PHES scores have limited impact on the risk of overt HE in patients with minimal HE.

BACKGROUND: Minimal hepatic encephalopathy, defined by the portosystemic hepatic encephalopathy score (PHES), is associated with a higher risk of subsequent OHE. It remains unclear if there is a stepwise increase in OHE risk with worse PHES results. METHODS: In this multicenter study, patients with minimal hepatic encephalopathy, as defined by abnormal PHES, were followed for OHE development. RESULTS: In all, 207 patients were included. There was no stepwise increase in OHE risk with worse PHES results. CONCLUSIONS: Abnormal PHES is associated with a higher OHE risk, but we found no stepwise increase in OHE risk with worse PHES results below the established cutoff.

How effective is topical miconazole or amorolfine for mild to moderately severe onychomycosis in primary care: the Onycho Trial - a randomised double-blind placebo-controlled trial.

OBJECTIVES: To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. DESIGN: Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio. SETTING: Primary care, recruitment from February 2020 to August 2022. PARTICIPANTS: 193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)). INTERVENTIONS: Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution). MAIN OUTCOME MEASURES: Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability. RESULTS: Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability. CONCLUSIONS: Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis. TRIAL REGISTRATION NUMBER: WHO ICTRP NL8193.

The severity of COVID-19 upon hospital admission is associated with plasma omega-3 fatty acids.

Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids-eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)-as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p < 0.001) and Interleukin-6 (p = 0.002). Furthermore, the concentration of F2-Isoprostanes was higher in Group 4 than in Group 1 (p = 0.009), while no significant changes were observed for other oxylipins among groups. Multivariate analysis did not present any standard of biomarkers, suggesting the high complexity of factors involved in the disease severity. Our hypothesis was confirmed in terms of EPA/AA ratio. A higher EPA/AA ratio upon hospital admission was found to be associated with lower concentration of C-Reactive Protein and Interleukin-6, leading to a better prognosis of hospitalized SARS-CoV-2 patients. Importantly, this beneficial outcome was achieved without any form of supplementation. The trial also provides important information that can be further applied to reduce the severity of infections associated with an uncontrolled synthesis of pro-inflammatory cytokines.Trial registration: https://clinicaltrials.gov/study/NCT04449718 -01/06/2020. ClinicalTrials.gov Identifier: NCT04449718.

Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity.

COVID-19, caused by SARS-CoV-2, can lead to a severe inflammatory disease characterized by significant lymphopenia. However, the underlying cause for the depletion of T-cells in COVID-19 patients remains incompletely understood. In this study, we assessed the presence of different T-cell subsets in the progression of COVID-19 from mild to severe disease, with a focus on TCF1 expressing progenitor T-cells that are needed to replenish peripheral T-cells during infection. Our results showed a preferential decline in TCF1+ progenitor CD4 and CD8+ T-cells with disease severity. This decline was seen in various TCF1+ subsets including naive, memory and effector-memory cells, and surprisingly, was accompanied by a loss in cell division as seen by a marked decline in Ki67 expression. In addition, TCF1+ T-cells showed a reduction in pro-survival regulator, BcL2, and the appearance of a new population of TCF1 negative caspase-3 expressing cells in peripheral blood from patients with severe disease. The decline in TCF1+ T-cells was also seen in a subgroup of severe patients with vitamin D deficiency. Lastly, we found that sera from severe patients inhibited TCF1 transcription ex vivo which was attenuated by a blocking antibody against the cytokine, interleukin-12 (IL12). Collectively, our findings underscore the potential significance of TCF1+ progenitor T-cells in accounting for the loss of immunity in severe COVID-19 and outline an array of markers that could be used to identify disease progression.

Health locus of control and symptom distress: The mediating role of illness acceptance and symptom severity in acute leukemia patients.

OBJECTIVE: This study aims to explore the multiple mediating roles of illness acceptance and symptom severity between health locus of control and symptom distress in acute leukemia patients. METHODS: From June 2022 to March 2023, a convenience sampling method was used to recruit 208 acute leukemia patients in the inpatient center of a hospital in Hebei. The Chinese versions of Multidimensional Health Locus of Control Scale, Illness Acceptance Scale, and Anderson Symptom Assessment Scale was used in the cross-sectional study. RESULTS: All participants reported the presence of symptom distress. Symptom distress was significantly correlated with chance health locus of control, illness acceptance, and symptom severity (P＜0.05). Illness acceptance alone played a mediating role in the relationship between chance health locus of control and symptom distress in acute leukemia patients (ß=0.087, 95%CI 0.030-0.167). The indirect role of chance health locus of control on symptom distress through symptom severity alone was also statistically significant (ß=0.131, 95%CI 0.008-0.252). Furthermore, the multiple mediating role of chance health locus of control and symptom distress through illness acceptance and symptom severity combined was verified (ß=0.027, 95%CI 0.001-0.089). The alternative model is also valid, indicating bidirectional relationships between symptom severity, illness acceptance, and chance health locus of control, collectively influencing symptom distress. CONCLUSION: There is a positive relationship between chance health locus of control and symptom distress; additionally, increasing social psychological interventions for illness acceptance and strengthening the management of core symptoms will help alleviate the impact of health chance locus of control on symptom distress in acute leukemia patients. Longitudinal studies are needed to confirm the causal relationships among the variables explored within the model. IMPACT ON NURSING PRACTICE: It is recommended that healthcare professionals pay attention to the assessment of health locus of control in patients, identify patients with health chance locus of control in a timely manner, take measures to enhance their disease acceptance, and strengthen the management of core symptoms, thereby reducing their level of symptom distress.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Diet-induced obesity affects influenza disease severity and transmission dynamics in ferrets.

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesity's impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.

Early predictors of severe left main and/or three-vessel disease in patients with non-ST-segment elevation myocardial infarction: A dual-center retrospective study.

BACKGROUND: Early detection of patients concomitant with left main and/or three-vessel disease (LM/3VD) and high SYNTAX score (SS) is crucial for determining the most effective revascularization options regarding the use of antiplatelet medications and prognosis risk stratification. However, there is a lack of study for predictors of LM/3VD with SS in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We aimed to identify potential factors that could predict LM/3VD with high SS (SS > 22) in patients with NSTEMI. METHODS: This dual-center retrospective study included a total of 481 patients diagnosed with NSTEMI who performed coronary angiography procedures. Clinical factors on admission were collected. The patients were divided into non-LM/3VD, Nonsevere LM/3VD (SS ≤ 22), and Severe LM/3VD (SS > 22) groups. To identify independent predictors, Univariate and logistic regression analyses were conducted on the clinical parameters. RESULTS: A total of 481 patients were included, with an average age of 60.9 years and 75.9% being male. Among these patients, 108 individuals had severe LM/3VD. Based on the findings of a multivariate logistic regression analysis, the extent of ST-segment elevation observed in lead aVR (OR: 7.431, 95% CI: 3.862-14.301, p < .001) and age (OR: 1.050, 95% CI: 1.029-1.071, p < .001) were identified as independent predictors of severe LM/3VD. CONCLUSION: This study indicated that the age of patients and the extent of ST-segment elevation observed in lead aVR on initial electrocardiogram were the independent predictive factors of LM/3VD with high SS in patients with NSTEMI.

The prognostic value of lung ultrasound score (LUSS) in patients with COVID-19 admitted in Emergency Department: a prospective observational study.

BACKGROUND: The Lung Ultrasound (LUS) is routinely used as a point-of-care imaging tool in Emergency Department (ED) and its role in COVID-19 is being studied. The Lung UltraSound Score (LUSS) is a semi quantitative score of lung damage severity. Alongside instrumental diagnostic, the PaO2/FiO2 (P/F) ratio, obtained from arterial blood gas analysis, is the index used to assess the severity of the acute respiratory distress syndrome (ARDS), according to the Berlin definition. OBJECTIVES: The primary objective of the study was to evaluate a possible correlation between the LUSS score and the P/F Ratio, obtained from the arterial sampling in COVID-19 positive patients. MATERIALS AND METHODS: This was a cross-perspective monocentric observational study and it was carried out in the Emergency Department of the "AOU delle Marche" (Ancona, Italy), from 1 January 2023 to 28 February 2023. The study foresaw, once the patient was admitted to the ED, the execution of the LUS exam and the subsequent calculation of the LUSS score. RESULTS: The sample selected for the study was of 158 patients. The proportion of LUSS ≤4 was statistically higher in those with a P/F >300 (76.2%), compared to those with a P/F ≤300 (13.2%). On the other end, the proportion of LUSS >4 was lower in those who have P/F >300 (23.8%), while it was higher in those who have P/F ≤300 (86.8%). Those patients with a LUSS >4 were 1.76 (95% CI: 1.57 - 1.99) times more likely to have a P/F ≤300, compared to those with LUSS ≤4. The Odds Ratio of having a P/F ≤300 value in those achieving a LUSS >4, compared to those achieving a LUSS ≤4, was 21.0 (95% CI: 8.4 - 52.4). The study identified pO2, Hb and dichotomous LUSS as predictors of the level of P/F ≤300 or P/F >300. DISCUSSION: We found that the LUSS score defined by our study was closely related to the P/F ratio COVID-19 positive patients. Our study presented provides evidence on the potential rule of the LUSS for detecting the stage of lung impairment and the need for oxygen therapy in COVID-19 positive patients.

Study protocol: Early neurological deterioration in patients with minor stroke, frequency, predictors, and outcomes in Vietnam single-centre study.

Early neurological deterioration (END) is progressive neurological deterioration with an increase in NIHSS score of 2 points or more in the first 72 hours from the onset of acute ischemic stroke. END increases the risk of poor clinical outcomes at day 90 of ischemic stroke. We will study the frequency, predictors, and outcomes of patients with END in a case-control study at a comprehensive stroke centre in Vietnam. of the design is a descriptive observational study, longitudinal follow-up of patients with minor stroke hospitalized at the Stroke Center of Bach Mai Hospital from December 1, 2023, to December 1, 2024. Minor stroke patients characterized by NIHSS score ≤ 5 hospitalized within 24 hours of symptom onset will be recruited. The estimated END rate is about 30%, relative accuracy ε = 0.11, 95% reliability, expected 5% of patients lost data or follow-up, and an estimated sample size of 779 patients. This study will help determine the END rate in patients with minor stroke and related factors, thereby building a prognostic model for END. Our study determined the END rate in patients with minor stroke in Vietnam and also proposed risk factors for minor stroke management and treatment.

Relationship of regional ultraviolet index data with rash and systemic disease activity in youth with childhood-onset systemic lupus: results from the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To investigate the association between ultraviolet light index (UVI), as a marker for UV exposure, and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained zipcode level UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression models to examine associations between regional UVI (by zipcode)/season and odds of rash and severe SLEDAI-2 K score (≥ 5 vs. 0-4), adjusting for age, sex, race and income. RESULTS: Among 1222 participants, with a mean of 2.3 visits per participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2 K score ≥ 5. There were no associations between UVI during the month prior to visit or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but not increased disease activity. CONCLUSION: This study found no association between UVI and rash or UVI and disease activity. However, further studies directly measuring UV exposure and accounting for patient-level protective behavioral measures may help to better understand the complex relationship between sun exposure and SLE disease activity.

Gender differences in PTSD severity and pain outcomes: Baseline results from the LAMP trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms. AIM: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. METHODS: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. RESULTS: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). CONCLUSION: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

TYK2, IFITM3, IFNAR2 and OAS3 single-nucleotide polymorphisms among severe COVID-19 ICU patients in Morocco.

OBJECTIVES: This study aimed to explore the potential correlation between specific single nucleotide polymorphisms (TYK2, IFITM3, IFNAR2, and OAS3 variants) and the severity of COVID-19 in Moroccan patients. METHODS: A genetic analysis was conducted on 109 patients with PCR-confirmed SARS-CoV-2 infection in Morocco. Among these patients, 46% were hospitalized in the intensive care unit, while 59% were not hospitalized. Importantly, all patients lacked known risk factors associated with COVID-19 severity. Genotyping was performed to identify variations in TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079. Statistical analysis was applied using codominant, dominant and recessive logistic regression models to assess correlations with COVID-19 severity. RESULTS: Our findings revealed no significant correlation between TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079 with COVID-19 severity in Moroccan patients, as indicated in logistic regression models (p > .05). Interestingly, these results may offer insights into the mitigated impact of the COVID-19 pandemic and the reduced severity observed in SARS-CoV-2 infected patients in Morocco. Age, however, exhibited a significant correlation with severity (p < .001), with a trend towards increased likelihood of ICU admission with advancing age. Additionally, In the severe group, a higher proportion of patients were females (54%), indicating a statistically significant correlation with disease severity (p = .04). Nevertheless, female ICU patients aged above 60 years accounted for 37%, compared to 17% for males. CONCLUSION: This study underscores the absence of a genetic association between the selected polymorphisms and COVID-19 severity in Moroccan patients. Advanced age emerges as the primary factor influencing the severity of COVID-19 patients without comorbidities. We recommend setting the threshold for advanced age at 60 years as a risk factor for severe forms of COVID-19.

Comparison of Contemporary Treatment Strategies in Patients With Cardiogenic Shock Due to Severe Aortic Stenosis.

BACKGROUND: The aims of this study were to understand the incidence and outcomes of patients with cardiogenic shock (CS) due to severe aortic stenosis (AS), and the impact of conventional treatment strategies in this population. METHODS AND RESULTS: All patients admitted to the Cleveland Clinic cardiac intensive care unit between January 1, 2010 and December 31, 2021 with CS were retrospectively identified and categorized into those with CS in the setting of severe AS versus CS without AS. The impact of various treatment strategies on mortality was further assessed. We identified 2754 patients with CS during the study period, of whom 216 patients (8%) had CS in the setting of severe AS. Medical management was associated with the highest 30-day mortality when compared with either balloon aortic valve replacement or aortic valve replacement (surgical or transcatheter aortic valve replacement) (hazard ratio, 3.69 [95% CI, 2.04-6.66]; P<0.0001). Among patients who received transcatheter therapy, 30-day mortality was significantly higher in patients who received balloon aortic valvuloplasty versus transcatheter aortic valve replacement (26% versus 4%, P=0.02). Both surgical and transcatheter aortic valve replacement had considerably lower mortality than medical management and balloon aortic valvuloplasty at 30 days and 1 year (P<0.05 for both comparisons). CONCLUSIONS: CS due to severe AS is associated with high in-hospital and 30-day mortality, worse compared with those with CS without AS. In suitable patients, urgent surgical aortic valvuloplasty or transcatheter aortic valve replacement is associated with favorable short- and long-term outcomes. Although balloon aortic valvuloplasty may be used to temporize patients with CS in the setting of severe AS, mortality is ≈50% if not followed by definitive aortic valve replacement within 90 days.

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

Influence of nonalcoholic fatty liver disease severity on carotid adventitial vasa vasorum.

Introduction: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the world's population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis. Material and methods: This cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery. Results: Results revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density. Conclusion: These findings suggest that NASH severity doesn't independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.

FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. AIM: To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. METHODS: A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). RESULTS: MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. CONCLUSION: FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.

Resultados tras 5 años de cirugía o abordaje percutáneo en coronariopatía grave. Metanálisis de ensayos aleatorizados con reconstrucción del tiempo hasta el evento / Results beyond 5-years of surgery or percutaneous approach in severe coronary disease. Reconstructed time-to-event meta-analysis of randomized trials

Introducción y objetivos: Existe controversia sobre la mejor estrategia de revascularización en la enfermedad coronaria avanzada, incluidas la enfermedad del tronco coronario y la enfermedad multivaso. Varios metanálisis han comparado resultados a 5 años, pero no hay resultados después del quinto año. Se realizaron una revisión sistemática y un metanálisis de ensayos clínicos aleatorizados para comparar los resultados después del quinto año entre la cirugía de revascularización coronaria (CABG) y la intervención coronaria percutánea (ICP) con stents farmacoactivos.MétodosSe analizaron los ensayos clínicos publicados entre 2010 y 2023. El objetivo primario fue la mortalidad por cualquier causa. Las bases de datos originales se reconstruyeron a partir de las curvas de Kaplan-Meier simulando un metanálisis individual. Se realizaron comparaciones en ciertos puntos de corte (5 y 10 años). Se calculó la diferencia del tiempo medio de supervivencia restringida. Se aplicó el modelo de efectos aleatorios y de DerSimonian-Laird.ResultadosSe analizó a 5.180 pacientes. Durante los 10 años de seguimiento, las ICP muestran una mayor incidencia de mortalidad (HR=1,19; IC95%, 1,04-1,32; p=0,008). La ICP muestra un mayor riesgo de mortalidad a 5 años (HR=1,2; IC95%, 1,06-1,53; p=0,008), mientras que no hubo diferencias de 5 a 10 años (HR=1,03; IC95%, 0,84-1,26; p=0,76). La esperanza de vida de los pacientes sometidos a CABG fue ligeramente mayor (2,4 meses más).ConclusionesEntre los pacientes con enfermedad coronaria avanzada, incluidas la enfermedad del tronco coronario y la enfermedad multivaso, hubo mayor mortalidad tras una ICP que tras la CABG a los 10 años de seguimiento. En concreto, la ICP tiene mayor mortalidad durante los primeros 5 años y un riesgo comparable de 5 a 10 años. (AU)

Introduction and objectives: There is controversy about the optimal revascularization strategy in severe coronary artery disease (CAD), including left main disease and/or multivessel disease. Several meta-analyses have analyzed the results at 5-year follow-up but there are no results after the fifth year. We conducted a systematic review and meta-analysis of randomized clinical trials, comparing results after the fifth year, between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) using drug-eluting stents in patients with severe CAD.MethodsWe analyzed all clinical trials between January 2010 and January 2023. The primary endpoint was all-cause mortality. The databases of the original articles were reconstructed from Kaplan-Meier curves, simulating an individual-level meta-analysis. Comparisons were made at certain cutoff points (5 and 10 years). The 10-year restricted median survival time difference between CABG and PCI was calculated. The random effects model and the DerSimonian-Laird method were applied.ResultsThe meta-analysis included 5180 patients. During the 10-year follow-up, PCI showed a higher overall incidence of all-cause mortality (HR, 1.19; 95%CI, 1.04-1.32; P=.008)]. PCI showed an increased risk of all-cause mortality within 5 years (HR, 1.2; 95%CI, 1.06-1.53; P=.008), while no differences in the 5–10-year period were revealed (HR, 1.03; 95%CI, 0.84-1.26; P=.76). Life expectancy of CABG patients was slightly higher than that of PCI patients (2.4 months more).ConclusionsIn patients with severe CAD, including left main disease and/or multivessel disease, there was higher a incidence of all-cause mortality after PCI compared with CABG at 10 years of follow-up. Specifically, PCI has higher mortality during the first 5 years and comparable risk beyond 5 years. (AU)