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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 -
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 -
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 -
Inflammopharmacology Aug 2023Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the... (Meta-Analysis)
Meta-Analysis Review
Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, dose selection and the improvement of quercetin's bioavailability remain to be explored.
Topics: Animals; Quercetin; Oxidative Stress; Arthritis, Rheumatoid; Reactive Oxygen Species; Antioxidants; Tumor Necrosis Factor-alpha; Glutathione; NF-kappa B
PubMed: 37150762
DOI: 10.1007/s10787-023-01196-y -
Nutrition Reviews Nov 2023Although the stimulant and anxiogenic properties of caffeine are widely accepted, research on its specific effects on the brain remains controversial. Growing evidence...
CONTEXT
Although the stimulant and anxiogenic properties of caffeine are widely accepted, research on its specific effects on the brain remains controversial. Growing evidence shows that interindividual differences in caffeine response may be partly due to variations in genes such as CYP1A2 and ADORA2A, which have been used to identify individuals as "fast" or "slow" caffeine metabolizers and as having a "high" or "low" caffeine sensitivity, respectively.
OBJECTIVE
The objective of this review was to identify, evaluate, and discuss current evidence on the associations between common genetic variants, caffeine consumption, and brain-related outcomes in humans.
DATA SOURCES
PubMed and Embase databases were searched for relevant reports based on a predetermined search strategy.
DATA EXTRACTION
Reports of observational and experimental studies on healthy adults who underwent (a) genetic analysis for polymorphisms in genes associated with caffeine metabolism and effects and (b) measurements of brain-related effects such as anxiety, insomnia, and cognitive performance associated with the consumption of caffeine (habitual intake or supplementation) were included.
DATA ANALYSIS
Of the 22 records included, 15 were randomized controlled trials, 6 were cross-sectional studies, and 1 was a genome-wide association study. The main outcomes identified were cognitive performance (n = 9), anxiety (n = 7), and sleep disturbance/insomnia (n = 6). Polymorphisms in the CYP1A2 gene were associated with cognitive function, while variations in the ADORA2A gene were associated with anxiety and sleep disturbance.
CONCLUSION
The present review has provided evidence that variability in the CYP1A2 and the ADORA2A genes may modulate the association between caffeine and brain-related outcomes. Future studies are warranted to investigate the specific polymorphisms implicated in each brain outcome, which cognitive functions are particularly related to caffeine (simple vs complex), whether there are gender differences in anxiety effects, and how habitual caffeine intake may influence the acute effects of caffeine.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42021257556.
Topics: Adult; Humans; Caffeine; Cytochrome P-450 CYP1A2; Sleep Initiation and Maintenance Disorders; Genome-Wide Association Study; Randomized Controlled Trials as Topic; Brain
PubMed: 37029915
DOI: 10.1093/nutrit/nuad029 -
European Journal of Human Genetics :... Mar 2024The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to...
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy. A guideline describing the gene-drug interaction between the genes CYP2D6, CYP3A4 and CYP1A2 and antipsychotics is presented here. The DPWG identified gene-drug interactions that require therapy adjustments when respective genotype is known for CYP2D6 with aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol, and for CYP3A4 with quetiapine. Evidence-based dose recommendations were obtained based on a systematic review of published literature. Reduction of the normal dose is recommended for aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol for CYP2D6-predicted PMs, and for pimozide and zuclopenthixol also for CYP2D6 IMs. For CYP2D6 UMs, a dose increase or an alternative drug is recommended for haloperidol and an alternative drug or titration of the dose for risperidone. In addition, in case of no or limited clinical effect, a dose increase is recommended for zuclopenthixol for CYP2D6 UMs. Even though evidence is limited, the DPWG recommends choosing an alternative drug to treat symptoms of depression or a dose reduction for other indications for quetiapine and CYP3A4 PMs. No therapy adjustments are recommended for the other CYP2D6 and CYP3A4 predicted phenotypes. In addition, no action is required for the gene-drug combinations CYP2D6 and clozapine, flupentixol, olanzapine or quetiapine and also not for CYP1A2 and clozapine or olanzapine. For identified gene-drug interactions requiring therapy adjustments, genotyping of CYP2D6 or CYP3A4 prior to treatment should not be considered for all patients, but on an individual patient basis only.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Clopenthixol; Clozapine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Drug Interactions; Haloperidol; Olanzapine; Pharmacogenetics; Pimozide; Quetiapine Fumarate; Quinolones; Risperidone; Thiophenes
PubMed: 37002327
DOI: 10.1038/s41431-023-01347-3 -
Chemico-biological Interactions Sep 2023As part of a systematic review of the non-cancer and cancer hazards of propylene dichloride (PDC), with a focus on potential carcinogenicity in workers following... (Review)
Review
As part of a systematic review of the non-cancer and cancer hazards of propylene dichloride (PDC), with a focus on potential carcinogenicity in workers following inhalation exposures, we determined that a mode of action (MOA)-centric framing of cancer effects was warranted. In our MOA analysis, we systematically reviewed the available mechanistic evidence for PDC-induced carcinogenesis, and we mapped biologically plausible MOA pathways and key events (KEs), as guided by the International Programme on Chemical Safety (IPCS)-MOA framework. For the identified pathways and KEs, biological concordance, essentiality of KEs, concordance of empirical observations among KEs, consistency, and analogy were evaluated. The results of this analysis indicate that multiple biologically plausible pathways may contribute to the cancer MOA for PDC, but that the relevant pathways vary by exposure route and level, tissue type, and species; further, more than one pathway may occur concurrently at high exposure levels. While several important data gaps exist, evidence from in vitro mechanistic studies, in vivo experimental animal studies, and ex vivo human tumor tissue analyses indicates that the predominant MOA pathway likely involves saturation of cytochrome p450 2E1 (CYP2E1)-glutathione (GSH) detoxification (molecular initiating event; MIE), accumulation of CYP2E1-oxidative metabolites, cytotoxicity, chronic tissue damage and inflammation, and ultimately tumor formation. Tumors may occur through several subsets of inflammatory KEs, including inflammation-induced aberrant expression of activation-induced cytidine deaminase (AID), which causes DNA strand breaks and mutations and can lead to tumors with a characteristic mutational signature found in occupational cholangiocarcinoma. Dose concordance analysis showed that low-dose mutagenicity (from any pathway) is not a driving MOA, and that prevention of target tissue damage and inflammation (associated with saturation of CYP2E1-GSH detoxification) is expected to also prevent the cascade of processes responsible for tumor formation.
Topics: Propane; Humans; DNA Damage; Carcinogens; Inflammation; Cytochrome P-450 CYP2E1; Metabolic Networks and Pathways; Carcinogenesis; Animals; Cholangiocarcinoma; Glutathione
PubMed: 36754223
DOI: 10.1016/j.cbi.2023.110382 -
Critical Reviews in Food Science and... 2024Genetic background interacts with dietary components to modulate nutritional health status. This study aimed to review the evidence for gene-diet interactions in all...
Genetic background interacts with dietary components to modulate nutritional health status. This study aimed to review the evidence for gene-diet interactions in all forms of malnutrition. A comprehensive systematic literature search was conducted through April 2021 to identify observational and intervention studies reporting the effects of gene-diet interactions in over-nutrition, under-nutrition and micronutrient status. Risk of publication bias was assessed using the Quality Criteria Checklist and a tool specifically designed for gene-diet interaction research. 167 studies from 27 populations were included. The majority of studies investigated single nucleotide polymorphisms (SNPs) in overnutrition (n = 158). Diets rich in whole grains, vegetables, fruits and low in total and saturated fats, such as Mediterranean and DASH diets, showed promising effects for reducing obesity risk among individuals who had higher genetic risk scores for obesity, particularly the risk alleles carriers of rs9939609, rs1121980 and rs1421085. Other SNPs in , and genes were also commonly studied for interaction with diet on overnutrition though findings were inconclusive. Only limited data were found related to undernutrition (n = 1) and micronutrient status (n = 9). The findings on gene-diet interactions in this review highlight the importance of personalized nutrition, and more research on undernutrition and micronutrient status is warranted.
Topics: Humans; Nutritional Status; Malnutrition; Diet; Obesity; Micronutrients; Trace Elements; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 36222100
DOI: 10.1080/10408398.2022.2131727 -
Critical Reviews in Food Science and... 2024Despite enormous research efforts, a sufficiently sensitive and reliable biomarker for the assessment of zinc (Zn) status has not been identified to date. Zn affects... (Meta-Analysis)
Meta-Analysis
Despite enormous research efforts, a sufficiently sensitive and reliable biomarker for the assessment of zinc (Zn) status has not been identified to date. Zn affects fatty acid metabolism and alters the activity of certain desaturases; thus, desaturase activity has been proposed as a potential new biomarker of Zn status. This systematic review complied and assessed studies that examined changes in fatty acid desaturase 1 (FADS1) and fatty acid desaturase 2 (FADS2) activities in relation to modifications in dietary Zn intake. A systematic search was performed in PubMed, Web of Science, Scopus, Web of Knowledge, and Central with strictly defined search, inclusion, and exclusion criteria. Twenty-one studies were included, 8 animal and 13 human trials (5 randomized controlled trials, two non-randomized controlled trials, and 6 cross-sectional studies). This systematic review was performed using PRISMA guidelines and where feasible a random-effects meta-analysis was conducted. No significant correlation was seen between the delta 6 desaturase and Zn status (-0.0958, 95% CIs (-0.2912; 0.1074), p = 0.2928). Delta 6 desaturase seems to respond in a greater magnitude than Zn status to Zn-containing interventions (the standardized mean difference for delta 6 desaturase was -0.6052, 95% CIs (-2.7162; 1.5058), p = 0.4289, while for plasma/serum Zn it was 0.0319, 95% CIs (-0.9133; 0.9770), p = 0.9213). Finally, two separate meta-analyses on same studies that assessed the correlations between LA:DGLA and Zn intake and Zn status and Zn intake revealed that the magnitude of correlations was only slightly different (the pooled correlation coefficient between the LA:DGLA ratio and Zn intake had a value of -0.1050, 95% CIs (-0.5356; 0.3690), p = 0.454, while between plasma Zn and Zn intake had a value of -0.0647, 95% CIs (-0.4224; 0.3106), p = 0.5453). According to the descriptive analysis, the magnitude of variation in desaturase activities in response to Zn intake was not consistent among studies, FADS1 and FADS2 activity corresponded to dietary Zn manipulations, both in animals and humans. A plausible explanation for this observation might be the difference between the studies in study populations, types of dietary interventions, study durations, etc. In addition, several potential confounders and covariates are identified from the qualitative synthesis, such as gender, age, the type of fat provided within the dietary intervention, the size of Zn particles, among others. Further high-quality studies are needed to additionally clarify the suggested associations and applicability of utilizing fatty acid desaturase activities as Zn status biomarkers.
Topics: Animals; Humans; Fatty Acid Desaturases; Linoleoyl-CoA Desaturase; Zinc; Cross-Sectional Studies; Biomarkers; Polymorphism, Single Nucleotide
PubMed: 35880429
DOI: 10.1080/10408398.2022.2103790