Sudabeh Alatab

BACKGROUND: The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. METHODS: We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals (UI). FINDINGS: In 2017, there were 6·8 million (95% UI 6·4-7·3) cases of IBD globally. The age-standardised prevalence rate increased from 79·5 (75·9-83·5) per 100 000 population in 1990 to 84·3 (79·2-89·9) per 100 000 population in 2017. The age-standardised death rate decreased from 0·61 (0·55-0·69) per 100 000 population in 1990 to 0·51 (0·42-0·54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422·0 [398·7-446·1] per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6·7 [6·3-7·2] per 100 000 population). High Socio-demographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464·5 [438·6-490·9] per 100 000 population), followed by the UK (449·6 [420·6-481·6] per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1·8 [0·8-3·2] per 100 000 population) and Singapore had the lowest (0·08 [0·06-0·14] per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0·56 million (0·39-0·77) in 1990 to 1·02 million (0·71-1·38) in 2017. The age-standardised rate of DALYs decreased from 26·5 (21·0-33·0) per 100 000 population in 1990 to 23·2 (19·1-27·8) per 100 000 population in 2017. INTERPRETATION: The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. FUNDING: Bill & Melinda Gates Foundation.

OBJECTIVE: Our objective was to study in vivo biological effects of natalizumab on immune cell phenotype and function in multiple sclerosis (MS) patients. METHODS: Blood was obtained before and after serial monthly natalizumab infusions to track functional expression of VLA-4 and migratory capacity of immune cells. The impact of infusion on activation thresholds of immune cells was evaluated. RESULTS: Preinfusion VLA-4 expression differed across immune cell subsets. Natalizumab significantly, albeit partially, diminished VLA-4 expression on circulating immune cells. Cell subsets were differentially affected. Treatment significantly decreased migratory capacity of immune cells, correlating well with changes in VLA-4 expression. Effects of a single dose were not saturating and did not persist through the monthly dose interval. Infusion effect varied across patients but was remarkably stable in individual patients, over multiple infusions. Treatment significantly modulated proliferative responses of immune cells. INTERPRETATION: To our knowledge, we provide first proof of concept that natalizumab diminishes migratory capacity of immune cells. Our prospective study further shows that effects of therapy likely (1) differ for distinct immune cell subsets, (2) are not sustained over current dose interval, (3) have unique profiles in individual patients, and (4) include modulation of activation threshold of immune cells. Monitoring these parameters could be relevant to ongoing safety and efficacy considerations.

Many studies have shown that change in metabolism caused by diabetes can influence the bone metabolism in a way that quality and strength of bone is decreased. A 6 times and 2 times increased risk of fracture is reported in patients with type 1 and type 2 diabetes, respectively. There are several mechanisms by which diabetes can affect the bone. The fact that some of these mechanisms are acting in opposite ways opens the door for debate on pathways by which diabetes affects the bones. On the other hand, bone is not a simple organ that only get influence from other organs, but it is an endocrine organ that by secreting the agents such as osteocalcin, adiponectin and visfatin which can affect the insulin sensitivity and metabolism. In this paper we tried to briefly assess the latest finding in this matter.

INTRODUCTION: The incidence of urolithiasis has increased in both the developed and the developing countries during the past decades. Economically, the increase of urolithiasis contributes to the rise of the healthcare burden everywhere. Moreover, this increase has been associated with a change in the epidemiology of urolithiasis in terms of age and sex distribution, and also the location and type of calculi. MATERIALS AND METHODS: We searched the MEDLINE for relevant literature dating back to 1980. This review compared the trends in epidemiological factors affecting urolithiasis in the developed and the developing countries during the past decades. RESULTS: People in the developing countries are more likely to contract kidney calculi at a younger age than in the developed countries. Although calculus disease is still more prevalent in men than in women, the latter are increasingly affected in both worlds. Uric acid calculi are more prevalent in the developing than in industrialized countries. There is a progressive increase in the frequency of calcium oxalate and calcium phosphate calculi in the developing countries where these used to be less frequent. CONCLUSIONS: The incidence and prevalence of urinary calculi is increasing globally. Many factors including aging of the population, changes in diet, global warming, and employment of more accurate diagnostic tools seem to be involved in this increase. An increasing affluence and adaptation of Western diet habits in many developing countries seem likely to contribute to the changes.

PURPOSE: To compare the expression rate of sex steroid hormone receptors of estrogen (ER), progesterone (PR) and androgen (AR) in normal urothelium and urothelial bladder cancer (UBC) and to evaluate the possible associations of these receptors expression with cancer progression and patient's survival. MATERIALS AND METHODS: We evaluated the clinical data and tumor specimens of 120 patients with pathologically confirmed primary UBC with 132 normal healthy controls. Both patients and controls selected from list of subjects who have been referred to Sina Urology clinic, and had a minimum of one year follow-up duration. Data collected from medical cords. For evaluation of expression, immunohistochemistry was performed on paraffin-embedded tissue sections using a monoclonal antibody for androgen, estrogen and progesterone receptors. Presence of at least 10% positive cells defined as positive expression. RESULTS: None of the control subjects showed AR expression, while 22% of the patients were AR-positive. ER/PR expressions were observed in 4.2%/ and 2.5% of the cases and in 2.3% and 1.5% of the controls, respectively. A statistically significant correlation was found between AR expression and tumor stage and grade (P < .001). AR-positive patients showed a significantly poorer prognosis than AR-negative cases (log-rank test, P = .02, hazard ratio = 2.12; 95% confidence interval: 1.36-4.65). CONCLUSION: AR expression was significantly associated with higher grade and poorly differentiated tumors with unfavorable outcome. AR expression test might be useful as a diagnostic tool for determining the malignancy and outcome of UBC patients.