTS: Preoperative VA was worse in the NvAMD group (0.9 ± 0.5) compared with the reference group (0.6 ± 0.5). We observed no difference in the rate of posterior capsule rupture (PCR) (2.90% vs 2.77%; P = .889), dropped lens fragments (0.46% vs 0.29%; P = .618), or zonular dialysis (0.46% vs 0.58%, P = .749) between the 2 groups. Receiving ≥10 intravitreal injections before cataract surgery predicted the likelihood of PCR with an odds ratio of 2.86 (P = .027). Proportions of eyes achieving a visual gain of ≥0.3 logMAR (∼3 Snellen lines equivalent) was lower in NvAMD eyes (39.2% vs 63.7%; P < .0001). We observed 203 eyes (73%) in the active treatment group and 139 eyes (36%) in the inactive treatment group received >1 intravitreal injection after phacoemulsification (P < .0001). CONCLUSIONS: The risk for PCR was higher for eyes receiving ≥10 intravitreal injections before phacoemulsification. Only 39% of eyes with NvAMD had visual improvement by ≥3 Snellen lines.


Asunto(s)
Catarata , Cristalino , Degeneración Macular , Humanos , Complicaciones Intraoperatorias , Estudios Retrospectivos
8.
Liver Transpl ; 30(2): 192-199, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37146168

RESUMEN

Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (ß-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (ß-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (ß-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.


Asunto(s)
Metabolismo Energético , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Aumento de Peso , Obesidad , Ácidos Grasos
9.
Liver Transpl ; 30(5): 493-504, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38015449

RESUMEN

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%-28.1%). The incidence of minor complications was 17.3% (CI: 14.7%-20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%-6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%-0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%-11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%-6.2%) and respiratory complications (4.9%, CI: 3.8%-6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%-1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.


Asunto(s)
Trasplante de Hígado , Donadores Vivos , Humanos , Trasplante de Hígado/efectos adversos , Incidencia , Calidad de Vida , Resultado del Tratamiento , Estudios Retrospectivos
10.
Chem Rec ; 24(1): e202300105, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37222655

RESUMEN

Polyaniline (PANI) has piqued the interest of nanotechnology researchers due to its potential as an electrode material for supercapacitors. Despite its ease of synthesis and ability to be doped with a wide range of materials, PANI's poor mechanical properties have limited its use in practical applications. To address this issue, researchers investigated using PANI composites with materials with highly specific surface areas, active sites, porous architectures, and high conductivity. The resulting composite materials have improved energy storage performance, making them promising electrode materials for supercapacitors. Here, we provide an overview of recent developments in PANI-based supercapacitors, focusing on using electrochemically active carbon and redox-active materials as composites. We discuss challenges and opportunities of synthesizing PANI-based composites for supercapacitor applications. Furthermore, we provide theoretical insights into the electrical properties of PANI composites and their potential as active electrode materials. The need for this review stems from the growing interest in PANI-based composites to improve supercapacitor performance. By examining recent progress in this field, we provide a comprehensive overview of the current state-of-the-art and potential of PANI-based composites for supercapacitor applications. This review adds value by highlighting challenges and opportunities associated with synthesizing and utilizing PANI-based composites, thereby guiding future research directions.

11.
Clin Gastroenterol Hepatol ; 22(3): 488-498.e14, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37775028

RESUMEN

BACKGROUND & AIMS: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS: To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS: One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS: The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.


Asunto(s)
Diabetes Mellitus , Hígado Graso , Síndrome Metabólico , Humanos , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Cardiooncología
12.
Transplantation ; 108(1): 235-241, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37439776

RESUMEN

BACKGROUND: Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. METHODS: Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. RESULTS: Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (ß-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (ß-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (ß-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. CONCLUSIONS: VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.


Asunto(s)
Diabetes Mellitus , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Trasplante de Hígado/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/cirugía , Diabetes Mellitus/patología , Tejido Adiposo , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/cirugía , Cirrosis Hepática/complicaciones , Progresión de la Enfermedad , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/metabolismo
13.
Transplantation ; 108(2): 473-482, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37439778

RESUMEN

BACKGROUND: Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. METHODS: This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. RESULTS: Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. CONCLUSIONS: Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.


Asunto(s)
Diabetes Mellitus , Trasplante de Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Trasplante de Hígado/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Cirrosis Hepática/cirugía , Cirrosis Hepática/etiología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Factores de Riesgo , Supervivencia de Injerto
14.
Metabolism ; 152: 155744, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38029839

RESUMEN

BACKGROUND: High body mass index (BMI) is a major risk factor for cancer development, but its impact on the global burden of cancer remains unclear. METHODS: We estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study. RESULTS: From 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI. CONCLUSION: The global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.


Asunto(s)
Neoplasias Hepáticas , Humanos , Índice de Masa Corporal , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Europa (Continente)/epidemiología
15.
Hepatology ; 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38088872

RESUMEN

Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction-associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction-associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.

16.
J Am Heart Assoc ; 12(24): e031230, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38063161

RESUMEN

BACKGROUND: Literature suggests a bidirectional association between advanced hepatic fibrosis (AHF) and coronary artery disease (CAD). We evaluated the association of AHF with immune activation, systemic inflammation, and adverse outcomes in patients with CAD. METHODS AND RESULTS: A fibrosis-4 index cutoff value ≥2.67 was used to define AHF. Circulating levels of soluble urokinase plasminogen activator receptor and hsCRP (high-sensitivity C-reactive protein) were measured as markers for immune activation and systemic inflammation, respectively. The relationship of AHF with soluble urokinase plasminogen activator receptor, hsCRP, and adverse cardiovascular outcomes was evaluated. Among 3406 participants with CAD, 479 had AHF. Participants with AHF were older; were less likely to be Black individuals; and had a lower body mass index, worse renal function, and a prior history of heart failure. In multivariable linear regression models adjusted for clinical and demographic confounders, participants with AHF had 15.6% higher soluble urokinase plasminogen activator receptor and 24.0% higher hsCRP levels. They were more likely to experience the following adverse outcomes: all-cause death (adjusted hazard ratio [HR], 1.57 ([95% CI, 1.29-1.92]; P<0.001) and cardiovascular death: (subdistribution HR, 1.50 [95% CI, 1.14-1.95]; P=0.003). Mediation analysis showed that 47.0% (95% CI, 13.6%-81.2%]; P=0.006) of the indirect effect of AHF on cardiovascular death was mediated by circulating soluble urokinase plasminogen activator receptor levels. CONCLUSIONS: AHF is independently associated with immune activation, systemic inflammation, and adverse cardiovascular outcomes in patients with CAD. The association of AHF with adverse outcomes is partly mediated by immune activation, and targeting this pathway may help reduce the residual risk in patients with CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Proteína C-Reactiva/análisis , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Factores de Riesgo , Biomarcadores , Inflamación , Cirrosis Hepática/diagnóstico
17.
J Clin Lipidol ; 17(6): 828-833, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37957050

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is associated with atherogenic dyslipidemia and an increased risk of cardiovascular events. Previous studies have suggested an inverse relationship between NAFLD severity and lipoprotein(a) [Lp(a)] level, but contemporary data from the U.S. are lacking. Lp(a), lipid profile, apolipoproteins, and nuclear magnetic resonance-based lipoprotein particle concentrations were measured in 151 patients with biopsy-proven NAFLD. Levels were compared between those with nonalcoholic fatty liver (NAFL) on histology and non-alcoholic steatohepatitis (NASH). Median age was 55 [48, 62] years, 67% of patients were women, 83% were White, 43% had NAFL, and 57% had NASH. Triglyceride level was higher and high-density lipoprotein-cholesterol (HDL-C) was lower among those with NASH as compared with NAFL. Circulating apolipoprotein-B (ApoB) and low-density lipoprotein particle concentration (LDL-P) were 9% and 17% higher in the NASH group as compared with NAFL, respectively. Contrastingly, Lp(a) concentration was 50% lower in NASH relative to NAFL group. Hepatocyte ballooning, lobular inflammation, and fibrosis on histology were inversely associated with Lp(a) concentration. NAFLD severity has a discordant association with Lp(a) and other markers of atherogenic dyslipidemia. This relationship may have implications for prognosticating cardiovascular disease risk in patients with NAFLD.


Asunto(s)
Dislipidemias , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Persona de Mediana Edad , Masculino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Lipoproteína(a) , Inflamación/complicaciones , HDL-Colesterol , Dislipidemias/complicaciones , Dislipidemias/patología , Hígado/patología
18.
Sci Rep ; 13(1): 18677, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907585

RESUMEN

The global demand for crop production is rapidly growing due to the continued rise in world population. Crop productivity varies generally with soil nutrient profile and climate. The optimal use of fertilizers might help to attain higher crop yield in canola. To circumvent nutrient imbalance issues in soil, two separate field trials were conducted to determine (a) the best source of nitrogen (N) between ammonium sulfate (NH4)2SO4) and ammonium nitrate (NH4NO3), (b) significance of gibberellic acid (GA3) and potassium (K), in an attempt to enhance canola yield and yield attributes. Both experiments were carried out in randomized complete block design (RCBD) with three replicates. The nitrogen source in the form of NH4)2SO4 (0, 10, 20 and 30 kg/ha) and NH4NO3 (0, 50, 75 and 100 kg/ha) was applied in the rhizosphere after 3 and 7 weeks of sowing, referred to as experiment 1 (E1). In another separate experiment (E2), the canola crop was sprayed with four level of GA3 (0, 10, 15, 30 g/ha) and K (0, 2.5, 3.5, 6 g/ha) individually or in combination by using hydraulic spryer, 30 days after sowing (DAS). The data was collected at different growth stages of canola and analyzed statistically. The E1 trail showed that N fortification in the form of NH4NO3 (100 kg/ha) and (NH4)2SO4 (30 kg/ha) had a positive effect on the plant height, number of branches, fruiting zone, seed yield per plant, seed yield per hectare of canola except oil percentage. Moreover, canola plants (E2) also displayed a significant improvement on all studied features with high doses of GA3 (30 g/ha) and K (6 g/ha) individualy and in combined form. The correlation coefficient analysis of (NH4)2SO4 and NH4NO3 was highly significant to plant height, number of branches, fruiting zone, seed yield per plant, seed yield per hectare of canola In a nutshell, compared to both source of N, NH4NO3 was more efficient and readily available source of N. GA3 being a growth elicitor and potassium as a micronutrient serve as potential source to improve yield and to manage nutrient profile of canola.


Asunto(s)
Brassica napus , Producción de Cultivos , Suelo , Fertilizantes/análisis , Nitrógeno/análisis , Pakistán , Potasio/análisis , Suelo/química , Brassica napus/crecimiento & desarrollo
19.
Hepatobiliary Surg Nutr ; 12(5): 658-670, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37886204

RESUMEN

Background: Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease (NAFLD). However, there remains inadequate data regarding the effects of different bariatric procedures on various NAFLD parameters, especially for histological outcomes. Thus, this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic, biochemical, and histological parameters for patients with NAFLD. Methods: Medline and Embase were searched for articles relating to bariatric procedures and NAFLD. Pairwise meta-analysis was conducted to compare efficacy of bariatric procedures pre- vs. post-procedure with subgroup analysis to further compare restrictive against foregut bypass procedures. Results: Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures (n=1,460) and foregut bypass (n=1,895) were included. Both foregut bypass (P<0.01) and restrictive procedures (P=0.03) significantly increased odds of fibrosis resolution. Compared to restrictive procedures, foregut bypass resulted in a borderline non-significant decrease in fibrosis score (P=0.06) and significantly lower steatosis score (P<0.001). For metabolic parameters, foregut bypass significantly lowered body mass index (P=0.003) and low-density lipoprotein (P=0.008) compared to restrictive procedures. No significant differences were observed between both procedures for aspartate aminotransferase (P=0.17) and alkaline phosphatase (P=0.61). However, foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures (P=0.01) while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass (P=0.02). Conclusions: The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in NAFLD management.

20.
Transplantation ; 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37899382

RESUMEN

BACKGROUND: Preliver transplant diabetes mellitus (pre-LT DM) is a common comorbidity in LT recipients associated with poorer post-transplant survival. However, its relationship with other important outcomes, including cardiovascular and renal outcomes, remains unclear. This meta-analysis aims to provide an updated analysis of the impact of pre-LT DM on key post-LT outcomes. METHODS: A search was conducted in Medline and Embase databases for articles comparing the post-transplant outcomes between patients with and without pre-LT DM. Pairwise analysis using random effects with hazard ratios (HRs) was used to assess the longitudinal post-LT impacts of pre-LT DM. In the absence of HR, pooled odds ratios analysis was conducted for secondary outcomes. RESULTS: Forty-two studies involving 77,615 LT recipients were included in this analysis. The pooled prevalence of pre-LT DM amongst LT recipients was 24.79%. Pre-LT DM was associated with significantly lower overall survival (HR, 0.65; 95% confidence interval, 0.52-0.81; P<0.01) and significantly increased cardiovascular disease-related mortality (HR, 1.78; 95% confidence interval, 1.11-2.85; P=0.03). Meta-regression of other patient characteristics identified Asian ethnicity and hypertension to be significant predictors of worse overall survival, whereas African-American ethnicity was associated with significantly improved overall survival in patients with pre-LT DM. Further analysis of secondary outcomes revealed pre-LT DM to be a significant predictor of post-LT cardiovascular events and end-stage renal disease. CONCLUSIONS: The present study illustrates the impact of pre-LT DM on post-LT survival, and cardiovascular and renal outcomes and provides a sound basis for revision of preoperative management of pre-LT DM.

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