δ-Tocotrienol in Combination with Resveratrol Improves the Cardiometabolic Risk Factors and Biomarkers in Patients with Metabolic Syndrome: A Randomized Controlled Trial.

Background: Metabolic syndrome (MetS) is a cluster of central obesity, hypertension, hyperglycemia, and dyslipidemia. It is a global health issue with an increased risk of cardiovascular disease. Recently, a few natural products have been reported with promising anti-inflammatory and antioxidative effects. We aimed to evaluate the impact of δ-tocotrienol and resveratrol mixture (TRM) supplementation on cardiometabolic risk factors and biomarkers in patients with MetS. Methods: A randomized controlled trial was conducted at the hospitals of National University of Medical Sciences Rawalpindi, Pakistan. A total of 82 patients with MetS aged 18-60 years were enrolled based on International Diabetes Federation-2005 diagnostic criteria and randomly grouped into TRM (n = 41) and placebo (n = 41). Patients in the TRM group were given a 400 mg capsule (δ-tocotrienol 250 mg; resveratrol 150 mg), and a placebo (cellulose 400 mg) twice daily for 24 weeks. The biochemical tests were analyzed on ADVIA 1800 Chemistry® analyzer and inflammatory biomarkers by ELISA methods. Results: In the TRM group, a significant reduction in waist circumference, blood pressure, mean (95% confidence interval) of fasting plasma glucose -0.15 mmol/L (-0.22 to -0.08), serum triglyceride -0.32 mmol/L (-0.47 to -0.17), and increment in high-density lipoprotein cholesterol were observed as compared with placebo. TRM supplementation also improved biomarkers: high-sensitive C-reactive protein -0.61 mg/L (-0.89 to -0.33), interleukin-6-1.99 pg/mL (-2.50 to -1.48), tumor necrosis factor-α -2.19 pg/mL (-2.55 to -1.83), malondialdehyde -0.48 µmol/L (-0.65 to -0.30), and total antioxidant capacity 1.71 U/mL (1.29 to 2.13). Conclusion: TRM supplementations improved cardiometabolic risk factors and biomarkers of inflammation and oxidative stress without any significant side effects in the patients with MetS. Clinical Trials Registry: The clinical trial was registered in Sri Lanka Clinical Trials Registry (https://slctr.lk/trials/slctr-2019-021).

Is procalcitonin better than C-reactive protein for early diagnosis of bacterial pneumonia in children?

Early diagnosis of bacterial pneumonia plays a pivotal role in the management. We evaluated the diagnostic accuracy of procalcitonin (PCT) as compared with C-reactive protein (CRP) for the early diagnosis of bacterial pneumonia in children. In total, 92 children consisting of 46 patients of bacterial pneumonia were admitted in the Military hospital, Rawalpindi, Pakistan and equal number of controls were included. Patient's investigations were carried out at admission. PCT and CRP were analyzed on Vidas analyzer and Immulite 1000, respectively. Out of 46 pneumonia patients, 28 were male and 18 female, with a median age of 4 years. PCT levels were significantly high median (range) of 2.69 ng/ml (0.30-13.00) vs. 0.45 ng/ml (0.10-2.00) in controls. Serum CRP levels were moderately elevated with median (range) 6.5 mg/l (0.30-60) vs. 0.30 mg/l (0.30-5.0) in controls. The area under receiver characteristic curves for PCT and CRP were 0.89 (95% CI=0.83-0.96) and 0.79 (95% CI=0.70-0.88), respectively. In total, 38 patients were diagnosed to have bacterial pneumonia with PCT (sensitivity 83% at cutoff > or = 1 ng/ml) and 26 children with CRP (sensitivity 57% at cutoff > or = 6 mg/L). PCT has better diagnostic accuracy than CRP and can be utilized for early diagnosis of bacterial pneumonia in children.

Impact of CYP2C9 genetic polymorphism on warfarin dose requirements in Pakistani population.

Variations of cytochrome-P450 enzyme system (CYP2CP) are associated with impaired metabolism of warfarin. The objective of our study was to estimate the frequency of genetic and allelic variants of CYP2C9 in Punjabi population of Pakistan and their effects on warfarin dose requirement. One hundred and twenty unrelated Pakistani subjects belong to Punjab province, were randomly included from the registry of National Institute of Heart Disease Rawalpindi, Pakistan. The patients had stable international normalized ratio (INR) of 2 to 3 for last 3 months with warfarin therapy after heart valves replacement. The detection of CYP2C9 variant was done on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Total 120 patients (73 males; 47 females) of mean age of 37 years participated in the study. Nine patients had mutant allele CYP2C9*3 (7.5%), one CYP2C9*2 (0.8%) and 110 patients exhibited wild type CYP2C9*1 (91.7%). The frequency of CYP2C9 genotype was *1/*1 (0.858) ; *1/*3 (0.117) ; 2/*20 (0.08 ) and *3/*3 (0.017) in our study population. A high dose of warfarin (42.2+9.56) mg/week is required for patients with *1/*1 genotype as compared to patients with *2/*2 (17.5+1.9) and *1/*3 (16.6+2.3) allele (p<0.001). Individuals with CYP2C9*3/3* need lowest (8.75±1.76 mg/week) daily warfarin dose. In conclusion, the genetic variations in the CYP2C9 occur in 14% of Punjabi ethnic group in Pakistan. Presence of CYP2C9*2 or *3 variants is an independent predictor of low warfarin dose requirement in our patients. CYP2C9 variants assay may be used in high risk groups for appropriate dose adjustment to avoid complications on long term basis.

Effects of combined interferon alpha and ribavirin therapy on thyroid functions in patients with chronic hepatitis C.

OBJECTIVE: To determine the frequency of thyroid dysfunction in patients of chronic hepatitis C during treatment with interferon alpha-2b and ribavirin therapy. STUDY DESIGN: A cohort study. PLACE AND DURATION OF STUDY: Army Medical College and Military Hospital, Rawalpindi, from February 2006 to January 2007. METHODOLOGY: One hundred and sixty seven non-cirrhotic chronic hepatitis C patients were grouped into treatment group (n=107) and control group (n=60) awaiting treatment. Baseline serum(s.) Alanine Transferase (ALT) and S. Aspartate Transferase (AST) were measured by IFCC method. Serum Thyroid Stimulating Hormone (S. TSH), serum free thyroxine (S. Free T4) and serum total triiodothyronine (S.T3) level were determined by chemiluminescence. Study group patients underwent 24 weeks IFN and ribavirin therapy and were followed-up for thyroid dysfunction at weeks 0, 12 and 24. Control group patients underwent the same tests at weeks 0, 12 and 24. Statistical analysis was done on SPSS 15. RESULTS: Out of 107 patients of treatment group, 20 patients (18.69%) developed thyroid dysfunction. Females were at higher risk with Relative Risk (RR) of 11.25 and Attributable Risk (AR) of 91%. Hypothyroidism was more common than hyperthyroidism. CONCLUSION: Interferon-alpha and ribavirin therapy induces thyroid dysfunction in chronic hepatitis C patients. Hypothyroidism was more common. Females are at a higher risk of developing thyroid dysfunction.

Correlation of steatosis with fibrosis and necro-inflammation in chronic hepatitis C infection in the absence of confounding factors.

OBJECTIVE: To assess the frequency and degree of hepatic steatosis in patients of chronic hepatitis C infection and determine its correlation with stages of fibrosis and necro-inflammatory grades. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: The study was carried out in the Department of Pathology (Histopathology), Army Medical College, Rawalpindi, from March 2006 to March 2007. METHODOLOGY: Patients who had undergone a liver biopsy for evaluation of hepatitis C virus infection were included in the study. Demographic characteristics and laboratory data were collected at the time of biopsy. First hundred biopsy specimens meeting the inclusion criteria were assessed for steatosis, necro-inflammation and fibrosis. RESULTS: Steatosis was present in 46 patients and graded as mild (41.3%), moderate (54.3%) and severe (4.3%). An overall significant correlation was found between grades of steatosis with stage of fibrosis (p < 0.0001) but no correlation was found with necro-inflammatory grades. Only focal necrosis revealed weak correlation with grades of steatosis (p < 0.003). CONCLUSION: These results suggest a possible role of the hepatitis C virus itself in the pathogenesis of steatosis and indicate its close relationship with fibrosis and focal degeneration in chronic hepatitis C. Necro-inflammation seen in liver biopsy is host immune reaction to hepatitis C virus and is not related to steatosis.

Assessment of bone mineral metabolism derangements by K/DOQI guidelines in haemodialysis patients at Rawalpindi.

OBJECTIVE: To assess serum calcium, phosphorus and PTH levels with reference to K/DOQI targets in haemodialysis patients at Rawalpindi. Further more efficacy of calcium carbonate (CaCO3) was compared with calcium acetate (CaAc) for maintaining serum P and Ca levels in our ESRD patients. METHODS: One hundred and ninety patients on haemodialysis receiving calcium phosphate binders (CaCO3 n = 128 and CaAc n = 62) were selected from a tertiary care hospital at Rawalpindi, Pakistan. Serum Ca and P were assayed on chemistry analyzer. PTH was measured on immulite-1000. Data were compared with K/DOQI targets and analysed by using SPSS-15. RESULTS: The patients had mean serum Ca 2.34 +/- 0.29 mmol/L, Phosphorus 1.76 +/- 0.43 mmol/L and Parathyroid hormone (PTH) 38.7 +/- 35.6 nmol/L. The patients had achieved K/DOQI target ranges of Ca, P, PTH and Ca x P product in 37.9%, 41.1%, 22.6% and 61.5% respectively. Patients on CaCO3 had significantly higher serum Ca 2.38 +/- 0.31 mmol/L than those on CaAc therapy 2.26 +/- 0.22 mmol/L. CONCLUSION: Most of patients on maintenance haemodialysis at Rawalpindi, did not achieve the recommended K/DOQI target ranges. Appropriate phosphate binders are required for improvement of mineral metabolism and medical outcome in our patients.

Evaluation of diagnostic accuracy of APRI for prediction of fibrosis in hepatitis C patients.

BACKGROUND: Several non-invasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated Aspartate aminotransferase (AST) to platelet ratio index (APRI) in comparison with Metavir scoring for assessing the severity of hepatic fibrosis in the CHC patients in district Rawalpindi. METHODS: One hundred twenty CHC patients, naive for HCV treatment, underwent liver biopsy in tertiary care hospitals of district Rawalpindi, participated in the study. Liver biopsies were reviewed by Metavir scoring system. Serum AST was analyzed by IFCC method. Platelets were measured on a haematology Analyzer. Patients with mild fibrosis (F0, F1) were differentiated from significant fibrosis (F2, F3, F4) and those with mild/moderate fibrosis (F0, F1, F2) from advanced fibrosis (F3, F4) based on APRI score as compared to liver biopsy. RESULTS: Liver biopsies examination revealed that out of 120 patients 10 (8.3%) had no fibrosis (F0), 46 (38%) portal fibrosis (F1), 34 (28%) septal fibrosis (F2), 21 (18%) bridging fibrosis (F3) and 9 (8%) cirrhosis (F4). APRI correctly classified 58 (48%) patients of significant fibrosis with AUC = 0.82 (95% CI, 0.73-0.88) at cut-off 0.5 and 1.5 with negative predictive value (NPV), Positive predictive value (PPV), sensitivity and specificity of 78%, 72%, 66%, 83% and 58%, 90%, 41% and 90% respectively. Eighty-seven (66%) CHC patients were correctly classified for advanced fibrosis with AUC = 0.87 (95% CI 0.79-0.94) at cutoffs 0.90 and 1.75 with a 95%NPV at 0.90 and 78% PPV at 1.75. CONCLUSION: APRI could correctly identify significant fibrosis in 48% and advanced fibrosis in 66% cases with acceptable degree of diagnostic accuracy in CHC patients in our clinical practice.

Assessment of lipid dysfunction in patients on maintenance haemodialysis.

BACKGROUND: Dyslipidaemia is a major risk factor of cardiovascular disease in patients on maintenance haemodialysis. Both increased and decreased levels of cholesterol are associated with increased cardiovascular mortality in haemodialysis patients. OBJECTIVE: To assess the lipid dysfunction among patients on maintenance haemodialysis in a nephrology unit at Rawalpindi as compared with healthy individuals. METHODS: A descriptive comparative study was carried out in a nephrology unit at Rawalpindi, Pakistan. A total of 140 subjects were included consisting of 70 patients on maintenance haemodialysis (MHD) and 70 healthy controls. Body mass index (BMI) was measured according to WHO guidelines. Serum total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) were assayed on chemistry analyser. Low-density lipoprotein cholesterol (LDL-C) was calculated by Friedwald equation. RESULT: MHD patients had significantly lower BMI, mean (SD) 20.07 (3.66) as compared with the controls 22.88 (3.97) kg/m2 (p < 0.001). The lipid profile among MHD patients and controls are given as mean (SD): (a) Total Cholesterol 3.84 (1.06) vs 4.65 (0.97) (p < 0.001), (b) LDL-C 2.21(0.77) vs 2.93 (0.71) (p < 0.001), (c) HDL-C 0.95 (0.166) vs 0.97 (0.138) (p = NS), (d) Non HDL 2.88 (0.95) vs 3.67 (0.88) (p < 0.0001), (e) Triglycerides 1.68 (1.09) vs 1.69 (0.86) (p = NS). The most common abnormality observed in haemodialysis patients was low HDL-C (81%) followed by increased Non-HDL-C (23%) and increased serum triglycerides (19%). CONCLUSION: It is concluded that our patients on maintenance haemodialysis have significantly low BMI, total Cholesterol, LDL-C and Non-HDL-C depicting malnutrition leading to inflammation, accelerated atherosclerosis process and cardiovascular complications.

Estimation of ionized calcium, total calcium and albumin corrected calcium for the diagnosis of hypercalcaemia of malignancy.

OBJECTIVE: To measure levels of ionized calcium, total calcium and albumin corrected calcium in patients with different malignant disorders for the diagnosis of hypercalcaemia of malignancy. DESIGN: A case control comparative study. PLACE AND DURATION OF STUDY: The study was carried out in the Department of Pathology, Army Medical College Rawalpindi, Armed Forces Institute of Pathology and Department of Oncology CMH, Rawalpindi from March 2003 to December 2003. SUBJECTS AND METHODS: Ninetyseven patients of various malignant disorders, admitted in the Department of Oncology, CMH, Rawalpindi, and 39 age and gender-matched disease-free persons (as control) were included in the study. Blood ionized calcium (Ca++), pH, sodium (Na+) and potassium (K+) were analysed by Ion selective electrode (ISE) on Easylyte auto analyser. Other related parameters were measured by colourimetric methods. RESULTS: Blood Ca(++) levels in patients suffering from malignant disorders were found significantly high (mean +/- SD: 1.30+017 mmol/L) as compared to control subjects (mean +/- SD 1.23+0.03 mmol/L) (p<0.001). The number of patients with hypercalcaemia of malignancy detected by Ca(++) estimation was significantly higher (38%) as compared to total calcium (8.4%) and albumin corrected calcium ACC (10.6%) (p<0.001). There was no statistically significant difference in other parameters e.g. phosphate, urea, creatinine, pH, Na+ and K+ levels in study subjects and controls. CONCLUSION: Detection of hypercalcaemia can be markedly improved if ionized calcium estimation is used in patients with malignant disorders.

Accuracy of Non-Fasting Lipid Profile for the Assessment of Lipoprotein Coronary Risk.

OBJECTIVE: To determine the diagnostic accuracy of non-fasting lipid profile in the diagnosis of hyperlipidemia, taking fasting lipid profile as gold standard, in adult population. STUDY DESIGN: Cross-sectional validation study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from July to December 2014. METHODOLOGY: One hundred seventy-five adult patients coming for fasting lipid profile were included; their non-fasting samples were taken on the next day. Patients on anti-cholesterol treatment and indoor patients were excluded. Total cholesterol (TC), high density lipoprotein-cholestrol (HDL-C), and triglycerides were measured by direct enzymatic colorimetric method by Modular p-800®. Low density lipoprotein-cholesterol (LDL-C) was calculated by Friedewald's formula, but when triglyceride was greater than 4.5 mmol/l, then LDL-C was measured directly by homogenous enzymatic colorimetric method. Non-HDL-C was calculated by simple equation, i.e. TC-HDL-C. RESULTS: Non-fasting lipid profile had 93% specificity , 51% sensitivity, 94% positive predictive value and 49% negative predictive value; and 65% accuracy with 7.28 positive likelihood ratio and 0.52 negative likelihood ratio. Non-fasting TC and non-HDL-C were significantly higher than fasting TC and non-HDL-C by mean difference of 0.2 mmol/l each with p=0.001 and p=0.004, respectively. Fasting and non fasting HDL-C are comparable to each other with mean difference of 0.01 mmol/l (p=0.745). Receiver operating curve (ROC) of non-fasting non-HDL-C showed 0.804 (95%CI (0.738-0.870), (p=0.000) area under the curve (AUC) indicating that it was a significant test for ruling out hyperlipidemia. Bland-Altmann plot showed a significant difference between non-fasting, non-HDL-C and fasting LDL-C and non-fasting, non-HDL-C -0.087540 with bias -0.00109; therefore, these cannot be alternative to each other. CONCLUSION: Diagnostic accuracy of non-fasting lipid profile was found significantly higher than fasting lipid profile (p=0.004) for the assessment of lipoprotein coronary risk on the basis of non-HDL-C, which seemed to be significant test for ruling out hyperlipidemia.