Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study.

BACKGROUND: Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure. METHODS: This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences. RESULTS: A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels. CONCLUSION: This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Prediction of clear cell renal cell carcinoma ≤ 4cm: visual assessment of ultrasound characteristics versus ultrasonographic radiomics analysis.

Objective: To investigate the diagnostic efficacy of the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model based on ultrasonographic radiomics for the differentiation of small clear cell Renal Cell Carcinoma (ccRCC) and Renal Angiomyolipoma (RAML). Methods: The clinical, ultrasound, and contrast-enhanced CT(CECT) imaging data of 302 small renal tumors (maximum diameter ≤ 4cm) patients in Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2022 were retrospectively analyzed, with 182 patients of ccRCC and 120 patients of RAML. The ultrasound images of the largest diameter of renal tumors were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from ROI segmented images. The patients were randomly divided into training and internal validation cohorts in the ratio of 7:3. The Random Forest algorithm of the Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model. The efficacy of the prediction models was verified in an independent external validation cohort consisting of 69 patients, from 230 small renal tumor patients in two different institutions. The Delong test compared the predictive ability of three models and CECT. Calibration Curve and clinical Decision Curve Analysis were applied to evaluate the model and determine the net benefit to patients. Results: 491 ultrasonographic radiomics features were extracted from 302 small renal tumor patients, and 9 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. In the internal validation cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy of the clinical ultrasound imaging model, ultrasonographic radiomics model, comprehensive model, and CECT were 0.75, 76.7%, 60.0%, 70.0%; 0.80, 85.6%, 61.7%, 76.0%; 0.88, 90.6%, 76.7%, 85.0% and 0.90, 92.6%, 88.9%, 91.1%, respectively. In the external validation cohort, AUC, sensitivity, specificity, and accuracy of the three models and CECT were 0.73, 67.5%, 69.1%, 68.3%; 0.89, 86.7%, 80.0%, 83.5%; 0.90, 85.0%, 85.5%, 85.2% and 0.91, 94.6%, 88.3%, 91.3%, respectively. The DeLong test showed no significant difference between the clinical ultrasound imaging model and the ultrasonographic radiomics model (Z=-1.287, P=0.198). The comprehensive model showed superior diagnostic performance than the ultrasonographic radiomics model (Z=4. 394, P<0.001) and the clinical ultrasound imaging model (Z=4. 732, P<0.001). Moreover, there was no significant difference in AUC between the comprehensive model and CECT (Z=-0.252, P=0.801). Both in the internal and external validation cohort, the Calibration Curve and Decision Curve Analysis showed a better performance of the comprehensive model. Conclusion: It is feasible to construct an ultrasonographic radiomics model for distinguishing small ccRCC and RAML based on ultrasound images, and the diagnostic performance of the comprehensive model is superior to the clinical ultrasound imaging model and ultrasonographic radiomics model, similar to that of CECT.

Dynamic risk prediction of survival in liver cirrhosis: A comparison of landmarking approaches.

Electronic health records (EHR) data provides the researcher and physician with the opportunity to improve risk prediction by employing newer, more sophisticated modeling techniques. Rather than treating the impact of predictor variables on health trajectories as static, we explore the use of time-dependent variables in dynamically modeling time-to-event data through the use of landmarking (LM) data sets. We compare several different dynamic models presented in the literature that utilize LM data sets as the basis of their approach. These techniques include using pseudo-means, pseudo-survival probabilities, and the traditional Cox model. The models are primarily compared with their static counterparts using appropriate measures of model discrimination and calibration based on what summary measure is employed for the response variable.

Effects of BBIBP-CorV vaccine on gut microbiota and short-chain fatty acids in mice exposed to bis (2-ethylhexyl) phthalate and dioctyl terephthalate.

As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.

Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial.

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Molecular Stratification and Treatment Monitoring of Lung Cancer Using a Small Extracellular Vesicle-Activated Nanocavity Architecture.

Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples (n = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.

MRI Investigation of the Association of Left Atrial and Left Atrial Appendage Hemodynamics with Silent Brain Infarction.

BACKGROUND: Left atrial (LA) myopathy is thought to be associated with silent brain infarctions (SBI) through changes in blood flow hemodynamics leading to thrombogenesis. 4D-flow MRI enables in-vivo hemodynamic quantification in the left atrium (LA) and LA appendage (LAA). PURPOSE: To determine whether LA and LAA hemodynamic and volumetric parameters are associated with SBI. STUDY TYPE: Prospective observational study. POPULATION: A single-site cohort of 125 Participants of the multiethnic study of atherosclerosis (MESA), mean age: 72.3 ± 7.2 years, 56 men. FIELD STRENGTH/SEQUENCE: 1.5T. Cardiac MRI: Cine balanced steady state free precession (bSSFP) and 4D-flow sequences. Brain MRI: T1- and T2-weighted SE and FLAIR. ASSESSMENT: Presence of SBI was determined from brain MRI by neuroradiologists according to routine diagnostic criteria in all participants without a history of stroke based on the MESA database. Minimum and maximum LA volumes and ejection fraction were calculated from bSSFP data. Blood stasis (% of voxels <10 cm/sec) and peak velocity (cm/sec) in the LA and LAA were assessed by a radiologist using an established 4D-flow workflow. STATISTICAL TESTS: Student's t test, Mann-Whitney U test, one-way ANOVA, chi-square test. Multivariable stepwise logistic regression with automatic forward and backward selection. Significance level P < 0.05. RESULTS: 26 (20.8%) had at least one SBI. After Bonferroni correction, participants with SBI were significantly older and had significantly lower peak velocities in the LAA. In multivariable analyses, age (per 10-years) (odds ratio (OR) = 1.99 (95% confidence interval (CI): 1.30-3.04)) and LAA peak velocity (per cm/sec) (OR = 0.87 (95% CI: 0.81-0.93)) were significantly associated with SBI. CONCLUSION: Older age and lower LAA peak velocity were associated with SBI in multivariable analyses whereas volumetric-based measures from cardiac MRI or cardiovascular risk factors were not. Cardiac 4D-flow MRI showed potential to serve as a novel imaging marker for SBI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Presentation, management, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study.

BACKGROUND: Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients.  Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients. METHODS: A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated. RESULTS: A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis. CONCLUSION: In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment.

Identification and functional characterization of a novel heterozygous splice­site mutation in the calpain 3 gene causes rare autosomal dominant limb­girdle muscular dystrophy.

Limb-girdle muscular dystrophies are a group of extremely heterogenous neuromuscular disorders that manifest with gradual and progressive weakness of both proximal and distal muscles. Autosomal dominant limb-girdle muscular dystrophy (LGMDD4) or calpainopathy is a very rare form of myopathy characterized by weakness and atrophy of both proximal and distal muscles with a variable age of onset. LGMDD4 is caused by germline heterozygous mutations of the calpain 3 (CAPN3) gene. Patients with LGMDD4 often show extreme phenotypic heterogeneity; however, most patients present with gait difficulties, increased levels of serum creatine kinase, myalgia and back pain. In the present study, a 16-year-old male patient, clinically diagnosed with LGMDD4, was investigated. The proband had been suffering from weakness and atrophy of both of their proximal and distal muscles, and had difficulty walking and standing independently. The serum creatine kinase levels (4,754 IU/l; normal, 35-232 IU/l) of the patient were markedly elevated. The younger sister and mother of the proband were also clinically diagnosed with LGMDD4, while the father was phenotypically normal. Whole exome sequencing identified a heterozygous novel splice-site (c.2440-1G>A) mutation in intron 23 of the CAPN3 gene in the proband. Sanger sequencing confirmed that this mutation was also present in both the younger sister and mother of the proband, but the father was not a carrier of this mutation. This splice-site (c.2440-1G>A) mutation causes aberrant splicing of CAPN3 mRNA, leading to the skipping of the last exon (exon 24) of CAPN3 mRNA and resulting in the removal of eight amino acids from the C-terminal of domain IV of the CAPN3 protein. Hence, this splice site mutation causes the formation of a truncated CAPN3 protein (p.Trp814*) of 813 amino acids instead of the wild-type CAPN3 protein that consists of 821 amino acids. This mutation causes partial loss of domain IV (PEF domain) in the CAPN3 protein, which is involved in calcium binding and homodimerization; therefore, this is a loss-of-function mutation. Relative expression of the mutated CAPN3 mRNA was reduced in comparison with the wild-type CAPN3 mRNA in the proband, and their younger sister and mother. This mutation was also not present in 100 normal healthy control individuals of the same ethnicity. The present study reported the first case of CAPN3 gene-associated LGMDD4 in the Chinese population.

High Sensitivity and Ultra-Broad-Range NH3 Sensor Arrays by Precise Control of Step Defects on The Surface of Cl2-Ndi Single Crystals.

Vapor sensors with both high sensitivity and broad detection range are technically challenging yet highly desirable for widespread chemical sensing applications in diverse environments. Generally, an increased surface-to-volume ratio can effectively enhance the sensitivity to low concentrations, but often with the trade-off of a constrained sensing range. Here, an approach is demonstrated for NH3 sensor arrays with an unprecedentedly broad sensing range by introducing controllable steps on the surface of an n-type single crystal. Step edges, serving as adsorption sites with electron-deficient properties, are well-defined, discrete, and electronically active. NH3 molecules selectively adsorb at the step edges and nearly eliminate known trap-like character, which is demonstrated by surface potential imaging. Consequently, the strategy can significantly boost the sensitivity of two-terminal NH3 resistance sensors on thin crystals with a few steps while simultaneously enhancing the tolerance on thick crystals with dense steps. Incorporation of these crystals into parallel sensor arrays results in ppb-to-% level detection range and a convenient linear relation between sheet conductance and semi-log NH3 concentration, allowing for the precise localization of vapor leakage. In general, the results suggest new opportunities for defect engineering of organic semiconductor crystal surfaces for purposeful vapor or chemical sensing.

Increasing prevalence of cirrhosis among insured adults in the United States, 2012-2018.

BACKGROUND: Liver cirrhosis is a chronic disease that is known as a "silent killer" and its true prevalence is difficult to describe. It is imperative to accurately characterize the prevalence of cirrhosis because of its increasing healthcare burden. METHODS: In this retrospective cohort study, trends in cirrhosis prevalence were evaluated using administrative data from one of the largest national health insurance providers in the US. (2011-2018). Enrolled adult (≥18-years-old) patients with cirrhosis defined by ICD-9 and ICD-10 were included in the study. The primary outcome measured in the study was the prevalence of cirrhosis 2011-2018. RESULTS: Among the 371,482 patients with cirrhosis, the mean age was 62.2 (±13.7) years; 53.3% had commercial insurance and 46.4% had Medicare Advantage. The most frequent cirrhosis etiologies were alcohol-related (26.0%), NASH (20.9%) and HCV (20.0%). Mean time of follow-up was 725 (±732.3) days. The observed cirrhosis prevalence was 0.71% in 2018, a 2-fold increase from 2012 (0.34%). The highest prevalence observed was among patients with Medicare Advantage insurance (1.67%) in 2018. Prevalence increased in each US. state, with Southern states having the most rapid rise (2.3-fold). The most significant increases were observed in patients with NASH (3.9-fold) and alcohol-related (2-fold) cirrhosis. CONCLUSION: Between 2012-2018, the prevalence of liver cirrhosis doubled among insured patients. Alcohol-related and NASH cirrhosis were the most significant contributors to this increase. Patients living in the South, and those insured by Medicare Advantage also have disproportionately higher prevalence of cirrhosis. Public health interventions are important to mitigate this concerning trajectory of strain to the health system.

Where you live matters: Area deprivation predicts poor survival and liver transplant waitlisting.

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

Incorporating longitudinal history of risk factors into atherosclerotic cardiovascular disease risk prediction using deep learning.

It is increasingly clear that longitudinal risk factor levels and trajectories are related to risk for atherosclerotic cardiovascular disease (ASCVD) above and beyond single measures. Currently used in clinical care, the Pooled Cohort Equations (PCE) are based on regression methods that predict ASCVD risk based on cross-sectional risk factor levels. Deep learning (DL) models have been developed to incorporate longitudinal data for risk prediction but its benefit for ASCVD risk prediction relative to the traditional Pooled Cohort Equations (PCE) remain unknown. Our study included 15,565 participants from four cardiovascular disease cohorts free of baseline ASCVD who were followed for adjudicated ASCVD. Ten-year ASCVD risk was calculated in the training set using our benchmark, the PCE, and a longitudinal DL model, Dynamic-DeepHit. Predictors included those incorporated in the PCE: sex, race, age, total cholesterol, high density lipid cholesterol, systolic and diastolic blood pressure, diabetes, hypertension treatment and smoking. The discrimination and calibration performance of the two models were evaluated in an overall hold-out testing dataset. Of the 15,565 participants in our dataset, 2170 (13.9%) developed ASCVD. The performance of the longitudinal DL model that incorporated 8 years of longitudinal risk factor data improved upon that of the PCE [AUROC: 0.815 (CI 0.782-0.844) vs 0.792 (CI 0.760-0.825)] and the net reclassification index was 0.385. The brier score for the DL model was 0.0514 compared with 0.0542 in the PCE. Incorporating longitudinal risk factors in ASCVD risk prediction using DL can improve model discrimination and calibration.

Risk Factors of Chronic Pulmonary Aspergillosis in Patients with Etiology Positive Pulmonary Tuberculosis.

Objective: Pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) have many similarities in clinical symptoms. In patients with etiology-positive pulmonary tuberculosis (EPTB), Aspergillus infection is easily overlooked, and missed diagnosis occurs. We attempted to analyze the clinical characteristics and risk factors of EPTB combined with CPA (EPTB-CPA), and to suggest to clinicians the possibility of CPA in EPTB patients. Methods: 58 patients with EPTB-CPA diagnosed and treated in Wuhan Pulmonary Hospital from April 2021 to March 2022 were retrospectively collected as the case group. According to the age group of the case group, 174 patients with EPTB were randomly selected as the control group at a ratio of 1:3. Multivariate logistic regression analysis was utilized to analyze the risk factors. Results: Multivariate Logistic regression analysis was performed on the pulmonary cavity, chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, lung damage, anemia, and hypoproteinemia. Among them, pulmonary cavity (P = .001), COPD (P = .006), and bronchiectasis (P = .020) were statistically significant. Conclusion: Our findings suggest that when EPTB patients present with pulmonary cavities and comorbidities such as COPD or bronchiectasis, clinicians should consider the possibility of CPA. Identifying these risk factors can help improve the accuracy of diagnosis and facilitate early detection and management of EPTB-CPA.

Brief PROMIS Assessment Screens for Frailty and Predicts Hospitalizations in Liver Transplant Candidates.

BACKGROUND: Frailty is prevalent in patients with end-stage liver disease and predicts waitlist mortality, posttransplant mortality, and frequency of hospitalizations. The Liver Frailty Index (LFI) is a validated measure of frailty in liver transplant (LT) candidates but requires an in-person assessment. METHODS: We studied the association between patient-reported physical function and LFI in a single-center prospective study of adult patients with cirrhosis undergoing LT evaluation from October 2020 to December 2021. Frailty was assessed with the LFI and 4-m gait speed. Patient-reported physical function was evaluated using a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Eighty-one LT candidates were enrolled, with a mean model of end-stage liver disease-sodium of 17.6 (±6.3). The mean LFI was 3.7 (±0.77; 15% frail and 59% prefrail) and the mean PROMIS Physical Function score was 45 (±8.6). PROMIS Physical Function correlated with LFI ( r = -0.54, P < 0.001) and 4-m gait speed ( r = 0.48, P < 0.001). The mean hospitalization rate was 1.1 d admitted per month. After adjusting for age, sex, and model of end-stage liver disease-sodium, patient-reported physical function-predicted hospitalization rate ( P = 0.001). CONCLUSIONS: This study suggests that a brief patient-reported outcome measure can be used to screen for frailty and predict hospitalizations in patients with cirrhosis.

Discordance of patient-reported outcome measures with objectively assessed walking decline in peripheral artery disease.

OBJECTIVE: Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown. METHODS: A total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0-4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline. RESULTS: At 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (-10 vs +15 meters; mean difference, -25; 95% confidence interval, -38 to -13; P < .01). CONCLUSIONS: Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD.

Vitamin D modulates disordered lipid metabolism in zebrafish (Danio rerio) liver caused by exposure to polystyrene nanoplastics.

In this study, zebrafish (Danio rerio) were exposed to polystyrene nanoplastics (PS-NPs, 80 nm) at 0, 15, or 150 µg/L for 21 days and supplied with a low or high vitamin D (VD) diet (280 or 2800 IU/kg, respectively, indicated by - or +) to determine whether and how VD can regulate lipid metabolism disorder induced by PS-NPs. Six groups were created according to the PS-NP concentration and VD diet status: 0-, 0+, 15-, 15+,150-, and 150 +. Transmission electron microscopy showed that PS-NPs accumulated in the livers of zebrafish, which led to large numbers of vacuoles and lipid droplets in liver cell matrices; this accumulation was most prominent in the 150- group, wherein the number of lipid droplets increased significantly by 136.36%. However, the number of lipid droplets decreased significantly by 76.92% in the 150+ group compared with the 150- group. An examination of additional biochemical indicators showed that the high VD diet partially reversed the increases in the triglyceride and total cholesterol contents induced by PS-NPs (e.g., triglycerides decreased by 58.52% in the 150+ group, and total cholesterol decreased by 44.64% in the 15+ group), and regulated lipid metabolism disorder mainly by inhibiting lipid biosynthesis. Untargeted lipidomics analysis showed that exposure to PS-NPs was associated mainly with changes in the lipid molecular content related to cell membrane function and lipid biosynthesis and that the high VD diet reduced the content of lipid molecules related to lipid biosynthesis, effectively alleviating cell membrane damage and lipid accumulation. These findings highlight the potential of VD to alleviate lipid metabolism disorder caused by PS-NP exposure, thereby providing new insights into how the toxic effects of NPs on aquatic organisms could be reduced.