-
Journal of Cardiac Failure Feb 2020Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart...
Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart failure (HF), and whether the association, if present, is causal. A systematic search for publications that report coexisting zinc deficiency in patients with HF was performed to provide an overview of the pathophysiological and epidemiological aspects of this association (last search April 2019). Review of the literature suggests multiple potential pathophysiologic causes for zinc deficiency in HF as a result of impaired micronutrient consumption, hyper-inflammatory state, upregulation of the renin-angiotensin-aldosterone axis, diminished absorption, and hyperzincuria from HF medications. In a longitudinal study of patients with HF in the setting of intestinal malabsorption, there was partial cardiomyocyte and left ventricular ejection fraction recovery with intravenous selenium and zinc supplementation. Two randomized double-blind control trials evaluating micronutrient and macronutrient supplementation including zinc in patients with HF found improvement in echocardiographic findings compared with placebo. Two recently completed studies evaluated the role for zinc supplementation in 2 different HF populations: a trial of zinc supplementation in patients with non-ischemic HF, and a trial of micronutrient supplementation (including B vitamins, vitamin D, and zinc) in veterans with systolic dysfunction; the results of which are still pending. Several pathobiological pathways to link zinc deficiency with the development and deterioration of HF are presented. Preliminary clinical data are supportive of such an association and future studies should further investigate the effects of zinc supplementation on outcomes in patients with HF.
Topics: Cross-Sectional Studies; Heart Failure; Humans; Longitudinal Studies; Protein Structure, Secondary; Zinc
PubMed: 31935458
DOI: 10.1016/j.cardfail.2020.01.005 -
Orphanet Journal of Rare Diseases Oct 2020N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia... (Review)
Review
BACKGROUND
N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management.
METHODS
Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers.
RESULTS
In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported.
CONCLUSIONS
Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.
Topics: Amino-Acid N-Acetyltransferase; Ammonia; Humans; Hyperammonemia; Infant, Newborn; Urea Cycle Disorders, Inborn
PubMed: 33036647
DOI: 10.1186/s13023-020-01560-z -
Research and Practice in Thrombosis and... Aug 2023Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population...
BACKGROUND
Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis.
METHODS
Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical.
RESULTS
Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study.
CONCLUSION
The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.
PubMed: 37674867
DOI: 10.1016/j.rpth.2023.102157 -
Biochemical Pharmacology Dec 2023Adiponectin replacement therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how adiponectin acts against... (Review)
Review
Adiponectin replacement therapy holds the potential to benefit numerous human diseases, and ongoing research applies particular interest in how adiponectin acts against Metabolic-associated Fatty Liver Disease (MAFLD) and Nonalcoholic Steatohepatitis (NASH). However, the pharmacological limitations of the intact protein have prompted a focus on alternative options, specifically peptidic and small molecule agonists targeting the adiponectin receptor. AdipoRon is an extensively researched non-peptidic drug candidate in adiponectin replacement therapy. In turn, ADP355 is an adiponectin-based active short peptide. They have garnered significant attention due to their potential as substitutes for adiponectin. Researchers have studied AdipoRon's and ADP355's efficacy and therapeutic applications in various disease conditions. However, the effects of AdipoRon and ADP355 against NAFLD and NASH models advanced more, and no systematic review explored this area before. This systematic review was conceived to address the deficiency mentioned above and consider the lack of clinical evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. To assess the risk of bias in systematic review, The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed. Results from pre-clinical evidence show that AdipoRon and ADP355 represent promising effects in NAFLD and NASH-related models, including reducing hepatic steatosis, modulating inflammation, improving insulin sensitivity, enhancing mitochondrial function, and protecting against liver fibrosis. While AdipoRon and ADP355 exhibit promise in pre-clinical studies and experimental models, additional clinical trials are necessary to assess their effectiveness, safety, and potential translational therapeutic potential uses in NAFLD and NASH human cases.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Receptors, Adiponectin; Adiponectin
PubMed: 37866803
DOI: 10.1016/j.bcp.2023.115871 -
EMBO Molecular Medicine Dec 2021The cardinal stages of macroautophagy are driven by core autophagy-related (ATG) proteins, whose ablation largely abolishes intracellular turnover. Disrupting ATG genes... (Review)
Review
The cardinal stages of macroautophagy are driven by core autophagy-related (ATG) proteins, whose ablation largely abolishes intracellular turnover. Disrupting ATG genes is paradigmatic of studying autophagy deficiency, yet emerging data suggest that ATG proteins have extensive biological importance beyond autophagic elimination. An important example is ATG7, an essential autophagy effector enzyme that in concert with other ATG proteins, also regulates immunity, cell death and protein secretion, and independently regulates the cell cycle and apoptosis. Recently, a direct association between ATG7 dysfunction and disease was established in patients with biallelic ATG7 variants and childhood-onset neuropathology. Moreover, a prodigious body of evidence supports a role for ATG7 in protecting against complex disease states in model organisms, although how dysfunctional ATG7 contributes to manifestation of these diseases, including cancer, neurodegeneration and infection, in humans remains unclear. Here, we systematically review the biological functions of ATG7, discussing the impact of its impairment on signalling pathways and human pathology. Future studies illuminating the molecular relationship between ATG7 dysfunction and disease will expedite therapies for disorders involving ATG7 deficiency and/or impaired autophagy.
Topics: Apoptosis; Autophagy; Autophagy-Related Protein 7; Child; Humans; Signal Transduction
PubMed: 34725936
DOI: 10.15252/emmm.202114824 -
The Cochrane Database of Systematic... Nov 2022Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the... (Review)
Review
BACKGROUND
Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the absence or deficiency of a clotting factor protein. Staging classifications, such as the Arnold-Hilgartner classification for haemophilic arthropathy of the knee, radiologically reflect the extent of knee joint destruction with underlying chronic synovitis. Management of this highly morbid disease process involves intensive prophylactic measures, and chemical or radioisotope synovectomy in its early stages. However, failure of non-surgical therapy in people with progression of chronic arthropathy often prompts surgical management, including synovectomy, joint debridement, arthrodesis, and arthroplasty, depending on the type of joint and extent of the damage. To date, management of people with mild to moderate chronic arthropathy from haemophilia remains controversial; there is no agreed standard treatment. Thus, the benefits and disadvantages of non-surgical and surgical management of mild to moderate chronic arthropathy in people with haemophilia needs to be systematically reviewed. OBJECTIVES: To assess the efficacy and safety of surgery for mild to moderate chronic arthropathy in people with haemophilia A or B.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, and two trial registers to August 2022. We also handsearched relevant journals and conference abstract books.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs comparing surgery and non-surgical interventions, for any joint with chronic arthropathy, in people with haemophilia, who were at least 12 years old.
DATA COLLECTION AND ANALYSIS
The review authors did not identify any trials to include in this review.
MAIN RESULTS
The review authors did not identify any trials to include in this review.
AUTHORS' CONCLUSIONS
The review authors did not identify any trials to include in this review. Due to a lack of research in this particular area, we plan to update the literature search every two years, and will update review if any new evidence is reported. There is a need for a well-designed RCT that assesses the safety and efficacy of surgical versus non-surgical interventions for chronic arthropathy in people with haemophilia.
Topics: Child; Humans; Hemophilia A; Joint Diseases; Knee Joint; MEDLINE; Randomized Controlled Trials as Topic
PubMed: 36448638
DOI: 10.1002/14651858.CD013634.pub2 -
Journal of Clinical Gastroenterology 2017Vitamin deficiency is frequently associated with inflammatory bowel disease (IBD). Supplementation of vitamins could thus serve as an adjunctive therapy. The present... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin deficiency is frequently associated with inflammatory bowel disease (IBD). Supplementation of vitamins could thus serve as an adjunctive therapy. The present meta-analysis reviews the deficiencies and alterations in serum fat-soluble vitamins (A, D, E, and K) reported in IBD patients.
MATERIALS AND METHODS
PubMed database search was performed to identify all primary studies up to January 2015 that evaluated the serum concentrations of fat-soluble vitamin levels in IBD patients compared with healthy individuals. We estimated pooled mean differences between groups and estimated their relations with some compounding variables (age, disease duration, C-reactive protein, albumin), using a meta-regression analysis.
RESULTS
Nineteen case-control studies met selection criteria. In patients with Crohn's disease (CD), vitamin A, D, E, K status was lower than in controls [D=212 μg/L.92; 95% confidence interval (CI), 95.36-330.48 μg/L, P=0.0002; D=6.97 nmol/L, 95% CI, 1.61-12.32 nmol/L, P=0.01; D=4.72 μmol/L, 95% CI, 1.60-7.84 μmol/L, P=0.003; D=1.46 ng/mL, 95% CI, 0.48-2.43 ng/mL, P=0.003, respectively]. Patients with ulcerative colitis had lower levels of vitamin A than controls (D=223.22 μg/L, 95% CI, 44.32-402.12 μg/L, P=0.01). Patients suffering from CD for a longer time had lower levels of vitamins A (95% CI=7.1-67.58 y, P=0.02) and K (95% CI, 0.09-0.71 y, P=0.02). Meta-regression analysis demonstrated statistically significant associations between the levels of inflammatory biomarkers: C-reactive protein (P=0.03, 95% CI, -9.74 to -0.6 mgl/L) and albumin (P=0.0003, 95% CI, 402.76-1361.98 g/dL), and vitamin A status in CD patients.
CONCLUSION
Our meta-analysis shows that the levels of fat-soluble vitamins are generally lower in patients with inflammatory bowel diseases and their supplementation is undoubtedly indicated.
Topics: Avitaminosis; Colitis, Ulcerative; Crohn Disease; Humans; Vitamin A; Vitamin D; Vitamin E; Vitamin K
PubMed: 28858940
DOI: 10.1097/MCG.0000000000000911 -
Human Pathology Jul 2016Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to... (Meta-Analysis)
Meta-Analysis Review
Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to investigate the clinicopathological characteristics of MC in the colorectum through a systematic review and meta-analysis. The meta-analysis examined the incidence, age, sex, site, mismatch repair deficiency (MMRd), MMR protein expression, ARID1A expression, BRAF(V600E) mutation, KRAS mutation, and survival rate of MC. The 21469 CRCs included 462 MCs in 16 eligible studies, representing an estimated incidence of MC of 0.027 (95% confidence interval [CI] 26 0.016-0.045). MC frequently occurred in female patients and in the right colon. Lymph node metastasis of MC was significantly lower than that of poorly differentiated adenocarcinoma/undifferentiated adenocarcinoma (PDA/UDA). In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAF(V600E) mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma. Patients with MC had significantly better overall survival rate compared to patients with PDA/UDA (hazard ratio 0.441, 95% CI 0.262-0.742). However, there was no significant difference of overall survival rate between MC and conventional adenocarcinoma patients. MC predominantly occurred in females and in the right colon, and had different molecular characteristics and behaviors compared to PDA/UDA and conventional adenocarcinoma.
Topics: Adenocarcinoma; Age Distribution; Biomarkers, Tumor; Carcinoma, Medullary; Cell Differentiation; Colorectal Neoplasms; Female; Genetic Predisposition to Disease; Humans; Incidence; Lymphatic Metastasis; Male; Phenotype; Risk Factors; Sex Distribution; Survival Analysis; Time Factors
PubMed: 27001432
DOI: 10.1016/j.humpath.2016.02.018 -
Journal of Alzheimer's Disease : JAD 2023Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and...
BACKGROUND
Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and cognitive dysfunction have.
OBJECTIVE
The main purpose of this study was to determine micro- and macronutrients and food frequency intake among the LAC population with mild cognitive impairment (MCI) and dementia.
METHODS
A systematic review using PubMed, Cochrane, Lilacs, and Scielo databases. Energy intake as well as micro- and macronutrients intake were analyzed using a random-effect model and presented in a forest plot.
RESULTS
Nine articles were included, an estimated energy intake of 1598.47 kcal (95% CI 1351.07-1845.88) was obtained. A daily consumption of 73.64 g/day (95% CI 64.07-83.2) of protein; 262.17 g/day (95% CI 214.51-309.93) of carbohydrates, and 57.91 g/day (95% CI 49.16-66.66) of fats were reported. A micronutrients daily intake consumption of 201.35μg/day of vitamin B9 (95% CI 125.32-277.38); 5.61μg/day of vitamin B12 (95% CI 2.53-8.70), and 139.67 mg/day of vitamin C (95% CI 59.33-220.02). Mineral intake of 637.32 mg/day of calcium (95% CI 288.54-986.11) and 9 mg/day of iron (95% CI 2.28-15.71) was obtained. A low intake of fruits and vegetables was found.
CONCLUSION
Individuals with MCI and dementia from LAC have a nutritional deficiency characterized by a lower intake of fruits and vegetables, a high consumption of carbohydrates and protein, adequate fats intake and vitamins B12, vitamin C, and iron consumption, but a low intake of vitamin B9 and calcium.
Topics: Humans; Latin America; Calcium; Cognitive Dysfunction; Vitamins; Folic Acid; Energy Intake; Vitamin B 12; Ascorbic Acid; Eating; Dementia; Iron
PubMed: 37302035
DOI: 10.3233/JAD-230231 -
Clinical Nutrition ESPEN Apr 2023Malnutrition, sarcopenia, and frailty are three prevalent wasting conditions among older rehabilitation patients that lead to multiple health-related negative outcomes.... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Malnutrition, sarcopenia, and frailty are three prevalent wasting conditions among older rehabilitation patients that lead to multiple health-related negative outcomes. This systematic review and meta-analysis aimed to determine the post-discharge consequences of malnutrition, sarcopenia, and frailty in older adults admitted to inpatient rehabilitation.
METHODS
MEDLINE, Embase, Web of Science, and CINAHL databases were searched on 20 April, 2021 for longitudinal studies in older adults (≥65 years) admitted for inpatient rehabilitation. This systematic review included and synthesised studies that 1) measured malnutrition, sarcopenia, and/or frailty using a validated assessment tool or guideline; and 2) reported the association with post-discharge mortality, physical function, quality of life, or discharge location. The Academy of Nutrition & Dietetics Quality Criteria Checklist and GRADE criteria were used to assess risk of bias and evidence certainty. Where possible, data were pooled using Revman.
RESULTS
Twenty-six observational studies (n = 9709 participants in total) with similarly aged populations were included. Eight, seven, and eleven studies assessed malnutrition, sarcopenia, and frailty, respectively. Follow-up periods ranged from immediate to 7 years post-rehabilitation. Malnutrition was associated with discharge to a higher level of care (GRADE: very low), and worse quality of life (GRADE: very low) and physical function (GRADE: very low). Sarcopenia was associated with worse physical function (GRADE: very low) and lower rate of home discharge (OR: 0.14; 95%CI: 0.09-0.20; I:30%; GRADE: low). Frailty was associated with increased mortality (GRADE: very low), hospital readmission (GRADE: very low), and decreased home discharge (GRADE: very low).
CONCLUSION
Wasting conditions in older adults during rehabilitation admission may be associated with poorer quality of life, lower rates of home discharge, and higher rates of health service use, physical dysfunction, and mortality following discharge. Further research is needed to investigate the comparative and combined impacts, as well as the overlap of malnutrition, sarcopenia, and frailty during and after rehabilitation to guide priority screening and intervention.
Topics: Humans; Aged; Patient Discharge; Sarcopenia; Frailty; Protein-Energy Malnutrition; Quality of Life; Aftercare; Malnutrition
PubMed: 36963884
DOI: 10.1016/j.clnesp.2023.01.023