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Objective Acute ischemic cardiac events can complicate coronavirus disease 2019 (COVID-19). We report the in-hospital characteristics of patients with acute myocardial infarction and concomitant COVID-19. Methods This was a registry-based retrospective analysis of patients admitted with positive COVID-19 tests who suffered acute myocardial infarction either before or during hospitalization; from 1 March 2020 to 1 April 2020 in a tertiary cardiovascular center-Tehran Heart Center. We performed an exploratory analysis to compare the clinical characteristics of patients who died during hospitalization or were discharged alive. Results In March 2020, 57 patients who had acute myocardial infarction and a confirmed diagnosis of COVID-19 were included in the study. During hospitalization, 13 patients (22.8%) died after a mean hospital stay of 8.4 days. The deceased were older than the survivors. No significant association between mortality and sex or length of hospital stay was observed. Hypertensive individuals were more likely to have a fatal outcome. Previously receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers did not show any association with mortality. Regarding the laboratory data during hospitalization, higher cardiac troponin T, neutrophil count, C-reactive protein, urea, and blood urea nitrogen/creatinine ratio were observed in the mortality group. The deceased had a lower lymphocyte count than the survivors. Conclusions Markers of worsening renal function and immune system disturbance seem to be associated with mortality in concurrent acute myocardial infarction and COVID-19. Optimizing the management of acute coronary syndrome complicating COVID-19 requires addressing such potential contributors to mortality.

BACKGROUND Prediabetes, as a precursor stage, has an important role in development of overt diabetes as well as coronary artery disease (CAD). The aim of this study is to evaluate the association between prediabetes and adverse outcomes (major adverse cardiovascular and cerebrovascular events [MACCE] and all-cause mortality) in patients who underwent coronary artery bypass grafting (CABG). METHODS In this prospective study, we included 3754 patients with CAD who underwent elective isolated CABG between January 2016 to January 2020. Patients were categorized based on their glycemic status at the time of CABG as follows: diabetics (n = 2707), prediabetics (n = 471), and nondiabetics (n = 576). Primary endpoints were occurrence of all-cause mortality and MACCE. RESULTS We studied 3754 patients for a median of 32.25 months after CABG. MACCE occurred in 474 (12.6%) patients. After adjusting for potential confounders, diabetic patients had a higher risk of MACCE (hazard ratio [HR] 1.69; 95% confidence intervals [CI], 1.24-2.29) and death (HR 2.33, 95% CI, 1.45-3.7) compared with nondiabetic and prediabetic ones. However, patients with prediabetes had lower HR of MACCE, but the association was nonsignificant (HR 1.02; 95% CI, 0.67-1.56). CONCLUSIONS Diabetes is significantly associated with higher risk of mortality and MACCE; however, prediabetes did not show a prognostic impact in terms of overall and MACCE-free survival.

PURPOSE: Personalized medicine (PM) is the concept of managing patients based on their characteristics, including genotypes. In the field of cardiology, advantages of PM could be found in the diagnosis and treatment of several conditions such as arrhythmias and cardiomyopathies; moreover, it may be beneficial to prevent adverse drug reactions (ADR) and select the best medication. Genetic background can help us in selecting effective treatments, appropriate dose requirements, and preventive strategies in individuals with particular genotypes. METHOD: In this review, we provide examples of personalized medicine based on human genetics for the most used pharmaceutics in cardiology, including warfarin, clopidogrel, and statins. We also review cardiovascular diseases, including coronary artery disease, arrhythmia, and cardiomyopathies. CONCLUSION: Genetic factors are as important as environmental factors and they should be tested and evaluated more in the future by improving in genetic testing tools. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00840-0.

Background The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. Methods In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. Conclusion The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm mostly originates from pleura, but rarely from other parts of the body including pericardium. We report a case of a 44-year-old woman with dyspnea and intermittent edema in whom a large intrapericardial mass was discovered by echocardiography. Computed tomography (CT) revealed a focal pericardial calcification in right AV grove with pressure on right ventricle and right atrial, with no connection to cardiac chambers. Histopathological findings after complete resection of the mass revealed fibroconnective tissue with heavy calcification and no evidence of inflammation or malignancy. We reviewed the literature on pericardial solitary fibrous tumors up to 2020.

Abdominal aortic aneurysm (AAA) is a life-threatening condition which, in the absence of increasing diameter or rupture, often remains asymptomatic, and a diameter greater than 5.5 cm requires elective surgical repair. This study aimed to evaluate the cost-effectiveness of endovascular repair (EVAR) versus open surgical repair (OSR) in patients with AAA through a systematic review of published health economics studies. Using a systematic review method, an electronic search was conducted for cost-effectiveness studies published on AAA (both in English and Persian) on PubMed, Embase, ISI/Web of Science (WoS), SCOPUS, Global Health databases, and the national databases of Iran from 1990 to 2020 including the keywords “cost-effectiveness”, “endovascular”, “open surgical”, and “abdominal aortic aneurysms”. The quality of the studies was assessed using the Quality of Health Economic Studies (QHES) checklist. In total, 958 studies were found, of which 16 were eligible for further study. All studies were conducted in developed countries, and quality-adjusted life years (QALY) and life years (LY) were used to measure the outcomes. According to the QHES checklist, most studies were of good quality. In European countries and Canada, EVAR has not been cost-effective, while most studies in the United States regard this technique as a cost-effective intervention. For example, incremental cost-effectiveness ratio (ICER) values ranged from $14,252.12 to $34,446.37 per QALY in the USA, while ICER was €116,600.40 per QALY in Portugal. According to the results, the EVAR technique has been more cost-effective than OSR for high-risk patients, but the need for continuous follow-up, increased costs, and re-intervention over the long term and for low-risk patients has reduced the cost-effectiveness of this method. As the health systems vary among different countries (i.e. quality of care, cost of devices, etc.), and due to the heterogeneity of studies in terms of the follow-up period, time horizon, and threshold, all of which are inherent features of economic evaluation, generalizing the results should be done with much caution, and policymaking must be based on national evidence.

Background Studies demonstrated an association between vitamin B12 deficiency and vasovagal syncope (VVS) in pediatric patients. Moreover, some evidence suggested a pathophysiological role of plasma catecholamines elevation in VVS, which can arise from folate or vitamin B12 deficiency in terms of biochemical pathways. Purpose We aimed to evaluate the association of folate and vitamin B12 deficiency with VVS in adults. Methods In this case-control study, adult patients (18–70 years of age) with the diagnosis of VVS based on history and physical examination (2018 ESC guidelines) who underwent a head-up tilt test (HUTT) were included as the case group. The control group comprised age- and sex-matched individuals who participated in a population-based cohort study. The most important exclusion criteria were taking vitamin B12 or folate supplements, carbamazepine and phenobarbital, and a history of bariatric surgeries. Plasma levels of vitamin B12, folate, homocysteine, and thyroid-stimulating hormone (TSH), a possible confounder, were measured by Abbott Diagnostics chemiluminescence kits. We compared categorical variables and continuous variables by Chi-square and t-test, respectively. Logistic regression models were employed for adjusting for possible confounders, including age, sex, and TSH. Results From February 2020 to February 2021, we screened 157 patients with VVS, of whom 44 patients were included. After matching for age and sex, 44 healthy individuals without a history of syncope were examined as the control group. The mean age was 37.9 years in both groups, with 23 women (52.3%) in each group. Baseline characteristics were comparable across the study groups. There were no significant differences between serum levels of vitamin B12, folate, homocysteine, and TSH, as well as the prevalence of deficiency of folate and vitamin B12 between case and control groups (Table 1), even after adjusting for confounding variables. Serum levels of vitamin B12 were remarkably lower in patients with a lifetime syncopal episodes of ≥3 compared to patients with Conclusions In this study, we found that there is no significant difference between the prevalence of folate and vitamin B12 deficiency and serum levels of these vitamins in adult patients with VVS and healthy individuals; however, serum vitamin B12 was significantly lower in patients with recurrent VVS compared to patients with a lower burden of syncopal episodes. Future studies with larger sample sizes are recommended in the recurrent VVS subgroup. Therapeutic implications of these findings should be investigated in randomized-controlled trials. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Iran National Science Foundation Table 1Table 2

Background Therapeutic interventions in vasovagal syncope (VVS) are centered on lifestyle modifications aimed to counteract the recognized mechanisms that precipitate syncope. In patients with recurrent VVS, supervised training might help reduce the symptomatic burden by increasing adherence to lifestyle modifications. Purpose We aimed to evaluate the effect of an integrated supervised training program versus standard care on syncopal recurrence rate among patients with VVS. Methods This randomized, controlled, 1:1 parallel-design, open-label trial was conducted between November 2019 and February 2021. Eligible patients were those aged between 18 and 70 years with newly-diagnosed medication-naïve VVS who had experienced ≥2 syncopal episodes in the prior year. All participants received education and reassurance about the benign nature of VVS, were advised to increase salt and fluid intake, and practice counter-pressure maneuvers based on 2018 European Society of Cardiology syncope guideline (standard care). Patients were randomized to standard VVS care or the training program. The intervention program consisted of thrice-weekly four-hours-long sessions during the first month after randomization; including tilt training, aerobic exercise (with rowing ergometer, recumbent biking), and standardized counter-pressure maneuvers supervised by a team of physical medicine and rehabilitation specialist and a cardiologist. After the first month, the intervention group were planned to attend a four-hours-long session every three months. The control group were followed by phone calls after the initial visit every three months. The intended follow-up duration was one year and the primary outcome was time to first syncopal episode. Results Out of 332 patients screened, 50 (mean age: 33.5 years; 64% female, figure 1) were equally randomized. Follow-up was completed for all participants. After one year, there was a significant reduction in syncope with supervised training compared to standard care (hazard ratio: 0.28; 95% confidence interval: 0.11 to 0.68; p=0.005, figure 2). Furthermore, frequency of syncope was lower in the supervised training arm versus standard of care (median [interquartile range]: 0 [0–1] versus 1 [0–3]; p=0.017). Conclusions In patients with recurrent VVS, supervised training showed promising results in reducing syncopal recurrence. Future research should focus on similar approaches to alter patients' lifestyle as an effective treatment for VVS. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Tehran University of Medical Sciences Figure 1Figure 2

Head-up tilt test (HUTT) is a reasonable diagnostic evaluation for patients with suspected vasovagal syncope; however, its lengthy duration is a remarkable limitation. Although adenosine (AD), as an alternative provocative agent, is a promising option for tackling this shortcoming, it received little appreciation in the literature. We aimed to compare the efficacy and the time to elicit a positive response to HUTT for sublingual trinitroglycerin (TNG) and intravenous AD. Furthermore, we evaluated patients’ outcomes in the follow-up. Patients with a chief complaint of transient loss of consciousness (TLOC) were evaluated. We randomized patients with the diagnosis of unexplained syncope after diagnostic evaluations, to undergo TNG-augmented HUTT or AD-augmented HUTT. They were crossed over to receive the other medication in case of negative response to the test. In the follow-up, we evaluated traumatic and non-traumatic TLOCs, hospitalization due to syncope, and death in patients. We randomized 132 patients (41.70 ± 19.37 years, 52.3% female) to receive TNG (n = 66) or AD (n = 66). Respectively, the positivity rate of TNG and AD for the first and the crossover-HUTT was 31.1% and 26.7%, and 20.5% and 26.2% with no statistically significant differences in both tests (P ˃ 0.50). The time to positive response was significantly shorter for AD than TNG (P < 0.001). In the follow-up, re-admission was significantly more prevalent in HUTT-negative patients compared to HUTT-positive patients (P = 0.04). We found that diagnostic yield of TNG and AD in HUTT is comparable, while AD acts 4 times faster than TNG in evoking a vasovagal response.

Heart valve disease (HVD) affects 2.5% of the US population and one million individuals aged 65 years and older in the UK. Given its burden, the aim of the present review was to assess the cost-effectiveness of heart valve replacement with mechanical versus biological prosthesis in HVD patients. We performed a systematic search in various electronic databases from January 1990 to June 2019. Five out of 542 articles were entered into the study, from which 2 papers were subsequently excluded not meeting the minimum number of items of the CHEERS checklist. Quality-Adjusted Life Year, Life Years Gained, and the Incremental Cost-Effectiveness Ratio (ICER) regarding the type of replaced heart valve were extracted and reported. Studies were conducted in three different countries (Iran, France, and USA). ICER ranged from $1253 in Iran to €54,634 in France. Survival rate of mitral mechanical versus biological valves at 10 and 20 years was 72.9% versus 76.0% and 51% versus 30%, respectively. Survival rate at 20 years in patients undergoing atrial valve replacement was 20%. Ten- and 20-year death rates for biological valves were higher with respect to mechanical prosthesis (15.5% versus 8.4% at 10 years), with this difference becoming more relevant at 20 years (36.9% versus 13.9%). Due to higher ICER, mortality rate, and lower success rates in the long term for biological prostheses compared to mechanical ones, these appear to be more suitable for older patients (aged ≥ 70 years).

OBJECTIVE Current knowledge of the effects of prediabetes on the postsurgical outcomes of mortality and major adverse cardiovascular events (MACE) after coronary artery bypass graft surgery (CABG) is limited. The aim of this study is to evaluate the MACE and overall 1-year survival of patients with prediabetes who underwent elective isolated CABG. MATERIAL AND METHODS After a thorough analysis of CABG database since January 2016, 3741 patients were included. Patients were categorized as follows: diabetes mellitus type 2 (n = 2695), prediabetics (fasting blood sugar = 100-125 mg/dL and hemoglobin A1c (HbA1c) = 5.7%-6.4%) (n = 471), and nondiabetics (fasting blood sugar < 100 mg/dL and HbA1c < 5.7%) (n = 575). Primary end point (MACE) was the composite death, acute coronary syndrome, coronary revascularization, and cerebrovascular events after 1 month of surgery. Event-free survival was assessed and compared between groups over a median follow-up of 1 year. RESULTS In this retrospective cohort design, 3741 patients who underwent elective isolated CABG were evaluated. One-year overall survival percent was 100% for nondiabetic and prediabetic patients and 99.9% for diabetic patients (P value = 0.56). One-year event-free survival was 97.4% for nondiabetics, 98.1% for prediabetics, and 96.8% for diabetic patients (P value = 0.08). CONCLUSIONS One-year overall survival and also the event-free survival of prediabetic patients were similar to those without diabetes mellitus. Over the median follow-up of 1 year, descending trends shows the higher probability of adverse events in diabetic patients with longer follow-ups.

Context: This systematic review and meta-analysis intended to investigate the diagnostic accuracy of computed tomography angiography (CTA) in comparison with single-photon emission computed tomography (SPECT) for the diagnosis of coronary artery disease (CAD) in chest pain patients with no history of cardiovascular diseases (CVDs). Methods: Invasive angiography was considered as the reference test with a stenosis threshold of ≥ 50%. Cochrane, Scopus, Science Direct, PubMed, and Embase databases were comprehensively searched from the time of inception of these databases to May 15, 2018. A manual search in Google Scholar, a reference review of the obtained studies, and a review of gray literature (including those presented in conferences and congresses) regarding diagnostic performances of CTA and SPECT techniques were performed independently by two researchers. A meta-analysis was performed to determine pooling estimates of sensitivity, specificity, diagnostic odds ratio, and positive as well as negative likelihood ratios in CTA and SPECT tests. According to the 2 × 2 contingency table of each study, at 0.95 confidence interval, the diagnostic accuracy of CTA and SPECT was meta-analyzed by pooling estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and positive and negative likelihood ratios based on DerSimonian-Laird’s random-effects model. Heterogeneity was assessed by calculating I2. Analyses were performed using MetaDiSc version 1.4 and Stata version 11. The qualities of the selected studies were assessed independently by two researchers according to the quality assessment of diagnostic accuracy studies (QUADAS) questionnaire. Sensitivity analyses were performed by the Jackknife method. Publication bias was evaluated by Deeks’ funnel plot. Results: Fourteen studies related to CTA (1206 individuals) and 15 related to SPECT (1638 individuals) were eligible for meta-analysis. The pooled sensitivity and the specificity of CTA for CAD diagnosis were 91% (95% CI, 88% - 94%) and 87% (95% CI, 84% - 98%), respectively. The pooled positive and negative likelihood ratios, the diagnostic odds ratio, and the area under the ROC curve for CTA were 7.93 (95% CI, 5.11 - 12.29), 0.1 (95% CI, 0.06 - 0.17), 95.71 (95% CI, 59.81 - 153.15), and 0.96, respectively. The pooled sensitivity and the specificity of SPECT for CAD diagnosis were 81% (95% CI, 79% - 83%) and 74% (95% CI, 71% - 78%), respectively. The pooled positive and negative likelihood ratios, the diagnostic odds ratio, and the area under the ROC curve for SPECT were 3.03 (95% CI, 2.34 - 3.91), 0.25 (95% CI, 0.21 - 0.30), 13.56 (95% CI, 10.60 - 12.34), and 0.86, respectively. According to the sensitivity analyses, the removal of any single study at a time did not change the effect size of the remaining studies. We observed symmetry in the Deeks’ funnel plot, indicating that there was ignorable publication bias for CTA and SPECT studies. Conclusions: This study demonstrated that the diagnostic accuracies of CTA and SPECT tests lie in the ‘excellent’ and the ‘very good’ ranges, respectively. CTA is stronger evidence, than SPECT, to rule out CVDs in patients with low and intermediate risks of CAD with no history of cardiovascular diseases.

OBJECTIVES Coronary artery disease is becoming a major health concern in the young population. Male and female patients may experience different journeys after coronary artery disease events. We aimed to evaluate risk factors and compare outcomes between young male and female patients undergoing coronary artery bypass graft surgery (CABG). METHODS In this registry-based large sample size study, patients undergoing isolated CABG at a young age (premature isolated CABG) between 2007 and 2016 were included and followed up until 2020. Premature was defined as women and men younger than 55 years old. The main end points of the study were 7-year all-cause mortality and 7-year major adverse cardiovascular and cerebrovascular events (MACCEs). RESULTS Of a total of 24 428 patients who underwent CABG, 7217 patients (men-to-women ratio ≈4:1) with premature isolated CABG were included. The median follow-up duration was 78.5 months (75.2–81.6 months). The prevalence rates of diabetes mellitus, hypertension, dyslipidaemia and obesity were significantly higher in women than in men (58.3% vs 28.6%, 64.2% vs 38.5%, 69.7% vs 55.3% and 44.7 vs 23.9, respectively; all Ps < 0.05). The risk factor burden (mean of the risk factor count per year) was also higher among the female population. Diabetes mellitus was the common mortality predictor between men and women. In the subgroup analysis (interaction analysis in the adjusted model), hypertensive females had a higher rate of MACCE and a higher rate of mortality than hypertensive males; however, this difference was not significant in the non-hypertensive population. Opium addiction was a strong predictor of MACCE and all-cause mortality among men. Female patients had a higher rate of 7-year MACCE (hazard ratio, 1.33; 95% confidence interval, 1.16–1.51) and a higher rate of 7-year all-cause mortality (hazard ratio, 1.23; 95% confidence interval, 0.98–1.53). CONCLUSIONS The risk factor profile and predictors of outcomes were different between our female and male patients. Women carried a higher risk of events and mortality after CABG at a young age.

Background Studies showed that sibutramine or reboxetine reduced head-up tilt (HUT)-induced syncope and pre-syncope by 78%. Furthermore, in an open-label series of highly symptomatic patients with vasovagal syncope (VVS), sibutramine reduced frequency of vasovagal spells. In a recent proof of principle study, atomoxetine reduced number of HUT-induced syncopal episodes by about 50% compared to placebo. Purpose In this study, we aimed to evaluate the effectiveness of atomoxetine on preventing recurrence of syncopal and pre-syncopal episodes in patients with recurrent VVS after three months of follow-up. Moreover, we determined whether it can improve patients' anxiety and depression. Methods In this double-blind placebo-controlled randomized clinical trial, we screened 843 patients with VVS. Patients with 10 < age < 70 years who had ≥3 syncopal episodes in the past three months were included. Eventually, 46 patients were randomized to receive atomoxetine (20 mg daily for two weeks followed by 40 mg daily for two weeks, N=23) or placebo (for four weeks, N=23). The primary endpoint was the number of syncopal and pre-syncopal episodes at one and three months and was analyzed by the repeated measures analysis of variance. Secondary endpoints were decrements of depression and anxiety measured by the Hospital Anxiety and Depression Scale after three months and were analyzed by the Mann-Whitney U test. Results The primary endpoint was lower after three months in the atomoxetine arm (2.3±1.3 vs 4.3±1.7), with a significant between-subjects effect by atomoxetine versus placebo (P0.05, Figure). Conclusions In patients with VVS, atomoxetine significantly reduced the recurrence of a composite of syncopal and pre-syncopal episodes, and remarkably improved anxiety and depression at three months. Anxiety and Depression of the Patients Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Tehran University of Medical Sciences

Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10.8 million (95% uncertainty interval [UI] 9.51-12.1) deaths (19.2% [16.9-21.3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8.71 million (8.12-9.31) deaths (15.4% [14.6-16.2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253-350) DALYs (11.6% [10.3-13.1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0-9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10-24 years, alcohol use for those aged 25-49 years, and high systolic blood pressure for those aged 50-74 years and 75 years and older. Interpretation Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.

Introduction Heart failure (HF) is an unusual heart function that causes reduction in cardiac or pulmonary output. Cardiac resynchronization therapy (CRT) is a mechanical device that helps to recover ventricular dysfunction by pacing the ventricles. This study planned to systematically review cost-effectiveness of CRT combined with an implantable cardioverter-defibrillator (ICD) versus ICD in patients with HF. Methods We used five databases (NHS Economic Evaluation Database, Cochrane Library, Medline, PubMed, and Scopus) to systematically reviewed studies published in the English language on the cost-effectiveness of CRT with defibrillator (CRT-D) Vs. ICD in patients with HF over 2000 to 2020. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was applied to assess the quality of the selected studies. Results Five studies reporting the cost-effectiveness of CRT-D vs ICD were finally identified. The results revealed that time horizon, direct medical costs, type of model, discount rate, and sensitivity analysis obviously mentioned in almost all studies. All studies used quality-adjusted life years (QALYs) as an effectiveness measurement. The highest and the lowest Incremental cost-effectiveness ratio (ICER) were reported in the USA ($138,649per QALY) and the UK ($41,787per QALY), respectively. Conclusion Result of the study showed that CRT-D compared to ICD alone was the most cost-effective treatment in patients with HF.

Background: Coronary artery ectasia (CAE) is a rare condition with unclear pathophysiology, optimal treatment, and prognosis. We aimed to determine the prognostic implications of CAE following coronary angioplasty. Methods: We conducted a retrospective cohort study on 385 patients, including 87 subjects with CAE, who underwent percutaneous coronary intervention (PCI). Major adverse cardiovascular events (MACE) were considered to consist of mortality, nonfatal myocardial infarction (MI), repeated revascularization, and stroke. Results: The mean age of the participants was 57.31±6.70 years. Multivariate regression analysis revealed that patients with diabetes, ST-segment–elevation MI at presentation, and high thrombus grades were more likely to have suboptimal postPCI thrombolysis in myocardial infarction (TIMI) flow. However, CAE was not a predictor of a decreased TIMI flow (OR: 1.46, 95% CI: 0.78–8.32; P=0.391). The Cox-regression model showed that CAE, the body mass index, and a family history of MI were risk factors for MACE, while short lesion lengths (20 mm) had an inverse relationship. The adjusted hazard ratio (HR) for the prediction of MACE in the presence of CAE was 1.65 (95% CI: 1.08–4.78; P=0.391). All-cause mortality (HR: 1.69, 95% CI: 0.12–3.81; P=0.830) and nonfatal MI (HR: 1.03, 95% CI: 0.72–4.21; P=0.341) occurred similarly in the CAE and non-CAE groups. Conversely, CAE increased urgent repeat revascularization (HR: 2.40; 95% CI: 1.13–5.86; P=0.013) Conclusion: Although CAE had no substantial short-term prognostic effects on post-PCI TIMI flow, considerable concerns regarding adverse outcomes emerged during our extended follow-up. Stringent follow-ups of these patients should be underscored due to the high likelihood of urgent revascularization.

Cardiovascular disease, mental health, and injury are among the top health issues globally. In Tehran Cohort Study, we aimed to determine the prevalence, incidence, and trend of cardiovascular diseases, psychiatric symptoms, injury, and risk factors in Tehran households. We enrolled 4215 households in the recruitment phase from March 2016 to March 2019. Demographic characteristics, past medical history, medications, and familial history of the participants were collected. Rose angina pectoris, general health Questionnaire-28 (GHQ-28), and injury questionnaires were completed. Fasting blood samples were collected to measure routine biochemistry and store samples in the biobank. Anthropometric and physiological measurements and electrocardiograms were performed. The participants are followed every three years for up to 12 years. In total, 8296 individuals participated in the cardiovascular section, 10247 completed the GHQ-28, and 4167 households completed the injury questionnaire. The mean age of the participants was 48.2 (16.41), and 46.5% were male. 64.3% of recruited individuals had no symptoms of psychiatric disorders, and 3729 (89.5%) households did not have any severe injury requiring treatment. The participants' diversity and their invaluable data will help us provide a general picture of the current prevalence and incidence of the main study objectives.

Background Serum gamma-glutamyltransferase (GGT) has been introduced as a predictive factor for cardiovascular disease. In this study, we investigated the association of serum GGT and premature coronary artery disease (CAD) in candidates for coronary angiography. Methods In this cross-sectional study, we enrolled male subjects aged ≤45 years and female subjects ≤55 years who were candidates for elective coronary angiography due to typical chest pain or a positive non-invasive test. Baseline characteristics were recorded for all the participants and serum levels of blood glucose, lipid profile and GGT were measured. Patients were divided into CAD and non-CAD groups based on angiography for further comparisons. Results From a total of 367 patients (age 45.1 ± 6.1 years, 161 males [43.9%]), 176 (47.9%) patients had premature CAD. A high level of GGT was significantly associated with the presence of CAD (p < 0.001). A 10-unit increase in GGT could strongly predict the presence of premature coronary artery disease (OR: 13.34, 95% CI: 7.19–24.78; p < 0.001) after adjustment for confounders. The area under the receiver operating characteristic curve for GGT was 80.9% (range 76.5–85.3) and the sensitivity and specificity of GGT at a cut-point of 22.5 IU/l was 80.1% and 70.2%, respectively. Diagnostic accuracy of GGT was 74.9%. The positive predictive value and negative predictive value for GGT was 71.3 and 79.3, respectively. Conclusion We observed that GGT levels in patients with typical chest pain or positive non-invasive tests could predict the presence of premature CAD in young patients.

Objective A permanent pacemaker (PPM) is necessary for patients with a symptomatic third-degree or advanced second-degree atrioventricular (AV) block. An AV block due to medication use can often be reversed; however, subsequent relapse can occur and necessitate subsequent PPM implantation. The aim of this study was to explore the course and prognosis of patients with an AV block. Methods This historical cohort study was conducted between January 2013 and June 2018. A total of 1900 patient records were analyzed and 1123 subjects with an AV block on admission were enrolled. The patients were categorized into 2 groups: Group 1 comprised patients with an AV block due to medication use (n=316, 28%) and Group 2 included patients with an AV block caused by other etiologies (n=807, 72%). Data of the cause of AV block, recurrence, and PPM implantation were analyzed. Patients in both groups who did not require a PPM during the index admission were followed up regarding subsequent implantation of a PPM. Results AV conduction was recovered in 38 (12%) patients in Group 1 and 48 (6%) patients in Group 2 during the index hospitalization. However, recurrence of the AV block was observed in 18% of Group 1 patients and 40% of Group 2 patients. Only 25 patients in each group (4.5% of the whole study population) remained PPM-free during a median 3-year follow-up period. Conclusion The study findings suggest that drug-induced AV blocks may not be as benign as previously thought. The high relapse rate indicates that watchful follow-up may be required despite discontinuation of the responsible medication and that consideration of earlier PPM implantation in cases of early recurrence may be warranted.

Syncope or fainting refers to a temporary loss of consciousness usually related to insufficient blood flow to the brain and can be due to several causes, which are either simple or serious conditions. Syncope can be caused by life-threatening conditions not evident in the first evaluations, which can lead to serious outcomes, including death, after discharge from the hospital. We have developed a decision tool to identify syncope patients with 18 years of age or higher who are at risk of a serious event within 30 days after discharge from the hospital.We used the data provided by the Tehran Heart Clinic. In this dataset adults with 18 years old or above with syncope signs are enrolled. The patients presented themselves within 24 hours after the event to the THC. Standardized variables from clinical evaluation and investigations have been collected. Serious adverse events included death, Intracerebral hemorrhage (ICH) or Subarachnoid hemorrhage (SAH), Cerebrovascular accident (CVA), Device Implantation, myocardial infarction, arrhythmia, traumatic syncope or cardiac surgery within 30 days. 356 patients were enrolled with syncope; the mean age was 44.5 years and 53.6% were women. Serious events occurred among 26 (7.3%) of the patients within 30 days of discharge from the hospital.Different machine learning algorithms such as Decision Tree, SMO, Neural Networks, Naive Bayes and Random Forest have been used on the dataset to predict patients with serious adverse outcomes and the WEKA program has been used to validate the results.Results show that when using Random Forrest Algorithm, the accuracy rate and ROC Area reached 91.09% and 0.90. However, previous statistical risk scores such as the San Francisco Score resulted in lower ROC Area readings.

Coronary artery disease (CAD) has significant social and economic implications. It is necessary to create tools to identify the most cost-effectiveness treatments, which can assist clinicians in their therapeutic decisions so that the maximum possible benefit is reached with the lowest possible cost. Effectiveness must be measured by final treatment goals in which the most effective interventions are those with the lowest costs. This study is aimed to systematically review and compare the studies conducted on the cost-effectiveness of the three coronary artery disease treatment strategies (medical treatment, percutaneous coronary intervention, and coronary artery bypass graft). In this systematic review, the databases NHS Economic Evaluation Database, Embase, MEDLINE, Science Direct, and Scopus were searched for studies on the cost-effectiveness of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) compared to medical therapy (MT) in patients with coronary artery disease between 1 January 2004 to 30 September 2018. The quality appraisal of the included studies was examined using the Consolidated Health Economics Evaluation Reporting Standards (CHEERS) statement. Out of 186 unique retrievals, 8 studies were included. The results showed that the all studies clearly stated the time horizon of the study and included direct medical costs in their analysis. In addition, in most of the studies, quality-adjusted life years (QALY) were the main outcome used for measuring the effectiveness. The studies reported various ranges of the incremental cost-effectiveness ratio (ICER); accordingly, the highest ratio was observed in the USA ($212,800) for PCI v MT and the lowest ratio was observed in Brazil ($4403) for CABG v MT. Although the results of the studies were different in terms of a number of aspects, such as the viewpoint of the study, the study horizons, and the costs of expenditure items, they reached similar results. Based on the result of the present study, it seems that each three treatment strategies for CAD yielded improvements in QALY.

Background: Despite the reduced quality of life in patients with recurrent vasovagal syncope (VVS), pharmacologic treatment options remain limited. Studies indicate that norepinephrine reuptake inhibition reduces tilt-induced syncope/pre-syncope. This study aimed to evaluate the effects of atomoxetine on syncopal/pre-syncopal episodes in patients with recurrent VVS. Methods: In a placebo-controlled trial, we randomized patients with newly diagnosed VVS who experienced ≥3 syncopal episodes in the past three months to receive either atomoxetine (20 mg daily for two weeks followed by 40 mg daily for two weeks) or placebo. The primary endpoint was the combined number of syncopal and pre-syncopal episodes. Results: Among 843 patients initially screened, 46 were randomized (N = 23 in each group) and reevaluated at one and three months. Compared to placebo, atomoxetine significantly reduced the primary endpoint after three months (P

Background: Frequent hospital admissions and reduced quality of life are the main complications of heart failure (HF). Plasma B-type natriuretic peptide (BNP) levels have been considered as a cost-effective method of screening for left ventricular dys­function. Studies regarding BNP-guided therapy revealed reduction in death or hospital stay for HF. Aim: As saliva has fewer limitations than blood in regard to sampling, the aim of the present study was to test if salivary BNP concentration might be a new biomarker in patients with chronic HF. Methods: This pilot study involved 35 admitted patients with decompensated HF diagnosis and 35 HF patients who had come for a check-up at the Department of Cardiology. The control group consisted of 25 people with no history of cardiac events. Saliva and plasma samples of all the participants were collected. Results: Mean plasma NT-proBNP was found at higher levels in admitted HF patients compared to outpatient HF (9.37 vs. 6.62 pg/mL, p < 0.001) and control groups (9.37 vs. 4.69 pg/mL, p < 0.001). Also, mean salivary BNP levels were higher in admitted patients with HF (6.50 ng/L, p < 0.001); and outpatient HF group (5.87 ng/L, p = 0.02) compared to the control group (5.64 ng/L). Conclusions: Our study demonstrated that BNP could be detected in saliva and that the level is higher in HF patients, especially symptomatic ones. This means that salivary BNP may be useful in the diagnosis and follow-up for patients with HF, especially in emergency settings.

Aim Despite proven benefits of statins for secondary prevention of coronary artery diseases, their diabetogenic effect is still controversial. We aimed to examine the occurrence of type 2 diabetes mellitus (T2DM) in prediabetic patients after coronary artery bypass grafting (CABG). Methods The retrospective cohort population comprised of post-CABG patients who were prediabetic at the time of surgery and were taking statins. Patients were categorized into the high- and low-intensity statin regimens according to the commonly used dose during the follow-up. Moreover, we calculated the cumulative dose (milligrams*days) by taking into account that patients were on different doses of statins during different periods of time. We observed patients for occurrence of T2DM or major adverse cardiovascular events (MACE) as a composite of death, myocardial infarction, cerebrovascular accident, and hospitalization for unstable angina or heart failure. Results We studied 819 patients for a median of 37.8 months after CABG. T2DM occurred in 8.1% (n = 66). The rate of T2DM development was not different between the high- and low-intensity groups (P = 0.715) and also according to the cumulative dose (P = 0.962). Furthermore, we found no association (P = 0.938) even after adjustment for confounders including age, sex, body mass index, alcohol use, history of hypertension and hyperlipidemia, and family history of T2DM. Moreover, high- rather than low-intensity statin regimen was correlated with a lower occurrence of MACE (P = 0.027), even after adjustment for confounders (P = 0.015). Conclusions In prediabetic post-CABG patients, treatment with statins was not associated with the development of T2DM and reduced occurrence of MACE after 37 months.

Objective The pathophysiology of coronary slow flow phenomenon (CSFP) is poorly understood. Evidence suggesting endothelial dysfunction in patients with slow coronary flow (SCF) led to this evaluation of a possible correlation between microalbuminuria (MAU), as an indicator of endothelial dysfunction, and CSFP in order to investigate a mutual pathophysiology. Methods In this case-control study, 15786 patients who presented between September 2016 and April 2018 were screened. All patients with CSFP had chest pain and coronary angiography was indicated due to a positive noninvasive test. All cases had a Thrombosis in Myocardial Infarction (TIMI) flow grade of 2 or a corrected TIMI frame count of >27 without any evidence of obstructive coronary artery disease. The patients used as controls had completely normal coronary angiograms. Fasting mid-stream urine samples were analyzed using an immunoturbidimetric assay to determine the albumin-creatinine ratio (ACR) as a surrogate of microalbuminuria (MAU) (ACR: 30-300 mg/g). The prevalence of MAU in the case and control groups was analyzed. Results A total of 154 individuals with a normal coronary angiogram and 46 patients with SCF were enrolled in the study. The prevalence of MAU was greater in patients with SCF than in the control group (8.7% vs 1.9%, respectively; p=0.048). Even after adjustment for major risk factors, the association between MAU and CSPF remained significant. Conclusion The results of this study indicated that there was a relationship between MAU and CSFP and confirmed that endothelial dysfunction is a contributing factor to CSFP. These findings are of utmost importance due to the prognostic value of MAU for both all-cause and cardiovascular mortality rates.

Background Cardiovascular disease is a worldwide great burden on the health care syste early diagnosis and treatment of CAD can reduce the mortality and morbidity. We aimed to determine the association between upright T wave in lead V1 and coronary artery disease (CAD) in patients who presented with chest pain or positive non-invasive tests in emergency department. Methods In this retrospective cross sectional design we reviewed the clinical and coronary angiography data of patients who had normal ECG. Presence of coronary artery disease was compared between patients with and without upright T waves in V1. Results Data of 100 patients with upright T wave more than 1.5 mm in V1 was compared with 100 patients with completely normal ECG. Male patients with coronary artery disease (CAD) were dominant in upright T wave group. However, other traditional cardiovascular risk factors were not statistically different between groups. Based on the multivariate logistic regression model and after adjustment for confounding factors (i.e. gender, dyslipidemia and smoking), presence of upright T wave in the V1 and male gender were still associated with greater risk of coronary artery disease, Odds ratio 4.6 CI 95% (3.1 - 6.3) and 3.4 CI 95% (2.2 - 4.8), respectively. Conclusions In patients with chest pain and unremarkable ECG, presence of upright T wave in lead V1, is an early diagnostic tool for CAD. Male patients with chest pain and upright T wave in lead V1 probably have significant CAD.

Background: Left bundle branch block (LBBB) is an important and independent determinant of mortality among patients with cardiovascular disease (CVD). Close follow-up and management of isolated LBBB to prevent cardiomyopathy is controversial. Methods: In this retrospective cohort study, patients with isolated LBBB, with no concomitant evident cardiac disease, or risk factors of heart failure with reduced EF such as hypertension or diabetes mellitus (DM) were included. The mean follow-up of the patients was 56 months. At the onset of the study, coronary angiogram and EF of the patients were normal. Patients with reduced EF underwent coronary angiogram at the end of their follow-up interval. Results: In this study, 36 patients, with the mean age 62.1 years (45 - 81) were followed. LV ejection fraction (EF) was reduced in 24 patients, and the other 11 patients continued to have a normal EF during the follow-up. The follow-up interval between the 2 groups was not statistically different (Mann-Whitney, P = 0.9). Most of the patients with reduced EF were male (Mann-Whitney, P = 0.01). New- onset HTN had a negative correlation with a decrease in EF% (Spearman correlation coefficient = -0.36, P = 0.031). Based on surface ECG parameters, 8 new notched-QRS were detected, all of which had decreased EF during follow-up. Conclusions: Not all patients with isolated LBBB develop cardiomyopathy at a definite time interval. Male gender, notched-QRS in ECG, and longevity of conduction delay are important predictors of cardiomyopathy among these patients. They may benefit from anti-remodeling drugs and routine close follow-ups with echocardiogram.

Cystinosis is a rare, autosomal-recessive genetic disorder. The kidneys are commonly involved, as there is cystinosin protein malfunction, and nephropathic cystinosis ensues. Although cardiac and vascular involvements are rare, we describe a unique case of aortic dissection in a 25-year-old female with cystinosis. We discuss the possible aetiologies of aortic dissection in this condition.

Considering the role of neurohypophyseal peptides in normal development and function of higher cortical processes along with their proven abnormalities in schizophrenic patients, these pathways have recently attracted greater attention as treatment targets for schizophrenia. Desmopressin (DDAVP) is a synthetic analog of vasopressin. This study aimed to evaluate the efficacy and safety of DDAVP nasal spray as an adjunct to risperidone in improving negative symptoms of schizophrenia. In this randomized double-blind placebo-controlled clinical trial, forty patients aged 18-50 years with a DSM IV-TR diagnosis of chronic schizophrenia and a minimum score of 60 on positive and negative syndrome scale (PANSS) were equally randomized to receive DDAVP nasal spray (20mcg/day) or placebo in addition to risperidone for 8 weeks. Patients were partially stabilized and treated with a stable dose of risperidone (5 or 6mg/day) for at least four weeks prior to entry. Participants were rated by PANSS every two weeks and decrease in the PANSS negative subscale score was considered as our primary outcome. By the study endpoint, DDAVP-treated patients showed significantly greater improvement in the negative symptoms (P=0.001) as well as the PANSS total and general psychopathology subscale scores (P=0.005 and P=0.003; respectively) compared to the placebo group. Treatment group was the strongest predictor of changes in negative symptoms (β=-0.48, t=-3.67, P=001). No serious adverse event or fluid/electrolyte imbalance was reported in this trial. In conclusion, DDAVP nasal spray showed to be an effective and safe medication for improving negative symptoms in patients with chronic schizophrenia.

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia. The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia. In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8. Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699) = 37.366, p

Urbach-Wiethe disease (UWD) is an autosomal recessive disease characterized by both neurological and dermatological manifestations. Face specially eyelids are commonly involved. Alopecia, nail dystrophy and dental anomalies have been reported as less frequent symptoms. Some patients show evidences of epilepsy and psychiatric symptoms such as schizophrenia, mood disorders, and anxiety due to calcium deposits in different parts of the brain. In this report, we describe the case of a young woman affected by UWD presenting with neurological involvements and no dermatological manifestations. This patient is a unique case of UWD as she has partial seizures and hoarseness. Also we summarize relevant data from the literature.

Heart failure (HF) is a major health problem causing frequent hospital admissions and reduced quality of life. Cognitive impairment (CI) is a common finding in patients with HF that leads to higher mortality and less successful treatment. Evidences suggest that cognitive impairment can be diagnosed by common carotid flow velocity. As mild CI is not clinically measurable in most cases we can use ultrasound to develop a relevant screening model for cognitive dysfunction in HF.

Many studies have focused on the role of irregular mucosal immune response, but there are noteworthy evidences regarding the role of ischemia in pathogenesis of ulcerative colitis (UC). Hypoxia-ind...

Impairment of oxytocinergic function and/or oxytocin receptor genetic abnormalities has been demonstrated in patients with schizophrenia. Oxytocin reverses emotional recognition deficit and might restore sense of trust in patients with schizophrenia. Some short-term studies have shown efficacy and tolerability of oxytocin in patients with schizophrenia. However, there is a lack of evidence on the efficacy and tolerability of oxytocin in patients with schizophrenia beyond 3 weeks.The objective of this study was to assess the efficacy and tolerability of oxytocin intranasal spray (given as an adjuvant to risperidone) in patients with schizophrenia.This was an 8-week, randomized, double-blind, placebo-controlled study.Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study.Forty patients (male and female gender) aged 18-50 years with a diagnosis of schizophrenia (DSM-IV-TR) who were on a stable dose of risperidone for a minimum of 1 month and who were chronically partially responsive to antipsychotic monotherapy were included in the study.The patients were randomly assigned to oxytocin intranasal spray (Syntocinon(®); Novartis, Basel, Switzerland) or placebo intranasal spray containing normal saline (ACER, Tehran, Iran) for 8 weeks. Oxytocin spray was administered as 20 IU (five sprays) twice a day for the first week followed by 40 IU (ten sprays) twice a day for the following 7 weeks. Placebo spray was administered at the same dose as the oxytocin spray. In addition, participants were on a stable dose of risperidone (5 or 6 mg/day).The patients were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 0, 2, 4, 6 and 8. Primary outcomes were the differences in the PANSS scores between the two groups at the end of the trial. Adverse effects were recorded using a checklist and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, 6 and 8.All patients had at least one post-baseline measurement and 37 patients (19 in the oxytocin and 18 in the placebo group) completed the study. Repeated measure analysis of variance showed significant effect for time X treatment interaction on the PANSS total [F(2.291,87.065) = 22.124, p0.001], positive [F(1.285,48.825) = 11.655, p = 0.001], negative [F(2.754,104.649) = 11.818, p0.001] and general psychopathology [F(1.627,61.839) = 4.022, p = 0.03] subscale scores. By week 8, patients in the oxytocin group showed significantly greater improvement on the positive (Cohen's d = 1.2, 20 % vs. 4 % reduction in score, p0.001), negative (Cohen's d = 1.4, 7 % vs. 2 % reduction in score, p0.001) and general psychopathology (Cohen's d = 0.8, 8 % vs. 2 % reduction in score, p = 0.021) subscales and total (Cohen's d = 1.9, 11 % vs. 2 % reduction in score, p0.001) PANSS scores than the placebo group. Adverse effects including the sodium concentration change were similar between the two groups.Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients.

The objective of this study was to assess the efficacy and tolerability of minocycline add-on to risperidone in treatment of negative symptoms of patients with chronic schizophrenia. In a randomized double-blind placebo-controlled study, 40 patients with chronic schizophrenia who were stabilized on risperidone for a minimum duration of eight weeks were recruited. The patients were randomly assigned to minocycline (titrated up to 200 mg/day) or placebo in addition to risperidone (maximum dose of 6 mg/day) for eight weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Extrapyramidal Syndrome Rating Scale were used. Thirty-eight patients completed the study. Significant time × treatment interaction for negative [F(2.254,85.638)=59.046, P0.001] general psychopathology [F(1.703,64.700)=6.819, P=0.001], and positive subscales [F(1.655,62.878)=5.193, P=0.012] as well as total PANSS scores [F(1.677,63.720)=28.420, P0.001] were observed. The strongest predictors for change in negative symptoms were the treatment group (β=-0.94, t=-10.59, P0.001) followed by the change in PANSS positive subscale (β=-0.185, t=-2.075, P=0.045). Side effect profiles of the two treatment regimens were not significantly different. Minocycline seems to be an efficacious and tolerable short-term add-on to risperidone for treatment of negative and general psychopathology symptoms of schizophrenia.

Department of Surgery, University of Minnesota, Minneapolis, USAMany studies have focused on the role of irregularmucosal immune response, but there are noteworthyevidences regarding the role of ischemia in pathogen-esis of ulcerative colitis (UC). Hypoxia-induciblefactor-1 alpha (HIF1a) is an intranuclear proteinwhich is produced by decreased level of intracellularoxygen level. Increased levels of HIF1a in tissuespecimens and high levels of vascular endothelialgrowth factor (VEGF) in serum samples of UCpatients are novel findings, strongly congruent withthe role of ischemia in UC pathogenesis. The aim ofthis study is to evaluate the value of tissue hypoxia incellular level in pathogenesis of UC [1–3].Forty subjects in four groups were enrolled inour case control study as follows: 1) ten patientswithleftUC(toobtainbiopsyspecimensfromsparingpartsofthecolon);2)tenhealthyindividuals(referreddue to screening purposes); 3) ten formalin-fixedparaffin-embedded (FFPE) tissue samples frompatients with mesenteric ischemia; and 4) ten FFPEsamples from patients with infectious colitis. Subjectsin group 1 and 2 underwent colonoscopy. In group 1,two biopsy samples were taken, one from ulcerativetissue, and the other from spared intestinal tissue.In group 2, biopsy specimens were obtained from theleft colon. All subjects were evaluated for tissue hyp-oxia by a single expert pathologist utilizing HIF1aimmunohistochemical staining (Novus BiologicalsCompany, Clone ESEE122). Systemic and perirectalarteriolar oxygen saturation was then evaluated ingroups 1 and 2. Systemic oxygen saturation was mea-sured by radial artery blood sampling. Endoscopicultrasound was used for arteriolar blood sampling inperirectal level. The venules and arterioles were dis-tinguished according to wall thickness (Figure 1).Oxygen saturation was quantified within one minuteof blood sampling.Nine (90%) of the biopsy specimens of patientswith ulcerative colitis (ulcerative parts) as well as8 (80%) of the specimens of the subjects with mesen-teric ischemia showedtissue hypoxia in HIF-1a stain-ing. By contrast, only 1 (10%) of the biopsy samplesfrom subjects with infectious colitis and none of thesamples from healthy individuals and samples fromsparing parts of the colon of patients with UChad tissue hypoxia. There were no significant differ-ences between systemic saturation in groups 1 and2 (94.4 vs. 94.3%, p = 0.8), but pericapillary satura-tion was significantly higher in ulcerative colitispatients (96.4 vs. 94.3%, p = 0.001).Our data suggest that ischemia is the main pathol-ogy in a majority of UC patients. In support of ourconclusion, previous studies have shown that HIF1ais involved in triggering cell immune response [4] and

A majority of acute pericarditis cases have some degree of myocarditis. Viruses are the common etiological factor of this disease. Corticosteroids are considered for treatment, especially in recurrent models of the disease. In this article, we report the case of a 47-year-old man with myopericarditis who was under daily intra-muscular dexamethasone injection for an unknown reason. This is a unique case of spontaneous myopericarditis under corticosteroid abuse that has not been reported previously.