Citations

Abstract Background There has been increasing interest in the superficial circumflex iliac artery perforator (SCIP) flap as a source of thin, pliable soft tissue combined with a favorable donor site. Despite several clinical series from Asia, barriers to adoption include reluctance to perform submillimeter “supermicrosurgery” and the effect of body habitus on flap feasibility. The purpose of this study is to distinguish vascular anatomic characteristics of the SCIP flap in a North American population. Methods Computed tomography angiography was examined in 84 flaps in healthy prospective renal donor patients from a radiographic database. Descriptive statistics as well as linear regression comparing variables to body mass index (BMI) were performed. Results Mean BMI was 27.1 ± 3.5 kg/m2, while the mean patient age was 47.8 ± 11.4 years. The superficial circumflex iliac artery (SCIA) originated from the common femoral artery in 92% cases, with remainder originating from the profunda femoris. The mean vessel diameter was 1.85 mm at source vessel origin. Distance from skin to source vessel averaged 30.7 mm. Suprascarpal subcutaneous thickness averaged 16.5 mm. The mean distance from Scarpa's fascia to vessel origin was 14.1 mm. Direct three-dimensional distance from vessel origin to pubic tubercle was 50.2 mm. A medial and lateral perforator split off of the SCIA was observed in 38 cases (45%). Significant differences were shown when comparing BMI to skin to source vessel distance (p < 0.001), suprascarpal subcutaneous fat thickness (p < 0.001), and fascial distance to vessel origin (p < 0.001). BMI did not significantly affect vessel diameter. Conclusion Despite a significantly higher BMI than many previously published cohorts, the SCIP remains an excellent source of thin and pliable tissue. When dissected closer to the source vessel, a vessel caliber of nearly 2 mm can be achieved, which may obviate the need for “supermicrosurgery” in this population.

Abstract Context The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. Objective To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. Design A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally. Results There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia. Conclusions Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.

Summary This paper provides guidance for researchers with some mathematical background on the conduct of time‐to‐event analysis in observational studies based on intensity (hazard) models. Discussions of basic concepts like time axis, event definition and censoring are given. Hazard models are introduced, with special emphasis on the Cox proportional hazards regression model. We provide check lists that may be useful both when fitting the model and assessing its goodness of fit and when interpreting the results. Special attention is paid to how to avoid problems with immortal time bias by introducing time‐dependent covariates. We discuss prediction based on hazard models and difficulties when attempting to draw proper causal conclusions from such models. Finally, we present a series of examples where the methods and check lists are exemplified. Computational details and implementation using the freely available R software are documented in Supplementary Material. The paper was prepared as part of the STRATOS initiative.

Abstract Introduction The cytoprotective PTEN‐induced kinase 1 (PINK1)‐parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated ubiquitin (pS65‐Ub) for their autophagic removal (mitophagy). Because dysfunctions of mitochondria and degradation pathways are early features of Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis. Methods Morphology, levels, and distribution of the mitophagy tag pS65‐Ub were evaluated by biochemical analyses combined with tissue and single cell imaging in AD autopsy brain and in transgenic mouse models. Results Analyses revealed significant increases of pS65‐Ub levels in AD brain, which strongly correlated with granulovacuolar degeneration (GVD) and early phospho‐tau deposits, but were independent of amyloid beta pathology. Single cell analyses revealed predominant co‐localization of pS65‐Ub with mitochondria, GVD bodies, and/or lysosomes depending on the brain region analyzed. Discussion Our study highlights mitophagy alterations in AD that are associated with early tau pathology, and suggests that distinct mitochondrial, autophagic, and/or lysosomal failure may contribute to the selective vulnerability in disease.