Lifestyle factors are well-known important modifiable risk factors for obesity; the association between tobacco smoking and central obesity, however, is largely unknown in the Chinese population. This study examined the relationship between smoking and central obesity in 0.5 million Chinese adults, a population with a low prevalence of general obesity, but a high prevalence of central obesity.A total of 487,527 adults , aged 30-79 years, were enrolled in the baseline survey of the China Kadoorie Biobank (CKB) Study conducted during 2004-2008. Waist circumference (WC) and WC/height ratio (WHtR) were used as measures of central obesity.The prevalence of regular smokers was significantly higher among males (60.6%) than among females (2.2%). The prevalence of central obesity increased with age and BMI levels, with a significant gender difference . Of note, almost all obese adults (99.4%) were centrally obese regardless of gender. In multivariable regression analyses, adjusting for age, education, physical activity, alcohol use and survey site, regular smoking was inversely associated with BMI in males  and females . Of interest, in the BMI stratification analyses in 18 groups, all βs of regular smoking for WHtR were positive in both genders; the βs showed a significantly greater increasing trend with increasing BMI in males than in females. In the analyses with model adjustment for BMI, the positive associations between regular smoking and WHtR were stronger in males  than in females  (p<0.001 for gender difference). WC showed considerably consistent results.The data indicate that tobacco smoking is an important risk factor for central obesity, but the association is gender-specific and depends on the adjustment for general obesity. Obesity has reached an epidemic level worldwide in both children and adult populations despite efforts of research and prevention for decades –5. ObesiThe rapid economic growth has been accompanied by urbanization, westernization of lifestyle behaviors and rising rates of obesity in China during the past couple of decades ,5,17,18.The CKB Study is a prospective study of chronic disease in China. Details of the CKB study design and characteristics of the study participants have been described elsewhere ,26. BrieThe current analysis included participants who had a weight between 30 kg and 160 kg, a height of 145–200 cm  and 140–200 cm , a BMI between 18.5 and 45.0, and a waist circumference between 50 cm and 150 cm. People who were very underweight or extremely obese or were at the extremes of the height distribution may have underlying metabolic or growth disorders. A total of 25,364 participants were excluded based on the above selection criteria, and 487,527 adults  formed the sample for the current analysis.Ethical approval for the CKB study was obtained from the Ethical Review Committee of the Chinese Center for Disease Control and Prevention  and the Oxford Tropical Research Ethics Committee, University of Oxford (UK). In addition, approvals were obtained from the institutional research boards at the local Center for Disease Control and Prevention in each of the ten survey sites. Finally, written informed consent was obtained from all participants.In the baseline survey, trained interviewers administered a standardized questionnaire using a laptop-based direct data-entry system, with built-in functions to avoid logical errors and missing items. The questionnaire included detailed questions on socio-demographic status, medical history and health status, smoking, alcohol consumption, physical activity, and other lifestyle behaviors.Education was classified into five levels: Illiterate, elementary, middle school, high school, college and above. Total physical activity was converted into metabolic equivalent hours per day (MET-hours/day) spent on work, transportation, housework, non-sedentary recreation as described in our previous study . For assFor assessment of tobacco consumption, participants were asked how often they had smoked tobacco at the time of the survey, and those who did not smoke or only smoked occasionally were asked if there was a period prior to that when they had smoked some tobacco on most days or daily. In the present analysis, participants were classified into four main smoking categories: 1) nonsmokers were defined as those who did not smoke currently and had not smoked more than 100 cigarettes during his/her lifetime; 2) ex-smokers as those who currently do not smoke or only smoked occasionally but had smoked on most days or daily in the past; 3) occasional smokers as those who do not smoke currently but had smoked occasionally in the past or had smoked at least 100 cigarettes during his/her lifetime, or those who currently smoke occasionally and had not smoked on most days or daily in the past; 4) regular smokers as those who currently smoke daily or on most days. Information on duration (years) of smoking and number of packs smoked per day was obtained for regular smokers, and pack-years was calculated as a measure of cumulative burden of smoking.Standing height and body weight were measured in light indoor clothing without shoes to the nearest 0.1 cm and 0.1 kg, respectively. Waist circumference (WC) was measured midway between the iliac crest and the lower rib margin at the end of normal expiration using a plastic flexible tape to the nearest 0.1 cm. All measurements were made by trained staff using a standard protocol and instruments. WC/height ratio (WHtR) was calculated as WC divided by height and was used as a measure of central obesity . Body maStatistical analyses were performed using Stata Statistical Software . All analyses were performed separately by gender groups. Descriptive data were presented as mean and standard deviation (SD) for continuous variables, and percentages for categorical variables. General linear models were used to test differences in continuous study variables between gender groups, adjusting for age, and survey sites for the descriptive data. Chi-square test was used to test the differences in categorical study variables between gender groups.Multivariable linear regression analyses were performed  by gender, adjusting for age, survey site (included in the regression models as nine dummy variables using Qingdao as a reference), education , total physical activity (MET-hours/day) and alcohol use . Smoking was included in the model as both a categorical variable  and a continuous variable (pack-years). In order to assess the influence of adjustment for BMI on the association of tobacco smoking with WC and WHtR, males and females were stratified into 18 subgroups according to levels of BMI with equal numbers of subjects in each subgroup. Multivariable linear regression analyses were performed within each subgroup, adjusting for the above mentioned covariates. Standardized regression coefficients of regular smoking for WC and WHtR in the 18 BMI subgroups were plotted in males vs females. Linear regression models were used to assess significance of trends in the effect size of regular smoking on WC and WHtR across these 18 BMI subgroups; interaction regression models were used to test the difference in slopes of the regression lines between gender groups.In sensitivity analyses, the association of tobacco smoking with WC and WHtR was examined using multivariable linear regression models, with and without BMI adjustment, by groups of normal-weight (BMI = 18.5–23.9), over-weight (BMI = 24.0–27.9), and obesity (BMI = 28.0–45.0), adjusting for covariates as mentioned above.In order to assess the influence of adjustment for BMI on the association analyses of smoking with WC and WHtR, males and females were stratified into 18 subgroups with equal numbers of subjects in each subgroup according to levels of BMI. In order to confirm the results of BMI stratification analyses, a model adjustment for BMI was used. In sensitivity analyses, the association between smoking and WHtR was examined in linear regression models by groups of normal-weight (BMI = 18.5–23.9), over-weight (BMI = 24.0–27.9) and obesity (BMI = 28.0–45.0), without and with adjusting for BMI along with other covariates. In males, the standardized linear regression coefficients of regular smoking for WC were -0.009* without adjusting for BMI and 0.040** with adjusting for BMI in the normal-weight group, 0.067** and 0.077** in the over-weight group and 0.066** and 0.072** in the obesity group . In females, the standardized linear regression coefficients of regular smoking for WC were 0.001 without adjusting for BMI and 0.016** with adjusting for BMI in the normal-weight group, 0.016** and 0.018** in the over-weight group and 0.028** and 0.020** in the obesity group. In males, the standardized linear regression coefficients of regular smoking for WHtR were -0.032** without adjusting for BMI and 0.019** with adjusting for BMI in the normal-weight group, 0.043** and 0.054** in the over-weight group and 0.049** and 0.055** in the obesity group. In females, the standardized linear regression coefficients of regular smoking for WHtR were 0.001 without adjusting for BMI and 0.015** with adjusting for BMI in the normal-weight group, 0.013** and 0.015** in the over-weight group and 0.021** and 0.014** in the obesity group. The results of these sensitivity analyses indicated that the negative associations of regular smoking with WC and WHtR without adjusting for BMI were mainly because of the association patterns in the normal-weight group in males and females. The number of study subjects of the normal-weight group accounted for 54.2% of the entire study cohort.Asian populations have a relatively lower BMI, but a greater prevalence of central obesity than Caucasian populations ,11–16,28Epidemiologic studies have shown that body weight tends to be lower among smokers than among nonsmokers in many populations –24. SmokBy comparing the regression coefficients before and after adjustment for BMI in the model, completely opposite directions in the associations of regular smoking with WC and WHtR were noted in the current study. When BMI was not included in the model, current smoking showed a protective effect on WC and WHtR; whereas, current smoking was positively associated with these central obesity measures with BMI included in the model. The changes in the strength and direction of the association parameters suggested a considerable influence of BMI on these associations, particularly in the male normal-weight group as shown in the sensitivity analyses. When BMI was not adjusted for in regression analysis models, the negative association of regular smoking with WC (β = -0.009) and WHtR (β = -0.032) largely reflect the effect of smoking on BMI in the male normal-weight group. The smoking-BMI-central obesity relationship is similar to the mediation model proposed by Hernández-Díaz (The prevalence of overweight and obesity is higher among women than men, especially in developing countries . Women oThis population-based epidemiologic study has certain limitations. First, subjects voluntarily participated in the study, which might result in selection bias to some extent with respect to the population representativeness despite the large sample size. Second, the pathophysiological mechanisms underlying the association between smoking and central obesity cannot be investigated in the current study because the baseline survey data are observational in nature. Finally, the CKB study is not a nutritional survey, and detailed information on dietary patterns is not available. Therefore, dietary factors, which may be important, were not included in the current analyses.In conclusion, the current study demonstrates that there are considerable differences in the prevalence of tobacco smokers and central obesity between male and female Chinese adults; smoking is significantly and positively associated with central obesity measured as WC and WHtR, with males having substantially stronger association parameters than females. Importantly, the association patterns of regular smoking with central obesity were largely dependent on BMI adjustment. The present study emphasizes the importance of adjustment for BMI in the smoking-central obesity association analyses, especially for normal-weight adults. Sophisticated statistical models like structural equation modeling or mediation analysis are needed to investigate this issue in depth. These gender-specific results indicate that other important underlying mechanisms like sex hormones may be involved in the development of central obesity in females in addition to tobacco smoking. The study findings underscore the importance of undertaking preventive strategies for central obesity through smoking behavior control.


Intakes of protein , carbohydrates , and percentage of energy from fat  significantly increased the risk for the development of CRC. Saturated fat, dietary cholesterol and sodium intake showed a significant association with the risk of developing CRC , while vitamin E and caffeine intake were indicative of a protective effect against the development of CRC, OR = 0.002 (95% CI: 0.0003–0.011) and 0.023 (95%CI: 0.008–0.067), respectively. Conclusion: Our results suggest an increased risk for the development of CRC in subjects with high dietary intake of energy, protein, saturated fat, cholesterol, and sodium, and diets high in vitamin E and caffeine were suggestive of a protective effect against the risk of developing CRC. Impact: This is the first study in Jordan to suggest that it may be possible to reduce CRC risk by adjusting the intake of some macro-and micronutrients.Objective: Diet and lifestyle have been reported to be important risk factors for the development of colorectal cancer (CRC). However, the association between total energy and nutrient intake and the risk of developing CRC has not been clearly explained. The aim of our study is to examine the relationship between total energy intake and other nutrients and the development of CRC in the Jordanian population. Research Methods and Procedures: Dietary data was collected from 169 subjects who were previously diagnosed with CRC, and 248 control subjects . These control subjects were healthy and disease free. Data was collected between January 2010 and December 2012, using interview-based questionnaires. Logistic regression was used to evaluate the association between quartiles of total energy, macro- and micronutrient intakes with the risk of developing CRC in our study population. Results: Total energy intake was associated with a higher risk of developing CRC (OR = 2.60 for the highest  Published report suggests that colorectal cancer (CRC) is one of the three most common forms of cancer with nearly 1.4 million new cases diagnosed in the year 2012 . Diet anet al. [Dietary intakes of energy, macro- and micro-nutrients have been implicated in the etiology of CRC . Severalet al.  in the Cet al. . The foret al. .et al. [et al. [One local Jordanian study published by Arafa et al. , showed  [et al. , differeThe study sample consisted of 503 participants; with 232 diagnosed CRC cases and 271 controls . Participants were enrolled in the study from January 2010 to December 2012. Participating subjects were patients diagnosed with CRC (cases) who were recruited from five Jordanian hospitals specializing in oncology diagnosis and treatment. The hospitals included King Hussein Cancer Center (KHCC), King Abdullah University Hospital, Prince Hamzeh Hospital, Jordan University Hospital, and Al-Basheer Hospital. The control group was recruited from hospital personnel, outpatients, visitors and was matched as closely as possible for age, gender, occupation and marital status. Control subjects were excluded if any first- or second degree relatives were diagnosed with CRC. The study protocol was approved by KHCC Institutional Review Board (IRB) Committee  and other hospitals gave their approval accordingly. Written informed consent was obtained from all subjects before their interview. The following inclusion criteria for controls were used: Jordanian nationals aged 18 years or older, ability to communicate clearly and verbally, free of any type of diagnosed cancer, diabetes mellitus, liver disease and rheumatoid arthritis. For inclusion in the diagnosed CRC cancer group, subjects must have received their diagnosis less than 1 year prior to the time of the first interview. The exclusion criteria for this group included those who were considered “critically ill”, such as an in-patient at any facility and those who were unable to communicate verbally and clearly.n = 58); over-estimation of calorie intake  (n = 12); and under-estimation of calorie intake  (n = 16) [Socio-demographic, health and dietary data were collected by trained research assistants using interview-based questionnaires. The socio-demographic data included age, marital status, household income, education , occupation and tobacco usage (current and previous smokers were categorized as smokers and those who never smoked were set as non-smokers). The comprehensive health data included the participant’s full medical history to confirm that only CRC diagnosed subjects and healthy disease free subjects were included. A validated Arabic quantitative Food Frequency Questionnaire (FFQ), adapted from the Diet History Questionnaire (DHQ I) of the National Cancer Institute of the United States of America , was use(n = 16) . Dietary(n = 16) .et al. [The 7-day Physical Activity Recall (PAR), developed by Sallis et al.  was usedet al. .Body weight was measured to the nearest 0.1 kg, with minimal clothing and without shoes, using a calibrated portable scale. Height was measured to the nearest 0.5 cm with participants in the full standing position without shoes using a calibrated portable measuring rod. Body mass index (BMI) was calculated as the ratio of weight in kilograms to the square of height in meters .p = 0.05. For descriptive statistics, mean ± standard deviation (SD) and percentages were used. T-tests evaluated the differences between cases and controls in continuous variables, and Chi-square was used to detect differences among categorical variables.Statistical analysis was performed with SPSS IBM-20 software. The significance level was set at Because all nutrients were correlated with energy intake, variation due to energy intake and its associated measurement error was minimized by energy adjustment of the nutrients using the regression method . This meNutrient intakes were modeled using quartiles of distribution in the study population with quartile 1 being the lowest intake and quartile 4 the highest. Odds ratios (ORs) and 95% CIs (95% CIs) for CRC were calculated by using logistic regression models for quartiles of nutrient intakes, with the lowest quartile as the reference category. Confounders were selected based on known risk factors for CRC reported in the literature. Potential confounders were chosen based on previous studies  includinp < 0.05) compared to the control group. In addition, the CRC group had significantly higher intakes of folate, Iron, selenium as well as omega-3 (p < 0.05) when compared to the control group, and the control group had a higher percentage of calories from carbohydrate when compared to the CRC group (p < 0.05).The mean daily intakes of total energy, macronutrients, and micronutrients appear in versus the lowest quartile of intake) of total energy , and protein  were significantly associated with CRC. A significant positive trend in risk was found for carbohydrate (p = 0.043), but none of the quartiles are different from the reference category. The odds ratios for quartiles of fat intake as g/day were not calculated due to distribution issues (the bottom quartile had only 1 participant and the top quartile only 2 control participants). As noted in versus the lowest quartile of intake, and the trend tests were also significant. No association for intake of total fiber with CRC was detected, .12, D, K, and folate, beta-carotene, phosphate, and omega-3. Calcium showed a significant risk in the top two quartiles.Vitamin E intake showed significant protective effect against CRC with OR = 0.02 and 95% CI: 0.0003–0.011, . NeitherThe results from of the present study provide further evidence for an association between CRC risk and diet. Generally, the results of this case-control study on CRC risk illustrate a relationship between macro- and micronutrients intake and this type of cancer among Jordanians.As BMI was obtained at the time of interview for both patients and controls, the association between obesity and CRC in this study could not be evaluated. The lower BMI in cases may reflect the effect of chemotherapy and other therapies which cancer patients were exposed to before the interview time.in vitro [Our study revealed a direct association between total energy intake and the risk of developing CRC, as supported by several other studies ,19. Caloin vitro ,22. Elevin vitro ,24. Insuin vitro ,24.et al. [et al. [High carbohydrate intake may increase glycemic load, insulin levels, and IGF-1 ,21. A siet al.  reported [et al.  found a p-trend = 0.12). In the other two mentioned studies, significant associations in age-adjusted models disappeared after adjustment for other risk factors. In the Pooling Project analysis including data from 13 cohort studies the report showed statistically significant inverse associations for colorectal cancer in the age adjusted models , but not after multivariable adjustment  [vs. Quintile 1, HR 0.73, 95% CI: 0.65–0.82) disappeared after multivariable adjustment  [The effect of fiber on CRC incidence is inconsistent; some studies report a significant inverse association between total fiber intake and CRC risk ,29,30,3186–1.03) . Similar85–1.15) .et al. [p < 0.05). The proposed mechanism for fat involvement in colorectal carcinogenesis appears to be complex. However, Endo et al. [N-terminal kinase (JNK) pathway, which was reported to play a crucial role in insulin resistance during colorectal carcinogenesis in the presence of hyperinsulinaemia induced by a HFD. They found that colonic cell proliferation was promoted via the JNK pathway in the presence of a HFD providing an explanation of the effect of dietary fat intake on colon carcinogenesis through the JNK pathway [Similar to other studies ,12,26,35et al.  who repoet al. [et al. [p-trend = 0.002, 4th versus 1st quartile). However, Egeberg et al. [et al [In our study, protein intake was found to have a significant direct association with CRC. Arafa et al.  indicate [et al. , reporteg et al.  reportedg et al. . No assog et al. . Fifty p. [et al , we repo. [et al . In fact. [et al .et al. [In our study, vitamin E was found to have a significant inverse association with the risk of CRC development. The remarkable effect of vitamin E consumption on protecting against CRC could be attributed to the comparative ratio of 95 case/9 control participants at the lowest quartile compared to 12 case/92 control participants at the 3rd quartile of vitamin E consumption. These results are in agreement with other studies ,39,40,41et al. , that haet al. . PerhapsThe association between folate intake and CRC disease state is being debated and no significant association between folate and CRC risk has been reported ,43,44,45et al. [2+ + O2 in oxidant formation in biological systems and its pH dependency, activation of oxidative responsive transcription factors and pro-inflammatory cytokines, and iron-induced hypoxia signaling [Iron (Fe) intake was found to have a positive weak association with CRC risk . Our reset al.  study, tignaling ,48.In our study, the intake of selenium was found to have a significant trend for direct association with CRC risk. Other studies reported the presence of an inverse association between selenium intake and plasma levels with CRC risk ,50,51. Oet al. [p-trend of 0.008.The results of our study is in agreement with these reports. One potential explanation for this is the presence of chemical carcinogens such as N-nitroso compounds in salted foods such as processed meats, dairy products and canned foods, which can be formed by the reaction of sodium nitrate or sodium nitrite in the curing process or in the body, or heterocyclic amines, which have been detected in fish or meat cooked in high temperatures, such as grilling, which is commonly used for grilled meat [Some studies have shown an association between high sodium intake and CRC development ,53,54, aRegarding caffeine intake, our results are in agreement with other studies. Caffeine has been shown to have a negative association with CRC risk ,56. It iIn a study of this type we rely greatly on the ability and memory recall of participants to accurately and carefully provide information from a period when it was not necessarily important to remember the details of long digested meals, or physical activities that were undertaken. It is understandable that some individuals may have a greater recall than others, and that biases may exist in the minds of those being interviewed, and indeed, by the interviewer. Traumatic events such as the diagnosis of a life threatening disease condition may ultimately have a very significant role in the memory recall of some participants. Because of the obvious limitations placed on the recall of memory, we are using the only means currently available to us, the FFQ, which although prone to errors, is nevertheless an accepted and validated form used in many research studies.We did not take into account the possible effects of cooking on the bioavailability of the various nutrients, and although we attempted to control for a range of potential confounders, we did not measure alcohol use . Nor did we consider the use of food dietary supplements; however, we are aware that the use of dietary supplements is not common or widespread. Finally, the one year dietary recall time frame may not be sufficient to determine an association with a disease state that may take years to develop; nevertheless, we see this study as a pointer to the need for further long term studies involving journal and diary entries of nutritional intakes along with physical activities for designated period of time, whether it be five to fifteen years.A major strength of our study is the validated and detailed FFQ used to collect dietary data from our study population. Even though dietary data were collected at only one time, the FFQ has been reported to be an adequate instrument for measuring macro- and micronutrient intake . ConfirmThis study, conducted in a Jordanian population group provides additional evidence that diets containing high energy, protein, total fat, saturated fat, cholesterol, and sodium intakes may increase the risk of CRC development, whereas high intakes of insoluble fiber, vitamin E, and caffeine may decrease the risk of these diseases. These results suggest that dietary changes could help to reduce the incidences of CRC in the Jordanian population.


Robotic-assisted laparoscopy is popularly performed for colorectal disease. The objective of this meta-analysis was to compare the safety and efficacy of robotic-assisted colorectal surgery (RCS) and laparoscopic colorectal surgery (LCS) for colorectal disease based on randomized controlled trial studies.Literature searches of electronic databases  were performed to identify randomized controlled trial studies that compared the clinical or oncologic outcomes of RCS and LCS. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were mean differences and odds ratios for continuous and dichotomous variables, respectively. Fixed-effects or random-effects models were adopted according to heterogeneity.Four randomized controlled trial studies were identified for this meta-analysis. In total, 110 patients underwent RCS, and 116 patients underwent LCS. The results revealed that estimated blood losses (EBLs), conversion rates and times to the recovery of bowel function were significantly reduced following RCS compared with LCS. There were no significant differences in complication rates, lengths of hospital stays, proximal margins, distal margins or harvested lymph nodes between the two techniques.RCS is a promising technique and is a safe and effective alternative to LCS for colorectal surgery. The advantages of RCS include reduced EBLs, lower conversion rates and shorter times to the recovery of bowel function. Further studies are required to define the financial effects of RCS and the effects of RCS on long-term oncologic outcomes. Minimally invasive surgery for colorectal disease was introduced in 1991 . Since tTwo authors  participated in this search to independently identify all published RCT studies comparing RCS and LCS. The Pubmed, Web of Science and Cochrane Library databases were searched. The following medical subject heading terms and key words were used: robotic; telerobotic; colorectal; colon; rectal; random. None of the searches had any language limitations, and the most recent search time was 1 March 2013.For inclusion in this meta-analysis, the studies were required to meet the following criteria: (1) RCTs; (2) studies comparing the efficacy and safety of RCS and LCS for the treatment of colorectal disease; (3) studies that effectively reported both primary results and data adequate for meta-analysis.The effective data from all eligible RCTs were extracted by two reviewers . The extracted data included the following: first author; year and country of publication; surgical technique; operation type; basic patient characteristics, including age, body mass index (BMI), number of patients, diagnosis, tumor stage, intraoperative data, postoperative data; and pathological details including operation time, estimated blood loss, open conversion rate, time to recovery of bowel function, length of hospital stay, complication rate, proximal margin, distal margin, harvested lymph nodes and cost. All available data were extracted from the relevant texts, tables and figures. In cases of disagreement about whether a study was suitable for inclusion in the meta-analysis, an additional reviewer (WYY) assessed the article and made the final decision.Two reviewers  independently evaluated the bias of each study using the Cochrane tools . The ass2 and I2 tests. We considered heterogeneity to be present when the I2 statistic was >50%, and random-effects models were adopted in these cases. However, when the I2 statistic was <50%, we used fixed-effects models. P <0.05 was considered significant.This meta-analysis was performed using the Review Manager (RevMan) software, version 5.2, provided by the Cochrane Collaboration. Dichotomous variables were analyzed using estimations of the odds ratio (OR) and 95% CI, and continuous variables were analyzed using weighted mean difference (WMD) and 95% CI. Fixed-effects models or random-effects models were applied. Heterogeneity was evaluated using χA total of 71 potentially relevant articles were identified, and the selection process is illustrated in Figure All of the studies were RCTs, but none were double- or even single-blinded. Assessments of the risk of bias are illustrated in Figure P = 0.19), but the heterogeneity was high   indices before and after the surgical inventions were reported. These numbers revealed no significant difference between the two techniques [P = 0.003). Furthermore, there was no evidence of observed heterogeneity   ,14. Bothchniques . The pooP = 0.04), and there was no obvious heterogeneity among the four studies   and for 11 patients in the LCS group (9.48%). Analyses of the pooled data revealed that the conversion rate was significantly lower in the RCS group than in the LCS group  Figure .et al. [et al. [P =0.008, I2 = 0)  Figure .et al. [P <0.001). However, the other three studies reported no differences in hospital stays between the two groups. Analysis of all of the studies revealed no significant difference between the two techniques in terms of LOS . However, the heterogeneity was slightly high  . A meta-analysis of all of the studies in this index revealed that the complication rates of the two group were not obviously different (odds ratio (OR) 1.39, 95% CI 0.71 to 2.74, P = 0.33)   ; one study by Patriti et al. [I2 = 48%). The harvested lymph nodes were similar across all of the studies (I2 = 0), and analysis of the pooled data revealed that the two groups did not differ significantly in this regard   Figure . All of ) Figure . The stui et al.  found a ) Figure .et al. [As a newly developing surgical technique, it should prove to be safe and cost-effective until it is widely accepted worldwide. Thus, it is essential to evaluate the cost-effectiveness between RCS and LCS. In our meta- analysis, only one study addressed to this issue. Park et al.  reportedP = 0.55, Figure Complications were assessed by a funnel plot of the standard errors of the fixed-effect sizes between the RCS and LCS. This analysis revealed no evidence of publication bias or heterogeneity among the studies . There was no significant difference in the conversion rates of the two techniques . Analyses of the times to recovery of bowel function, complication rates, proximal margins, distal margins, and the harvested lymph nodes yielded similar results. However, the LOS of the RCS group were significantly shorter than those of the LCS group .A sensitivity analysis was performed by excluding the low-quality studies . As shown in Figure et al.  to have Laparoscopic surgery has been applied in many surgical fields and has not only been shown to be effective and safe but also to have certain benefits over traditional open surgery -19. HoweA previous meta-analysis  producedP = 0.06). This result is similar to that of a previous study [The present study is the first meta-analysis to compare robot-assisted and laparoscopic surgery for colorectal cancer based only on RCTs. The results of this meta-analysis revealed that RCS may provide additional benefits over LCS and that it is safe and effective ,4,26. Reus study . In contus study ,29. As tus study , and it EBL ranges between 90 ml and 320 ml for LCS  and betwWe found that the conversion rate was significantly lower in the RCS group and there was no significant heterogeneity across the four studies. Thus, the reduction in conversion rate may be one of the key benefits of RCS. Conversion rate is a valuable index of surgical quality. Lower conversion rates are associated with fewer postoperative complications . The redAs observed in the studies, robotic surgery has other advantages. The time to the recovery of bowel function was shorter in the RCS than in the LCS group. This reduction may be another potential benefit of RCS because faster returns to normal diets are associated with faster recoveries. We discovered that the LOS was not significantly different between the two groups; indeed, LOS was similar between the two techniques . The comet al. [Although we conducted this meta-analysis based on four RCTs, this meta-analysis still has the following limitations. First, the included studies were not double-blind studies or even single-blind studies; the studies may have been biased; therefore, the interpretation of their results may also have been biased. Second, although we focused on colorectal surgery, different types of diseases  that involved different types of surgery were included, which may have caused heterogeneity. Third, the surgery in the included cases were not performed by the same surgeon, and the experience and technique of the surgeons may have affected some of the indices, such as the operation time, EBL and conversion rate. However, in this meta-analysis, no significant heterogeneities among the four studies were found for conversion rate or EBL; only operation time exhibited significant heterogeneity. Fourth, long-term follow-up evaluations assessing oncologic outcomes were not available from the selected studies, and only Patriti et al.  reportedet al. . Finallyet al. . This stet al. ,39,40. Tet al. . Furtheret al. . Future This meta-analysis suggests that RCS is safe and effective and has some advantages over LCS. These benefits include a reduced conversion rate, reduced blood loss and reduced time to recovery of bowel function. Regarding the other variables, such as operation time, complication rate and LOS, there were no significant differences between the two groups. However, RCS was associated with a significant increase in total costs relative to LCS. Further well-designed, prospective controlled randomized trials should be conducted to assess the financial benefits and the long-term oncologic outcomes of RCS.BMI: body mass index; EBL: estimated blood loss; LCS: laparoscopic colorectal surgery; OR: odds ratio; RCS: robotic-assisted colorectal surgery; RCT: randomized controlled trial; WMD: weighted mean difference.The authors declare that they have no competing interests.GXL, ZHZ, YWY and SHL conceived the study and participated in its design, the literature research, data extraction, manuscript drafting. RL, JRC, SSD and HJD participated in manuscript drafting, and editing. All authors read and approved the final manuscript.


Background: Cardiovascular disease (CVD) represents a leading cause of mortality worldwide, especially in the elderly. Lowering the number of CVD deaths requires preventive strategies targeted on the elderly.Objective: The objective was to generate evidence on the association between WHO dietary recommendations and mortality from CVD, coronary artery disease (CAD), and stroke in the elderly aged ≥60 y.Design: We analyzed data from 10 prospective cohort studies from Europe and the United States comprising a total sample of 281,874 men and women free from chronic diseases at baseline. Components of the Healthy Diet Indicator (HDI) included saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, dietary fiber, and fruit and vegetables. Cohort-specific HRs adjusted for sex, education, smoking, physical activity, and energy and alcohol intakes were pooled by using a random-effects model.Results: During 3,322,768 person-years of follow-up, 12,492 people died of CVD. An increase of 10 HDI points  was, on average, not associated with CVD mortality , CAD mortality , or stroke mortality . However, after stratification of the data by geographic region, adherence to the HDI was associated with reduced CVD mortality in the southern European cohorts  and in the US cohort .Conclusion: Overall, greater adherence to the WHO dietary guidelines was not significantly associated with CVD mortality, but the results varied across regions. Clear inverse associations were observed in elderly populations in southern Europe and the United States. The prevention of cardiovascular disease (CVD)Diet is an important modifiable risk factor for CVD incidence , even inDeriving comparable data on dietary quality across cohorts requires a globally applicable dietary quality score , 8. The The aim of this meta-analysis was to add to the current knowledge regarding the potential benefits of adhering to a healthy diet (HDI) by preventing CVD mortality in the elderly. Furthermore, we evaluated whether this association would differ by age, sex, and geographic location. The current analysis complements a previous study that we conducted within CHANCES on the association between a healthy diet and longevity using all-cause mortality as the outcome . In the www.chancesfp7.eu). Its aim is to combine and integrate prospective cohort studies to produce, improve, and clarify the evidence on the distribution and risks factors for chronic diseases in the elderly and their socioeconomic implications. Elderly were defined by the CHANCES consortium as being aged ≥60 y. The cohorts of CHANCES were chosen because they undertook the efforts to harmonize all variables needed for this project according to predefined rules. The harmonization rules were discussed among the CHANCES partners until a consensus was reached.We conducted an individual participant–based meta-analysis within CHANCES , and an unknown cause of death. A total number of 281,874  remained for further analysis. The Rotterdam Study and NIH-AARP showed dietary intake outliers, which we removed by Box-Cox transformation .We included participants aged ≥60 y (according to the definition of elderly by CHANCES) from the European Prospective Investigation into Cancer and Nutrition Elderly study (EPIC-Elderly)  , smoking status , energy intake , and vigorous physical activity (yes or no). Participants with missing data for the confounding variables were included by a separate category for these variables. BMI was initially not included in the main model because of its potential influence on the association as an intermediate factor. However, to assess whether BMI had any influence on the pooled results, additional adjustment was performed in a sensitivity analysis. We included “center” for EPIC-Elderly multicenter cohorts (ES and NL) and “region” for SENECA in all models to adjust for potential differences in baseline hazards across centers or regions.trans fatty acids, and sodium) to the association between WHO guidelines and CVD mortality, we additionally investigated the complete HDI score based on 10 WHO components in HAPIEE, NIH-AARP, and the Rotterdam Study.In an additional analysis, we ran models for the Rotterdam Study, EPIC-Elderly GR, and NIH-AARP, for which we had additional data available on hypertension at baseline, use of statins, and multivitamins. Inclusion of those variables did not change the hazard estimates to any material extent. To examine the importance of excluded HDI components , Netherlands, and Switzerland (Burgdorf)] and southern  European countries. EPIC-elderly ES and GR were classified as southern Europe, and EPIC-Elderly NL and SE were classified as northern Europe.Potential effect modification by age, sex, BMI, smoking, education, and alcohol consumption was investigated in each cohort by including an interaction term between these variables and the HDI score. Furthermore, we stratified the results on a healthy diet and CVD mortality for potential effect modifiers to address heterogeneity. To examine possible sources of heterogeneity, we compared the pooled HR estimates and In a sensitivity analysis, we studied the influence of possible dietary changes after disease occurrence on HRs. We excluded participants who died within the first 2 y of follow-up, as performed earlier . FinallyP value <0.05 was considered to be statistically significant.Cohort-specific data were analyzed by using SAS version 9.2. For the random-effects meta-analysis, the metafor package in R (version 2.15.0) was used. A I2 = 68%). Additional adjustment for BMI did not influence the pooled HR estimate for CAD , CVD , and stroke .I2 = 67%). HR estimates for stroke mortality ranged from 0.74 for HAPIEE (CZ) to 1.23 for the Rotterdam Study. Overall average risk reduction for stroke mortality amounted to 5% .For CAD mortality, HRs ranged from 0.75 for EPIC-Elderly GR and HAPIEE (RUS) to 1.40 for EPIC-Elderly NL; no association was observed across cohorts  (I2 = 24%) between HDI and CVD mortality was observed for participants with a BMI ≥27 but not for participants with a BMI <27. Significant inverse associations with low heterogeneity were also observed in former smokers, medium-level-educated subjects, and no or high alcohol users.The significance levels for interaction derived in each cohort separately did not suggest effect modification. However, stratified analysis showed reduced levels of heterogeneity after stratification in most cases. For CVD deaths, the pooled HRs were similar for men and women (I2 = 81%) in contrast with the overall result derived in these 5 cohorts .The inclusion of additional WHO components in the HDI score, in the 5 cohorts with available data, showed estimates similar to the results derived in the main analysis. We observed a narrower CI but a greater level of heterogeneity  cohorts but not in the central eastern European  and northern European  cohorts  and southern European . The analysis showed robust pooled HR estimates for CVD and stroke mortality, ranging from 0.93 for CVD and 0.94 for stroke  mortality to 0.96 for CVD (excluding fruit and vegetables) and 0.97 for stroke mortality (excluding PUFAs and fruit and vegetables). HR estimates for CAD were less robust and mostly influenced by PUFAs (HR: 0.92) and cholesterol (HR: 0.91)Finally, further sensitivity analyses were carried out to investigate the importance of the single HDI components by excluding them one at a time from the HDI and including them as a covariable instead  is associated with a reduction in CVD mortality of 13% to 15%. This indicates that the guidelines translated in dietary patterns frequently used in highly educated US seniors and elderly from southern Europe are likely to be beneficial from a cardiovascular point of view.I2 values decreased considerably after stratification. Regional differences partly explained the level of heterogeneity, at least for the southern European countries. The level of heterogeneity within northern and central eastern Europe remained high and may have been related to differences in the study design and dietary-assessment methods used. Moreover, differences in the quality of health care systems  in some cohorts may have influenced the HR estimates on mortality, which may have resulted in a greater level of heterogeneity.Our findings are based on a meta-analysis of individual participant data. Combining cohort studies in a meta-analysis typically results in a high level of heterogeneity . I2 valuDivergent associations across smoking, alcohol use, and education categories showed small levels of heterogeneity due to large CIs overlapping all point estimates. The differences found in BMI were mainly driven by SENECA and EPIC-Elderly SE, which both presented a positive association in the low-BMI group and an inverse association in the high-BMI group, which could also be driven by chance findings.Measurement error of dietary exposure was a major concern in the current study, as it is in all large cohort studies of diet and chronic disease. The methods used were validated, but—especially for the FFQs, which aim to rank subjects according to intake rather than to estimate absolute intake levels—a calibration step may be needed when different cohorts are combined . HoweverNote that one limitation of studying an elderly population may be the presence of selection bias and missing follow-up data by “unhealthy” participants. This may have caused an underestimation of the overall pooled results , 55. ParMajor advantages of this meta-analysis were the use of harmonized variables and identical analysis scripts across cohorts, the use of large data sets, the diversity of the population, and access to the original data. Furthermore, the score construction was based on the average 85th percentile across cohorts. This allowed a sufficient level of variation in the HDI score across cohorts and not only for a specific subcohort on which a cutoff level could have been assigned. A drawback of most diet scores, including the HDI score, may be related to missing weighing factors per recommendation. However, our sensitivity analysis, which excluded one HDI component at a time, showed comparable HR estimates for CVD with different levels of precision, which indicated that each recommendation is equally important. Nevertheless, the inclusion of weighing factors may improve the validity of the HDI. Even though the HDI was shown to decrease the risk of premature death , 11, 12,In conclusion, the results of this study show that a healthy diet, based on the WHO guidelines, is significantly associated with decreased CVD mortality in US and southern European elderly. However, nonsignificant associations found for the northern European countries are possibly attributable to a less healthy underlying food pattern in comparison with the US and southern European cohorts. Future studies using the HDI or other nutrient-based scores should additionally focus on the underlying food pattern of the studied population.


Background. Ovarian cancer is the most fatal malignancy of the female genital tract and is associated with high mortality. The American Congress of Obstetricians and Gynecologists (ACOG) and the United States Preventive Services Task Force (USPSTF) recommend against screening for ovarian cancer in asymptomatic, average-risk women. Objective. To assess the ovarian cancer screening practices in asymptomatic, average-risk women among obstetricians and gynecologists (Ob/Gyn) in Puerto Rico. Methodology. From 2011 to 2012, self-administered anonymous questionnaires were mailed to all licensed obstetricians and gynecologists in PR. Results. Response rate was 25%. Overall, 53.9% were screening for the disease. Reported screening methods were CA-125 and transvaginal ultrasound (TVUS), 39.2%, TVUS only, 30.4%, and CA-125 only, 9.8%. In the logistic regression model, the odds that a given health practitioner routinely screened for ovarian cancer in the asymptomatic, average-risk population increased by 8% with every unit increase in his or her years in practice. Conclusion. The majority of the practicing Ob/Gyn in PR who participated are not following the guidelines established by the ACOG and the USPSTF for ovarian cancer screening. Ovarian cancer is a low-incidence but highly lethal disease, which makes it the most fatal malignancy of the female genital tract. It is the fifth and seventh leading cause of death among women in the United States (US) and Puerto Rico (PR), respectively , 2. In PNumerous efforts have been directed towards the identification of a reliable screening test. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial  was a laBased on the available data and current guidelines discussed above, obstetricians and gynecologists should not be routinely screening the asymptomatic, average-risk women for ovarian cancer. Given the lack of data on the ovarian cancer screening practices of physicians in Puerto Rico, our objective in this study was to assess such practices of obstetricians and gynecologists in this average-risk population. This information would be valuable in the implementation of more aggressive patient and physician education programs since undergoing nonvalid screening tests could result in increased costs, increased patient anxiety, and unnecessary surgeries.n = 440) in Puerto Rico from 2011 through 2012. Participants were not asked to specify if they had any subspecialty. We believe this had no effect on selection bias, as there were only 3 gynecologic oncologists in the whole island during the study period. Participants were followed up by sending 2 mail letters. Addresses were obtained from the corresponding section of the College of Physicians and Surgeons of Puerto Rico. Nonpracticing physicians were excluded from the study. The questionnaire included general questions related to age, gender, practice setting, and years in practice as well as specific questions on the use of screening tests for ovarian cancer in the asymptomatic, average-risk population.After obtaining Institutional Review Board approval from the Medical Sciences Campus of the University of Puerto Rico, a self-administered anonymous questionnaire was mailed to all of the licensed obstetricians and gynecologists  were also included in the questionnaire: (1) whether the physician normally recommended routine screening for ovarian cancer and (2) three different variables about the modalities that physician most commonly used as a first test to screen for ovarian cancer: (a) CA-125, (b) transvaginal ultrasound, and (c) both. The ages of the patients when their physicians began and stopped screening them for ovarian cancer were collected as a continuous variable. The frequency of screening for ovarian cancer in asymptomatic, average-risk women was analyzed as a categorical variable. This variable was classified into the following 9 categories: yearly, every 2 years, every 3 years, every 1 to 2 years, every 2 to 3 years, every 3 to 5 years, at every visit, according to symptoms, and occasionally. The reasons provided in questionnaires by participants for not screening for ovarian cancer were categorized as (1) too expensive, (2) unproved effectiveness, or (3) other . Information regarding different sources of knowledge for current screening recommendations was also collected; those sources were (1) professional organization statements, (2) medical journals, (3) scientific meetings, and (4) other.The ages of the study participants (range: 31–85 years) were described as a continuous variable. Practice setting was defined as25, P75). Categorical data was summarized as frequency distributions. Comparisons of proportions and means between ovarian cancer screening practices (yes/no) groups were based on Fisher's exact/Pearson's chi-squared test and the t-test, respectively. For dependent variables not normally distributed, the Wilcoxon-Mann-Whitney test was used. Logistic regression modeling was used to determine the factors associated with ovarian cancer screening practices. For all tests, a P value of less than 0.05 was considered statistically significant. Statistical analysis was performed using STATA, v. 11.2.Normally distributed data was summarized as means with their respective standard deviations, and non-normally distributed data was presented as medians with their respective percentiles (PQuestionnaires were returned by 102 participants (25% response rate). n = 102). Most of the physicians reported professional organizations and medical journals as being their principal sources of knowledge for current screening recommendations  routinely screened their asymptomatic, average-risk patients for ovarian cancer despite their low risk for the disease and no genetic or family history . The disndations .P < 0.001). The mean number of years in practice was also significantly higher (P < 0.001) among physicians who routinely screen for ovarian cancer (27.9 ± 1.5 years) than it was among those who do not (19.9 ± 1.6 years) routinely screen for ovarian cancer. No significant differences (P > 0.05) in screening practices were seen in terms of the participating physicians' genders (P > 0.05) (data not shown).There was a statistically significant difference between the mean age of the physicians that routinely screen their patients for ovarian cancer and that of those that do not , after adjusting for gender (data not shown). Only years in practice were considered in the model, as this variable was strongly correlated to physician age. The remaining variables that were analyzed were not statistically significant (data not shown).To date, no screening test for ovarian cancer in asymptomatic, average-risk women has been recommended by any organization, including the ACOG and the USPSTF . This isTo our knowledge, this is the first study to describe the use of ovarian cancer screening tests in asymptomatic, average-risk women by obstetricians and gynecologists in PR and Latin America. Our findings indicate that the majority (53.9%) of obstetricians and gynecologists in PR who participated in this survey perform ovarian cancer screening on their patients. This is in spite of the absence of recommendations supporting this practice and, in fact, the numerous studies showing evidence against it, evidence that includes the current guidelines from the ACOG and the USPSTF , 11.The questionnaires used to gather the data included a section that allowed us to learn how obstetricians and gynecologists stay current on new guidelines and scientific developments. Based on the results, we have ascertained that respondents use resources such as professional organizations, medical journals, and scientific meetings to learn about current recommendations and do so more or less equally. A discrepancy is noted with the results presented above, as many of them affirmed that they recommended yearly screening for ovarian cancer using CA-125 and TVUS. This information is valuable in the implementation of more effective physician education programs at our community. It is well known that unnecessary procedures performed on patients may cause psychological harm, may affect health-related quality of life (HRQoL) and health insurance, could result in excessive personal costs, and could lead to more invasive procedures , 22.Various studies have been conducted to evaluate the impact that screening for diseases, without performing any interventions, has on patients. In addition, multiple studies –24 have This study had the following limitations: a low response rate (25%), which may alter the results (selection bias) and limit that of being generalized to the entire population of obstetricians and gynecologists in PR. Nonetheless, our response rate of 25% was expected and is comparable to other mailed surveys in the US , 27, whe


Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Since only limited data on the Chinese population, which is the largest in the world, is available, we conducted an epidemiological study on the prevalence and risk factors of AF in mainland China.This population-based study conducted by cluster sampling comprised 29079 participants forming 14 cohorts from 13 provinces across China, where the population was nearly 1 billion. Every participant underwent electrocardiogram and physical examinations and responded to the interviewer-led questionnaire(s). Univariate and multiple statistical analyses were conducted to explore the relationship between AF prevalence and risk factors.P = 0.013); several significant risk factors  were identified for AF in the general population. Stroke prevalence was much higher in AF patients than in non-AF people . AF was confirmed to be a significant independent risk factor for stroke prevalence in the studied population . We found that AF patients received poor treatment .The age-standardized prevalence of AF in China (≥30 y) was 0.65%, and it increased with age. Men showed a higher prevalence of AF than women (0.91%  vs. 0.65% [0.63%], This study conducted on a large sample size demonstrates that AF prevalence in mainland China is slightly lower than that in Western countries and similar to that in Asian areas, and confirms that AF is a serious public health problem in China. We identified several potential risk factors, but their associations with AF still need to be further studied. Several preliminary epidemiological studies based on US and European populations indicated that the prevalence of AF was on the increase with each passing decade.3-5Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance encountered in clinical practice. According to European and Northern American experiences, AF accounts for massive health care system expenses.3,6-8 The Framingham Heart Study reported that men showed a higher AF prevalence than women.5 Data from the same study cohort also revealed AF to be an independent risk factor for stroke.6 Several risk factors of AF have been identified by studies based on white cohorts.9 These factors include age, congestive heart failure, valvular heart disease, male sex, a history of myocardial infarction, hypertension, and diabetes.9Epidemiological studies in Western countries have shown that in older people, the prevalence of AF increases with age from less than 1% for persons younger than 60 y of age to approximately 10% for those who are 80 or above.10 Data from Asian countries like Japan,11,12 Singapore,13 and Korea14 also showed a lower prevalence of AF (0.7%-1.5%) compared to those from Western series. However, the prevalence of AF in China, which accounts for nearly one-fourth of the world population, has not been published in international journals. In order to clarify the prevalence of AF and explore its potential risk factors in China, we performed the first large-scale epidemiological study on AF in mainland China. This study provided data for analyzing the epidemiological characteristics of AF in the Chinese population, studying the association between stroke and AF, and comparing Chinese cohorts with other populations. The present study is an advanced version of the former preliminary study.15For other ethnical populations, the Epidemiology, Practice, Outcomes, and Costs of Heart Failure (EPOCH) study indicated that the African-American race was associated with a lower prevalence of AF.16 and the expected prevalence of AF (approximately 1%) was obtained from the preliminary data of the Western series.3,6-8A target sample size of approximately 30000 was calculated on the basis of the method introduced by Minassian DC,In the first stage, 14 centers based on 14 population-based cohorts from 13 provinces across China were established, such that they represented the average standards of living, education, and health care in mainland China. The cohorts were selected such that they represented the average characteristics of each province. There was no significant heterogeneity across these sites. The provinces studied included Guangdong, Hebei, Henan, Hubei, Hunan, Inner Mongolia, Shandong, Shanxi, Sichuan, Tianjin, Yunan, Zhejiang, and Jiangxi.Given below is a map of the location of the clusters.In the second stage, which was based on the data collected from the local household registration system in each chosen area, subjects were selected by cluster random sampling from each population established in the first stage. Each participating center was responsible for 2000-2500 subjects (born in or after 1972), and among the participants, a male to female ratio of 1:1 was required. The selected subjects were asked to come to the appointed center for examinations and interviews. This study was approved by the Health Ministry of the Peoples Republic of China and the local governments. A regular hospital or health agency in each area was appointed to provide the equipments and venues for this study. All the participants received a detailed introduction to this study by the local government and medical organizations. The participants’ informed consent was obtained by the local medical organizations. All the examinations were conducted free of charge, and no participant was compensated.17 The third part included a copy of an electrocardiogram (ECG) with a written interpretation. Patients with AF and suspected AF were required to provide information on the use of anticoagulants.We developed an interviewer-led questionnaire specifically for the survey. The first part of the questionnaire was recorded by the physicians, who conducted face-to-face interviews with the patients. The interviewers obtained information regarding the patients’ demographic characteristics and recorded the family medical history; they inquired about their smoking habits; drinking habits; and a medical history of other diseases, including diabetes, hypertension, dyslipidemia, rheumatic heart disease (RHD), coronary heart disease (CHD), hyperthyroidism, stroke, and AF. Besides, participants with self-reported RHD underwent further physical examinations and echocardiography if the diagnosis was unclear. We did not routinely perform blood tests for thyroid function, blood sugar, and blood lipid. Participants with a self-reported history of stroke were all required to provide their medical records from hospital visits and/or visits to primary care practitioners, which were carefully reviewed by qualified local neurologists. The second part of the questionnaire was recorded by 2 trained technicians who obtained the blood pressure, pulse rate, height, weight, waist, and hip measurements. After asking the patient to rest for at least 10 min in the sitting position, the blood pressure in the right arm was measured in the sitting position with the use of a standardized mercury column sphygmomanometer with a standardized protocol.Hypertension was defined by a systolic blood pressure of 140mmHg or higher, diastolic blood pressure of 90mmHg or higher, the use of antihypertensive agents, or a combination of these. Participants were considered to be smokers if they were smokers at the time of the investigation or if they had quit smoking less than 6 month earlier. They were considered non-drinkers if they did not consume alcohol regularly or had quit for not less than 6 months. Diagnoses of diabetes, hyperthyroidism, dyslipidemia, and CHD were classified by physicians (interviewers) as “yes” on the basis of positive self-reported histories of these diseases. Education attainment was classified as “yes” if a subject was a high school graduate or had higher education.Several steps were used to ensure standardization of the methods: (1) Physicians and technicians from each center received unified training prior to the screening process. (2) All participants were asked to respond to the interviewer-led questionnaire. (3) Blood pressure, pulse rate, height, weight, waist, and hip measurements were recorded by trained technicians. (4) All participants underwent an ECG examination, which was performed by trained technicians and trained physicians in each center. The physicians provided a primary written interpretation for each ECG, all of which were reviewed by an appointed senior cardiologist daily. (5) Monitors were sent to each center to supervise the standardized procedures. (6) Trained interviewers contacted those who did not come to the interview by telephone, and then conducted a family interview wherever possible to encourage response from the patient. The screening work for each center was performed within 3 months in 2003.18,19). AF determination based on the ECG was first conducted by a physician, who acted as the interviewer, and then verified by an appointed senior physician or cardiologist. ECGs and medical records obtained outside the study center were copied for further verification. The ECG criteria and classification for AF were in accordance with the ACC/AHA/ESC 2001 guidelines.19Subjects who were diagnosed with AF during the ECG examination in the screening process were defined as AF cases. Those who were not found to have AF according to the ECG test, but had previous medical records from visits to qualified affiliated hospital(s) of medical universities or any prior ECG record(s) for AF episode(s) were also defined as having AF , which might have been diagnosed by primary care practitioners or ECG technicians, received further reviews of their medical records within 1 y from hospital visits, visits to primary care practitioners, and other potential evidences. Their health records, if present, were also fully searched in the database of local medical organizations. Then, all these suspected AF cases were further investigated by senior cardiologists to confirm or disconfirm the diagnosis.2 test or Fisher’s exact test when appropriate. The exact confidence intervals (C.I.) of the prevalence were calculated by StatPages.net (http://statpages.org/confint.html) based on binomial distribution. We calculated the overall as well as age- and sex-stratified point prevalence of AF in the participants.20 The direct age standardization method20 was chosen to calculate the age-standardized prevalence and expected number of AF patients in the 13 studied provinces and in all of China, on the basis of the standard age distribution data from China’s fifth national population census in 2000.We used Borland Delphi 6.0 to build a database management system to handle the data obtained in this study. Data analysis was conducted with the SPSS statistical software, version 12.0.1. Differences between groups were tested with Pearson’s χP < 0.25 were chosen as independent variables to construct the model for multivariable analyses (backward stepwise logistic regression model). The other logistic model was used to explore the association between AF and the prevalence of stroke, where the dependent variable was stroke (yes/no) and the independent variables based on previous studies21 included age, diabetes, hypertension, dyslipidemia, smoking, and drinking. In the backward stepwise logistic regression model, the criterion for inclusion of the variables was P < 0.05, and that for exclusion was P > 0.10. The values for odds ratios (ORs) were linked to the prevalence of AF, i.e., values greater than 1 indicated an increased risk of high AF prevalence and values less than 1 indicated a reduced risk of high AF prevalence.Two main multiple logistic regression models were constructed. In one model, the dependent variable was AF (yes/no), and the backward stepwise method was used to investigate the associations between the potential risk factors and AF prevalence. For potential independents, we defined age and waist-hip ratio (WHR) as continuous variables and the following as binomial categorical independent variables: sex , diabetes (yes/no), hyperthyroidism (yes/ no), hypertension (yes/no), RHD (yes/no), CHD (yes/no), smoking (yes/no), drinking (yes/no), dyslipidemia (yes/no), and education attainments (high school graduate or not). Univariate analyses were first conducted to test the correlation between AF prevalence and each potential independent variable. In the univariate analysis, variables with The study included 29079 subjects  from 14 different Chinese cohorts , among which 224 participants were identified as having AF. The overall response rate was approximately 96%. The most common reason for nonparticipation (4%) was refusal to undergo examination. Among the 224 AF patients, 204 (91.1%) were identified on the basis of the ECGs during the screening process, and the rest  were identified via previous medical records and ECGs. Prior to data analysis, we ensured that all participants were examined for AF or suspected AF. Our results showed that the crude prevalence of AF in the studied Chinese population (≥30 y) was 0.77% . On the basis of the age composition data in the 13 studied provinces and all of China , the age-standardized prevalence of AF in both genders in the Chinese (≥30 y) was 0.65% ; the estimated number of AF patients (≥30 y) was calculated to be 2456573 in all the provinces studied and 4193857 in all of China.P = 0.013). In each age group, the prevalence of AF in men was higher than that in women, except for the 50-59 age group  , but they were statistically insignificant after adjustment. As another anthropometric index, body mass index (BMI) was not significantly associated with AF prevalence even when it was not adjusted with the other variables (P = 0.552). WHR (per 0.1) became a significant risk factor for AF  when only the male population was considered. Collinearity diagnosis was routinely performed, and no independent variable was found to have a tolerance of <0.1. Analysis of variance inflation factor (VIF), Eigenvalue, and the condition index did not show significant multicollinearity.Four significant risk factors, including age, hyperthyroidism, RHD, and CHD, were located via the backward stepwise logistic regression model see . Among t.05) see . WHR  removed from steps 2, 3, 4, and 5 were hypertension, diabetes, education attainment, and WHR respectively.P < 0.001) (See P < 0.001)  See . Moreove001) See .This study demonstrates that the age-standardized prevalence of AF in the general Chinese population was 6.5 per 1000 people, and that it increased with age. Given China’s 6.4 billion population (≥30 y), it has been estimated that at least 4 million adults suffer from AF in mainland China today, which can be a substantial burden on public health. Here, we confirm that AF is a disease that is largely prevalent in the elderly in the general Chinese population, with the great majority of cases present among people aged 60 y and above.3,5-8,22-24 Firstly, it should be brought to notice that ascertaining the diagnosis of AF and the characteristics of the population studied would significantly affect the final result of a study. Wolf et al.5 included the AF cases diagnosed from ECGs that were obtained from the subjects’ private physicians and during interim hospitalizations. Inclusion of such AF cases could prevent the loss of cases with acute paroxysmal AF, which may have occurred25 in the present or Friberg’s study.22 Majeed et al.3 used a large and well-validated general practice-derived database to diagnose AF, which is more sensitive than the single ECG used in the present study; moreover, they gained baseline data from clinical practices when there was a lack of completely healthy subjects, and therefore, they tended to obtain a higher prevalence of AF. AF prevalence according to a community study on middle-aged to elderly Japanese people was only 1.3%,12 whereas that in ill, hospitalized, elderly people could reach as high as 22%.26 As such, the lower prevalence of related diseases, such as coronary artery disease, diabetes, and dyslipidemia, in the population studied contributed to a lower AF prevalence. Secondly, the use of different data sets is also an important reason for the difference. It has recently been indicated that AF prevalence varies according to race,27 which may partly explain why AF prevalence found in this study is much closer to the results from Asian cohorts10-14 outside China than to those from the Western series. Moreover, another essential reason is the different age strata among the studies, because AF increases with age. Studies based on younger populations often indicated a lower prevalence of AF,1,12,28,29 and those based on older participants showed a higher prevalence.6,23,24,30,31 In conclusion, it can be said that AF is a disease that is increasing in prevalence;5 therefore, it should be noted that the prevalence of AF obtained in this study may actually be lower than that reported in previous studies.The age-specific prevalence of AF in China rose dramatically from 0% in the 30-39 age group to 7.5% in the 80-89 age group. Similar trends were found in nearly all the previous studies on AF prevalence. The present study showed a lower prevalence rate of AF in Chinese people, especially in the middle-aged cohort, than in Western cohorts.32 Luc Djousse et al. concluded that long-term alcohol consumption was a strong predictor of the incidence of AF adjusted for other risk factors.7 The reason as to why no significant association was found between AF prevalence and these lifestyle-related factors was probably due to the cross-sectional design of the present study.We found no significant association between smoking or drinking and the prevalence of AF. Kannel WB et al. reported that smoking was a significant risk factor in women when adjusted only for age.7,29,30 Hypertension is a major contributing factor to the development of AF in longitudinal studies, but it is not always a risk factor for AF in cross-sectional analyses. Patients who have developed AF usually tend to show a lowering of systolic blood pressure (“decapitated” hypertension) compared to the blood pressure levels prior to the onset of AF. Second, some drugs used for the treatment of hypertension also suppress AF, such as beta-blocker and certain calcium channel blockers. These factors may attenuate the relationship between elevated blood pressure and the prevalence of AF in a cross-sectional analysis.In this study, hypertension was not significantly associated with the prevalence of AF, whether it was adjusted only for age or for all risk factors, although it was by far a powerful predisposing factor for AF incidence.33 Considering that the proportion of menopause almost reaches 100% among women aged 60 y or above and increases with age among women aged 30-59 y (see P = 0.59). Educational attainment was not significantly associated with AF prevalence in this study. The older Chinese people are, the lower their average level of educational attainment; this may affect the result.Bailey et al. indicated that estrogen plays a role in the occurrence of AF.59 y see , we analOn the basis of the present study, we found a significantly higher prevalence of stroke in subjects with AF than in non-AF subjects. In the multiple logistic regression model, AF was also confirmed to be one of the leading contributors to the prevalence of stroke after adjustment for age and several other known risk factors. Therefore, the strong link between AF and stroke was confirmed in the Chinese population studied. Due to the much higher prevalence of stroke in AF cases, anticoagulation therapy is highly recommended in China for stroke prevention in patients with AF. Unfortunately, the number of AF patients who took anticoagulants regularly  was rather small. Health education and public policies are urgently required for Chinese AF patients.34 and community-dwelling populations,13 respectively, no data on the general population has demonstrated the incidence of AF and the correlation between it and the risk factors; this area requires to be explored by a carefully designed follow-up study.The present study had some limitations. Firstly, we did not find a significant association between AF and several predisposing factors. The reasons may be due to both the cross-sectional study and the relatively low number of diagnosed AF participants. Secondly, the prevalence of diabetes was very low  compared with that of hypertension , which may reflect the lack of biochemical examinations. Only 91 (0.3%) of 29079 participants were found to have RHD, which may explain the wide confidence intervals for RHD. Moreover, although we obtained a single ECG recording for each participant and tried to obtain complete information from those diagnosed with AF, it was still hard to discover paroxysmal AF in some cases; this limitation is also true for other studies. Therefore, the prevalence of AF revealed in this study may represent the lower boundary of the true prevalence. With regard to the Chinese, though Dr. Qi et al. and Dr. Yap et al. reported some results based on hospitalized patients


Objectives. Evaluation of chondroitin sulfate (CS), as an early marker of aggrecan degradation, and chondroitin sulfate 846 epitope (CS846), as a biomarker of CS synthesis, is an attempt at answering the question whether the therapy used in juvenile idiopathic arthritis (JIA) patients contributes to the normalization of biochemical changes in aggrecan. Methods and Results. Serum levels of CS and CS846 as well as catalase (CT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in erythrocyte were assessed in patients before and after treatment. In the course of JIA, aggrecan metabolism is disturbed, which is reflected by a decrease (p < 0.001) in CS serum level and an increase (p < 0.05) in CS846 concentration. Furthermore, increased (p < 0.001) activities of CT, SOD, and GPx in untreated JIA patients were recorded. The anti-inflammatory treatment resulted in the normalization of CS846 level and SOD and GPx activities. In untreated patients, we have revealed a significant correlation between serum CS and CS846, CT, CRP, ESR, MMP-3, and ADAMTS-4, respectively, as well as between CS846 and CT, GPx, CRP, ESR, and TGF-β1, respectively. Conclusion. The observed changes of CS and CS846 in JIA patients indicate a further need of the therapy continuation aimed at protecting a patient from a possible disability. Articular cartilage is an avascular hypocellular hyaline connective tissue that has a limited capacity for self-repair. Once damaged by mechanical trauma or pathology, it is highly susceptible to structural degradation, making it particularly difficult to restore –4. This Aggrecan is a multimodular molecule expressed by chondrocytes. Its core protein is composed of three globular domains and a large extended region, for glycosaminoglycan (GAG) chains attachment, that is, chondroitin sulfates  and keratan sulfates , 6, 8. Dβ1) or platelet-derived growth factor-BB (PDGF-BB), which were assayed in the blood of JIA patients [Catabolic processes of ECM components, which take place in the cartilage, are probably not balanced by the biosynthesis of these compounds. This assumption seems to be confirmed by elevated concentrations of factors which stimulate ECM biosynthesis, that is, a transforming growth factor-beta , as a biomarker of aggrecan synthesis, is an attempt at answering the question whether the therapy used in JIA patients, whose purpose is to reduce the inflammatory and immunological parameters of the disease activity, simultaneously contributes to the normalization of biochemical changes in aggrecan and thus inhibits the dysfunction of articular cartilage. Moreover, considering antioxidative CS effects and the presence of oxidative stress in JIA patients, the aim of the study was to determine the relation of CS and CS-846 with levels of the most important enzymes for detoxification of peroxides in living cells, that is, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) determined in the blood of patients with newly diagnosed JIA and in the same patients after therapy modifying inflammation.The clinical study was carried out on the blood obtained from 30 children , aged from 2 to 15 years (mean 7.27  ±  4.49), with newly diagnosed JIA, and 30 individuals with the same age. The patients were diagnosed and classified according to the International League of Associations for Rheumatology (ILAR) criteria as oligoarthritis or polyarthritis. Moderate disease activity was assessed in all patients, using Juvenile Arthritis Disease Activity Score. The exclusion criteria constituted other forms of JIA according to the ILAR criteria, as well as any other chronic and autoimmune diseases. Moreover, the accuracy of diagnosis was confirmed by laboratory tests, namely, by determining indicators of inflammatory responses, that is, C-reactive protein  and erythrocyte sedimentation rate , measuring rheumatoid factor , and determining the titre of antinuclear antibodies  .β1, and PDGF-BB were obtained in our earlier investigations [Presented in igations , 9 usingThe tests were repeated on the same patients after therapy, when the clinical outcome improved (11.60 ± 0.21 months after the beginning of the therapy). The clinical improvement was determined by 30 ACR Pediatric criteria. The applied treatment was based on stable doses of nonsteroidal anti-inflammatory drugs, oral glucocorticoids , and methotrexate (≤15 mg per square meter of body-surface-area once a week).Informed consent was obtained from teenage participants under the age of 16 according to the ethical guidelines of the Helsinki Declaration. For all underage patients, parents or legal guardians signed the informed consent. The Local Ethics Committee of the Medical University of Silesia approved the research protocol used in this study. No conflicts of interest have occurred during implementation and completion of the study.Venous blood samples were collected after overnight fasting and placed into tubes without anticoagulant and heparin-treated tubes. In the first case, serum was obtained after centrifugation and used for assessment of the CS and CS846 levels whereas, after centrifugation, plasma was removed from samples collected in heparin-treated tubes but remaining erythrocytes were washed three times with 0.9% NaCl and lysed in 1 : 1 (v/v) of double-deionised water. Erythrocyte lysates were used for determination of catalase, superoxide dismutase, and glutathione peroxidase activity as well as hemoglobin concentrations. Serum samples and erythrocyte lysates were stored at −80°C until needed for biochemical analyses.The determination of one parameter was completed within one day; consequently the interassay variation was insignificant.3COOK was added to the precipitate. The obtained GAG solution was treated with 3 volumes of ethanol. GAGs were allowed to precipitate for 12 h at 4°C. Following centrifugation, precipitate was dissolved in H2O and GAGs were isolated by precipitation after the addition of cetylpyridinium chloride (CPC). After incubation and centrifugation, GAGs precipitated by CPC were finally washed with C2H5OH containing NaCl and centrifuged once more. The supernatants were discarded and a final precipitate (isolated and cleared serum GAGs) was stored at −80°C until the use for a biochemical analysis. The total amount of GAGs, including CS, was determined by the hexuronic acid assay according to the Blumenkrantz and Asboe-Hansen [Blood glycosaminoglycans are comprised of GAGs chains of native proteoglycans and GAGs derived from the degradation of both blood and tissue PGs. CS represents the major GAGs in circulation, and their isolation from serum was conducted with the use of methods developed by Volpi et al.  and Olcze-Hansen  method, Hexuronic acids concentration, as a measure of CS concentration, was determined both prior to and after the use of agents specifically degrading glycans other than CS. CS concentration was determined as the difference of obtained values. Flavobacterium heparinum); then, the mixture of heparinase I and heparinase III (both from Flavobacterium heparinum) was added to a reaction medium in order to remove heparin sulfate/heparin. Digestion was carried out according to the manufacturer's instructions. All enzymes were obtained from Sigma Aldrich (USA).Thus, dermatan sulfate was removed from isolated GAGs samples using depolymerisation with chondroitinase B , according to the manufacturer's instructions. The minimal detectable concentration of this compound was 20.00 ng/mL. The intra-assay variation of the CS846 levels was less than 6%.CS846 level was measured using blindly tested coded serum samples, in duplicate. The tested compound was quantitatively measured using anTo assess antioxidant defense system activity, the samples were assayed for catalase, superoxide dismutase, and glutathione peroxidase activities.Catalase activity was determined by measuring the decomposition of hydrogen peroxide at 240 nm, according to the method of Aebi , and expSuperoxide dismutase activity was measured using the kit of Randox Superoxide Dismutase (Ransod), supplied by Randox Laboratories (United Kingdom), according to the manufacturer's protocol. The appropriate Test Ransod Control was used as a quality control test. The coefficient of intra-assay variation was less than 6.2%.Glutathione peroxidase activity was measured using the kit of Randox Glutathione Peroxidase (Ransel), supplied by Randox Laboratories (United Kingdom), according to the manufacturer's protocol. For the control of precision, Test Ransel Control was used. The coefficient of intra-assay variation was less than 4.2%.Hemoglobin was measured using a commercially available kit. t-test was used to evaluate the differences between untied variables. To compare the same parameters in each patient, before the treatment and after the restoration of clinical improvement, the paired Student's t-test was used. Pearson's correlation coefficient was employed for the statistical analysis of correlations between two variables. p values of less than 0.05 were considered significant.A statistical analysis was carried out using Statistica 10.0 package . The normality of distribution was verified with the Shapiro-Wilk test. The data obtained were expressed as mean values and standard deviation. Since the variables were normally distributed, the parametric Student'sp < 0.001) level of these GAGs, compared to the controls. It was observed that the therapy modifying the course of inflammation, which was employed in JIA patients, resulted in a significant increase (p < 0.001) in serum levels of CS in these patients. However, treated JIA patients still had a markedly lower (p = 0.04) serum level of the CS than the control subjects. When compared to the control values, the mean decrease in CS level was by 15%.The results are presented in r = −0.59, p = 0.014) and CS and ESR , respectively. We recorded insignificant relationships between CS and CRP  as well as CS and ESR  in patients with JIA whose clinical condition had stabilized.Low concentration of CS, recorded in serum of JIA patients with untreated arthroplasty, was negatively statistically significantly correlated with the concentrations of laboratory inflammatory markers, that is, CRP and ESR. The obtained values were as follows: CS and CRP  and ADAMTS-4  levels, respectively. Corresponding correlations were not found in treated JIA patients ; CS and ADAMTS-4 ).Since the metabolism of cartilage CS is associated with the activity of proteolytic enzymes, we decided to assess the relationship between serum CS level and MMP-3 and ADAMTS-4. A correlation analysis revealed that in the untreated JIA patients there was a significant negative correlation between CS level and MMP-3 (p = 0.013) levels of this parameter in the serum of untreated JIA patients than in the control group. Compared to the control values, the mean increase in serum CS846 was by 52%. Anti-inflammatory treatment led to a significant decrease (p = 0.006) in this marker concentration versus pretreatment situation. The blood concentration of CS846 in treated children with JIA corresponded to its concentration in the control group.A quantitative assessment of CS846 revealed significantly higher  and ESR , respectively, whereas in treated patients the following correlations were recorded: CS846 and CRP  as well as CS846 and ESR , respectively.Correspondingly to the above-described relations between CS and inflammatory markers, there was a negative correlation between CS846 and these markers only in the group of children with untreated JIA. In untreated patients, the correlations were as follows, CS846 and CRP , but insignificant relationship between CS846 and PDGF-BB  in untreated patients with JIA. Furthermore, no correlation was recorded between CS846 and TGF-β1  as well as PDGF-BB , respectively, in treated JIA patients.Due to the fact that CS846 blood concentration reflects the size of aggrecan synthesis, we decided to evaluate the relation between CS846 and TGF-p < 0.001), 38% (p < 0.001), and 41% (p < 0.001), respectively, versus the control values.To assess antioxidant defense system activity, the samples (red blood cells) obtained from the control and JIA patients were assayed for catalase (CT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. The analysis of the enzyme activity showed that in the course of untreated JIA, significantly increased catalase, superoxide dismutase, and glutathione peroxidase activities were observed. The mean increase in CT, SOD, and GPx activities was by 62% (p < 0.001) in all antioxidant enzyme activities in red blood cells versus pretreatment situation. While the activity of SOD and GPx was the same as the enzyme activity in the controls, the activity of CT was still significantly higher (p = 0.006) than in healthy children, contributing 121% of this value.It was also found that the employed therapy, which resulted in suppressing inflammation, simultaneously contributed to a significant decrease  as well as significant positive correlation between serum CS level and CT activity . No correlation was recorded between this GAG's serum level and SOD  and GPx  activities, respectively. Corresponding correlations were found in the same patients after symptoms improvement due to an anti-inflammatory therapy. Thus, in treated JIA patients serum CS level correlated significantly with CS846 , CT , and GPx , but not with SOD , respectively. As shown in r = 0.43, p = 0.011) as well as GPx  but not with SOD , respectively. Corresponding correlations were not found in treated JIA patients or in controls (A correlation analysis, whose results are presented in controls .κB activation with a consequent reduction in cartilage damage [κB, a transcription factor that plays a central role in the transformation of cytokines, chemokines, or ROS, involved in the immune response [At present, no single biomarker has been validated as an indicator of joint damage in the course of JIA. Despite the fact that chondroitin sulfates, as the main components of aggrecan, could function as markers of cartilage damage in patients with JIA, it cannot be considered as a specific indicator of cartilage turnover due to its presence in other tissues. Our studies showed that CS serum levels in children with newly diagnosed arthropathy were significantly lower than the concentration of these GAGs both in the same children when clinical improvement was observed and in healthy controls. Although early steps of cartilage ECM degradation process should be reflected by the increase in blood GAG levels, it seems that degradation taking place over a prolonged time may result in gradual decrease in serum GAGs pool. We have concluded that the concentration of CS in blood of children with the arthropathy is directly related to the activity of both inflammatory processes and proteolytic degradation of ECM components. Recorded low concentrations of CS in untreated patients with JIA were significantly negatively correlated with inflammatory markers and with high plasma levels of MMP-3 and ADMTS-4 in these patients. It should be also mentioned that catabolism of ECM components is related to oxidation caused by ROS , 18. In e damage , 20. Theresponse –21.When trying to explain aggrecan changes in children with JIA, we also demonstrated a significant increase in the serum level of CS846 –24. The β1 and PDGF-BB [β1 is statistically correlated with the CS846 level. This compound confirms the dependence between signaling paths related to TGF-β and cartilage elasticity, which is conditioned by aggrecan structure [β produced by cultured myofibroblasts. Moreover, the rigidity of the ECM also alters the response of cells to TGF-β stimulation via the phosphatidylinositol 3-phosphate/Akt signaling pathway [The factors which participate in modeling of ECM component synthesis are, among others, TGF- PDGF-BB , 9. The tructure . It is b pathway , 27.The evaluation of the relations between CS846 and antioxidative enzymes, which was carried out in this study, allowed us to find the relationship of the evaluated biomarker with the CT activity and its weaker relationship with GPx. Thus, we can conclude that an increase in the synthesis of CS is bigger in persons with higher antioxidative protection. This reconstruction is also greater in young patients with less intense inflammation, which is confirmed by the observed negative correlations between CS-846 and CRP and ESR. To answer the question of the influence of inflammation modifying treatment on cartilaginous aggrecan alterations were the aim of the study; however it is difficult to offer an unequivocal opinion. The employed therapy, which contributed to clinical improvement in patients, simultaneously did not result in complete normalization of changes in articular cartilage. This is our conclusion since we observed a lack of normalization of CS serum level in treated patients. A probable mechanism of such a state is related to autoimmune background of JIA. It is suggested that the core protein of aggrecan may be the first original target of autoreactivity . MoreoveIn the course of JIA, the structure of cartilaginous aggrecan is disrupted, which is reflected by increase in CS846 and indirectly by a decrease in CS blood serum levels in patients. The anti-inflammatory therapy relieves the symptoms of JIA by decreasing both the pain and the intensification of inflammatory processes, although it does not lead to total regeneration of ECM elements, which are damaged by proteolytic-oxidative factors. The observed quantitative changes of CS in JIA patients indicate a further need of the therapy continuation aimed at protecting a patient from a possible disability.