Establishment of reference intervals for free light chains and immunoglobulins in Saudi population.

OBJECTIVES: Testing of serum-free light chains kappa (κ) and lambda (λ), along with ratio (FLCR) is essential for the diagnosis and management of monoclonal gammopathies. Accurate clinical diagnosis depends upon appropriate local population reference intervals (RIs). This study examined the Saudi population for serum-free light chains and other immunoglobulins to establish RIs and to explore variations in the test results by using the International Federation for Clinical Chemistry and Laboratory Medicine's global protocol for harmonized implementation of RI study. METHODS: A total of 180 healthy Saudi adults were recruited. All serum samples were assayed using the Freelite reagents from the Binding Site. The variation in reference values attributable to sex, age, BMI, and region was calculated by ANOVA as a standard deviation ratio (SDR). The RIs for the FLCR were derived by the parametric method and validated by using samples from patients with hypo- and hypergammaglobulinemia. RESULTS: The new RIs for free κ and FLCR were shifted to a higher side from the manufacturer-adapted RIs. Based on the SDR cutoff value (>0.4), between-sex partition RIs were not required for all analytes except IgM. Validation using patients with hypo- or hypergammaglobulinemia and without multiple myeloma, was all within the new RI. BMI, smoking, and exercise were not relevant sources of variation for any analyte. CONCLUSIONS: Locally derived RIs for free light chains and immunoglobulins analytes specific for Saudis were established after careful consideration of various factors. These RIs were more reliable than those provided as guidance by the manufacturer, or from other countries, for appropriate classification and prediction of disease progression for Saudi patients.

Establishment of reference intervals for hematological parameters of adult population in the western region of Saudi Arabia.

BACKGROUND: Most of hematology laboratories in Saudi Arabia utilize the reference intervals (RIs) provided by instrument manufacturers. This study aimed to define RIs of hematological parameters for adult population in the western region of Saudi Arabia and to explore their specific features from an international perspective. METHOD: This study was conducted according to the harmonized protocol of IFCC Committee on RIs and Decision Limits. Blood samples collected from 409 healthy Saudi males and females adults were analyzed for complete blood count (CBC) by using Cell-Dyn Sapphire analyzer and for iron profile by using Architect analyzers. The needs for RIs partitioned by sex and age was based on standard deviation ratio (SDR) and/or bias ratio (BR). RIs were derived parametrically with/without application of the latent abnormal values exclusion method (LAVE). RESULTS: Based on thresholds of SDR≥0.4 and/or BR≥0.57, RIs were partitioned by sex for red-blood cell count, hemoglobin, hematocrit, red cell distribution width, erythrocyte sedimentation rate, iron, transferrin, ferritin, eosinophil, platelet, plateletcrit, etc. Partitioning by age was not necessary for any of the analytes. LAVE procedure caused appreciable changes in RI limits for most erythrocyte and iron parameters but not for leukocyte parameters. Comparable to other non-IFCC studies on CBC RIs, the RBC and hematocrit (Ht) ranges have shifted to a higher side in both genders. After applying the LAVE method, the male and female RIs for Hb were 4.56 to 6.22 ×106/µL and 3.94 to 5.25 ×106/µL respectively while RIs for Ht were 40.2 to 52.0% and 33.6 to 44.5% respectively. CONCLUSION: LAVE method contributed to reducing the influence of latent anemia in deriving RIs for erythrocyte related parameters. Using the up-to-date methods, the RIs of CBC determined specifically for Saudis will help to improve the interpretation of test results in medical decision making.

Effect of hematocrit, galactose and ascorbic acid on the blood glucose readings of three point-of-care glucometers.

Glucometers are commonly used in a variety of healthcare settings and use in critically ill patients should not be assumed without appropriate tool validation. The study objective was to evaluate the accuracy of three point-of-care glucometers (POCGs) to assess glucose concentration in human blood sample. The POCGs tested included three different instruments and utilized three factors (hematocrit [Hct], galactose and ascorbic acid) in glucose measurements to determine the glucometers' accuracy and compared to the reference laboratory biochemical analyzer (Cobs 8000, Roche, Basal, Switzerland). In this study, the Nova StatStrip glucometer showed no significant variation compared to the laboratory method at high glucose level with various Hct%. ACCU-Chek Inform II overestimated the glucose results at Hct 22% and underestimated at Hct 62%. The Freestyle glucometer showed lower glucose levels compared to the Cobas 8000 at Hct 62%. The ACCU-Check showed significant increase of blood glucose with low Hct% levels when compared to the laboratory method. The Freestyle showed a decreased level of glucose with high Hct 62% interference compared to the Cobas 8000. Galactose interference 100 and 200 mg/dL dramatically affected the accuracy of ACCU-Chek Inform II. Nevertheless, among all three POCGs in this study, the Nova StatStrip showed the most reliable and stable results for glucose level in the presence of interference. Especially, those in critical care units, whereas the Freestyle Precision Pro and ACCU-Chek Inform II were insufficiently accurate for critically ill patients.

Prevalence and factors associated with dyslipidemia among adolescents in Saudi Arabia.

Dyslipidemia is a major risk factor for atherosclerosis. Screening for dyslipidemia at an early age is essential to prevent and control its consequences. This study aimed to determine prevalence of dyslipidemia and its correlates among adolescents in Saudi Arabia. Data of 5854 adolescents aged 10-19 years from all 13 regions of Saudi Arabia were obtained from the Jeeluna study; a national cross-sectional, multistage stratified cluster sample survey. Dyslipidemia was defined based on the National Heart Lung and Blood Institute and National Cholesterol Education Program guidelines for adolescents. We found that a quarter of Saudi adolescents have dyslipidemia (males: 33.3%, females: 17.9%). Significant variation was observed by region (p < 0.001). Prevalence of abnormal Total Cholesterol was 6.7%, LDL-C 7.1%, HDL-C 12.8%, Non-HDL-C 8.3%, and Triglycerides 9.6%. Factors independently associated with dyslipidemia were male gender (OR = 2.19, 95% CI 1.78-2.70, p < 0.001), BMI (underweight OR = 0.80, 95% CI 0.69-0.94, overweight OR = 1.76, 95% CI 1.50-2.06, obese OR = 2.80, 95% CI 2.34-3.34, p < 0.001, vs. normal) and serum ferritin (high OR = 7.02, 95% CI 1.49-34.79, low OR = 0.82, 95% CI 0.67-1.01, p = 0.04 vs. normal) and ≥ 1 daily intake of carbonated beverage (OR = 1.10, 95% CI 1.00-1.20, p = 0.03 vs. no or not daily intake). Public health interventions for improving lipid profile of adolescents are urgently needed.

Timing of Puberty and Late Pubertal Height in Saudi Schoolboys: Riyadh Puberty Study II.

Objective: Puberty has a significant contribution to the final height. Therefore, it is crucial to understand the normal variations in the onset and tempo of puberty in a specific population. In this study, we aimed to provide normative data on the timing of puberty and late pubertal height (LPH) in Saudi schoolboys in Riyadh. Methods: This is a cross-sectional field study (2011-2013) including Saudi schoolboys (grades 1-12; aged 6 to 19 years). Schools were chosen to represent the population from urban and rural areas in the Riyadh region. Pubertal maturity staging for gonads was assessed by measuring testicular size using a Prader orchidometer and assessing the Tanner staging of pubic hair. The marginal mean age was calculated using regression analysis. Results: We recruited 1086 schoolboys. The estimated mean age of pubertal onset at G2 was 11.8 (95% CI 11.60-12.0) years, for gonadal development at G3 was 13.2 (95% CI 12.9-13.5), G4 = 15.0 (95% CI 14.7-15.2), and G5 = 16.1 (95% CI 15.9-16.3) years, and for pubic hair stage 2 (PH2) was 12.6 (95% CI 12.4-12.9) years. The estimated time from G2/PH2 to G5/PH5 was 4.3 and 3.9 years, respectively. At the onset of puberty, the mean height was 144.7 cm and it reached 167.8 cm at G5 with a pubertal height gain of 23.1 cm. Conclusion: Our data present the norms of the timing of puberty and LPH in Saudi schoolboys. Saudi adolescent males are shorter than some European and American comparatives mainly due to shortness during childhood. However, they could have shorter LPH than Turkish, Greek, Thai, and Japanese due to a less pubertal height gain.

Can Fasting Blood Sugar be Used as an Indicator of Long-Term Diabetic Control Instead of Estimated Average Glucose?

BACKGROUND: Diabetes mellitus is a chronic illness that is a worldwide issue. HbA1c has been used to monitor glycemic control in patients with diabetes for many years. Although HbA1c measurement is needed for calculating estimated average blood glucose (eAG), it is now recommended that eAG is used instead of HbA1c for expression of blood glucose control and communication with patients and health care providers. This study, investigated fasting blood glucose (FBS) as an indicator of overall chronic blood sugar control by assessing the correlation between FBS with eAG derived from HbA1c. METHODS: The blood samples for HbA1c assay were collected in EDTA tubes and were analyzed by an HPLC analyzer (G8 Tosoh, Japan). Blood samples for FBS were collected in serum separator tubes, transported, and centrifuged for 15 minutes at 3,000 g. FBS levels were determined in serum samples with the enzymatic hexokinase method by a clinical chemistry analyzer (Architect 8000, Abbott, USA). RESULTS: Statistical analysis was performed on 1,740 patients with type 2 diabetes mellitus with HbA1c levels above 6.5 mmol/L. The difference between FBS (9.3 ± 3.7 mmol/L) and eAG (11.14 ± 2.7 mmol/L) was statistically signif-icant (p < 0.0001). The correlation coefficient between FBS and eAG was r = 0.65 (95% CI; 0.62 - 0.69), with a p-value < 0.0001. While the correlation coefficient between FBS and eAG at HbA1c < 6.5% was r = 0.251 (95% CI, 0.16 - 0.34), with a significant p-value of < 0.00001. The combined data, standard deviation (SD), median, and interquartile range of eAG and FBS for all of the diabetic groups (n = 2,315), were 10.1 ± 3.00 mmol/L, 9.5 mmol/L, and 7.75 - 12.03 mmol/L for eAG, respectively. Similarly, these values were 8.5 ± 3.6 mmol/L, 7.5 mmol/L, and 6.0 - 10.00 mmol/L for FBS, respectively. CONCLUSIONS: We concluded that there is a moderate and significant positive correlation between fasting blood sugar and the estimated average blood glucose derived from HbA1c. Although FBS might be helpful for daily monitoring of diabetes. Further studies must be conducted to provide solid results to support that FBS and its derived variable eAG can replace HbA1c as an indicator of long-term overall control of T2DM patients.

Establishment of reference intervals for immunoassay analytes of adult population in Saudi Arabia.

Background This is a second part of report on the IFCC global multicenter study conducted in Saudi Arabia to derive reference intervals (RIs) for 20 immunoassay analytes including five tumor makers, five reproductive, seven other hormones and three vitamins. Methods A total of 826 apparently healthy individuals aged ≥18 years were recruited in three clinical laboratories located in western, central and eastern Saudi Arabia using the protocol specified for the global study. All serum specimens were measured using Abbott, Architect analyzers. Multiple regression analysis (MRA) was performed to explore sources of variation of each analyte: age, body mass index (BMI), physical exercise and smoking. The magnitude of variation of reference values (RVs) attributable to sex, age and region was calculated by ANOVA as a standard deviation ratio (SDR). RIs were derived by the parametric (P) method. Results MRA revealed that region, smoking and exercise were not relevant sources of variation for any analyte. Based on SDR and actual between-sex differences in upper limits (ULs), we chose to partition RIs by sex for all analytes except for α-fetoprotein and parathyroid hormone (PTH). Age-specific RIs were required in females for ferritin, estradiol, progesterone, testosterone, follitropin, luteotropin and prolactin (PRL). With prominent BMI-related increase, RIs for insulin and C-peptide were derived after excluding individuals with BMI > 32 kg/m2. Individuals taking vitamin D supplements were excluded in deriving RIs for vitamin D and PTH. Conclusions RIs of major immunoassay analytes specific for Saudi Arabians were established in careful consideration of various biological sources of variation.

Correlations between Direct and Calculated Low-Density Lipoprotein Cholesterol Measurements in Children and Adolescents.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C), as a modifiable risk factor for atherosclerotic cardiovascular disease, should be assessed and monitored. This study compared directly measured and Friedewald-estimated LDL-C values in children and adolescents. METHODS: Blood samples were collected from 464 children and adolescents. Calculated LDL-C (CLDL-C) levels were estimated using the Friedewald formula for any triglyceride value below 4.6 mmol/L. Direct LDL-C (DLDL-C) levels were measured on an ARCHITECT c8000 Abbott Clinical Chemistry Analyzer. The differences in LDL-C were then calculated. RESULTS: The correlation coefficients (R) between DLDL-C and CLDL-C were 0.978 (P = .148) and R = 0.970 (P = .052) for children and adolescents, respectively. Children with LDL-C values above 4.92 mmol/L had a correlation value of 0.971 (P = .419). The correlation and agreement between DLDL-C and CLDL-C in adolescents were moderate for LDL-C below 2.85 mmol/L (R = 0.806; 84.1%) and improved above 2.85 mmol/L (R = 0.978; 91.5%). In children, good correlations between DLDL-C and CLDL-C were observed for normal (<0.85 mmol/L), borderline (0.85-1.12 mmol/L), and abnormal (≥1.13 mmol/L) triglyceride levels (R = 0.9782, 0.990, and 0.951, respectively). The rates of agreement were better for normal (80.5%) and borderline (82.9%) but not abnormal (68.2%) triglyceride levels. CONCLUSION: We observed good agreement between DLDL-C and CLDL-C in both children and adolescents. The Friedewald formula provided an adequate estimate of LDL-C for most fasting specimens. LDL-C difference percentage can also be used as a quality indicator to check laboratory analyzer performance in healthy subjects.

Prevalence of Obesity and Overweight among School-Aged Children in Saudi Arabia and Its Association with Vitamin D Status.

BACKGROUND: Childhood obesity is a significant global public health problem. Worldwide data showed an increasing trend over the years. We aimed to explore the prevalence of obesity, and its association with vitamin D status. METHODS: This cross-sectional study was conducted during the period from 2016 to 2017. The study included 3613 schoolchildren aged 6-19 years in the western, central, and eastern regions in Saudi Arabia. Anthropometric data including age, sex and body mass index (BMI) was collected and the serum 25OH- vitamin D (25OHD) was measured. Age-sex standardized BMI Z-scores using the 2007 World Health Organization growth standards were applied. RESULTS: Data from 3613 school-aged children (females = 51.8%), with equal percentage of participants from each region were analyzed. Prevalence of obesity and overweight was estimated at 7.1% and 14.4% respectively. An increasing trend was detected with age (p: 0.006). Obesity started to increase at the age of 10 years and continued to increase until 19 years. Most of the obese children (64.2%) had deficient vitamin D levels, compared to 33.7% of them with suboptimal levels and only 2.0% with optimal levels (p: <0.001). CONCLUSIONS: This large cohort study revealed a high prevalence (21.5%) of obesity and overweight in school children aged between 6-19 years with increasing trend with age.  Children with high BMI showed extremely high prevalence of VDD and VDI. These findings are alarming and point to the need for effective national interventions that include improving and encouraging access to physical activity and exposure to sunlight, educational activities for students, parents, and schoolteachers and possible enrichment of staple food with vitamin D.

Leptin, Ghrelin, and Leptin/Ghrelin Ratio in Critically Ill Patients.

The objective of this study was to evaluate leptin, ghrelin, and leptin/ghrelin ratio in critically ill patients and association of leptin/ghrelin ratio with outcomes. This is a sub-study of the PermiT trial (ISRCTN68144998). A subset of 72 patients who were expected to stay >14 days in the Intensive care unit were enrolled. Blood samples were collected on days 1, 3, 5, 7, and 14. Samples were analyzed for leptin and active ghrelin in addition to other hormones. Baseline leptin/ghrelin ratio was calculated, and patients were stratified into low and high leptin/ghrelin ratio based on the median value of 236. There was a considerable variation in baseline leptin level: Median 5.22 ng/mL (Q1, Q3: 1.26, 17.60). Ghrelin level was generally low: 10.61 pg/mL (Q1, Q3: 8.62, 25.36). Patients with high leptin/ghrelin ratio compared to patients with low leptin/ghrelin ratio were older, had higher body mass index and more likely to be diabetic. There were no differences in leptin/ghrelin ratio between patients who received permissive underfeeding and standard feeding. Multivariable logistic regression analysis showed that age and body mass index were significant independent predictors of high leptin-ghrelin ratio. Leptin-ghrelin ratio was not associated with 90-day mortality or other outcomes. Age and body mass index are predictors of high leptin/ghrelin ratio. Leptin/ghrelin ratio is not affected by permissive underfeeding and is not associated with mortality.

Higher serum alkaline phosphatase activity in infants born to vitamin D-deficient mothers.

Our research shows that the newborns of vitamin D-deficient mothers have higher serum alkaline phosphatase (ALP) activity compared with those of vitamin D-non-deficient mothers, which is likely related to increased bone turnover rather than just being a marker for bone formation. This has a potential negative impact on fetal bone development and subsequent skeletal growth. PURPOSE/INTRODUCTION: Low maternal serum 25-hydroxy vitamin D (25(OH)D) level during pregnancy contributes to vitamin D deficiency in infants at birth, which is associated with multiple potential adverse effects on fetal skeletal mineralization and growth. We studied the relationship between maternal 25(OH)D level and newborn serum alkaline phosphatase activity (ALP) at term. METHODS: In this prospective cross-sectional hospital-based study, venous blood samples of healthy pregnant mothers were drawn to measure 25(OH)D levels within 6 h of delivery. Cord blood samples were examined for calcium, phosphorus levels, and ALP activity immediately after birth. In addition, we also recorded the newborns' anthropometric measurements. RESULTS: Seventy-two percent (n = 108/150) of mothers in our study were vitamin D-deficient (serum 25(OH)2D < 25 nmol/l). In a multivariate logistic regression model, young maternal age (odds ratio (OR) = 0.94, 95% CI 0.88-0.99, p = 0.04) and increased weight (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) as well as decreased milk intake (OR = 0.31, 95% CI 0.13-0.74, p = 0.009) were all significantly associated with maternal vitamin D deficiency. ALP activity was significantly higher in newborns of vitamin D-deficient compared with vitamin D-non-deficient mothers (median = 176 (IQR = 139-221) and 156 (IQR = 132-182), respectively, p = 0.04). A significant inverse correlation (Pearson's coefficient = - 0.18, p = 0.03) was observed between maternal 25(OH)D levels and babies' ALP activities. This association persisted in a multivariate logistic regression model (OR = 3.46, 95% CI 1.18-10.18, p = 0.024). CONCLUSIONS: Our findings indicate that newborns of vitamin D-deficient mothers have higher serum ALP activity than those of non-deficient mothers, which might be related to increased bone turnover rather than just being a marker for bone formation. This could have a potential negative impact on fetal bone development and subsequent skeletal growth.

Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

PURPOSE: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients. METHODOLOGY: This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time. RESULTS: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups (P-value < 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups (P-value < 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 (P-value < 0.01). For TF, there was a significant association with age (P-value < 0.01). CONCLUSIONS: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied.

Free Fatty Acids' Level and Nutrition in Critically Ill Patients and Association with Outcomes: A Prospective Sub-Study of PermiT Trial.

OBJECTIVES: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness. PATIENTS/METHOD: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for ≥14 days in the intensive care unit. We measured FFAs level on day 1, 3, 5, 7, and 14 of enrollment. Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level >0.45 mmol/L in females and >0.6 mmol/L in males). RESULTS: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level. During the study period, patients with high FFAs level had higher blood glucose and required more insulin. On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36; 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29; 95% CI: 11.64, 11.19, p = 0.003). Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups. FFAs level was not associated with 90-day mortality (aOR: 0.49; 95% CI: 0.09, 2.60, p = 0.40). CONCLUSION: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.

Oxidative stress, caloric intake and outcomes of critically ill patients.

BACKGROUND: The aim of this study was to investigate the patterns of oxidative stress in critically ill patients and the association with caloric intake and outcomes. METHODS: In this pre-planned sub-study of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients Trial- ISRCTN68144998), we included patients expected to stay in the ICU for ≥14 days. Serum samples were collected on days 1, 3, 5, 7 and 14 of enrollment. We measured total anti-oxidant capacity (TAC), protein carbonyl concentration (a measure of protein oxidation) and 8-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-OHdG) (a measure of DNA oxidation). We used principal component analysis (PCA) and hierarchical cluster analysis (HCA) to group patients according to oxidative stress. RESULTS: Principal component analysis identified 2 components that were responsible for 79% of the total variance, and cluster analysis grouped patients in three statistically distinct clusters. Majority of patients 78.6% (44/55) were included in cluster 1 with lowest TAC, protein carbonyl and 8-OHdG levels and cluster 2 which accounted for 16.1% (9/55) of patients had the highest levels of TAC and intermediate levels of protein carbonyl levels. Cluster 3 patients 5.4% (3/56) had the highest protein carbonyl levels. Incident renal replacement therapy was highest in cluster 2 (4/8, 50.0%), compared to cluster 1 (4/42, 9.5%) and cluster 3 (1/3, 33.3%, p 0.01). When adjusted to oxidative stress cluster membership, permissive underfeeding was not associated with 90-day mortality (adjusted odds ratio, aOR 1.37, 95% CI 0.36, 5.25, p 0.64) but was associated significantly with lower incident renal replacement therapy (aOR 0.02, 95% CI < 0.001, 0.57, p 0.02). CONCLUSIONS: There are different distinct patterns of oxidative stress in critically ill patients. Incident renal replacement therapy was different among the three clusters. Our data suggest a protective effect of permissive underfeeding on incident renal replacement therapy that may differ by clusters of oxidative stress.

Permissive underfeeding, cytokine profiles and outcomes in critically ill patients.

BACKGROUND: During critical illness in humans, the effects of caloric restriction on the inflammatory response are not well understood. The aim of this study is to examine the associations of caloric restriction, inflammatory response profiles and outcomes in critically ill patients. METHODS: This is a sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998). Serum samples were collected on study days 1, 3, 5, 7 and 14 and analyzed for a panel of 29 cytokines. We used principal component analysis to convert possibly correlated variables (cytokine levels) into a limited number of linearly uncorrelated variables (principal components). We constructed repeated measures mixed linear models to assess whether permissive underfeeding compared to standard feeding was associated with difference cytokine levels over time. RESULTS: A total of 72 critically ill patients were enrolled in this study (permissive underfeeding n = 36 and standard feeding n = 36). Principal component analysis identified 6 components that were responsible for 78% of the total variance. When adjusted to principal components, permissive underfeeding was not associated with 90-day mortality (adjusted odds ratio 1.75, 95% confidence interval 0.44, 6.95, p = 0.43) or with incident renal replacement therapy. The cytokines did not differ with time between permissive underfeeding and standard feeding groups. CONCLUSIONS: The association of permissive underfeeding compared to standard feeding with mortality was not influenced by the inflammatory profile. Permissive underfeeding compared to standard feeding was not associated with differences in the serum levels of cytokines in critically ill patients.

Association analysis between four vitamin D receptor gene polymorphisms and developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a congenital condition characterized by abnormality in acetabulum size and/or shape. The incidence rate of DDH differs between different populations with risk factors including positive family history, breech presentation, sex, firstborn status, side of the hip, mode of delivery and oligohydramnios. It is recognized that DDH has a genetic component that exhibit autosomal dominant patterns. Many candidate genes have been studied and found to be associated with the disease; most of them are normally involved in cartilage development and joint metabolism. In this study, the association of four single-nucleotide polymorphisms (SNPs) (rs731236, rs1544410, rs7975232 and rs2228570) in the vitamin D receptor (VDR) gene was studied by a case-control analysis. The study sample involves 50 cases with confirmed DDH presentation and 50 nonDDH controls. SNPs were genotyped using conventional polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) techniques. Genotype and allele frequencies were analysed using SPSS software. No significant associations were found between the VDR polymorphisms analysed and DDH. Further work need to be performed using genomewide analysis to elucidate the genetic basis of DDH.

The Role of Urinary Neutrophil Gelatinase-Associated Lipocalin in Predicting Acute Kidney Dysfunction in Patients With Liver Cirrhosis.

BACKGROUND: Early detection of acute kidney dysfunction (AKD) in cirrhotic patients is crucial. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been identified as an early marker of AKD. The aim of the study was to evaluate serial uNGAL as a marker and predictor of AKD in liver cirrhosis patients. METHODS: Serial uNGAL and serum creatinine (sCr) levels were measured daily during the first 6 days of admission. Furthermore, sCr levels and the estimated glomerular filtration rate (eGFR) were measured after 3 - 6 weeks. The uNGAL levels in patients with and without abnormal sCr were compared. RESULTS: Fifty-seven consecutive cirrhotic patients were enrolled in the study. Eight of 14 patients (57%) who developed abnormal uNGAL level also had abnormal sCr level (odds ratio (OR) = 3.4, 95% CI: 0.99 - 12.03, P = 0.05). After 6 weeks, 41% of patients exhibited an abnormal uNGAL level and abnormal sCr (OR = 6.7, 95% CI: 1.55 - 28.85, P = 0.01). Area under the curve (AUROC) and the best cut-off point for highest NGAL in 6 days were 0.64 and 72.55 ng/mL, respectively. CONCLUSIONS: There is a modest association between highest uNGAL in the first 6 days of admission and sCr at week 6 in all participants. This may indicate that in cirrhotic patients, uNGAL level during the first 6 days of admission has a potential predictability for the development of high sCr and low eGFR 6 weeks later. The AUROC of 0.64 quantifies the overall ability of uNGAL to discriminate between those individuals who will have a raised sCr levels and those who will not.

Prevalence of vitamin D deficiency and its associated factors in three regions of Saudi Arabia.

OBJECTIVES: To measure prevalence of vitamin D deficiency in Saudi Arabia, unveil the life style, nutritional habits and status, as well as identify the potential risk factors. Method: A school-based survey targeting Saudi school students and employees was conducted during the  period from 2013 to 2014 using multistage cluster random sample in Central, Western and Eastern regions. The prevalence of vitamin D deficiency and difference between various population subgroups were calculated. Logistic regression analysis was used to determine the predictors of potential risk factors. Results: Prevalence of vitamin D deficiency was 49.5% in students and 44% in employees. Life style was not adequate to protect against vitamin D depletion. Unhealthy nutritional habits were widespread, some manifested in childhood while others manifested later in life. Living in the Eastern region, females, 16-19 years of age, low economic class, obese and lack of omega 3 supplements were risk factors in students. Employees living in the Eastern region, females, middle-income class, carbonated soft drink consumers, and lack of multivitamin supplements were at higher risk. Conclusion: There is a need for a health awareness program using evidence-based recommendations. Screening for early detection and correction of the condition should be proposed to be part of the national health strategy. There is need for identifying the burden of vitamin D deficiency on other diseases to control and improve the prognosis of these conditions.

Vitamin D status correction in Saudi Arabia: an experts' consensus under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (ESCEO).

BACKGROUND: Vitamin D deficiency is common in the Middle East and in Saudi Arabia, in particular. While several international recommendations on the management of vitamin D deficiency have been documented and practiced globally, these recommendations should be adapted to the conditions of the Middle Eastern region. To address this challenge, the Prince Mutaib Chair for Biomarkers of Osteoporosis (PMCO) in King Saud University (KSU), Riyadh, KSA, together with local experts and in cooperation with the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), organized a panel that formulated unified recommendations in the diagnosis and treatment of vitamin D deficiency in the region. METHODS: The selection of local and international experts commenced during the 2nd International Vitamin D Symposium conducted in Riyadh, Saudi Arabia, last January 20--21, 2016. Reviews of the most recent literature were done, and face-to-face meetings were conducted for revisions and final recommendations. RESULTS: Vitamin D sufficiency is defined as circulating serum 25(OH)D ≥50 nmol (≥20 ng/ml) for the general population and vitamin D adequacy as serum 25(OH)D >75 nmol/L l (>30 ng/ml) for the frail and osteoporotic elderly. Despite overwhelming prevalence of vitamin D deficiency, universal screening is not recommended. Recommendations for the general population, children, pregnant/lactating women, post-menopausal women, the elderly, and those with subsequent metabolic diseases were provided. RESULTS: Vitamin D sufficiency is defined as circulating serum 25(OH)D ≥50 nmol (≥20 ng/ml) for the general population and vitamin D adequacy as serum 25(OH)D >75 nmol/L l (>30 ng/ml) for the frail and osteoporotic elderly. Despite overwhelming prevalence of vitamin D deficiency, universal screening is not recommended. Recommendations for the general population, children, pregnant/lactating women, post-menopausal women, the elderly, and those with subsequent metabolic diseases were provided. CONCLUSION: Vitamin D supplementation/correction is advised in all persons whose serum 25(OH)D falls below 50 nmol/l (20 ng/ml), and achieving a target of 75 nmol/l (30 ng/ml) is particularly suited for frail, osteoporotic, and older patients. Conducting well-designed clinical trials in the region that will address economic implications and investigations on the treatment persistence and compliance to vitamin D treatment in the region are encouraged.

Prevalence of Vitamin D Deficiency and Calcium Homeostasis in Saudi Children.

OBJECTIVE: Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are significant health problems all over the world. The aim of this study was to determine the prevalence of VDD and VDI in children and adolescents residing in 8 provinces in the Kingdom of Saudi Arabia and to also investigate calcium homeostasis in these subjects. METHODS: A cross-sectional study was conducted in 2110 participants aged between 6 and 15 years. Information on socio-demographic status, anthropometric measurements, knowledge about vitamin D, color of the skin, dietary intake, sun exposure experience, smoking, and physical activity were collected through a questionnaire given to the parents of all subjects. The subjects were divided into three groups as vitamin D deficient, vitamin D insufficient, and vitamin sufficient according to their blood level of vitamin D [VDD ≤25 nmol/L (25 hydroxy vitamin D), VDI >25-50 nmol/L, and VDS >50 nmol/L]. RESULTS: VDD was highly prevalent in this group of children. 95.3 of the subjects had either VDD (45.5%) or VDI (49.9%). The prevalence rate of VDD combined with VDI was higher in females (97.8%) compared to males (92.8%) (p<0.001). Only 1.6% had significant hypocalcaemia. Children with dark skin had lower concentrations of vitamin D and higher concentrations of parathormone. A positive correlation was observed between 25 hydroxy vitamin D level and serum calcium, inorganic phosphate, and alkaline phosphatase concentrations. onclusion: The results showed a high prevalence of VDD and VDI in Saudi children with significantly higher prevalence in girls. These findings necessitate the set-up of a national program for vitamin D supplementation and health education for this vulnerable group.