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Background and aims The role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results Seven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041). Conclusions This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.

Purpose The purpose of this review is to perform a meta-analysis of studies reporting meniscus repair outcomes. Pooled analyses of such studies will provide an accurate estimate of the outcomes that can be expected following meniscal repair at various postoperative time points. Methods A meta-analysis of meniscal repair failure (defined as persistent symptoms, lack of healing on magnetic resonance imaging or revision surgery) and other clinical outcomes was performed following meniscal repair. Patients included had traumatic, nondegenerative meniscal tears, were skeletally mature, and had specific time-points after surgery. Repairs included were performed either in isolation, or with concomitant ACL reconstruction. Because of the inherent heterogeneity of single-arm meta-analyses, pooled analyses were performed using a random-effects model. Results Rates of all-cause meniscal repair failure was pooled to be 12% at 0-1 years (95% CI: .09-.16), 15% at 2-3 years (95% CI: .11-.20), and 19% at 4-6 years (95% CI: .13-.24). Sensitivity analysis for studies performing meniscal repair entirely on patients with concomitant ACL reconstruction (ACLR) showed comparable rates of failure at similar time intervals. Development of osteoarthritis, in patients with knees previously free from articular pathologies, was 4% at 2-3 years (95% CI: .02-.07), and 10% at 4-6 years (95% CI: .03-.25). Conclusion Meniscus repair for traumatic injuries have an all-cause failure rate that increases from 12% to 19% through a time period ranging from 1-6 years following surgery. The failure rates were comparable for patients with meniscal repairs performed with concomitant ACLRs. Level of Evidence IV; Systematic Review of Level II-IV Studies.

Background: Meniscal allograft transplant (MAT) is an important treatment option for young patients with deficient menisci; however, there is a lack of consensus on the optimal method of allograft fixation. Hypothesis: The various methods of MAT fixation have measurable and significant differences in outcomes. Study Design: Meta-analysis; Level of evidence, 4. Methods: A single-arm meta-analysis of studies reporting graft failure, reoperations, and other clinical outcomes after MAT was performed. Studies were stratified by suture-only, bone plug, and bone bridge fixation methods. Proportionate rates of failure and reoperation for each fixation technique were pooled with a mixed-effects model, after which reconstruction of relative risks with confidence intervals was performed using the Katz logarithmic method. Results: A total of 2604 patients underwent MAT. Weighted mean follow-up was 4.3 years (95% CI, 3.2-5.6 years). During this follow-up period, graft failure rates were 6.2% (95% CI, 3.2%-11.6%) for bone plug fixation, 6.9% (95% CI, 4.5%-10.3%) for suture-only fixation, and 9.3% (95% CI, 6.2%-13.9%) for bone bridge fixation. Transplanted menisci secured using bone plugs displayed a lower risk of failure compared with menisci secured via bone bridges (RR = 0.97; 95% CI, 0.94-0.99; P = .02). Risks of failure were not significantly different when comparing suture fixation to bone bridge (RR = 1.02; 95% CI, 0.99-1.06; P = .12) and bone plugs (RR = 0.99; 95% CI, 0.96-1.02; P = .64). Allografts secured using bone plugs were at a lower risk of requiring reoperations compared with those secured using sutures (RR = 0.91; 95% CI, 0.87-0.95; P < .001), whereas allografts secured using bone bridges had a higher risk of reoperation when compared with those secured using either sutures (RR = 1.28; 95% CI, 1.19-1.38; P < .001) or bone plugs (RR = 1.41; 95% CI, 1.32-1.51; P < .001). Improvements in Lysholm and International Knee Documentation Committee scores were comparable among the different groups. Conclusion: This meta-analysis demonstrates that bone plug fixation of transplanted meniscal allografts carries a lower risk of failure than the bone bridge method and has a lower risk of requiring subsequent operations than both suture-only and bone bridge methods of fixation. This suggests that the technique used in the fixation of a transplanted meniscal allograft is an important factor in the clinical outcomes of patients receiving MATs.

Background The COVID-19 pandemic has affected patients with ST-segment elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI) worldwide. In this review we examine the global effect of the COVID-19 pandemic on incidence of STEMI admissions, and relationship between the pandemic and door to balloon time (D2B), all-cause mortality, and other secondary STEMI outcomes. Methods We performed a systematic review and meta-analysis to primarily compare D2B time and in-hospital mortality of STEMI patients who underwent primary PCI during and before the pandemic. Subgroup analyses were performed to investigate the influence of geographical region and income status of a country on STEMI care. An online database search included studies that compared the aforementioned outcomes of STEMI patients during and before the pandemic. Results In total, 32 articles were analyzed. Overall, 19,140 and 68,662 STEMI patients underwent primary PCI during and before the pandemic, respectively. Significant delay in D2B was observed during the pandemic (weighted mean difference, 8.10 minutes; 95% confidence interval [CI], 3.90-12.30 minutes; P = 0.0002; I2 = 90%). In-hospital mortality was higher during the pandemic (odds ratio [OR], 1.27; 95% CI, 1.09-1.49; P = 0.002; I2 = 36%), however this varied with factors such as geographical location and income status of a country. Subgroup analysis showed that low–middle-income countries observed a higher rate of mortality during the pandemic (OR, 1.52; 95% CI, 1.13-2.05; P = 0.006), with a similar but insignificant trend seen among the high income countries (OR, 1.17; 95% CI, 0.95-1.44; P = 0.13). Conclusions The COVID-19 pandemic is associated with worse STEMI performance metrics and clinical outcome, particularly in the Eastern low–middle-income status countries. Better strategies are needed to address these global trends in STEMI care during the pandemic.

Aim To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post-orthotopic liver transplant (OLT) patients. Methods Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post-OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta-analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single-arm meta-analysis. Results Post-OLT fracture incidence was reported in nine studies (n=591). Total fracture incidence was 6.6% (CI: 3.4% to 12.4%) in bisphosphonate group and 19.1% (CI: 14.3% to 25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n = 591; OR = 0.037; CI: 0.18 to 0.77; p=0.008) Overall fractures were significantly lower in the oral group (n= 263; OR = 0.26; CI: 0.08 to 0.85, p=0.02) but not in the IV group (n = 328; OR = 0.45; CI: 0.16 to 1.26, p=0.129). Conclusion Both oral and IV bisphosphonates are effective in reducing fracture incidence post-OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post-OLT.

BACKGROUND Recent clinical trials have demonstrated favorable outcomes associated with trans-anal colonic pull-through for rectal resection followed by delayed coloanal anastomoses (DCA), resulting in a resurgence in popularity of the technique. This meta-analysis aims to review existing literature to evaluate the postoperative complications associated with DCA, and to make comparisons with immediate coloanal anastomoses (ICA) after colorectal resection to assess the suitability of DCA as an alternative form of surgical treatment. METHODS Medline and Embase databases were reviewed from inception until 31 July 2020 in accordance with PRISMA guidelines. Single-arm studies that involved patients undergoing DCA for benign or malignant causes were selected, and meta-analysis of proportions was conducted to determine the prevalence of postoperative complications following DCA. Comparative studies comparing postoperative outcomes between DCA and ICA were also included for comparative meta-analysis. RESULTS Patients undergoing DCA were significantly less likely to require diverting stoma construction as compared to ICA (odds ratio [OR] = 0.04; confidence interval [CI]: 0.02-0.07; P

Following liver transplant (LT), osteoporosis is a severe complication that causes morbidity. However, the incidence and risk factors of osteoporosis and fractures have not been well described. Single-arm meta-analysis of studies reporting osteopenia, osteoporosis, and fractures post-LT was performed with meta-regression for study period. Dichotomous variables, continuous variables and time-to-event variables were pooled in odds ratio, weighted mean difference and hazard ratio, respectively. For risk factors with limited data, a systematic review of literature was conducted. There was a significant increase in both osteoporosis and fractures compared to non-LT patients. Osteopenia, osteoporosis and incident fractures were newly diagnosed in 34.53% (CI: 0.17-0.56, n = 301), 11.68% (CI: 0.05-0.24, n = 1251) and 20.40% (CI: 0.13-0.30, n = 4322) of LT patients, respectively. Female gender (P = 0.017) increased risks of osteoporosis but not older age and BMI. Older age, lower pre-LT bone mineral density (BMD), presence of bone disease pre-LT were significant risk factors for fractures but not female gender, post-menopausal state, BMI, smoking and alcohol. There is a high incidence of skeletal complications post-LT. Older age, lower pre-LT BMD and presence of bone disease pre-LT are significant risk factors that are associated with incident fractures physicians should be cognisant of in liver transplant recipients.

Conventional colectomy, and the Japanese Society for Cancer of the Colon and Rectum (JSCCR) D2 Lymphadenectomy (LND2), are currently considered standard of care for surgical management of colon cancer. Colectomy with complete mesocolic excision (CME) and JSCCR D3 Lymphadenectomy (LND3) are more radical alternative approaches and provide a greater degree of lymph nodal clearance. However, controversy exists over the long-term benefits of CME/LND3 over non-CME colectomies (NCME)/LND2. In this study, we performed a systematic review and meta-analysis to compare the surgical, pathological, and oncological outcomes of CME/LND3 with NCME/LND2. Embase, Medline and CENTRAL databases were searched from inception until May 15, 2020, in accordance with PRISMA guidelines. Studies were included if they compared curative intent CME/LND3 with NCME/LND2. Weighted mean differences (WMD) and odds ratios (OR) were estimated for continuous and dichotomous outcomes respectively. Out of 1310 unique citations, 106 underwent full-text review, and 30 were included for analysis. In total, 21,695 patients underwent resection for colon cancer. 11,625 received CME/LND3, and 10,070 underwent NCME/LND2. No significant differences were found in post-operative morbidity and mortality. Both overall and disease-free survival favored CME/LND3 (5-year OS: OR = 1.29; 95% CI 1.02 to 1.64, p = 0.03; 5-year DFS: OR = 1.61; 95% CI 1.14 to 2.28; p = 0.007). This is the first systematic review and meta-analysis to demonstrate that CME/LND3 has superior long-term survival outcomes compared to NCME/LND2.

Background: Matrix-induced chondrogenesis (MIC) is a promising treatment option for critical-size cartilage lesions of the knee; however, there exists substantial heterogeneity in the choice of acellular scaffold matrix for MIC cartilage repairs. Hypothesis: The choice of acellular matrix will not affect patient outcomes after MIC cartilage repair procedures, and the addition of concentrated bone marrow aspirate (cBMA) will improve short-term patient outcomes regardless of matrix choice. Study Design: Meta-analysis; Level of evidence, 4. Methods: Studies were stratified by matrix type: multilayered, single layered, and gel based. Continuous outcomes were analyzed with pairwise meta-analysis using the inverse variance model with random effects applied. Binary outcomes were analyzed as pooled proportions in a single-arm fashion; after which, reconstruction of relative risks (RRs) with confidence intervals was performed using the Katz logarithmic method. Results: A total of 876 patients were included: 469 received multilayered bioscaffolds; 238, gel-based scaffolds; and 169, single-layered scaffolds. The mean age of patients was 36.2 years (95% CI, 33.9 to 38.4), while the mean lesion size was 3.91 cm2 (95% CI, 3.40 to 4.42). The weighted mean follow-up was 23.8 months (95% CI, 20.1 to 27.6). Multilayered bioscaffolds were most effective at improving visual analog scale scores ( P = .03; weighted mean difference [WMD], −4.44 [95% CI, −4.83 to −4.06]; P < .001). There were significantly lower risks of incomplete defect filling for gel-based scaffolds when compared with multilayered scaffolds (RR, 0.78 [95% CI, 0.69 to 0.88]; P < .001) and single-layered scaffolds (RR, 0.58 [95% CI, 0.41 to 0.81]; P = .001). Augmentation with cBMA further improved clinical scores across all scaffolds, with significant improvements in Tegner score ( P = .02), while decreasing incomplete defect filling rates as well. There was significantly greater improvement in visual analog scale scores ( P = .01) for single-layered scaffolds with cBMA augmentation (WMD, −4.88 [95% CI, −5.38 to −4.37]; P < .001) as compared with single-layered scaffolds without cBMA augmentation (WMD, −4.08 [95% CI, −4.46 to −3.71]; P < .001). All significant improvements were below their respective minimum clinically important differences. Conclusion: While cartilage repair with acellular scaffolds provides significant improvements in pain and function for patients, there is insufficient clinical evidence to suggest which scaffold material is the most superior in influencing such improvements. The enhancement of cartilage repair procedures with cBMA may provide further functional improvements and improve defect filling; however, more long-term evidence is required to evaluate the effects.

Introduction Conventional colectomy, and the Japanese Society for Cancer of the Colon and Rectum (JSCCR) D2 Lymphadenectomy (LND2), are the standards of care for the surgical management of colon cancer. Colectomy with complete mesocolic excision (CME) and JSCCR D3 Lymphadenectomy (LND3) are alternative, and more radical procedures, that provide greater lymph nodal clearance. However, controversy exists over the long-term survival benefits of CME/LND3 over non-CME colectomies (NCME)/LND2. Method In this study, we performed a meta-analysis to compare the survival outcomes of CME/LND3 with NCME/LND2. Medline and Embase databases were searched for articles reporting survival outcomes of both CME/LND3 and NCME/LND2, with comparisons presented using odds ratios (OR). Results Ten studies were included in this analysis. Overall and disease-free survival favored CME/LND3 (3-year OS: OR = 1.56; CI 1.22-2.00; p = 0.0004, 5-year OS: OR = 1.29; CI 1.02-1.64, p = 0.03, 3-year DFS: OR = 1.45; CI 1.12-1.88; p = 0.005, 5-year DFS: OR = 1.61; CI 1.14-2.28; p = 0.007). Overall and disease-free survival rates at five years were 79.8% and 85.9%, and 74.6% and 78.0%, in the CME/LND3 and NCME/LND2 groups respectively. Conclusions This is the first meta-analysis to demonstrate that CME/LND3 has superior long-term survival outcomes compared to NCME/LND2, hence a strong case can be made for incorporating CME/LND3 into standard care practice.

Introduction Learning research in medical school can be daunting and difficult with many lacking appropriate guidance. Particularly, research in surgery can be difficult with most clinicians tied to long hours from clinical duties, leaving medical students lost to learn the ropes for medical research. Method We started a surgical research group in January of 2020 under a shepherd sheep model. Shepards were senior medical students who had previous experience in research and were provided resources from consultants on statistics and research designs. Thereafter, each Shepard were paired with junior medical students (sheep) and a resident to provide clinical background. Research was then carried out small teams with minimal guidance from consultants. Results To date, the group has published 11 articles (median impact factor: 2.41, range: 1.89 - 3.42), 3 articles in revision and 9 articles in review. Conclusions We provide preliminary evidence of a successful model for building medical student research in surgery. While current analysis was limited to meta-analysis and systematic review due to the availability of data, current expansion is currently underway to expand to observational studies.

Introduction Post-operative recurrence after Crohn’s surgery poses a significant challenge to clinicians with an estimated of 70-90% recurrence rate. However, with the advent of biologics, reduction of recurrence after surgery has been observed in various landmark trials. Hence, we aim to quantify the rate of recurrence with post-operative biologics. Method Searches were done on Embase and Medline database for articles using biologics for post-operative management. A single arm meta-analysis with generalized linear mixed model and Clopper-Pearson method confidence interval was applied in the synthesis of the data on six months, one year, two year and five year. Results A total of 1,864 abstracts were identified, with a final total of 24 articles and 1042 patients were included in the meta-analysis. The one-year rate of recurrence for surgical, endoscopic and clinical was 3.08% (CI: 0.74% - 11.95%), 19.93% (15.81% - 24.81%) and 13.06% (CI: 8.18% - 18.92%) respectively. Correspondingly, the five-year recurrence 16.90% (CI: 9.57% - 28.11%), 84.21% (CI: 72.35% - 91.57%), 5.60% (CI: 9.92% -23.66%) respectively. Conclusions An observed reduction in surgical rates was reduced at five years with post-operative Crohn’s disease with biologics. Biologics therapy thus can be considered as a suitable alternative for reducing post-operative recurrence in individuals with higher risk.

Introduction The role and optimal regimen of radiotherapy in curative-intent treatment of metastatic rectal cancer is unclear and hence a single arm meta-analysis was performed. Method Medline, Embase and Cochrane Library databases were searched up to 16 May 2020. A Meta-analysis of binomial data was performed using a Freeman-Tukey double arcsine transformation, and pooled estimates were used to construct risk ratios and confidence intervals via the Katz-logarithmic method. Additionally, comparative meta-analysis was performed with the Mantel Haenszel model. Results 18 studies were included. Rectal pathological complete response (pCR) was observed in 14% of tumours treated with radiotherapy (n = 57/388, CI 0.07 to 0.23). Comparative meta-analysis of cohort studies showed that treatment regimens including radiotherapy were associated with higher pT1 tumour and better oncological outcomes compared to regimens without radiotherapy. Katz-logarithmic method showed that neoadjuvant radiotherapy had a higher proportion of pN0 staging (RR = 1.81, 95% CI 1.06 to 3.09, p = 0.029) and better oncological outcomes compared to adjuvant radiotherapy, and that short course radiotherapy (SCRT) had a lower proportion of pT3 tumours (RR = 0.778, 95% CI 0.609 to 0.994, p = 0.044) and similar oncological outcomes compared to long course radiotherapy (LCRT). Conclusions This study supports the evidence that radiotherapy should be used in curative intent metastatic rectal cancer.

Background Prevention of post-operative recurrence of Crohn's disease poses a significant challenge to clinicians. With the advent of biologics, reduction of recurrence after surgery has been observed in various studies. Hence, we performed a systematic review and meta-analysis to identify the rate of post-operative recurrence at different timepoints in the era of anti-TNF-α therapy biologics use. Methods We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing post-operative recurrence of Crohn's disease. Data were extracted, and a single arm meta-analysis with generalized linear mixed model and Clopper-Pearson method for confidence interval was performed to identify the endoscopic, clinical, and surgical recurrence rates at six-months, one-, two- and five-years post-operatively. Results 24 articles were included in the meta-analysis. The endoscopic, clinical, and surgical postoperative recurrence rate with the use of anti-TNF-α agents at one-year was 21.72% (95%CI: 16.28% - 28.37%), 13.06% (95%CI: 8.18% - 18.92%) and 3.76% (95%CI: 1.37% - 9.91%) respectively. The five-year recurrence rate was 84.21% (95%CI: 72.35% - 91.57%) and 17.49% (95%CI: 9.17% - 30.80%) for endoscopic and surgical recurrence respectively. Subgroup analysis at one-year for type of anti-TNF-α agent or timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rate. Conclusion Anti-TNF-α agents are effective at preventing clinical, endoscopic, and surgical postoperative Crohn's disease recurrence. The timing of initiating biological therapy after surgery has no significant effect on the rate of postoperative recurrence. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.

Background The COVID-19 pandemic profoundly impacted healthcare institutions worldwide. Particularly, orthopedic departments had to adapt their operational models. Purpose This review aimed to quantify the reduction in surgical and outpatient caseloads, identify other significant trends and ascertain the impact of these trends on orthopedic residency training programs. Methods Medline and Embase were searched for articles describing case load for surgeries, outpatient clinic attendance, or emergency department (ED) visits. Statistical analysis of quantitative data was performed after a Freeman-Tukey double arcsine transformation. Results were pooled with random effects by DerSimonian and Laird model. When insufficient data was available, a systematic approach was used to present the results instead. Results A total of 23 studies were included in this study. The number of elective surgeries, trauma procedures and outpatient attendance decreased by 80% (2013/17400, 0.20, CI: 0.12 to 0.29), 47% (3887/17561, 0.53, CI: 0.37 to 0.69) and 63% (84174/123967, 0.37, CI: 0.24 to 0.51) respectively. During the pandemic, domestic injuries and polytrauma increased. Residency training was disrupted due to diminished clinical exposure and changing teaching methodologies. Additionally, residents had more duties which contributed to a lower quality of life. Conclusions The COVID-19 pandemic has made an unprecedented impact on orthopedics departments worldwide. The slow return of orthopedic departments to normalcy and the compromised training of residents due to the pandemic points to an uncertain future for healthcare institutions worldwide, wherein the impact of this pandemic may yet still be felt far in the future.

Background and Aims: The role of laparoscopic rectal cancer resection remains controversial. Previous meta-analyses of survival outcomes have utilized a standard meta-analytical approach less amenable to the incorporation of flexible and robust survival models. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods: Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results: Seven randomized trials, with a median follow-up of six years, involving 1,767 laparoscopic and 1,293 open resections for rectal cancer in 3,060 patients were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78 – 1.06, p =0.241) and 0.86 (95% CI: 0.73 - 1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI: 0.54 - 0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI: 0.55 - 0.99, p =0.041). Conclusions: This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer. Funding: No funding was required for this work. Declaration of Interest: None to declare.

To examine risk factors that might be associated with thyroid eye disease (TED) in patients with Graves' disease (GD), which may guide physicians in the prevention and management of TED.Medline and Embase were searched for articles discussing risk factors of TED. Comparisons were made between GD patients with and without TED, and between active and inactive TED GD patients. Weighted mean differences (WMDs) and odds ratios (ORs) were determined for continuous and dichotomous outcomes, respectively. Results were pooled with random effects using the DerSimonian and Laird model.Fifty-six articles were included in the analysis. Smoking, inclusive of current and previous smoking status, was a significant risk factor for TED (OR: 2.401; CI: 1.958-2.945; P.001). Statistical significance was found upon meta-regression between male sex and the odds of smoking and TED (β = 1.195; SE = 0.436; P = .013). Other risk factors were also examined, and patients with TED were significantly older than those without TED (WMD: 1.350; CI: 0.328-2.372; P = .010). While both age (WMD: 5.546; CI: 3.075-8.017; P.001) and male sex (OR: 1.819; CI: 1.178-2.808; P = .007) were found to be significant risk factors for active TED patients compared to inactive TED patients, no statistical significance was found for family history, thyroid status, cholesterol levels, or body mass index.Factors such as smoking, sex, and age predispose GD patients to TED, and TED patients to active TED. A targeted approach in the management of GD and TED is required to reduce the modifiable risk factor of smoking.