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Acta Bio-medica : Atenei Parmensis Aug 2023To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS). (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS).
METHODS
Literature on the association of CYP17rs74357 gene polymorphism and susceptibility to PCOS was retrieved by searching databases such as PubMed, Science Direct, Google Scholar and Embase from. The association measure was analyzed using an Odds Ratio (OR) and 95% Confidence Interval (CI). All the statistical analyses were executed using CMA 3.0 Software.
RESULTS
In the present meta-analysis,24 studies including 3462 PCOS and 2898 controls were analyzed. The overall results validated that the 17 CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in 5 genetic models: recessive model (fixed and random effect), dominant model (random effect), CC vs. TT (fixed effect), CT vs. TT (fixed effect), and allele contrast (random effect). Stratified analyses by ethnicity/country also detected significant association between Asian and Caucasian under the recessive, dominant, CC vs. TT, CC vs. CT, and the allele contrast models.
CONCLUSIONS
In the present study, CYP17 T/C (rs74357) gene polymorphism increase the susceptibility of PCOS, and the recessive C allele, can be proposed as a predictive factor for the risk of PCOS or an important pathway in PCOS associated metabolic and hormonal dysregulation especially insulin resistance.However, larger sample size andmultiracial studies are needed in the future to confirm the findings.
Topics: Female; Humans; Genetic Predisposition to Disease; Polycystic Ovary Syndrome; Polymorphism, Genetic; Steroid 17-alpha-Hydroxylase
PubMed: 37539608
DOI: 10.23750/abm.v94i4.14229 -
European Journal of Anaesthesiology Oct 2023Pain after cardiac surgery via median sternotomy can be difficult to treat, and if inadequately managed can lead to respiratory complications, prolonged hospital stays...
BACKGROUND
Pain after cardiac surgery via median sternotomy can be difficult to treat, and if inadequately managed can lead to respiratory complications, prolonged hospital stays and chronic pain.
OBJECTIVES
To evaluate available literature and develop recommendations for optimal pain management after cardiac surgery via median sternotomy.
DESIGN
A systematic review using PROcedure-SPECific Pain Management (PROSPECT) methodology.
ELIGIBILITY CRITERIA
Randomised controlled trials and systematic reviews published in the English language until November 2020 assessing postoperative pain after cardiac surgery via median sternotomy using analgesic, anaesthetic or surgical interventions.
DATA SOURCES
PubMed, Embase and Cochrane Databases.
RESULTS
Of 319 eligible studies, 209 randomised controlled trials and three systematic reviews were included in the final analysis. Pre-operative, intra-operative and postoperative interventions that reduced postoperative pain included paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), intravenous magnesium, intravenous dexmedetomidine and parasternal block/infiltration.
CONCLUSIONS
The analgesic regimen for cardiac surgery via sternotomy should include paracetamol and NSAIDs, unless contraindicated, administered intra-operatively and continued postoperatively. Intra-operative magnesium and dexmedetomidine infusions may be considered as adjuncts particularly when basic analgesics are not administered. It is not clear if combining dexmedetomidine and magnesium would provide superior pain relief compared with either drug alone. Parasternal block/surgical site infiltration is also recommended. However, no basic analgesics were used in the studies assessing these interventions. Opioids should be reserved for rescue analgesia. Other interventions, including cyclo-oxygenase-2 specific inhibitors, are not recommended because there was insufficient, inconsistent or no evidence to support their use and/or due to safety concerns.
Topics: Humans; Pain Management; Acetaminophen; Sternotomy; Dexmedetomidine; Magnesium; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Pain, Postoperative; Analgesics, Opioid; Cardiac Surgical Procedures
PubMed: 37501517
DOI: 10.1097/EJA.0000000000001881 -
Genetics in Medicine : Official Journal... Sep 2023Elevated serum phenylalanine (Phe) levels due to biallelic pathogenic variants in phenylalanine hydroxylase (PAH) may cause neurodevelopmental disorders or birth defects...
PURPOSE
Elevated serum phenylalanine (Phe) levels due to biallelic pathogenic variants in phenylalanine hydroxylase (PAH) may cause neurodevelopmental disorders or birth defects from maternal phenylketonuria. New Phe reduction treatments have been approved in the last decade, but uncertainty on the optimal lifespan goal Phe levels for patients with PAH deficiency remains.
METHODS
We searched Medline and Embase for evidence of treatment concerning PAH deficiency up to September 28, 2021. Risk of bias was evaluated based on study design. Random-effects meta-analyses were performed to compare IQ, gestational outcomes, and offspring outcomes based on Phe ≤ 360 μmol/L vs > 360 μmol/L and reported as odds ratio and 95% CI. Remaining results were narratively synthesized.
RESULTS
A total of 350 studies were included. Risk of bias was moderate. Lower Phe was consistently associated with better outcomes. Achieving Phe ≤ 360 μmol/L before conception substantially lowered the risk of negative effect to offspring in pregnant individuals (odds ratio = 0.07, 95% CI = 0.04-0.14; P < .0001). Adverse events due to pharmacologic treatment were common, but medication reduced Phe levels, enabling dietary liberalization.
CONCLUSIONS
Reduction of Phe levels to ≤360 μmol/L through diet or medication represents effective interventions to treat PAH deficiency.
Topics: Pregnancy; Female; Humans; United States; Genetics, Medical; Phenylalanine; Phenylketonurias; Phenylalanine Hydroxylase; Phenylketonuria, Maternal; Genomics
PubMed: 37470789
DOI: 10.1016/j.gim.2022.12.005 -
Blood Purification 2023Anemia is a common finding among patients with advanced chronic kidney disease, especially those on dialysis. The recent introduction of hypoxia-inducible factor prolyl... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anemia is a common finding among patients with advanced chronic kidney disease, especially those on dialysis. The recent introduction of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) has raised some concerns about the cardiovascular and thrombotic complications of this class of drugs.
OBJECTIVES
This meta-analysis aimed to assess the safety of HIF-PHIs in patients with end-stage kidney disease (ESKD) versus standard therapy with erythropoiesis-stimulating agents (ESAs).
METHODS
Databases were searched on April 2022. Studies that reported incidence of all-cause mortality; major cardiovascular adverse events (MACEs); myocardial infarction (MI); stroke and thrombotic events in the use of HIF-PHIs or ESA on ESKD patients in hemodialysis or peritoneal dialysis were evaluated. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations.
RESULTS
12,821 patients from ten randomized controlled trials were included in this study. Most patients (83%) were on hemodialysis. 6,461 (50.3%) were using HIF-PHIs, and 6,360 (49.6%) were in the ESA group. The pooled estimated incidence of all-cause mortality was 769 in the HIF-PHIs group (relative-risk ratios (RR): 1.04; confidence interval (CI): 0.95-1.14; p = 0.52; I2 = 0%). There was no difference in the groups regarding the outcomes of MACE in the analysis of the three studies that reported this outcome (RR: 0.95; CI: 0.87-1.04; p = 0.69; I2 = 0%). In addition, there was no statistical difference among the outcomes of MI, stroke, or thrombotic events.
CONCLUSIONS
Among patients with ESKD on dialysis, the use of HIF-PHIs was non-inferior regarding the safety outcomes when compared to standard of care therapy.
Topics: Humans; Prolyl-Hydroxylase Inhibitors; Prolyl Hydroxylases; Renal Dialysis; Hematinics; Renal Insufficiency, Chronic; Thrombosis; Kidney Failure, Chronic; Stroke; Hypoxia; Randomized Controlled Trials as Topic
PubMed: 37459846
DOI: 10.1159/000531274 -
Expert Opinion on Drug Safety 2023Pretherapy assessment of specific genetic polymorphism (TPMT, NUDT15, FTO, RUNX1, etc) or enzyme levels (for TPMT) may help personalize the dose of thiopurines and avoid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pretherapy assessment of specific genetic polymorphism (TPMT, NUDT15, FTO, RUNX1, etc) or enzyme levels (for TPMT) may help personalize the dose of thiopurines and avoid adverse effects.
RESEARCH DESIGN AND METHODS
A systematic review of randomized controlled trials (RCTs) comparing personalized versus standard strategy for initial thiopurine dosing was performed. The electronic databases were searched on 27 September 2022. The outcomes were overall adverse effects, myelotoxicity, drug interruptions, and therapeutic efficacy with either strategy. The certainty of evidence was assessed using GRADE methodology.
RESULTS
We included six randomized trials, done dominantly in patients with inflammatory bowel disease (IBD). The personalized strategies were genotype testing in 4 trials (TPMT in three trials, NUDT15 in two) and enzyme levels for TPMT in two trials. The pooled risk of myelotoxicity in personalized dosing was lower [RR = 0.72 (95%CI, 0.55-0.94, I = 0%)]. The pooled risk of pancreatitis (RR = 1.10I, 0.78-1.56, I = 0%), hepatotoxicity (RR = 1.13, 0.69-1.88, I = 45), and GI intolerance (RR = 1.01, 0.92-1.10, I = 0) were similar in two groups. The pooled risk of drug interruption in individualized dosing was similar to the standard dosing group (RR = 0.97, I = 68%).
CONCLUSION
Personalized testing-based initial thiopurine dosing is protective against myelotoxicity as compared to standard weight-based dosing.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Randomized Controlled Trials as Topic; Inflammatory Bowel Diseases; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37436005
DOI: 10.1080/14740338.2023.2236554 -
Annales D'endocrinologie Feb 2024Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of...
BACKGROUND
Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.
METHODS
Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens.
RESULTS
In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively.
CONCLUSION
We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.
Topics: Male; Infant; Female; Adolescent; Humans; Infant, Newborn; Infant, Premature; Gynecomastia; Androgens; Follicle Stimulating Hormone; Gonadotropins; Aromatase; Infertility, Male; Metabolism, Inborn Errors; 46, XX Disorders of Sex Development
PubMed: 37348676
DOI: 10.1016/j.ando.2023.05.010 -
Clinical Pharmacokinetics Jun 2023To investigate the association of single nucleotide polymorphisms (SNPs) of various genes known to influence mean daily warfarin dose (MDWD) in the Han Chinese... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association of single nucleotide polymorphisms (SNPs) of various genes known to influence mean daily warfarin dose (MDWD) in the Han Chinese population.
METHODS
The study is a systematic review and meta-analysis. Selected studies retrieved by searching Pubmed, Embase (Ovid), Medline, CNKI, Wanfang data, and SinoMed (from their inception to 31 August 2022) for the cohort studies assessing genetic variations that may possibly influence MDWD in Chinese patients were included.
RESULT
A total of 46 studies including a total of 10,102 Han Chinese adult patients were finally included in the meta-analysis. The impact of 20 single nucleotide polymorphisms (SNPs) in 8 genes on MDWD was analyzed. The significant impact of some of these SNPs on MDWD requirements was demonstrated. Patients with CYP4F2 rs2108622 TT, EPHX1 rs2260863 GC, or NQO1 rs1800566 TT genotype required more than 10% higher MDWD. Furthermore, patients with ABCB1 rs2032582 GT or GG, or CALU rs2290228 TT genotype required more than 10% lower MDWD. Subgroup analysis showed that patients with EPHX1 rs2260863 GC genotype required 7% lower MDWD after heart valve replacement (HVR).
CONCLUSION
This is the first systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) of various genes known to influence MDWD besides CYP2C9 and VKORC1 in the Han Chinese population. CYP4F2 (rs2108622), GGCX (rs12714145), EPHX1 (rs2292566 and rs2260863), ABCB1 (rs2032582), NQO1 (rs1800566), and CALU (rs2290228) SNPs might be moderate factors affecting MDWD requirements.
REGISTERED INFORMATION
PROSPERO International Prospective Register of Systematic Reviews (CRD42022355130).
Topics: Adult; Humans; Anticoagulants; Asian People; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 4; East Asian People; Genotype; Polymorphism, Single Nucleotide; Vitamin K Epoxide Reductases; Warfarin
PubMed: 37273173
DOI: 10.1007/s40262-023-01258-y -
European Journal of Clinical... Jul 2023Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population... (Review)
Review
BACKGROUND AND OBJECTIVES
Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population pharmacokinetic (PPK) studies have been performed to facilitate individualized therapy. This review summarized published PPK models of TAC in non-transplant patients, aiming to clarify factors affecting PKs of TAC and identify the knowledge gap that may require further research.
METHODS
The PubMed, Embase databases, and Cochrane Library, as well as related references, were searched from the time of inception of the databases to February 2023, to identify TAC population pharmacokinetic studies modeled in non-transplant patients using a non-linear mixed-effects modeling approach.
RESULTS
Sixteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, eleven and four were carried out in pediatric and adult patients, respectively. One-compartment models were the commonly used structural models for TAC. The apparent clearance (CL/F) of TAC ranged from 2.05 to 30.9 L·h (median of 14.9 L·h). Coadministered medication, genetic factors, and weight were the most common covariates affecting TAC-CL/F, and variability in the apparent volume of distribution (V/F) was largely explained by weight. Coadministration with Wuzhi capsules reduced CL/F by about 19 to 43%. For patients with CYP3A5*1*1 and *1*3 genotypes, the CL/F was 39-149% higher CL/F than patients with CYP3A5*1*1.
CONCLUSION
The optimal TAC dosage should be adjusted based on the patient's co-administration, body weight, and genetic information (especially CYP3A5 genotype). Further studies are needed to assess the generalizability of the published models to other ethnic groups. Moreover, external validation should be frequently performed to improve the clinical practicality of the models.
Topics: Adult; Humans; Child; Tacrolimus; Immunosuppressive Agents; Cytochrome P-450 CYP3A; Models, Biological; Ethnicity; Genotype
PubMed: 37261481
DOI: 10.1007/s00228-023-03503-6 -
Drug Discoveries & Therapeutics Jul 2023Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the...
Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-β, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.
Topics: Mice; Animals; Cornus; Diabetes Mellitus, Type 2; Polyphenols; NF-kappa B; Diabetes Mellitus, Experimental; C-Peptide; Liver; Pancreas; Insulin
PubMed: 37245985
DOI: 10.5582/ddt.2022.01097 -
Cells Apr 2023Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline -oxide (ANO) is...
Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline -oxide (ANO) is carcinogenic, and the underlying mechanisms remain unclear. In this systematic review, we analyzed recent studies on the roles of arecoline and ANO in cancer and strategies to block carcinogenesis. In the oral cavity, flavin-containing monooxygenase 3 oxidizes arecoline to ANO, and both alkaloids conjugate with -acetylcysteine to form mercapturic acid compounds, which are excreted in urine, reducing arecoline and ANO toxicity. However, detoxification may not be complete. Arecoline and ANO upregulated protein expression in oral cancer tissue from areca nut users compared to expression levels in adjacent normal tissue, suggesting a causal relationship between these compounds and oral cancer. Sublingual fibrosis, hyperplasia, and oral leukoplakia were diagnosed in mice subjected to oral mucosal smearing of ANO. ANO is more cytotoxic and genotoxic than arecoline. During carcinogenesis and metastasis, these compounds increase the expression of epithelial-mesenchymal transition (EMT) inducers such as reactive oxygen species, transforming growth factor-β1, Notch receptor-1, and inflammatory cytokines, and they activate EMT-related proteins. Arecoline-induced epigenetic markers such as sirtuin-1 hypermethylation, low protein expression of miR-22, and miR-886-3-p accelerate oral cancer progression. Antioxidants and targeted inhibitors of the EMT inducers used reduce the risk of oral cancer development and progression. Our review findings substantiate the association of arecoline and ANO with oral cancer. Both of these single compounds are likely carcinogenic to humans, and their mechanisms and pathways of carcinogenesis are useful indicators for cancer therapy and prognosis.
Topics: Arecoline; Cyclic N-Oxides; Mouth Neoplasms; Carcinogenesis; Humans; Animals; Mice; Areca; Oxygenases; Oxidation-Reduction; Acetylcysteine; Epigenesis, Genetic; Carcinogens
PubMed: 37190117
DOI: 10.3390/cells12081208