Phenotype and outcomes of very early onset and early onset inflammatory bowel diseases in a Montreal pediatric cohort.

Objectives: The incidence of very-early-onset inflammatory bowel disease (VEO-IBD) and early-onset IBD (EO-IBD) is increasing. Here, we report their phenotype and outcomes in a Montreal pediatric cohort. Methods: We analyzed data from patients diagnosed with IBD between January 2014 and December 2018 from the CHU Sainte-Justine. The primary endpoint was to compare the phenotypes of VEO-IBD and EO-IBD. The secondary endpoints involved comparing outcomes and rates of steroid-free clinical remission (SFCR) at 12 (±2) months (m) post-diagnosis and at last follow-up. Results: 28 (14 males) and 67 (34 males) patients were diagnosed with VEO-IBD and EO-IBD, respectively. Crohn's disease (CD) was more prevalent in EO-IBD (64.2% vs. 39.3%), whereas unclassified colitis (IBD-U) was diagnosed in 28.6% of VEO-IBD vs. 10.4% of EO-IBD (p < 0.03). Ulcerative colitis (UC) and IBD-U predominantly presented as pancolitis in both groups (VEO-IBD: 76.5% vs. EO-IBD: 70.8%). Combining all disease subtypes, histological upper GI lesions were found in 57.2% of VEO-IBD vs. 83.6% of EO-IBD (p < 0.009). In each subtype, no differential histological signature (activity, eosinophils, apoptotic bodies, granulomas) was observed between both groups. At 12 m post-diagnosis, 60.8% of VEO-IBD and 62.7% of EO-IBD patients were in SFCR. At a median follow-up of 56 m, SFCR was observed in 85.7% of VEO-IBD vs. 85.0% of EO-IBD patients. Conclusion: The rate of patients in SFCR at 1-year post-diagnosis and at the end of follow-up did not significantly differ between both groups.

Epstein-Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease.

Background and Aim: Patients with inflammatory bowel disease (IBD) are at increased risk for life-threatening complications of Epstein-Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection. Methods: We included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2-year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre-treatment viral load of EBV. Results: One hundred twenty patients were included in the study. Fifty-three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine. Conclusion: EBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1.

The enzyme activation-induced deaminase (AID) deaminates deoxycytidine at the immunoglobulin genes, thereby initiating antibody affinity maturation and isotype class switching during immune responses. In contrast, off-target DNA damage caused by AID is oncogenic. Central to balancing immunity and cancer is AID regulation, including the mechanisms determining AID protein levels. We describe a specific functional interaction between AID and the Hsp40 DnaJa1, which provides insight into the function of both proteins. Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. Conversely, DnaJa1, but not DnaJa2, depletion reduces AID levels, stability and isotype switching. In vivo, DnaJa1-deficient mice display compromised response to immunization, AID protein and isotype switching levels being reduced by half. Moreover, DnaJa1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AID protein levels in B cells. Thus, DnaJa1 is a limiting factor that plays a non-redundant role in the functional stabilization of AID.

Cytotoxic agents in the treatment of laryngeal sarcoidosis: a case report and review of the literature.

SUMMARY: Sarcoidosis is a multisystem disease with various clinical manifestations. It is characterized primarily on a histopathologic basis by the presence of noncaseating granulomata. Laryngeal involvement reportedly occurs in 3-5% of cases, and it is typically localized to the supraglottic region. Patients often present with hoarseness, dysphagia, stridor, or dyspnea. Laryngoscopy typically demonstrates a pale, edematous epiglottis studded with nodules. Tissue biopsy reveals the classic noncaseating granuloma; however, the finding is not diagnostic. Sarcoidosis remains a diagnosis of exclusion to be entertained once other verifiable etiologies for granulomatous disease of the larynx, such as TB, syphilis, fungal infection, berylliosis, or Wegener's granulomatosis, have been ruled out. Systemic corticosteroids remain the mainstay of treatment; however, new steroid-sparing therapies that target the inflammatory response of sarcoidosis are currently being investigated. The case history of a patient with laryngeal sarcoidosis who was managed with the immunosuppressant azathioprine (Imuran) is summarized along with a discussion of other treatment options.

Obstructing tracheobronchial schwannoma.

Endotracheal and endobronchial schwannomas are extremely rare tumors of neurogenic origin. These tumors often present late. Common symptoms of hemoptysis and dyspnea result from the size and location of the tumors. Two cases of tracheobronchial schwannoma with proximal airway obstruction are reported. Various diagnostic modalities employed in the evaluation of these tumors are reviewed. Because malignant transformation is exceedingly rare, operative resection of tracheobronchial schwannomas based on the principle of conservation of lung parenchyma is emphasized.

Comparison of data obtained from sedated versus unsedated wireless telemetry capsule placement: does sedation affect the results of ambulatory 48-hour pH testing?

OBJECTIVES: The introduction of 48-hour wireless pH testing provides a novel technique of evaluating persons with suspected reflux disease. The wireless capsule can be placed in a sedated individual at the time of esophagogastroduodenoscopy (EGD) or in an unsedated individual at a time after the initial EGD, at the time of esophageal manometry or at the time of transnasal esophagoscopy. The effect that sedation has on the results of 48-hour wireless pH testing has not been evaluated. PURPOSE: To evaluate the day to day variability and the effect of sedation on the results of 48-hour wireless pH testing. METHODOLOGY: The charts of all patients at a tertiary swallowing center undergoing 48-hour wireless pH testing between June 1, 2003 and December 31, 2004 were retrospectively evaluated. Data concerning study indications, route of pH capsule placement, duration of pH recording, and test results were collected. Day to day variability was evaluated, and the results obtained from persons with sedated and unsedated pH capsule placement were compared. RESULTS: Two hundred and six studies were performed. The indications for the examination were gastroesophageal reflux disease (146/206), chronic cough (36/206), and laryngopharyngeal reflux (24/206). Sixty-two percent (128/206) of the studies were performed without sedation and 38% (78/206) with sedation. The overall reproducibility of the daily pH recordings (day 1 vs. day 2) was 77%. Although some trends were observed, there was no significant association between the use of sedation and any of the reflux parameters on pH testing (P > .05). CONCLUSIONS: The day to day reproducibility of 48-hour wireless pH testing was 77%. Intravenous sedation does not appear to have a significant effect on the results of 48-hour wireless pH testing.

Application of high-dose propofol during ischemia improves postischemic function of rat hearts: effects on tissue antioxidant capacity.

Previous studies have shown that reactive oxygen species mediated lipid peroxidation in patients undergoing cardiac surgery occurs primarily during cardiopulmonary bypass. We examined whether application of a high concentration of propofol during ischemia could effectively enhance postischemic myocardial functional recovery in the setting of global ischemia and reperfusion in an isolated heart preparation. Hearts were subjected to 40 min of global ischemia followed by 90 min of reperfusion. During ischemia, propofol (12 microg/mL in saline) was perfused through the aorta at 60 microL/min. We found that application of high-concentration propofol during ischemia combined with low-concentration propofol (1.2 microg/mL) administered before ischemia and during reperfusion significantly improved postischemic myocardial functional recovery without depressing cardiac mechanics before ischemia, as is seen when high-concentration propofol was applied prior to ischemia and during reperfusion. The functional enhancement is associated with increased heart tissue antioxidant capacity and reduced lipid peroxidation. We conclude that high-concentration propofol application during ischemia could be a potential therapeutic and anesthetic strategy for patients with preexisting myocardial dysfunction.

Effects of oxidant-induced injury on heme oxygenase and glutathione in cultured aortic endothelial cells from atherosclerosis-susceptible and -resistant Japanese quail.

Recent studies on cultured aortic endothelial cells (AECs) from atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail suggest that differences in atherosclerosis susceptibility between RES and SUS may be due to differences in endothelial heme oxygenase (HO) and antioxidant components. We have now investigated the effects of oxidant-induced injury on HO and glutathione (GSH) in AECs from SUS and RES quail. We report that cultured AECs from SUS and RES birds differ in their response to oxidative stress. AECs from the SUS strain cells are more susceptible than those from the RES strain to oxidative stress induced by tert-butylhydroperoxide, as judged by lower HO activity, HO-1 expression, ferritin and GSH levels. Aortic endothelial cells from SUS birds also showed higher levels of catalytic iron, TBARS production and LDH release compared with RES cells, indicating that SUS AECs are more susceptible to oxidative stress than cells from the resistant strain. Furthermore, independently of genetic status, AECs from old birds have higher TBARS and lower levels of HSP70 induction than AECs from younger birds, suggesting that aging is associated with a decreased ability of AECs to respond to oxidative stress, and this may be relevant to the permissive effect of aging on the process of atherogenesis. Our results indicate that genetic factors and endogenous antioxidant systems in the blood vessel wall may be important in determining the susceptibility of vascular cells to oxidative stress and atherosclerotic plaque formation.

Heme oxygenase and antioxidant status in cultured aortic endothelial cells isolated from atherosclerosis-susceptible and -resistant Japanese quail.

We have investigated heme oxygenase (HO) and antioxidant status in the novel isolation and characterization of aortic endothelial cells (AECs) from a random bred wild-type strain (WILD) and selectively bred atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail. Cultured AECs expressed acetylated LDL, and were probed with endothelial and smooth muscle cell specific antibodies to confirm purity of culture. Subconfluent monolayers of RES AECs had higher HO activity than SUS AECs. At confluence, HO activity levels were similar among strains. However, RES AECs had higher HO-1 protein than WILD and SUS cells. Although ferritin protein levels were similar among the three strains, catalytic iron was higher in SUS AECs than WILD and RES cells. Glutathione levels were highest in SUS cells, intermediate in WILD, and lowest in RES, while glutathione reductase was higher in WILD and RES AECs than SUS AECs. We suggest that differences in atherosclerosis susceptibility between RES and SUS may be due, at least in part, to differences in endothelial HO and antioxidant components.