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Foods (Basel, Switzerland) Jun 2024Metabolic syndrome (MetS) significantly predisposes individuals to diabetes and is a prognostic factor for the progression of diabetic nephropathy (DN). This study aimed...
Metabolic syndrome (MetS) significantly predisposes individuals to diabetes and is a prognostic factor for the progression of diabetic nephropathy (DN). This study aimed to evaluate the efficacy of (-)-gallocatechin gallate (GCG) in alleviating signs of MetS-associated DN in mice. We administered GCG and monitored its effects on several metabolic parameters, including food and water intake, urinary output, blood glucose levels, glucose and insulin homeostasis, lipid profiles, blood pressure, and renal function biomarkers. The main findings indicated that GCG intervention led to marked improvements in these metabolic indicators and renal function, signifying its potential in managing MetS and DN. Furthermore, transcriptome analysis revealed substantial modifications in gene expression, notably the downregulation of pro-inflammatory genes such as , , , , , , , -, , , and and the upregulation of the anti-oxidative gene . These genetic alterations suggest significant effects on pathways related to inflammation and oxidative stress. In conclusion, GCG demonstrates therapeutic efficacy for MetS-associated DN, mitigating metabolic disturbances and enhancing renal health by modulating inflammatory and oxidative responses.
PubMed: 38890983
DOI: 10.3390/foods13111755 -
Journal of Applied Genetics Jun 2024Water-Soluble Palm Fruit Extract (WSPFE) has been shown to confer anti-diabetic effects in the Nile rat (NR) (Arvicanthis niloticus). Liquid and powder WSPFE both...
Water-Soluble Palm Fruit Extract (WSPFE) has been shown to confer anti-diabetic effects in the Nile rat (NR) (Arvicanthis niloticus). Liquid and powder WSPFE both deterred diabetes onset in NRs fed a high-carbohydrate (hiCHO) diet, but the liquid form provided better protection. In this study, NRs were fed either a hiCHO diet or the same diet added with liquid or powder WSPFE. Following feeding of the diets for 8 weeks, random blood glucose levels were measured to categorize NRs as either diabetes-resistant or diabetes-susceptible, based on a cut-off value of 75 mg/dL. Livers were then obtained for Illumina HiSeq 4000 paired end RNA-sequencing (RNA-Seq) and the data were mapped to the reference genome. Consistent with physiological and biochemical parameters, the gene expression data obtained indicated that WSPFE was associated with protection against diabetes. Among hepatic genes upregulated by WSPFE versus controls, were genes related to insulin-like growth factor binding protein, leptin receptor, and processes of hepatic metabolism maintenance, while those downregulated were related to antigen binding, immunoglobulin receptor, inflammation- and cancer-related processes. WSPFE supplementation thus helped inhibit diabetes progression in NRs by increasing insulin sensitivity and reducing both the inflammatory effects of a hiCHO diet and the related DNA-damage compensatory mechanisms contributing to liver disease progression. In addition, the genetic permissiveness of susceptible NRs to develop diabetes was potentially associated with dysregulated compensatory mechanisms involving insulin signaling and oxidative stress over time. Further studies on other NR organs associated with diabetes and its complications are warranted.
PubMed: 38890243
DOI: 10.1007/s13353-024-00880-1 -
American Journal of Respiratory and... Jun 2024Many children undergo allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of malignant and non-malignant conditions. Unfortunately, pulmonary...
Detection of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation. An Official American Thoracic Society Clinical Practice Guideline.
BACKGROUND
Many children undergo allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of malignant and non-malignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common non-infectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent National Institutes of Health workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children.
METHODS
A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of post-HSCT BOS in children. Systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations.
RESULTS
The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed.
CONCLUSIONS
This document provides an evidence-based approach to detection of post-HSCT BOS in children, while also highlighting considerations for implementation of each recommendation. Further, the document describes important areas for future research.
PubMed: 38889365
DOI: 10.1164/rccm.202406-1117ST -
International Orthopaedics Jun 2024Acute compartment syndrome (ACS) remains a devastating complication of orthopaedic trauma. The tibial diaphysis is especially implicated in the development of ACS, both...
PURPOSE
Acute compartment syndrome (ACS) remains a devastating complication of orthopaedic trauma. The tibial diaphysis is especially implicated in the development of ACS, both at the time of injury and after operative management. Identification of risk factors for ACS for these distinct scenarios has been investigated in a large cohort of patients.
METHODS
This is a retrospective cohort study of all adults (age 18 years and older) presenting to a level 1 trauma centre with a diaphyseal tibia fracture. ACS was determined by a combination of clinical signs and symptoms and compartmental pressure monitoring. Potential risk factors were subject to univariate analysis with significant variables undergoing binary logistic regression analysis.
RESULTS
1147 tibial diaphyseal fractures over a twelve year period were studied. Age, multifragmented fracture pattern, male gender, high energy mechanism and intra- articular extension all showed a statistically significant association for ACS. Increasing body mass index (BMI) and treatment with an intramedullary nail favoured development of ACS post-operatively.
CONCLUSION
Risk factors for the development of ACS specifically in tibial diaphyseal fractures have been highlighted. Patients managed with IMN or high BMI may warrant particular observation following operative intervention.
PubMed: 38888756
DOI: 10.1007/s00264-024-06235-z -
Annals of Emergency Medicine Jun 2024The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI)...
STUDY OBJECTIVE
The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol.
METHODS
The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI.
RESULTS
There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68).
CONCLUSION
A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.
PubMed: 38888531
DOI: 10.1016/j.annemergmed.2024.04.024 -
The Annals of Pharmacotherapy Jun 2024To review the literature leading to the Food and Drug Administration (FDA) approval of the first medication, resmetirom, for the treatment of nonalcoholic... (Review)
Review
OBJECTIVE
To review the literature leading to the Food and Drug Administration (FDA) approval of the first medication, resmetirom, for the treatment of nonalcoholic steatohepatitis (NASH), including the pharmacology, pharmacokinetics, clinical studies, dosing, and adverse effects. Relevant data will be used to discuss how resmetirom impacts clinical practice.
DATA SOURCES
A literature search was conducted using MEDLINE from database inception to May 12, 2024. Keywords included non-alcoholic steatohepatitis, nonalcoholic fatty liver disease, and resmetirom. Study selection, data extraction and all English-language studies involving the use of resmetirom for nonalcoholic fatty liver disease (NAFLD)/NASH were included.
DATA SYNTHESIS
Resmetirom, a thyroid hormone receptor agonist, is administered at daily doses of either 80 mg or 100 mg. The drug was shown to provide NASH resolution as assessed by the NAFLD activity score, 80 mg-24.2%, 100 mg-25.9% compared to 14.2% with the placebo group ( < 0.001). Resmetirom, improved liver fibrosis, 80 mg-25.9%, 100 mg-29.9% compared to 9.7% with the placebo group ( < 0.001). Resmetirom's ability to improve fibrosis in patients with F2-F3 fibrosis offers valuable benefit for patients at risk of progressing to cirrhosis.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Resmetirom expands the medication options available to treat patients with NASH which can be given alongside other medications to optimize metabolic factors such as glucagon-like peptide-1 and hydroxymethylglutaryl-coenzyme A reductase inhibitors. Resmetirom was well tolerated in studies.
CONCLUSION
Resmetirom serves as an attractive option in patients diagnosed with NASH with evidence of advanced fibrosis (F2-F3) in combination with exercise, diet, and other multimodal therapies targeting metabolic risk factors.
PubMed: 38887011
DOI: 10.1177/10600280241259528 -
Diabetology & Metabolic Syndrome Jun 2024Elevations in the gut metabolite trimethylamine-N-oxide (TMAO) have been linked to cardiovascular and metabolic diseases. Whether elevated TMAO levels reflect early...
BACKGROUND
Elevations in the gut metabolite trimethylamine-N-oxide (TMAO) have been linked to cardiovascular and metabolic diseases. Whether elevated TMAO levels reflect early mechanistic involvement or a sequela of evolving disease awaits elucidation. The purpose of this study was to further explore these potential associations.
METHODS
We investigated relationships between circulating levels of TMAO and its pre-cursor substrates, dietary factors, gut microbiome profiles and disease risk in individuals with a Healthy BMI (18.5 < BMI < 25, n = 41) or key precursor states for cardiometabolic disease: Overweight (25 < BMI < 30 kg/m, n = 33), Obese (BMI > 30, n = 27) and Metabolic Syndrome (MetS; ≥ 3 ATPIII report criteria, n = 39).
RESULTS
Unexpectedly, plasma [TMAO] did not vary substantially between groups (means of 3-4 µM; p > 0.05), although carnitine was elevated in participants with MetS. Gut microbial diversity and Firmicutes were also significantly reduced in the MetS group (p < 0.05). Exploratory analysis across diverse parameters reveals significant correlations between circulating [TMAO] and seafood intake (p = 0.007), gut microbial diversity (p = 0.017-0.048), and plasma [trimethylamine] (TMA; p = 0.001). No associations were evident with anthropometric parameters or cardiometabolic disease risk. Most variance in [TMAO] within and between groups remained unexplained.
CONCLUSIONS
Data indicate that circulating [TMAO] may be significantly linked to seafood intake, levels of TMA substrate and gut microbial diversity across healthy and early disease phenotypes. However, mean concentrations remain < 5 µM, with little evidence of links between TMAO and cardiometabolic disease risk. These observations suggest circulating TMAO may not participate mechanistically in cardiometabolic disease development, with later elevations likely a detrimental sequela of extant disease.
PubMed: 38886825
DOI: 10.1186/s13098-024-01368-y -
Journal of the American Academy of... Jun 2024This study compared trends in use, predictive factors, and reimbursement of endoscopic carpal tunnel release (ECTR) withthose of open carpal tunnel release (OCTR) from... (Comparative Study)
Comparative Study
BACKGROUND
This study compared trends in use, predictive factors, and reimbursement of endoscopic carpal tunnel release (ECTR) withthose of open carpal tunnel release (OCTR) from 2010 to 2021 using a national administrative database.
METHODS
ECTR and OCTR patients were identified in the PearlDiver M151Ortho data set. Numeric and proportional utilization of these procedures was characterized for each year of study. Multivariate analysis was conducted to identify predictive factors for having ECTR performed. The average 90-day reimbursement of ECTR and OCTR was determined.
RESULTS
From 2010 through 2021, 441,023 ECTR and 1,767,820 OCTR procedures were identified. The proportional use of ECTR compared with OCTR rose from 2010 (15.7% of procedures) to 2021 (26.1%). Independent predictors of having ECTR performed rather than OCTR included geographic variation (compared with having surgery in the Midwest, Northeast odds ratio [OR], 1.53; West OR, 1.62; and South OR, 1.66), having Medicare or commercial insurance (compared with commercial, Medicare OR, 0.94, and Medicaid OR, 0.69), female sex, and fewer comorbidities. The average 90-day reimbursement for ECTR was $3,114.82, compared with $3,087.62 for OCTR.
DISCUSSION
As of 2021, over one-fourth of carpal tunnel releases are done endoscopically. Several factors independently predict whether patients receive ECTR or OCTR.
Topics: Humans; Carpal Tunnel Syndrome; Female; Male; Middle Aged; Endoscopy; Aged; United States; Adult; Decompression, Surgical; Databases, Factual; Medicare
PubMed: 38885416
DOI: 10.5435/JAAOSGlobal-D-24-00077 -
Journal of Investigative Medicine High... 2024The , a black scorpion species endemic to the fauna of Trinidad, has been implicated in envenomation with devastating clinical sequelae such as acute pancreatitis and...
The , a black scorpion species endemic to the fauna of Trinidad, has been implicated in envenomation with devastating clinical sequelae such as acute pancreatitis and major adverse cardiovascular events. We present the first in-Caribbean case of a 59-year-old Caribbean South Asian male with human immunodeficiency virus who presented with a non-ST-segment-elevation acute coronary syndrome after being stung, which was managed with comprehensive, guideline-directed medical therapy. The clinician should be cognizant of scorpion-induced acute coronary syndrome (ACS) as a potential sequela of envenomation and its clinical management.
Topics: Humans; Male; Acute Coronary Syndrome; Middle Aged; Scorpion Stings; Animals; Electrocardiography; Scorpions; Trinidad and Tobago
PubMed: 38884537
DOI: 10.1177/23247096241261255 -
Indian Journal of Otolaryngology and... Jun 2024Osmotic Demyelination Syndrome (ODS) is one of the primary cause of demyelination in alcoholics and malnourished resulting in various kind of clinical manifestations in...
Osmotic Demyelination Syndrome (ODS) is one of the primary cause of demyelination in alcoholics and malnourished resulting in various kind of clinical manifestations in pontine symptoms, neuro-behavioural symptoms movement disorders as well as speech and language and swallowing difficulties. The study was done to introspect the prognosis of swallowing therapy in a patient with ODS using MASA (Mann Assessment of Swallowing Ability). A 36 years old male with a history of regular alcohol intake and hypertensiom reported in our healthcare centre with hypoaklemia and speech, language and swallowing difficulty. Magnetic resonance imaging of the brain showed bilateral symmetrical T2 and T2 FLAIR (fluid attenuated inversion recovery) hyperintensity lesion in the bilateral basal ganglia involving the caudate nuclei, putaminal region and bilateral thalami with similar lesion along the mid brain. There were no areas of acute restriction in diffusion study. The findings suggested of Osmotic Demyelination Syndrome (ODS).When accessed with N-DAT, WAB and MASA; patient was diagnosed with Spastic Dysarthria, Transcortical Motor Aphasia and Moderate Dysphagia. Intervention was provided using speech and swallowing therapy and when introspected with MASA scores, improvement was seen within 5 days and statistically 97% of variance was seen inferring the progressing trend in the MASA scores. This study concludes that MASA can be an effective tool in introspecting the prognosis of Dysphagia in ODS and early intervention in the management of dysphasia shows positive results.
PubMed: 38883499
DOI: 10.1007/s12070-023-04457-y