Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis

AbstractBackgroundRheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition.ObjectivesThe aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin.MethodsA total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits.ResultsThe CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis.ConclusionOur findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Polimorfismos dos genes metilenotetrahidrofolato redutase, fator de crescimento transformador β1 e linfotoxina‐α e susceptibilidade à artrite reumatoide

ResumoAntecedentesA artrite reumatoide é uma doença autoimune amplamente prevalente com sugerida predisposição genética.ObjetivosDetectar o padrão de polimorfismo dos genes metilenotetrahidrofolato redutase (MTHFR C677T e A1298C), fator de crescimento transformador β1 (TGF‐β1 T869C) e linfotoxina‐α (LT‐α A252G) em pacientes com artrite reumatoide e correlacionar esses padrões com a atividade da doença e os níveis séricos de fator de necrose tumoral alfa (TNF‐α), fator ativador de linfócitos B (BAFF) e osteopontina.MétodosForam genotipados 194 indivíduos – 90 controles e 104 com artrite reumatoide – à procura de polimorfismos dos genes MTHFR C677T e A1298C, TGF‐β1 T869C e LT‐α A252G com uma metodologia baseada na PCR‐RFLP. Mensuraram‐se também os níveis séricos de TNF‐α, osteopontina e BAFF com kits de Elisa.ResultadosO genótipo CT e o alelo T do MTHFR C677T e o genótipo GG e alelo G do LT‐α A252G estão associados ao risco de AR e a níveis mais elevados da citocina pró‐inflamatória TNF‐α em pacientes com artrite reumatoide.ConclusãoOs achados do presente estudo sugerem que há associação entre os polimorfismos dos genes MTHFR C677T e LT‐α A252G e um risco aumentado de AR nessa amostra da população egípcia.AbstractBackgroundRheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition.ObjectivesThe aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677T and A1298C), transforming growth factor‐β1 (TGF‐β1 T869C) and lymphotoxin‐α (LT‐α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor‐alpha (TNF‐α), B‐Cell Activating Factor (BAFF), and osteopontin.MethodsA total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677T and A1298C, TGF‐β1 T869C and LT‐α A252G polymorphisms using a methodology based on PCR‐RFLP. Also serum levels of TNF‐α, osteopontin and BAFF were measured by ELISA kits.ResultsThe CT genotype and T allele of MTHFR C677T and GG genotype and G allele of LT‐α A252G are associated with the risk of RA and with higher levels of the pro‐inflammatory cytokine, TNF‐α in patients with rheumatoid arthritis.ConclusionOur findings suggest that there is association between MTHFR C677T and LT‐α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis

ABSTRACT Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research