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Clinical Rheumatology Sep 2023Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality... (Review)
Review
Systematic r eview to evaluate the quality of the clinical practice guidelines (CPG) for rheumatoid arthritis (RA) management and to provide a synthesis of high-quality CPG recommendations, highlighting areas of consistency, and inconsistency. Electronic searches of five databases and four online guideline repositories were performed. RA management CPGs were eligible for inclusion if they were written in English and published between January 2015 and February 2022; focused on adults ≥ 18 years of age; met the criteria of a CPG as defined by the Institute of Medicine; and were rated as high quality on the Appraisal of Guidelines for Research and Evaluation II instrument. RA CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organization of care and did not include interventional management recommendations; and/or included other arthritic conditions. Of 27 CPGs identified, 13 CPGs met eligibility criteria and were included. Non-pharmacological care should include patient education, patient-centered care, shared decision-making, exercise, orthoses, and a multi-disciplinary approach to care. Pharmacological care should include conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), with methotrexate as the first-line choice. If monotherapy conventional synthetic DMARDs fail to achieve a treatment target, this should be followed by combination therapy conventional synthetic DMARDs (leflunomide, sulfasalazine, hydroxychloroquine), biologic DMARDS and targeted synthetic DMARDS. Management should also include monitoring, pre-treatment investigations and vaccinations, and screening for tuberculosis and hepatitis. Surgical care should be recommended if non-surgical care fails. This synthesis offers clear guidance of evidence-based RA care to healthcare providers. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework ( https://doi.org/10.17605/OSF.IO/UB3Y7 ).
Topics: Adult; Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hydroxychloroquine; Methotrexate; Sulfasalazine; Practice Guidelines as Topic
PubMed: 37291382
DOI: 10.1007/s10067-023-06654-0 -
Nutrients Nov 2023This review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and its implications on... (Review)
Review
This review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis; disruption in DNA methylation; and impacts on embryogenesis, pregnancy outcomes, neurodevelopment, and disease risk. Notably, these consequences stretch beyond the immediate effects, potentially influencing future generations through epigenetic reprogramming. The molecular mechanisms underlying these effects were examined, including altered one-carbon metabolism, the accumulation of unmetabolized folic acid, vitamin-B12-dependent mechanisms, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, differences in the effects and mechanisms mediated by folic acid compared with natural folate are highlighted. Given the widespread folic acid supplementation, it is imperative to further research its optimal intake levels and the molecular pathways impacted by its excessive intake, ensuring the health and well-being of the global population.
Topics: Pregnancy; Female; Humans; Folic Acid; Dietary Supplements; Vitamin B 12; Folic Acid Deficiency; DNA Methylation
PubMed: 37960352
DOI: 10.3390/nu15214699 -
Annals of the Rheumatic Diseases May 2024New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the...
OBJECTIVE
New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.
METHODS
Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined.
RESULTS
The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed.
CONCLUSION
These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.
Topics: Arthritis, Psoriatic; Humans; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate; Biological Products
PubMed: 38499325
DOI: 10.1136/ard-2024-225531 -
Cancer Research Jan 2024The one-carbon folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across... (Review)
Review
The one-carbon folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across numerous cancer types, promotes growth and metastasis of cancer, and correlates with poorer survival. Recent studies have developed small-molecule inhibitors to the isozymes MTHFD2 and MTHFD1 that show promise as anticancer agents through different mechanisms. This review discusses the current understanding of the function of MTHFD2 in cancer and the status of inhibitors for treating MTHFD2-overexpressing cancers.
Topics: Humans; Neoplasms; Methylenetetrahydrofolate Dehydrogenase (NADP); Antineoplastic Agents; Folic Acid; DNA Repair
PubMed: 37922465
DOI: 10.1158/0008-5472.CAN-23-1290 -
Gut Microbes Dec 2023Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of...
Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of , , and depletion of . These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between , , and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria , metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community.
Topics: Animals; Mice; Gastrointestinal Microbiome; Analgesics, Opioid; Dysbiosis; Multiomics; Opioid-Related Disorders; Riboflavin; Morphine Derivatives; Lipids
PubMed: 37610102
DOI: 10.1080/19490976.2023.2246184 -
BMC Ophthalmology Oct 2023Folate, a pteroylglutamic acid derivative, participates in fundamental cellular metabolism. Homocysteine, an amino acid, serves as an intermediate of the methionine... (Review)
Review
Folate, a pteroylglutamic acid derivative, participates in fundamental cellular metabolism. Homocysteine, an amino acid, serves as an intermediate of the methionine cycle and can be converted back to methionine. Hyperhomocysteinemia is a recognized risk factor for atherosclerotic and cardiovascular diseases. In recent decades, elevated plasma homocysteine levels and low folate status have been observed in many patients with retinal vascular diseases, such as retinal vascular occlusions, diabetic retinopathy, and age-related degeneration. Homocysteine-induced toxicity toward vascular endothelial cells might participate in the formation of retinal vascular diseases. Folate is an important dietary determinant of homocysteine. Folate deficiency is the most common cause of hyperhomocysteinemia. Folate supplementation can eliminate excess homocysteine in plasma. In in vitro experiments, folic acid had a protective effect on vascular endothelial cells against high glucose. Many studies have explored the relationship between folate and various retinal vascular diseases. This review summarizes the most important findings that lead to the conclusion that folic acid supplementation might be a protective treatment in patients with retinal vascular diseases with high homocysteine or glucose status. More research is still needed to validate the effect of folate and its supplementation in retinal vascular diseases.
Topics: Humans; Folic Acid; Hyperhomocysteinemia; Endothelial Cells; Methionine; Diabetic Retinopathy; Glucose; Homocysteine
PubMed: 37833663
DOI: 10.1186/s12886-023-03149-z -
Annual Review of Nutrition Aug 2023Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant... (Review)
Review
Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant potential, and metabolic interactions with other micronutrients, including iron, vitamin B, and folate. Severe riboflavin deficiency, largely confined to low-income countries, clinically manifests as cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, and severe anemia with erythroid hypoplasia. Subclinical deficiency may be much more widespread, including in high-income countries, but typically goes undetected because riboflavin biomarkers are rarely measured in human studies. There are adverse health consequences of low and deficient riboflavin status throughout the life cycle, including anemia and hypertension, that could contribute substantially to the global burden of disease. This review considers the available evidence on causes, detection, and consequences of riboflavin deficiency, ranging from clinical deficiency signs to manifestations associated with less severe deficiency, and the related research, public health, and policy priorities.
Topics: Humans; Riboflavin Deficiency; Riboflavin; Causality; Antioxidants; Bone Marrow Failure Disorders; Disease Progression; Lip Diseases
PubMed: 37603429
DOI: 10.1146/annurev-nutr-061121-084407 -
Ugeskrift For Laeger Nov 2023Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes...
Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes on the face and extremities, muscle pain and weakness. This is a case report of a ten-year-old boy initially suspected of having lupus erythematosus. He was later diagnosed with JDM by dermatologists. Treatment with methotrexate and prednisolone proved to be effective.
Topics: Male; Child; Humans; Dermatomyositis; Methotrexate; Skin; Inflammation; Prednisolone
PubMed: 37987452
DOI: No ID Found -
International Journal of Medical... 2023B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide... (Randomized Controlled Trial)
Randomized Controlled Trial
A functional evaluation of anti-fatigue and exercise performance improvement following vitamin B complex supplementation in healthy humans, a randomized double-blind trial.
B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide energy, each B vitamin acts as a cofactor in energy metabolism processes. Based on the evidence presented above, we hypothesized that a 28-day supplementation of vitamin B would enhance physical performance and reduce physical fatigue. The objective of this study was to evaluate the anti-fatigue effect of vitamin B supplementation, specifically vitamin B1, B2, B6, and B12, and its potential to improve exercise performance. We employed a randomized double-blind crossover design with a 28-day supplementation period. Sixteen male and sixteen female subjects, aged 20-30 years, were divided into two groups: the placebo group (n=16, equal gender distribution) and the Ex PLUS group (n=16, equal gender distribution). The participants received either placebo or Ex PLUS (one tablet per day) for 28 consecutive days. Following the intervention, there was a 14-day wash-out period during which the subjects did not receive any further interventions. After supplementation with Ex PLUS, we found a significant increase in the running time by 1.26-fold ( 0.05) to exhaustion compared to that before supplementation and that in the placebo group. In addition, the Ex PLUS supplementation group presented significantly reduced blood lactate and blood ammonia concentrations during exercise and at rest after exercise compared with placebo ( < 0.05). In conclusion, 28 consecutive days of vitamin B complex (Ex PLUS) supplementation significantly improved exercise endurance performance and reduced exercise fatigue biochemical metabolites in not athletes. In addition, it does not cause adverse effects in humans when taken at appropriate doses.
Topics: Humans; Male; Female; Vitamin B Complex; Dietary Supplements; Folic Acid; Health Status; Fatigue; Double-Blind Method
PubMed: 37786445
DOI: 10.7150/ijms.86738 -
The Ocular Surface Oct 2023Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia... (Review)
Review
Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia and Keratoconus. Some effects of the procedure such as induced mechanical stiffening, corneal flattening, and cellular toxicity are well-known, but others remain more controversial. Authors report a variety of contradictory effects, and provide evidence based on individual results and observations. A full understanding of the effects of and mechanisms behind this procedure are essential to predicting its outcome. A growing interest in modifications to the standard UVA CXL protocol, such as transepithelial or accelerated UVA CXL, makes analyzing the literature as a whole more urgent. This review presents an analysis of both the agreed-upon and contradictory results reported and the various methods used to obtain them.
Topics: Humans; Cornea; Ultraviolet Rays; Collagen; Riboflavin; Keratoconus; Cross-Linking Reagents; Photosensitizing Agents; Corneal Stroma
PubMed: 37683969
DOI: 10.1016/j.jtos.2023.09.003