Celiac Disease and Inflammatory Bowel Disease are Associated with Increased Risk of Eating Disorders: An Ontario Health Administrative Database Study.

BACKGROUND: Previous national registry studies have reported an increased risk of eating disorders in immune-mediated conditions (inflammatory bowel disease [IBD] and celiac disease). Our objective was to examine the association between immune-mediated GI diseases and incident eating disorders in Ontario. METHODS: This was a retrospective matched cohort study of individuals <50 years of age with a diagnosis of an immune-mediated GI disease between 2002 and 2020 ("cases"). Those with a pre-existing eating disorder were excluded. Cases (n=83,920) were matched with controls (n=167,776) based on birth year, sex, and region of residence. Incidence rate ratio and hazard ratio were estimated using Poisson regression model and adjusted Cox proportional models, respectively. RESULTS: Over the follow-up period (up to January 31, 2022), 161 cases and 160 controls were identified with eating disorders. The overall incidence rate ratio (95% CI, p-value) of eating disorders in immune-mediated GI disease was 1.99 (1.6-2.5, p<0.001). The adjusted hazard ratios for eating disorder in cases with immune-mediated GI diseases was 1.98 (1.6-2.5, p<0.001). In the pediatric group of incident cases (≤18 years of age), overall adjusted hazard ratio was 2.62 (1.9-3.7, p<0.001)) compared to 1.56 (1.02-2.4, p=0.041) for adults (>18 years of age). The largest hazard ratio of 4.11 (1.6-10.3, p=0.003) was observed for pediatric incident cases of ulcerative colitis. CONCLUSION: IBD and celiac disease are associated with the development of eating disorders. The magnitude of the association was stronger in the pediatric age group, underscoring the need for early screening and detection.

Chronic kidney disease stage affects small, dense low-density lipoprotein but not glycated low-density lipoprotein in younger chronic kidney disease patients: a cross-sectional study.

BACKGROUND: Small, dense low-density lipoprotein (sd-LDL) and glycated LDL (g-LDL) have been associated with cardiovascular disease (CVD) in chronic kidney disease (CKD) in patients >60 years of age. Since young adult and paediatric patients have shorter exposure to Framingham-type risk factors, our study aims to determine whether younger CKD patients exhibit the same sd-LDL and g-LDL pattern. METHODS: After ethics board approval, this cross-sectional study was conducted at two universities with 44 patients (mean ± standard deviation age 12.6 ± 4.9, range 2-24 years) with CKD stage of 1-5. Laboratory parameters studied were Cystatin C (CysC), CysC estimated glomerular filtration rate (eGFR) (calculated from the Filler formula), sd-LDL, g-LDL and albumin. Lipid samples were measured for sd-LDL and g-LDL using ELISA. Non-linear correlation analysis was performed to determine the relationship between g-LDL, sd-LDL and eGFR. Clinical Trials Registration is at clinicaltrials.gov, NCT02126293, https://clinicaltrials.gov/ct2/show/NCT02126293. RESULTS: Triglycerides, but not total cholesterol and calculated LDL, were associated with CKD stages (ANOVA P = 0.0091). As in adults, sd-LDL was significantly associated with CKD stages (ANOVA P = 0.0133), CysC eGFR (r = -0.6495, P < 0.00001), and body mass index (r = -0.3895, P = 0.0189), but not with age. By contrast, there was no significant correlation between g-LDL and CKD stages or CysC eGFR (P = 0.9678). CONCLUSIONS: Our study demonstrates that only triglycerides and sd-LDL were associated with CKD stages in this young cohort without confounding Framingham-type CVD risk factors. While larger studies are needed, this study suggests that lowering sd-LDL levels may be a potential target to ameliorate the long-term CVD risks in paediatric CKD patients.

Does Vitamin D Affect Chronic Renal Allograft Function in Pediatric Transplant Patients?

BACKGROUND Correction of hypovitaminosis D is simple, but it is unclear whether it is associated with an accelerated decline of renal allograft function in pediatric renal transplantation patients. This retrospective single center cohort study aimed at analyzing the effect of vitamin D and covariates on the slope of 1/creatinine after the first year. MATERIAL AND METHODS After ethics committee approval, 37 (14 male) pediatric renal transplant recipients on mycophenolate mofetil, who were followed between 2006 and 2014, were included in this study. We analyzed the slope of 1/creatinine, length of follow-up, average vitamin D levels, calcium, phosphate, alkaline phosphatase levels, intact parathyroid hormone (PTH) levels, and therapeutic drug monitoring parameters. RESULTS Median slope of 1/creatinine was -2.587e-006 L/µmol. We divided the 37 patients into two groups based on slope: 18 patients with a poorer slope and 19 patients with a good slope, with the median slope of 1/creatinine being significantly different between the two groups. Creatinine and cystatin C at one-year post-transplantation did not differ between the two groups. Average vitamin D levels were 71.4±31.01 pmol/L and identical in each group (averages 71.67 and 69.23 pmol/L, respectively). Only the mycophenolic acid coefficient of variation (MPA CV), which may promote formation of donor-specific antibodies, and PTH levels were significantly associated with 1/creatinine slope. CONCLUSIONS Our data suggest that the impact of mild and moderate decreased levels of vitamin D can have a mild impact on the progression of allograft dysfunction in transplant recipients. However, given the medication burden and adherence challenges in adolescents, correction of mildly decreased vitamin D levels may not be necessary.

Comparison of efficacy and safety of lateral-to-medial continuous transversus abdominis plane block with thoracic epidural analgesia in patients undergoing abdominal surgery: A randomised, open-label feasibility study.

BACKGROUND: We recently described a lateral-to-medial approach for transversus abdominis plane (LM-TAP) block, which may permit preoperative initiation of the block. OBJECTIVE: Our objective was to evaluate the feasibility of continuous LM-TAP blocks in clinical practice in comparison with thoracic epidural analgesia (TEA). DESIGN: A randomised, open-label study. SETTING: University Hospital, London Health Sciences Centre, London, Ontario, Canada from July 2008 to August 2012. PATIENTS: Fifty adult patients undergoing open abdominal surgery via laparotomy were allocated randomly to receive preoperative catheter-congruent TEA or ultrasound-guided continuous bilateral LM-TAP block for 72 h postoperatively. Reasons for noninclusion were American Society of Anesthesiologists' physical status more than 4, known allergy to study drugs, chronic pain/opioid dependence, spinal abnormalities or psychiatric illness. INTERVENTIONS: In the TEA group (n = 24), patient-controlled epidural analgesia was maintained using bupivacaine 0.1% with hydromorphone 10 µg ml⁻¹ after establishment of the initial block. In the LM-TAP group (n = 26), ultrasound-guided LM-TAP catheters were inserted on each side preoperatively after a bolus of 30 ml of ropivacaine 0.5% (20 ml subcostal and 10 ml subumbilical injections on both sides). Analgesia was maintained with an infusion of ropivacaine 0.35% at a rate of 2 to 2.5 ml h⁻¹ through each catheter, along with rescue intravenous patient-controlled analgesia. MAIN OUTCOME MEASURES: The primary outcome was pain score on coughing 24 h after the end of surgery. Secondary outcomes were pain scores from 24 to 72 h, intraoperative and postoperative opioid consumption, time to onset of bowel movement and side effect profiles. RESULTS: Mean [95% confidence interval (95% CI)] pain scores at rest ranged from 1. 7 (0.9 to 2.5) to 2.3 (1.1 to 3.4) in TEA vs. 1.5 (0.7 to 2.2) to 2.2 (1.3 to 3.0) in LM-TAP (P = 0.829). The dynamic pain scores ranged from 2.9 (1.5 to 4.4) to 3.8 (2.8 to 4.8) in TEA vs. 3.3 (2.4 to 4.3) to 3.8 (2.7 to 4.9) in LM-TAP (P = 0.551). The variability in pain scores was lower in the LM-TAP group than in the TEA group in the first 24 h postoperatively. Patient satisfaction and other secondary outcomes were similar. CONCLUSION: Continuous bilateral LM-TAP block can be initiated preoperatively and may provide comparable analgesia to TEA in patients undergoing laparotomy. CLINICAL TRIALS REGISTRY: not registered because registration was not mandatory at the time of starting the trial.

NKT cells stimulated by long fatty acyl chain sulfatides significantly reduce the incidence of type 1 diabetes in nonobese diabetic mice [corrected].

Sulfatide-reactive type II NKT cells have been shown to regulate autoimmunity and anti-tumor immunity. Although, two major isoforms of sulfatide, C16:0 and C24:0, are enriched in the pancreas, their relative role in autoimmune diabetes is not known. Here, we report that sulfatide/CD1d-tetramer(+) cells accumulate in the draining pancreatic lymph nodes, and that treatment of NOD mice with sulfatide or C24:0 was more efficient than C16:0 in stimulating the NKT cell-mediated transfer of a delay in onset from T1D into NOD.Scid recipients. Using NOD.CD1d(-/-) mice, we show that this delay of T1D is CD1d-dependent. Interestingly, the latter delay or protection from T1D is associated with the enhanced secretion of IL-10 rather than IFN-g by C24:0-treated CD4(+) T cells and the deviation of the islet-reactive diabetogenic T cell response. Both C16:0 and C24:0 sulfatide isoforms are unable to activate and expand type I iNKT cells. Collectively, these data suggest that C24:0 stimulated type II NKT cells may regulate protection from T1D by activating DCs to secrete IL-10 and suppress the activation and expansion of type I iNKT cells and diabetogenic T cells. Our results raise the possibility that C24:0 may be used therapeutically to delay the onset and protect from T1D in humans.