Association between homocysteine and coronary artery disease-trend over time and across the regions: a systematic review and meta-analysis.

BACKGROUND: The association of homocysteine with coronary artery disease (CAD) has been explored previously with mixed findings. The present Systematic Review and Meta-Analysis (SRMA) has assessed the pooled estimate of association between homocysteine (Hcy) and CAD, and its variation over the period and geography. METHODS: Systematic literature search was done in PubMed, Scopus and Cochrane to identify the observational studies that have reported mean Hcy among cases (CAD) and control. The SRMA was registered in PROSPERO (ID-CRD42023387675). RESULTS: Pooled standardized mean difference (SMD) of Hcy levels between the cases and controls was 0.73 (95% CI 0.55-0.91) from 59 studies. Heterogeneity was high (I2 94%). The highest SMD was found among the Asian studies (0.85 [95% CI 0.60-1.10]), while the European studies reported the lowest SMD between the cases and controls (0.32 [95% CI 0.18-0.46]). Meta-regression revealed that the strength of association was increasing over the years (Beta = 0.0227, p = 0.048). CONCLUSIONS: Higher homocysteine levels might have a significant association with coronary artery diseases, but the certainty of evidence was rated low, owing to the observational nature of the studies, high heterogeneity, and publication bias. Within the population groups, Asian and African populations showed a greater strength of association than their European and American counterparts, and it also increased over the years.

Association of serum cathelicidin and Vitamin D levels with infectiousness in patients with pulmonary tuberculosis: A prospective cohort study.

Background: The immunomodulatory effects of Vitamin D expand to induce the synthesis of an antimicrobial peptide, cathelicidin. There is evidence showing altered levels of cathelicidin in tuberculosis (TB). It has been suggested that Vitamin D-mediated antimicrobial activity depends on its ability to induce cathelicidin. The present study was designed to assess the alterations in serum anti-microbial peptide cathelicidin and 25-hydroxy Vitamin D levels in patients with newly diagnosed pulmonary TB at different treatment times and to study the association between serum Vitamin D levels and cathelicidin. Methods: Serum 25-hydroxyvitamin D and cathelicidin levels were estimated in 147 patients with newly diagnosed pulmonary TB at different times: at the start of anti-tubercular treatment, end of the intensive phase of treatment, and at the end of treatment. Results: There was a statistically significant difference between the levels of serum 25-hydroxyvitamin D and serum cathelicidin at different treatment periods. However, no significant correlation was found between serum Vitamin D and cathelicidin levels or between serum Vitamin D and cathelicidin levels with infectiousness in patients with pulmonary TB. Conclusion: Serum Vitamin D levels and serum cathelicidin levels were significantly reduced at diagnosis, and there was an incremental increase following treatment. However, there was no correlation between the levels of serum cathelicidin and serum Vitamin D or with the infectiousness of the illness.

Sequential Application and Post-Test Probability for Screening of Bladder Cancer Using Urinary Proteomic Biomarkers: A Review based Probabilistic Analysis.

BACKGROUND: Bladder cancer is one of the most common cancers in the world, with men being affected more than women. Diagnosis by cystoscopy, cytology and biopsy is invasive. Urine cytology, a non-invasive modality is not sensitive. This study is undertaken to evaluate whether non- invasive urinary proteomic profiling is more sensitive, specific for bladder cancer. OBJECTIVE: To evaluate the sensitivity and specificity of various urinary proteomic biomarkers as a screening tool for bladder cancer. METHODS: PubMed database was searched from 4th December 2011 to 30th November 2021 using Mesh terms and n = 10,364 articles were found. PRISMA guidelines were followed and Review articles, animal studies, Urinary tract infections, non-bladder cancer and other irrelevant articles were excluded. All studies who have reported mean/median (SD/IQR), sensitivity, specificity, cut off values (ROC analysis) were included (n=5). Post-test probability of various biomarkers was calculated using sequential approach. Pooled analysis was depicted using Forest plot. RESULTS: Analysis of diagnostic studies of bladder cancer showed the post-test probability of CYFRA21-1 was 36.6%. Using sequential approach, the panel of biomarkers CYFRA 21-1, CA-9, APE-1, COL13A1 has post-test probability of 95.10% to diagnose bladder cancer. Analysis of two observational studies with APOE (n= 447) showed non-significant increase of APO-E levels in bladder cancer cases (WMD: 66.41with 95% CI 52.70-185.51; p=0.27, I2 92.4%). CONCLUSION: In patients presenting with hematuria, a panel of CYFRA 21-1, CA-9, APE-1, COL13A1 markers can be considered for screening of bladder cancer.

Decreased circulatory levels of Vitamin D in Vitiligo: a meta-analysis

Abstract Background: The serum Vitamin D status in patients with vitiligo is ambiguous when compared to controls. A systematic review and updated meta-analysis were conducted to evaluate the association between Vitamin D and vitiligo. Methods: Relevant studies were identified by searching PubMed and other databases. The random effects model was used to obtain standardized mean differences and pooled correlation coefficients. Meta-regression and sub-group analyses were conducted to explore heterogeneity. The presence of publication bias and the study robustness were tested using funnel plot and sensitivity analyses, respectively. Results: This meta-analysis finally included 31 studies. Compared with controls, vitiligo patients showed significantly decreased serum Vitamin D levels (standardized mean difference = −1.03; p < 0.0001). The sub-group analysis showed that vitiligo patients with indoor/urban work had a significantly lower Vitamin D level when compared to their outdoor/rural counterparts (standardized mean differences = −0.45; p = 0.03). The sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. Study limitations: Varied sample sizes and heterogeneous study populations from different countries are the limitations of this study. However, the between-study heterogeneity has been addressed by the random-effects model with meta-regression and sensitivity analyses. Conclusions: This meta-analysis showed significantly decreased Vitamin D level in vitiligo, and its association with indoor/outdoor type of work of vitiligo patients. This study highlights the need to assess Vitamin D status for improving its level in vitiligo.

Decreased circulatory levels of Vitamin D in Vitiligo (ViViD Study): a meta-analysis

Abstract Background: The serum Vitamin D status in patients with vitiligo is ambiguous when compared to controls. A systematic review and updated meta-analysis were conducted to evaluate the association between Vitamin D and vitiligo. Methods: Relevant studies were identified by searching PubMed and other databases. The random effects model was used to obtain standardized mean differences and pooled correlation coefficients. Meta-regression and sub-group analyses were conducted to explore heterogeneity. The presence of publication bias and the study robustness were tested using funnel plot and sensitivity analyses, respectively. Results: This meta-analysis finally included 31 studies. Compared with controls, vitiligo patients showed significantly decreased serum Vitamin D levels (standardized mean difference = −1.03; p < 0.0001). The sub-group analysis showed that vitiligo patients with indoor/urban work had a significantly lower Vitamin D level when compared to their outdoor/rural counterparts (standardized mean differences = −0.45; p = 0.03). The sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. Study limitations: Varied sample sizes and heterogeneous study populations from different countries are the limitations of this study. However, the between-study heterogeneity has been addressed by the random-effects model with meta-regression and sensitivity analyses. Conclusions: This meta-analysis showed significantly decreased Vitamin D level in vitiligo, and its association with indoor/outdoor type of work of vitiligo patients. This study highlights the need to assess Vitamin D status for improving its level in vitiligo.

Decreased circulatory levels of Vitamin D in Vitiligo: a meta-analysis.

BACKGROUND: The serum Vitamin D status in patients with vitiligo is ambiguous when compared to controls. A systematic review and updated meta-analysis were conducted to evaluate the association between Vitamin D and vitiligo. METHODS: Relevant studies were identified by searching PubMed and other databases. The random effects model was used to obtain standardized mean differences and pooled correlation coefficients. Meta-regression and sub-group analyses were conducted to explore heterogeneity. The presence of publication bias and the study robustness were tested using funnel plot and sensitivity analyses, respectively. RESULTS: This meta-analysis finally included 31 studies. Compared with controls, vitiligo patients showed significantly decreased serum Vitamin D levels (standardized mean difference = -1.03; p < 0.0001). The sub-group analysis showed that vitiligo patients with indoor/urban work had a significantly lower Vitamin D level when compared to their outdoor/rural counterparts (standardized mean differences = -0.45; p = 0.03). The sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. STUDY LIMITATIONS: Varied sample sizes and heterogeneous study populations from different countries are the limitations of this study. However, the between-study heterogeneity has been addressed by the random-effects model with meta-regression and sensitivity analyses. CONCLUSIONS: This meta-analysis showed significantly decreased Vitamin D level in vitiligo, and its association with indoor/outdoor type of work of vitiligo patients. This study highlights the need to assess Vitamin D status for improving its level in vitiligo.

Higher skin autofluorescence detection using AGE-Reader™ technology as a measure of increased tissue accumulation of advanced glycation end products in dialysis patients with diabetes: a meta-analysis.

This meta-analysis was conducted to compare skin autofluorescence (SAF) levels as a measure of advanced glycation end products (AGEs) accumulation between diabetic and non-diabetic dialysis patients. Relevant studies were identified primarily by searching PubMed/MEDLINE and other online databases and manual searching of cross-references. Random-effects model was used to obtain standardized mean differences (SMD) as a summary statistic. Heterogeneity was tested with meta-regression and sub-group analyses. Publication bias and robustness of this meta-analysis were tested using funnel plot and sensitivity analyses. A total of 11 reports comparing SAF between diabetic and non-diabetic dialysis patients were finally included in this meta-analysis. Dialysis patients with diabetes showed significantly higher circulatory SAF levels than their non-diabetic counterparts (SMD = 0.39; P < 0.0001). The difference was more evident in hemodialysis modality (SMD = 0.40; P < 0.0001). A one-study leave-out sensitivity analysis validated the robustness of this meta-analysis. The presence of diabetes in dialysis patients is associated with increased AGEs accumulation reflected through SAF measurements using a novel and non-invasive AGE-Reader™ technology. Our findings are in support of considering anti-AGE therapeutic strategies in addition to standard glycemic management in dialysis patients with diabetes.

Association of Vitamin D and Parathyroid Hormone Levels in Overweight and Obese Adolescents.

Vitamin D deficiency in known to be high in obese and overweight adolescents. Few studies in other countries have shown lower parathyroid hormone (PTH) levels in obese adolescents despite high vitamin D deficiency. The aim of the study is to assess vitamin D and PTH levels and their relationship in overweight and obese adolescents in Telangana. This cross-sectional study was carried out in 108 overweight and obese boys and girls aged 12-18 years. A pretested Questionnaire was administered to collect information on demographics, sun exposure, medical and nutritional history. Anthropometry and blood sample was collected for estimating 25 hydroxy vitamin D, and PTH. Body mass index Z scores (WHO growth standards) were used for assessing overweight and obesity in adolescents. 54.6% of the subjects were boys. Mean (SD) levels of vitamin D and PTH were 18.25 (9.26) ng/mL and 45.39 (28.23) ng/L respectively. The prevalence of vitamin D deficiency and insufficiency in the current study was 54.6% and 25.9% respectively. However, PTH levels were high only in 24.2% of subjects (> 65 ng/L). There was an inverse but non-significant correlation between vitamin D and PTH. The association was same after adjusting for age, gender and weight. Our study highlights the high prevalence of vitamin D deficiency among overweight and obese adolescents in Telangana. Despite high vitamin D deficiency, very few had high PTH levels and the vitamin D-PTH axis may be altered in overweight and obese adolescents.

Maternal serum ischemia modified albumin as a marker for hypertensive disorders of pregnancy: a pilot study.

BACKGROUND: Hypoxia driven oxidative stress of the placenta contributes to the pathogenesis of preeclampsia. Serum Ischemia Modified Albumin (IMA) has recently emerged as an oxidative stress marker, used in diagnosis of cardiac ischemia. Aim: To determine the efficiency of serum IMA in differentiating hypertensive disorders of pregnancy (pregnancy induced hypertension, preeclampsia) from normal pregnancy. METHODS: It was a case control study. Pregnant women ≥32 weeks of gestation. Study population were included 3 groups, 19 Normotensive Pregnant (NP) women as controls, 18 pregnant women with Pregnancy Induced Hypertension (PIH) and 19 with preeclampsia (PE). Serum IMA was estimated by Enzyme Linked Immune Sorbent Assay (ELISA). Results were analyzed by student 't'test. Critical values for serum IMA were obtained by Receiver Operation Characteristics (ROC) curves. RESULTS: Serum IMA levels were significantly elevated in PE (56.84 ± 21.57 ng/ml) when compared with PIH (36.24 ± 14.51 ng/ml) and NP (35.47 ± 11.58 ng/ml) (P value <0.001). With a cutoff of 38.33 ng/ml, sensitivity and specificity for preeclampsia was 88.9% and 73.7% respectively. CONCLUSIONS: Our study demonstrated that serum IMA, an oxidative stress marker is elevated in PE & PIH. Hence serum IMA can undergo further evaluation as a marker of PE.

Relationship of serum uric acid, serum creatinine and serum cystatin C with maternal and fetal outcomes in rural Indian pregnant women.

BACKGROUND: Hypertensive disorders are the most common in pregnancy. Several studies showed a positive correlation between elevated maternal serum uric acid (UA), serum creatinine and adverse maternal and fetal outcomes, but only a few studies are available on serum cystatin C and maternal and fetal outcomes. The present study was undertaken to study the association of serum UA, creatinine and cystatin C with maternal and fetal outcomes. METHODS: Out of 116 pregnant women 69 women had no hypertension and 47 had hypertension with or without proteinuria. Serum UA, creatinine and cystatin C was measured by modified Uricase method, modified kinetic Jaffe's reaction and particle-enhanced immunonephelometric assay respectively. Multivariate logistic regression was performed to determine the independent effects of serum UA, creatinine and cystatin C on maternal and fetal outcomes using stata 13.1. RESULTS: The adjusted odds ratio (OR) was 3.73 (95% CI: 1.18-11.75; P=0.024) for UA; 15.79 (95% CI: 3.04-81.94; P=0.001) for creatinine and 2.03 (95% CI: 0.70-5.87; P=0.192) for cystatin C in hypertensive disorders of pregnancy. All the three renal parameters were not significantly associated with birth weight, gestational age of delivery and mode of delivery after adjusting for the confounding factors. CONCLUSIONS: Serum creatinine and uric acid are independent risk factors for hypertensive disorders of pregnancy. High serum uric acid is associated with low birth weight and delivery by caesarian section whereas high serum creatinine with preterm delivery only before adjustment for confounding factors and not after adjustment. Serum cystatin C was not significantly associated with the maternal and fetal outcomes.

Comparative Analysis of Urinary Total Proteins by Bicinchoninic Acid and Pyrogallol Red Molybdate Methods.

BACKGROUND: The concentration of total proteins in urine is a good index of renal function, but its determination is found to be unreliable. The pyrogallol red molybdate (PRM) method for urine total proteins is being widely used in most of the hospitals because of its high sensitivity, better precision and its practicability. Bicinchoninic acid method (BCA) is also used for protein estimation and there have been no studies comparing this method with the PRM method in human urine samples. BCA method overestimates the urinary protein concentration in the presence of interfering substances. After removing the interfering substances present in the human urine samples the results of BCA method were compared with the PRM method. AIM: The purpose of the study is to identify whether the results of urine total proteins by BCA method are comparable to PRM method and can be used as an alternative to the PRM method. SETTING AND DESIGN: This is a cross-sectional study done on fresh urine specimens from the hospital laboratory, covering a wide range of protein concentrations. MATERIAL AND METHODS: Fresh urine specimens covering a wide range of protein concentrations (urine dipstick: nil, trace, 1+, 2+ and ≥ 3+) of 36 patients were analysed by both the methods. STATISTICAL ANALYSIS: Imprecision was determined by repeated analysis study and Inaccuracy was assessed by comparing the results of the patient's urine samples by both the methods using correlation plots, Bland and Altman, and Passing and Bablok regression analyses. RESULTS: The coefficient of variation and mean (SD) for the BCA method were 4.6% and 799.1 (882.5) mg/L and for the PRM method were 5.1% and 802.1 (911.9) mg/L. The Pearson correlation coefficient, r was 0.93 (p < 0.0001). Method agreement studies showed no significant constant and proportional bias between both the methods. CONCLUSION: In urine which is subjected to removal of interfering substances, the BCA results are comparable to PRM method.

The Urinary Uric Acid/Creatinine Ratio is An Adjuvant Marker for Perinatal Asphyxia.

OBJECTIVE: To assess the urinary uric acid/creatinine ratio (UA/Cr) in relation to Apgar score and cord blood gas analysis in identification of perinatal asphyxia and to define the cutoff values. DESIGN: case control study. SETTING: The newborns admitted in the department of pediatrics and NICU of Mediciti Institute of Medical Science, Ghanpur, Medchal mandal, Telangana from May-July 2011 were enrolled. PARTICIPANTS/PATIENTS: The study was conducted on 31 (18 males, 13 females) controls and 18 (12males, 6 females) asphyxiated neonates. OUTCOME MEASURES: 5ml of arterial cord blood of newborn collected at the time of birth and spot urine samples were collected within 24-72 hours of life. Cord blood gas analysis were done immediately and Urinary uric acid was measured by modified Uricase method, urinary creatinine by modified kinetic Jaffe's reaction. RESULTS: The mean urinary uric acid and creatinine ratio (2.58± 0.48 vs 1.89 ± 0.59) is significantly higher in Asphyxiated group than in the control group. The umbilical cord blood pH had significant positive correlation with 1st minute Apgar score (r= 0.41, p=0.003), 5th minute Apgar (r= 0.44, p=0.002), while urinary UA/Cr ratio had significant negative correlation with cord blood pH (r= -0.63, p=0.002). Urinary UA/Cr ratio with criterion of >2.43 had 80% sensitivity, 87.5% specificity with AUC of 0.84 (p=0.003) had a better predictive value. CONCLUSIONS: Urinary UA/Cr ratio is easy, non-invasive, painless and economical adjuvant parameter with better predictive value for diagnosing perinatal asphyxia with simple diagnostic equipment.

Study of serum uric acid and creatinine in hypertensive disorders of pregnancy.

BACKGROUND: Renal dysfunction, increased xanthine oxidase activity and oxidative stress in placenta contributes to the elevated uric acid levels in preeclampsia (PE). OBJECTIVE: To determine serum uric acid and creatinine in hypertensive disorders of pregnancy and correlate with fetal outcome. MATERIALS AND METHODS: Pregnant women ≥32 weeks of gestation. Study population included 3 groups, 31 normotensive pregnant (NP) women as controls, 30 pregnant women with gestational hypertension (GH) and 30 with PE. RESULT: Serum uric acid and creatinine levels were significantly elevated in PE (6.26±1.19 and 0.94±0.26 mg/dL) when compared with Pregnancy induced hypertension (PIH) (4.27± 1.0 and 0.66 ±0.19 mg/dL) and NP (4.25 ± 0.8 and 0.63± 0.13 mg/dL) (P-value <0.001 and <0.001) respectively. Receiver operation characteristics curves demonstrated greater sensitivity and specificity for uric acid (86.7% and 83.9%, respectively) in PE than for creatinine (80% and 77.4%, respectively). Uric acid had strong and negative correlation with fetal birth weight in PE (r = -0.59, P = 0.006), where as creatinine had negative but weak correlation (r= -0.03, P=0.87). CONCLUSION: Serum uric acid is a better diagnostic and predictive marker for PE and fetal outcome respectively.

Study of Insulin Resistance in Subclinical Hypothyroidism.

BACKGROUND: Thyroid hormones influences glucose homeostasis. The association of insulin resistance in overt hypothyroidism is well proven, but very less information is available about insulin action on subclinical hypothyroidism. OBJECTIVE: This study was done to evaluate the association between thyroid hormones and insulin resistance in subclinical hypothyroidism (SCH). MATERIALS AND METHODS: Thirty subjects diagnosed as SCH and 30 age matched euthyroids were included. Serum TSH, FT3, FT4, fasting plasma glucose and insulin were estimated. Homeostasis Model Assessment was used to assess insulin resistance (HOMA- IR). RESULTS AND CONCLUSION: Serum TSH levels were significantly increased in SCH (14.20 ± 5.23 µU/ml) when compared with euthyroids (2.24 ±1.43µU/ml; P< 0.0001). Serum FT3, FT4 levels in SCH (2.96±0.80 pg/ml & 1.15 ± 0.52 ng/dl) were within the normal range. The mean insulin levels were significantly elevated in SCH (9.07±3.41 µU/ml) when compared with euthyroids (5.28± 2.18 µU/ml; P-value < 0.0001). The mean HOMA IR was significantly elevated in SCH (2.03 ± 0.95) when compared with euthyroids (1.05±0.45, P-value < 0.0001). TSH levels positively and moderately correlated with insulin (r= 0.43 P=0.03) and HOMA IR (r =0.48; P= 0.01). FT3 levels negatively and strongly correlated with insulin (r= -0.5, P=0.004) and moderately with HOMA IR (r= -0.38, P= 0.04). FT4 levels negatively and weakly correlated with insulin and IR (r= - 0.11, P=0.54; r= - 0.07, P=0.69 respectively). To conclude, SCH is associated with insulin resistance. Hence there is an increased risk of insulin resistance associated disorders such as metabolic syndrome, cardiovascular events in SCH.

Rural-urban epidemiologic transition of risk factors for coronary artery disease in college students of Hyderabad and nearby rural area--a pilot study.

OBJECTIVES: Massive urbanization in developing nations like India is predicted to cause epidemiologic transition to increased Coronary Artery Disease (CAD). To evaluate the rural-urban epidemiologic transition, risk factors for CAD were measured in two groups of subjects; Rural and Urban college students. METHODS: Subjects included 232 college students (58 men and 58 women in each group) aged between 18-22 years (mean 19.2 +/- 1.0). Since the age of urban youth was significantly higher (19.9 vs 18.4 years), age-adjusted analysis was performed. RESULTS: Age-adjusted BMI was significantly higher in urban (21.8 vs 17.8); 69.8% of rural and 13.8% of urban were underweight whereas 3.5% of rural and 31.9% of urban were either overweight or obese. Waist circumference (73.2 vs 61.9 cm), waist: hip circumference ratio (0.80 vs 0.75), diastolic BP (72.7 vs 67.9 mmHg), fasting blood glucose (82.4 vs 79.0 mg/dl), total cholesterol (147.9 vs 129.2 mg/dl), and LDL (89.3 vs 71.9 mg/dl) were significantly higher in the urban group. Triglycerides (79.1 vs 76.5 mg/dl), VLDL (15.9 vs 15.2 mg/dl) and systolic BP (114 vs 115 mmHg) were not significantly different. HDL (43.3 vs 40.7 mg/dl) and Cholesterol/HDL ratio (3.5 vs 3.3) were higher in urban group but with borderline significance (p = 0.057 and 0.056 respectively). CONCLUSION: Epidemiologic transition to higher risk for CAD is found in urban youth of Hyderabad compared to nearby villages, with increases in values of most parameters which are associated with increased risk for CAD. These findings need to be confirmed in extended studies to plan public health interventions to counteract the adverse effects of urbanization in early life.