Whole-exome sequencing (WES) is an effective approach to identify the susceptibility of genetic variants of autism spectrum disorder (ASD). The Israel Ministry of Health supports WES as an adjunct tool for ASD diagnosis, despite its unclear diagnostic yield and cost effectiveness. To address this knowledge gap, we applied WES to a population-based sample of 182 Bedouin and Jewish children with ASD from southern Israel, and assessed its yield in a gene panel of 205 genes robustly associated with ASD. We then compared the incremental cost-effectiveness ratios (ICERs) for an ASD diagnosis by WES, chromosomal microarray analysis (CMA), and CMA + WES. Overall, 32 ASD candidate variants were detected in 28 children, corresponding to an overall WES diagnostic yield of 15.4%. Interestingly, the diagnostic yield was significantly higher for the Bedouin children than for the Jewish children, i.e., 27.6% vs. 11.1% (p = 0.036). The most cost-effective means for genetic testing was the CMA alone, followed closely by the CMA + WES strategy (ICER = USD 117 and USD 124.8 per child). Yet, WES alone could become more cost effective than the other two approaches if there was to be a 25% increase in its yield or a 50% decrease in its cost. These findings suggest that WES should be recommended to facilitate ASD diagnosis in Israel, especially for highly consanguineous populations, such as the Bedouin.

Background: Chronic kidney disease (CKD) manifested as reduced GFR and/or albuminuria, has been known to accelerate arterial stiffness and early vascular aging (EVA). Diabetes, hypertension, and glomerular disorders are the leading causes of CKD and renal failure. The question which etiology contributes more to this vascular phenomenon-hypertensive and diabetic CKD or CKD secondary to immune-mediated glomerulonephritis—remained unclear. Objective: To compare pulse wave velocity (PWV), a marker of arterial stiffness, between CKD patients of different etiologies: hypertensive and diabetic nephrosclerosis. vs. CKD secondary to glomerular disorders. Methods: Clinical data were collected on 56 patients followed at the Nephrology and Hypertension Institute in Samson Assuta Ashdod University Hospital. All patients had at least one visit at our Nephrology clinics prior to recruitment. All patients with a glomerular disorder had a clinical-pathological diagnosis based on a recent kidney biopsy. Pulse wave velocity (PWV) was measured using a validated Sphygmocor XCEL^® device. Univariate and multivariate analyses were performed to compare PWV between hypertensive/diabetic CKD and CKD secondary to glomerular disorders. Results: PWV was significantly higher in the hypertensive/diabetic CKD group, compared to the CKD-GN group, with an average of. 12.2 m/s vs 8.3 m/s, respectively (p < 0.001). In a multivariate linear regression model, having CKD secondary to glomerulonephritis was associated with a significantly lower PWV (B = − 3.262, p < 0.001), compared with CKD secondary to hypertension and diabetes, with adjustment of age, creatinine, and comorbidities. Conclusion: CKD Patients secondary to glomerulonephritis, have lower PWV when compared to CKD patients with diabetes and/or hypertension, even after adjusting for age, renal function, and the presence of comorbidities. It is intriguing to further study the possible protective role of immunosuppression on the arterial properties of CKD patients.

Background/Objectives: Dehydration is an under-recognized cause of hypercalcemia, and no validated bedside marker exists to distinguish it from other etiologies. We evaluated the urinary calcium-to-creatinine ratio (uCa/Cr) and the fractional excretion of calcium (FeCa) as predictors of dehydration across a spectrum of hypercalcemic and normocalcemic states. Methods: We conducted a retrospective cohort study of 96 patients admitted to an internal medicine ward with dehydration and/or hypercalcemia. Dehydration was identified using a combination of clinical criteria (presenting complaint, physical examination findings of volume depletion, and admitting physician assessment) and biochemical criteria (elevated plasma urea, creatinine, or sodium, or elevated urine osmolality). Patients were classified into three groups: non-dehydrated hypercalcemic (n = 37), dehydrated hypercalcemic (n = 24), and dehydrated normocalcemic (n = 35). Urinary analyses were performed on patients not receiving chronic diuretic therapy (n = 70 with complete data). Logistic regression, receiver operating characteristic (ROC) analysis, and CKD-stratified sensitivity analyses were performed. Results: uCa/Cr differed significantly across all three groups (medians 1.046, 0.484, and 0.056 mmol/mmol respectively; p < 0.001 for all pairwise comparisons). Hypocalciuria-defined as reduced urinary calcium excretion (uCa/Cr < 0.2 mmol/mmol)-was absent in non-dehydrated patients and present in 59.5% of dehydrated patients; this should not be confused with hypocalcemia (low serum calcium). ROC analysis yielded an AUC of 0.894 (95% CI: 0.819–0.969), significantly superior to FeCa (AUC 0.813; DeLong p = 0.012). At a threshold of 0.2 mmol/mmol, specificity and positive predictive value were both 100%. uCa/Cr remained independently associated with dehydration after adjustment for chronic kidney disease (CKD), age, and sex (OR 0.112, 95% CI: 0.030–0.307, p < 0.001). PTH suppression was significantly less frequent in dehydrated than non-dehydrated patients (24.4% vs. 51.5%, p = 0.018). Conclusions: Random uCa/Cr is a highly specific, CKD-independent predictor of dehydration. A uCa/Cr value below 0.2 mmol/mmol, particularly combined with non-suppressed PTH, should prompt consideration of dehydration as the primary cause of hypercalcemia.