Post-transplant diabetes mellitus in pediatric liver transplantation

Abstract:  To determine the characteristics of pediatric liver transplant recipients who develop GI and/or PTDM, data on children undergoing their first liver transplant from the SPLIT database were analyzed (n = 1611). Recipient and donor characteristics that were evaluated included age at transplant, gender, race, primary disease, hospitalization status at transplant, BMI, recipient and donor CMV status, donor type, donor age, and primary immunosuppression. GI/PTDM was found in 214 individuals (13%) of whom 166 (78%) were diagnosed within 30 days of transplantation (early GI/PTDM). Multivariate analyses suggests that age >5 yr at transplant, hospitalization at transplant, a primary diagnosis other than BA, early steroid use, and tacrolimus use are associated with increased incidence of early GI. Routine monitoring for the development of GI and post-transplant diabetes is indicated in the short- and long-term care of children after liver transplantation.     

Inflammatory bowel disease-associated malignancies and considerations for radiation impacting bowel: a scoping review

BackgroundInflammatory bowel disease (IBD), subdivided into Crohn’s disease (CD) and ulcerative colitis (UC), is an auto-inflammatory gastrointestinal condition with an established increased risk of certain malignancies. Compared to sporadic cancers in the general population, IBD-associated malignancies present unique challenges to providing quality care. Radiation therapy (RT) targeting IBD-associated malignancies may directly impact inflamed bowel, with special considerations for the risk of toxicities. Historically, patients with IBD have been less likely to receive radiotherapy in proximity to bowel due to a poor understanding of the potential for acute and chronic toxicities and unclear treatment outcomes. We present a scoping review, to more fully assess IBD-associated malignancies and their treatment. As opposed to a systematic review, this approach allows us to analyze the broadest range of literature, including experimental and non-experimental research, and reflect on current guidelines and practices.MethodsLiterature search: a systematic, scoping search of published literature was conducted using applicable PRISMA scoping review (ScR) guidelines. The literature search was conducted on PubMed and was searched systematically by screening all publications from January 1990 to June 2021. Citations from the included articles were also manually searched. Relevant National Comprehensive Cancer Network guidelines were reviewed. Final query was December 2021 in editing. Articles were selected for full text reading if the abstract reported on malignancy in IBD or bowel toxicities.ResultsThe pelvic malignancies found in the IBD patient population, including colorectal carcinoma, anal carcinoma, lymphoma, small bowel adenocarcinoma (SBA), and prostate cancer (PCa) are outlined in this scoping review. Additional cancers that have a contested relationship with IBD, including cervical, bladder, and upper GI cancers, are also explored. This review provides literature guided recommendations on the eligibility of patients with IBD to receive RT, management of IBD during and after treatment, and counseling for radiation-induced toxicities.ConclusionsAfter review of the literature, IBD should not be considered an absolute contraindication to radiation therapy, given the lack of evidence for increased toxicities, and the evolution of RT techniques which limit radiation dose to the bowel.     

Functional recovery of glycine receptors in spastic murine model of startle disease

Clinical variability is common in inherited gene defects of the central nervous system in humans and in animal models of human disorders. Here, we used the homozygous spastic (spa) mutant mice, which resemble human hereditary hyperekplexia, to determine the molecular remodeling of the spinal cord through the course of the disease, and develop a model for clinical disparity between littermates. The spa mutation is an insertion of a LINE-1 element in the gene for the beta subunit of the glycine receptor, Glrb. The insertion causes aberrant splicing in the beta subunit of glycine receptor gene with a consequent important reduction of glycine receptors. At young ages, all homozygous spa animals were spastic, showed loss of glycine receptors, increased expression of vesicular glycine/GABA transporter and NMDA receptors, induction of activated caspase3, and preferential loss of glycinergic interneurons consistent with neurotransmitter toxicity model. Those littermates that recovered from symptoms showed strong over-expression of the glycine receptor alpha 1 subunit (Glra1), and increased myelination and synaptic plasticity. Littermates that showed a deteriorating clinical course failed to over-express Glra1, and also showed relative loss of gephyrin (receptor clustering). These molecular changes were associated with a preferential loss of GABAergic interneurons, and extensive motorneuron loss. These data suggest that functional recovery is likely due to expression of homomeric glycine receptors, rescue from excitotoxicity, and subsequent neuronal remodeling. We propose that human patients with hyperekplexia show remodeling similar to that of the recovering spa mice, as human patients also show a lessening of symptoms as a function of age.     

Sonographic NASCET index: a new doppler parameter for assessment of internal carotid artery stenosis

BACKGROUND AND PURPOSE: Established Doppler parameters for carotid stenosis assessment do not reflect North American Symptomatic Carotid Endarterectomy Trial (NASCET)-style methodology. We derived a Doppler parameter, termed sonographic NASCET index (SNI), and hypothesized that the SNI would provide greater angiographic correlation and better accuracy in predicting stenosis of 70% or greater than that of currently used peak systolic velocity (PSV) measurements. METHODS: Inclusion criteria of angiographically proved carotid stenoses of 40-95% and measured proximal and distal internal carotid artery Doppler PSV values were established. Occlusions and near occlusions were specifically excluded. Doppler and angiographic data meeting the inclusion criteria from 32 carotid bifurcations were identified; actual angiographic stenoses ranged 40-89%. SNI values were calculated for each vessel. PSV and SNI were correlated with angiography by using linear regression analysis. Accuracies of SNI and PSV in predicting stenosis of 70% or greater were compared at two thresholds. RESULTS: Correlation between SNI and angiography was superior to that between PSV and angiography (r2=0.64 vs 0.38). PSV and SNI values that corresponded to 70% angiographic stenosis were 345 cm/s and 45.5, respectively. Accuracy of PSV of 345 cm/s or greater in predicting stenosis of 70% or greater was 78%, compared with 88% for SNI of 45.5 or greater. The SNI value that corresponded to a PSV threshold of 250 cm/s was 33. Accuracy of PSV of 250 cm/s or greater in predicting stenosis of 70% or greater was 81%, compared with 88% for SNI of 33 or greater. CONCLUSION: Correlation between SNI and angiography was greater than that between PSV and angiography. Accuracy of SNI in predicting stenosis of 70% or greater was also superior to that of PSV at two thresholds. These results suggest that SNI may be a better predictor of high-grade carotid stenosis than is PSV.     

Postpartum glycated hemoglobin A1c and glucose tolerance test in mothers of large babies

An attempt to study macrosomia and carbohydrate metabolism was made by determination of glycated hemoglobin A1c and by the oral glucose tolerance test (OGTT) in early puerperium. We studied 76 women who gave birth to large babies greater than or equal to 4.5 kg, 74 women whose babies were 3-4 kg as controls, and 36 type II diabetics. The median of HbA1c concentration in the diabetics (8.06%) was significantly higher than in the controls (6.49%), and the large babies' mothers (6.48%), P less than 0.001. No significant difference was found between HbA1c or glucose intolerance in mothers of large babies and mothers with average size babies. HbA1c showed an association with glucose levels in the diabetics and controls, P less than 0.001, but not in the large baby group. Mothers of large babies were as old and obese as the diabetics. We speculate that the relationship of postpartum GTT, HbA1c and gestational diabetes is unwarranted.     

Os odontoideum in identical twins: perspectives on etiology

Most authorities favor the hypothesis of an acquired etiology of os odontoideum. We present the cases of identical twin sisters with os odontoideum in association with a congenital partial fusion of the posterior elements of the second and third cervical vertebrae, and discuss the implications. We believe that this is the first report of familial os odontoideum in a context which suggests a genetic etiology.     

The early response in fMRI: a modeling approach.

A mathematical model is presented to study the generation of the early response phenomenon in fMRI. Initially, we demonstrate that a simple combination of the changes taking place in cerebral blood volume and flow could create the transient early signal decrease, by analyzing their effects on total per voxel deoxyhemoglobin content. Also, we examine the traditional paradigm for the early response: that it may be caused by an early burst of oxidative metabolism and conclude that such changes also explain the early transient response. We suggest that the volume effect may play a role in the generation of the early response phenomenon along with an early upregulation of oxidative metabolism, and that this role may be important if the early response phenomenon is shown to occur at the level of the venous blood pool, and not just at the level of the capillary bed.