Bone Activity Biomarkers and Bone Mineral Density in Children with Chronic Kidney Disease

Introduction: Chronic kidney disease - mineral and bone disorder (CKD-MBD) is a spectrum of bone minerals changes that range from high turnover lesions of secondary hyperparathyroidism to the low turnover lesions of adynamic bone disease. Bone biopsy is the gold standard for the diagnosis, but it is not routinely performed because it is invasive technique. Methods: Fifteen CKD children on regular hemodialysis (group I) and 15 CKD children on conservative management (group II) were selected from the nephrology clinics of Zagazig University Hospitals along with 15 age and sex-matched healthy controls. Participants were subjected to biochemical assessment that included osteocalcin (OC), total and bone-specific alkaline phosphatase (tALP and bALP), isomerized beta form of type I collagen cross-linked telopeptide (β-Crosslaps) and intact parathyroid hormone (iPTH) levels. Patients with CKD also had their bone mineral density (BMD) measured using dual energy X-ray absorptiometry (DEXA) at lumbar spine and femoral neck. Results: Serum β-Crosslaps, OC and bALP were significantly higher in patient groups than controls and in group I compared to group II .There was a negative significant correlation between mean Z-score at lumbar spines and bALP, OC and iPTH in group I and with β-Crosslaps in both patient groups. The mean Z-score at femoral neck correlated negatively with bALP in group I, with OC in group II and with iPTH and β-Crosslaps in both groups. Conclusion: Biochemical bone markers and assessment of BMD in patients with CKD may have a role in the early detection of CDK-MBD. Keywords: chronic kidney disease; bone mineral density; bone biomarker

Well as its Microcapsules in Rats

ABSTRACT Ketorolac is a potent non-steroidal analgesic drug. It is 36 times more potent than phenyl butazone, and twice as that of indomethacin. The oral administration of ketorolac is associated with high risk of adverse effects such as irritation, ulceration, bleeding of gastrointestinal tract, edema as well as peptic ulceration. These attributes make ketorolac a good candidate for controlled release dosage forms, so as to ensure slow release of the drug in the stomach. The present study reports on the formulation of ketorolac loaded Eudragit RS100, Eudragit RL100 as well as Ethyl cellulose as a controlled release drug delivery system. Solid dispersion and microencapsulation by air suspension method were the techniques of choice in order to coat the drug so as to improve bioavailability and stability and also target a drug at specific sites. The ratio of (1:3) drug to polymer from all polymers used was selected from solid dispersions systems as well as microcapsules to conduct further in vivo evaluation, since it was the best ratio which achieved significant reduction in the release of ketorolac at acidic pH of the stomach and maximal release at alkaline pH of the intestine. The effects of various formulations on ulcer index as well as ulcer incidence were studied. The obtained results indicate that microencapsulation technique was able to protect the stomach from ulcerogenic effect ketorolac compared to solid dispersion technique

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030