Letter to Editor: Role of Pharmacotherapy in Patients With Coexisting Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

We read with interest a recent article written by Yan et al.(1) The authors conducted a randomized trial in patients with coexisting type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) to receive liraglutide, sitagliptin, or insulin glargine as add-on to metformin. The authors observed glycemic control and a reduction in body weight, intrahepatic lipid, and visceral adipose tissue in patients who received liraglutide or sitagliptin and then reported these add-on therapies to be novel pharmacotherapeutic therapies in patients with NAFLD and T2DM. However, the clinical meaningfulness of these pharmacologic treatments has not been conclusively established, especially since histopathology was not used to diagnose and determine the severity of NAFLD in that study. This article is protected by copyright. All rights reserved.

Whey Protein Supplementation Improves Body Composition and Cardiovascular Risk Factors in Overweight and Obese Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous literature shows possible benefits of whey protein supplementation in promoting weight loss. However, most studies do not have enough power to show beneficial effects on body composition and cardiovascular disease (CVD) risk factors. This meta-analysis evaluated effects of whey protein in individuals who are overweight and obese. METHODS: We comprehensively searched the databases of MEDLINE, Embase, and Cochrane databases. The inclusion criteria were published randomized control trials (RCTs) comparing whey protein supplementation to placebo or controls in individuals who are overweight or obese. The primary outcome was the differences in the change in body composition (body weight, waist circumference, total fat mass, body lean mass). We also examined the changes in CVD risk factors as secondary outcomes. We calculated pooled mean difference (MD) with 95% confidence intervals (CIs) using a random effects model. RESULTS: Nine RCTs were included in the meta-analysis. There was a significant reduction of body weight (MD = 0.56, 95% CI: 0.30-0.81), lean mass (MD = 0.77, 95% CI: 0.59-0.96), and fat mass (MD = 1.12, 95% CI: 0.77-1.47) favoring the whey protein group. There were improvements in multiple CVD risk factors including levels of systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, and total cholesterol (all p values <0.05). CONCLUSIONS: Whey protein supplementation seems to improve body weight, total fat mass, and some CVD risk factors in overweight and obese patients. Further studies regarding optimal dosage and duration of whey protein supplementation would be helpful to assess potential favorable effects in individuals who are overweight or obese.

Helicobacter pylori infection in systemic sclerosis: a systematic review and meta-analysis of observational studies.

OBJECTIVES: It has been proposed that Helicobacter pylori (H.pylori) infection causes several extra-gastrointestinal disorders. However, the role of H.pylori infection in the pathogenesis of systemic sclerosis (SSc) is still debatable. This meta-analysis is aimed at exploring the association between SSc and H.pylori infection. METHODS: A comprehensive search of the MEDLINE and EMBASE databases was performed from inception through February 2018. The inclusion criterion was observational studies evaluating H.pylori infection in SSc. The pooled odds ratio (OR) of H.pylori infection and their 95% confidence interval (CI) were calculated using a random-effects meta-analysis to compare risk between SSc patients and healthy controls. The between-study heterogeneity of effect-size was quantified using the Q statistic and I2. RESULTS: Data were extracted from 8 observational studies involving 1,446 subjects. The pooled results demonstrated an increased H.pylori infection in SSc compared with healthy controls (OR=2.10; 95% CI: 1.57-2.82, p value<0.01, I2=13%). Subgroup analysis showed an increased risk of H.pylori infection measured with H.pylori ELISA test (OR=2.49; 95% CI: 1.82-3.40, p value<0.01, I2=0%). CONCLUSIONS: Our study has shown that patients with SSc have an increased prior existence of H.pylori infection. This finding implies that the role of previous infection may cause an abnormal immunological cascade in the pathogenesis of SSc. Further studies that could elucidate the inflammatory response in the pathogenesis of SSc are warranted.

Association between primary Sjögren's syndrome, cardiovascular and cerebrovascular disease: a systematic review and meta-analysis.

OBJECTIVES: Acute systemic inflammation and chronic systemic vasculitis are associated with endothelial dysfunction and atherosclerotic plaque formation. Studies on cardiovascular or cerebrovascular events in primary Sjögren's syndrome (pSS) are limited, with conflicting results. This meta-analysis aimed to explore the risk of cardiovascular and cerebrovascular disease in pSS. METHODS: A comprehensive search of the MEDLINE and EMBASE databases was performed from date of inception through August 2017. The inclusion criterion was observational studies evaluating the association between pSS and cardiovascular disease or cerebrovascular event. Outcomes are diagnosis of ischaemic heart disease, myocardial infarction, ischaemic stroke or haemorrhagic stroke. The pooled odds ratio (OR) of the cerebrovascular event or cardiovascular disease and their 95% confidence interval (CI) were calculated using a random-effect meta-analysis to compare risk between patients with pSS and controls. The between-study heterogeneity of effect-size was quantified using the Q statistic and I2. RESULTS: Data were extracted from 10 observational studies involving 165,291 subjects. Pooled result demonstrated a significant increase in risk of having cardiovascular disease or cerebrovascular event in pSS patients compared with controls (OR=1.28; 95% CI: 0.11-1.46, p value<0.01, I2=68%). Subgroup analyses showed no difference in risk for cerebrovascular event (OR=1.31; 95% CI: 0.96-1.79, p value=0.09, I2=71%), but an increased risk of cardiovascular disease (OR=1.30; 95% CI: 1.09-1.55, p value=0.003, I2=74%). CONCLUSIONS: Our study has shown an increased risk of cardiovascular or cerebrovascular disease in patients with pSS. These results support multiple studies' finding of increased arterial stiffness in patients with pSS.

Nonalcoholic fatty liver disease and osteoporosis: a systematic review and meta-analysis.

Several major risk factors for osteoporosis have been identified. One of these risk factors is chronic inflammation. Several recent studies have supported the association between low bone mineral density (BMD) and nonalcoholic fatty liver disease (NAFLD), which comprises a spectrum of disorders involving liver inflammation. However, conflicting evidence regarding this association has been obtained thus far. We, therefore, conducted a meta-analysis of observational studies to show the association between NAFLD and BMD. The Cochrane Central Register of Controlled Trials, Cochrane Library, Medline, and Embase were searched from database inception to November 2014 for all observational studies evaluating the association between NAFLD or nonalcoholic steatohepatitis (NASH) and bone mass, BMD, or osteoporosis. All patients were ≥18 years of age and had no other cause of liver disease, osteoporosis, or pathological bone disease at baseline. Risk factors were NAFLD and NASH; control subjects were individuals without NAFLD. Eleven articles underwent full-length review. Data were extracted from five cross-sectional studies involving 1276 participants; 638 had NAFLD. The main meta-analysis showed no significant difference in BMD between patients with fatty liver disease and controls. Among all variables analyzed, body mass index had the strongest and most significant predictive effect on the difference in BMD. Controversy exists regarding the effect of BMD on NAFLD. Further studies are required to fully show this relationship.

Risk factors for delayed colonic post-polypectomy bleeding: a systematic review and meta-analysis.

PURPOSE: Delayed post-polypectomy bleeding (PPB) is an infrequent but serious adverse event after colonoscopic polypectomy. Several studies have tried to identify risk factors for delayed PPB, with inconsistent results. This meta-analysis aims to identify significant risk factors for delayed PPB. METHODS: MEDLINE and EMBASE databases were searched through January 2016 for studies that investigated the risk factors for delayed PPB. Pooled odds ratio (OR) for categorical variables and mean differences (MD) for continuous variables and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity of effect size was quantified using the Q statistic and I 2. RESULTS: Twelve articles involving 14,313 patients were included. The pooled delayed PPB rate was 1.5% (95%CI, 0.7-3.4%), I 2 = 96%. Cardiovascular disease (OR = 1.55), hypertension (OR = 1.53), polyp size > 10 mm (OR = 3.41), and polyps located in the right colon (OR = 1.60) were identified as significant risk factors for delayed PPB, whereas age, sex, alcohol use, smoking, diabetes, cerebrovascular disease, pedunculated morphology, and carcinoma histology were not. CONCLUSIONS: Cardiovascular disease, hypertension, polyp size, and polyp location were associated with delayed PPB. More caution is needed when removing polyps in patients with these risk factors. Future studies are warranted to determine appropriate preventive hemostatic measures in these patients.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY PROTOCOL FOR STANDARDIZED PRODUCTION OF CLINICAL PRACTICE GUIDELINES, ALGORITHMS, AND CHECKLISTS - 2017 UPDATE.

Clinical practice guideline (CPG), clinical practice algorithm (CPA), and clinical checklist (CC, collectively CPGAC) development is a high priority of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE). This 2017 update in CPG development consists of (1) a paradigm change wherein first, environmental scans identify important clinical issues and needs, second, CPA construction focuses on these clinical issues and needs, and third, CPG provide CPA node/edge-specific scientific substantiation and appended CC; (2) inclusion of new technical semantic and numerical descriptors for evidence types, subjective factors, and qualifiers; and (3) incorporation of patient-centered care components such as economics and transcultural adaptations, as well as implementation, validation, and evaluation strategies. This third point highlights the dominating factors of personal finances, governmental influences, and third-party payer dictates on CPGAC implementation, which ultimately impact CPGAC development. The AACE/ACE guidelines for the CPGAC program is a successful and ongoing iterative exercise to optimize endocrine care in a changing and challenging healthcare environment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists ACC = American College of Cardiology ACE = American College of Endocrinology ASeRT = ACE Scientific Referencing Team BEL = best evidence level CC = clinical checklist CPA = clinical practice algorithm CPG = clinical practice guideline CPGAC = clinical practice guideline, algorithm, and checklist EBM = evidence-based medicine EHR = electronic health record EL = evidence level G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GAC = guidelines, algorithms, and checklists HCP = healthcare professional(s) POEMS = patient-oriented evidence that matters PRCT = prospective randomized controlled trial.

Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis.

INTRODUCTION AND AIM: Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. MATERIAL AND METHODS: A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (CI) comparing between subjects with and without NAFLD by using random-effects model. RESULTS: Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. CONCLUSION: Our meta-analysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.

Bone mineral density is decreased in fibromyalgia syndrome: a systematic review and meta-analysis.

Previous studies have shown that fibromyalgia syndrome (FMS) is associated with low level of physical activity and exercise, which may lead to an increased risk of osteoporosis. However, studies of bone mineral density (BMD) in fibromyalgia have shown conflicting results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between FMS and BMD. A comprehensive search of the databases MEDLINE and EMBASE was performed from inception through May 2016. The inclusion criterion was the observational studies' assessment of the association between fibromyalgia and bone mineral density in adult subjects. Fibromyalgia was diagnosed in accordance with the American College of Rheumatology criteria for the diagnosis of fibromyalgia syndrome. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Pooled mean difference (MD) of BMD at each site and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The between-study heterogeneity of effect size was quantified using the Q statistic and I 2. Data were extracted from four observational studies involving 680 subjects. At lumbar spine (L2-L4), BMD is significantly decreased in patients with FMS compared with controls with pooled MD of -0.02 (95% CI -0.03 to -0.01, P value = 0.003, I 2 = 0%) (Fig. 1). At femoral neck, BMD is not significantly decreased in patients with FMS compared with controls with pooled MD of 0.01 (95% CI -0.02 to 0.01, P value = 0.23, I 2 = 0%) (Fig. 2). In this meta-analysis, we observe that BMD at lumbar spine is decreased in FMS compared with normal individuals. Patients with FMS should be assessed for risk of osteoporosis. Fig. 1 Forest plot of bone mineral density at the lumbar spine, for patients with and without fibromyalgia syndrome. CI-confidence interval Fig. 2 Forest plot of bone mineral density at the femoral neck, for patients with and without fibromyalgia syndrome. CI-confidence interval.

Effects of visceral adipose tissue reduction on CVD risk factors independent of weight loss: The Look AHEAD study.

OBJECTIVES: To determine if the reduction of visceral adipose tissue (VAT) volume by lifestyle intervention improved risk factors for cardiovascular disease (CVD) independent of weight loss amount. DESIGN: Ancillary study of randomized-controlled trial. SETTING: Data analysis using multivariable regression models. PARTICIPANTS: Participants of the Look AHEAD (Action for HEAlth in Diabetes) Fatty Liver Ancillary Study. MAIN OUTCOME MEASURES: Correlations between changes in VAT and in CVD risk factors, while adjusting for weight loss and treatment (intensive lifestyle intervention [ILI] vs. diabetes support and education [DSE]). RESULTS: Of 100 participants analyzed, 52% were women, and 36% were black, with a mean age of 61.1 years. In the DSE group, mean weight and VAT changed by 0.1 % (p=0.90) and 4.3% (p=0.39), respectively. In the ILI group, mean weight and VAT decreased by 8.0% (p<0.001) and 7.7% (p=0.01), respectively. Across both groups, mean weight decreased by 3.6% (p<0.001), and mean VAT decreased by 1.2% (p=0.22); the decrease in VAT was correlated with the increase in HDL-cholesterol (HDL-C; R=-0.37; p=0.03). There were no correlations between changes in VAT and blood pressure, triglycerides, LDL-C, glucose, or HbA1c. After adjusting for age, race, gender, baseline metabolic values, fitness, and treatment group, changes in HDL-C were not associated with changes in VAT, while weight changes were independently associated with decrease in glucose, HbA1c, and increase in HDL-C. CONCLUSIONS: VAT reduction was not correlated with improvements of CVD risk factors in a sample of overweight and obese adults with type 2 diabetes after adjusting for weight loss.

Risk of colorectal adenomas, advanced adenomas and cancer in patients with colonic diverticular disease: Systematic review and meta-analysis.

BACKGROUND AND AIM: Diverticular disease and colorectal neoplasia are common digestive disorders worldwide. Both diseases share epidemiological trends and certain risk factors including advancing age, physical inactivity, and Western diet and lifestyle. Studies assessing the association between these diseases reported inconsistent results. Thus, we conducted a systematic review and meta-analysis to determine the association between diverticular disease and colorectal adenomas, advanced adenomas and cancer. METHODS: A comprehensive search of the databases MEDLINE and EMBASE was done from inception through March 2016. Inclusion criterion was the observational studies' assessment of the association between diverticular disease and colorectal neoplasia in adult participants. Pooled OR and 95% confidence interval (CI) were calculated using a random effect. RESULTS: Data were extracted from 14 observational studies (11 cross-sectional studies, one case-control study and two cohort studies). Diverticular disease was associated with increased odds of adenomas (OR = 1.67, 95% CI 1.27-2.21, 10 studies), but not associated with advanced adenomas (OR = 1.19, 95% CI 0.88-1.62, I2  = 52%, four studies) or colorectal cancer (OR = 1.36, 95% CI 0.47-3.92, I2  = 98%, seven studies). CONCLUSIONS: Our meta-analysis demonstrated that diverticular disease was associated with colorectal adenomas. Colonoscopists should be aware of this association and carefully examine the entire large bowel in individuals with diverticulosis.

Underweight and obesity increase the risk of mortality after lung transplantation: a systematic review and meta-analysis.

Many studies have found an association between abnormal body mass index (BMI) and poor outcomes among lung transplant recipients. We performed a systematic review and meta-analysis to identify outcomes associated with an abnormal pretransplant BMI after lung transplantation (LTx). The MEDLINE and EMBASE databases were searched from inception to May 2015 with focus on original observational studies with post-transplant survival data in candidates with abnormal BMI (underweight, overweight, or obese). We performed meta-analyses examining survival and primary graft dysfunction after LTx. We identified 866 citations; 13 observational cohort studies involving 40 742 participants met our inclusion criteria for systematic review. Seven of the 13 were included in the meta-analysis. There was a significant risk of mortality after LTx in candidates with underweight and obesity (underweight versus normal, relative risk [RR] 1.36, 95% confidence interval [CI] 1.11-1.66, I(2)  = 0%; obesity vs. normal, RR 1.90, 95% CI 1.45-2.56, I(2)  = 0%; overweight vs. normal, RR 1.36, 95% CI 1.11-1.66, I(2)  = 0). There was also a significant risk of primary graft dysfunction in obese (RR 1.92, 95% CI 1.39-2.65, I(2)  = 0%) and overweight (RR 1.72, 95% CI, 1.32-2.24, I(2)  = 0%) candidates. Lung transplant candidates who are underweight or obese have a higher risk of post-transplant mortality than recipients with a normal BMI.

Significant Association Between Gallstone Disease and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are common digestive disorders worldwide. Both conditions share certain risk factors including obesity, insulin resistance and diabetes. Several epidemiologic studies have reported the relationship between these two conditions. AIM: We conducted a systematic review and meta-analysis to characterize the association between GD and NAFLD. METHODS: A comprehensive search of the databases MEDLINE and EMBASE was performed from inception through November 2015. The inclusion criterion was the observational studies' assessment of the association between GD and NAFLD in adult participants. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using a random-effects model. RESULTS: Data were extracted from 12 observational studies (9 cross-sectional studies, 1 case-control study and 2 cohort studies). The pooled OR of NAFLD in patients who had GD was 1.55 (95 % CI 1.31-1.82). The statistical between-studies heterogeneity (I (2)) was 64 %. The association remained significant when limited to cohort studies with pooled OR 1.33 (95 % CI 1.14-1.55, I (2) = 0 %). CONCLUSION: Our meta-analysis demonstrated that GD is significantly associated with NAFLD. Further prospective studies exploring the underlying mechanism of this association should be pursued.

WITHDRAWN: Calciphylaxis in a nondialysis patient treated with sodium thiosulfate and high dose of oxygen
.

Ahead of Print article withdrawn by publisher. BACKGROUND: Calciphylaxis in a nondialysis patient is a rare condition and is characterized by calcific deposition in tissue. We present a case of calciphylaxis in a nondialysis patient who was diagnosed by clinical presentation and skin biopsy and was treated with sodium thiosulfate with improvement of skin lesions. CASE: A 43-year-old female with type 2 diabetes and atrial fibrillation taking oral anticoagulation medication presented with reddish drainage from the right buttock. On physical examination, a large perirectal abscess overlying necrosis was found. She also developed acute kidney injury with creatinine of 3.7 mg/dL at peak from 0.8 mg/dL at baseline. She received antibiotics intravenously and wound debridement. During hospitalization, she developed areas of numerous painful erythematous lesions with central dusky necrosis on bilateral lower extremities. Punch biopsy was done, which initially revealed small-vessel vasculitis. However, those lesions did not respond to steroid therapy. A second biopsy was done showing extensive fat necrosis and medial calcification of vessel walls consistent with calciphylaxis. She was treated with high-flow oxygen and sodium thiosulfate intralesionally and intravenously for 6 months. The lesions remarkably reduced in size and were less painful on follow-up. CONCLUSION: High-dose oxygen and sodium thiosulfate could potentially be effective treatments for calciphylaxis in nondialysis patients.
.

Effect of cholecalciferol supplementation on arterial stiffness: a systematic review and meta-analysis.

BACKGROUND: Vitamin D deficiency increases risk of cardiovascular diseases, arterial stiffness, and endothelial dysfunction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the impact of vitamin D supplementation on arterial stiffness. METHODS: A comprehensive search of the databases of the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE was performed from inception through November 2015. The inclusion criterion was RCTs that assessed the impact of cholecalciferol supplementation in adults on the surrogate markers of arterial stiffness (aortic pulse wave velocity (PWV) and augmentation index (AIx)). Outcome was the pooled mean difference (MD) of PWV and AIx between the vitamin D supplementation (intervention) group and placebo. RESULTS: The initial search yielded 1164 articles. Twenty-eight articles underwent full-length review and data were extracted from seven RCTs involving totally 547 participants. Dose of cholecalciferol supplementation varied from 1000 IU/day to 120,000 IU/month of cholecalciferol. Duration of treatment ranged from 2 to 12 months. There was no significant difference in the change of PWV (pooled MD = 0.18, 95% CI: -0.17 to 0.52 or AIx (pooled MD = 2.39, 95% CI: -4.43 to 4.92) between the intervention group and placebo. CONCLUSIONS: There was no improvement of markers of arterial stiffness after vitamin D supplementation.

Low 25-hydroxyvitamin D levels are associated with vitiligo: a systematic review and meta-analysis.

BACKGROUND: Vitamin D deficiency is associated with a number of autoimmune diseases. We completed a meta-analysis of observational studies to establish whether there was a relationship between hypovitaminosis D and the autoimmune skin disease vitiligo. METHODS: Comprehensive search was applied in the MEDLINE and EMBASE databases from their inception to December 2015. Inclusion criteria were observational studies that assessed 25-hydroxyvitamin D (25(OH)D) levels in adults with vitiligo. The main outcome was the mean difference in serum 25(OH)D level between patients with vitiligo and controls. RESULTS: Our search strategy identified 383 articles; seventeen studies met the criteria for full-length review and seven studies, containing the data of 1200 patients, were included in a random-effects model meta-analysis. The pooled mean difference in serum 25-hydroxyvitamin D concentration between patients with vitiligo and controls was -7.45 ng/ml (95% confidence interval, -12.99 to -1.91, P-value = 0.01). The between-study heterogeneity (I(2) ) was 96%, P = value<0.001. CONCLUSIONS: This meta-analysis identifies a significant relationship between low 25-hydroxyvitamin D levels and vitiligo, but does not prove causation. Our findings emphasize the importance of measuring 25-hydroxyvitamin D levels in patients with vitiligo. Further studies will be needed to establish whether vitamin D supplementation in this population improves the outcome of vitiligo.

Risk of ischemic stroke in patients with systemic sclerosis: A systematic review and meta-analysis.

BACKGROUND: Several chronic inflammatory disorders, such as rheumatoid arthritis and idiopathic inflammatory myositis, have been shown to increase risk of ischemic stroke but the data on systemic sclerosis (SSc) remains unclear. METHODS: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of ischemic stroke in patients with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Four retrospective cohort studies were identified and included in our data analysis. We found a statistically significant elevated ischemic stroke risk in patients with SSc with a pooled risk ratio of 1.68 (95% CI, 1.26-2.24). The statistical heterogeneity was moderate with an I(2) of 69%. CONCLUSIONS: Our study demonstrated a statistically significant increased ischemic stroke risk among patients with SSc.

Patients with giant cell arteritis have a lower prevalence of diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to compare the prevalence of diabetes mellitus (DM) in patients who are recently diagnosed with giant cell arteritis (GCA) with age- and sex-matched controls. METHODS: We conducted a systematic review and meta-analysis of observational studies that (1) consisted of GCA cohort and non-GCA cohort that was randomly selected from the same population and (2) provided prevalences of DM at the time of diagnosis for patients with GCA and at the index date for controls. Pooled odds ratios and 95% confidence intervals (CIs) were calculated using a random-effect, Mantel-Haenszel analysis. RESULTS: Five studies with 903 patients with GCA and 1064 controls were identified and included in our data analysis. We demonstrated a statistically significant lower prevalence of DM among patients with GCA with the pooled OR of 0.74 (95% CI, 0.57-0.97). CONCLUSION: At diagnosis, patients with GCA had a lower prevalence of DM. Whether DM could be a protective factor against the development of GCA needs further investigations.

Treatment outcomes of surgery, antifungal therapy and immunotherapy in ocular and vascular human pythiosis: a retrospective study of 18 patients.

OBJECTIVES: Human pythiosis is a life-threatening disease for which no standard treatment protocols with proven efficacy exist. We present the results of our institutional pythiosis treatment protocol, composed of surgery, antifungal agents, iron chelator (only vascular cases) and immunotherapy. METHODS: We retrospectively analysed patients with proven vascular and ocular pythiosis in King Chulalongkorn Memorial Hospital from April 2003 to May 2013. Fisher's exact test and Wilcoxon's rank-sum test were used. The MICs of seven antifungal agents and combination drugs were investigated in eight clinical Pythium insidiosum strains. RESULTS: Eighteen patients were evaluated. Disease-free surgical margins were obtained in all surviving patients with vascular pythiosis (P = 0.08). Patients who underwent eye enucleation were significantly older than those who did not (P < 0.05). Patients with vascular or ocular pythiosis did not differ significantly in the median time from disease onset to first surgery or in the relationship between the type of P. insidiosum antigen and treatment outcomes. In vitro susceptibility profiles of all isolates demonstrated that no single agent or combination treatment was substantially more effective than the others. The highest MIC was detected for amphotericin B, followed in order by voriconazole, fluconazole, anidulafungin, caspofungin, itraconazole and terbinafine. No synergistic effects of the combination drug treatments were found. CONCLUSIONS: Surgery with adequate surgical margins is a crucial determinant of survival in patients with vascular pythiosis. Itraconazole and terbinafine do not have synergistic effects on Thai P. insidiosum strains. The role of immunotherapy remains inconclusive for both vascular and ocular pythiosis.