Eosinophils and mast cells as therapeutic targets in pediatric functional dyspepsia

There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.

Validation of methods to assess potential biomarkers in pediatric patients with esophageal eosinophilia

AIM:To validate methods for determining mast cell density,extracellular major basic protein content,and presence of fibrosis in esophageal eosinophilia.METHODS:Twenty specimens with > 20 eosinophils/high-power field(hpf) classified as high eosinophil density(HE) and 20 specimens with < 5 eosinophils/hpf classified as low esophageal density(LE) were identified.All 40 specimens underwent immunohistochemical staining and trichrome staining.Mast cell density,extracellular major basic protein(MBP) density,and presence of subepithelial fibrosis were assessed in a standardized manner.All specimens were evaluated by two separate observers and by a single observer on two separate occasions to evaluate reproducibility of the methods.RESULTS:A strong inter-observer correlation was noted for both peak and mean mast cell counts(r = 0.725,P < 0.0001 and r = 0.823,P < 0.0001).A strong intraobserver correlation also was noted for both peak and mean mast cell counts(r = 0.752,P < 0.0001 and r =0.878,P < 0.0001).A very strong inter-observer correlation was noted for both peak(τ = 0.867,P < 0.0001)and mean extracellular MBP densities(r = 0.925,P <0.0001).A very strong intra-observer correlation was noted for both peak(τ = 0.875;P < 0.0001) and mean extracellular MBP densities(r = 0.956,P < 0.0001).Excellent inter-rater reliability was found for fibrosis(κ= 0.887).Mast cell and MBP densities,as well as presence of fibrosis,were significantly increased in HE vs LE.The HE group had significantly higher intraepithelial mast cell peak(29.35 ± 21.61 vs 12.45 ± 8.26,P =0.002) and mean(19.84 ± 15.81 vs 6.35 ± 4.5,P =0.001) densities than the LE group.The HE group had significantly higher peak extracellular MBP(2.35 ± 0.67vs 0.45 ± 0.61,P < 0.001) and mean extracellular MBP(1.95 ± 0.76 vs 0.20 ± 0.29,P < 0.0001) densities than the LE group.Seventy-three percent of patients with HE(11/15) had fibrosis,whereas only 10% of patients with LE(1/10) had fibrosis(P < 0.01).MBP performed the best in predicting classification of HE vs LE,with mean MBP demonstrating 100% sensitivity and95% specificity at the optimal cut point.CONCLUSION:This study provides methodology and proof-of-concept for future evaluation of these biomarkers for differentiating esophageal eosinophilic diseases such as reflux esophagitis and eosinophilic esophagitis.

Ethambutol Induced Optic Neuritis Associated with Tenofovir Nephrotoxicity

Morbidity and mortality associated with human immunodeficiency virus (HIV) has decreased with highly active anti-retroviral therapy (HAART). Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) that is preferred by the Department of Health and Human Services (DHHS) HIV treatment guidelines and is widely used for the initial treatment of HIV. Although tenofovir is generally well-tolerated, it has been associated with rare cases of acute nephrotoxicity. HIV-infected patients frequently have co-morbidities that require treatment, thus adding another level of complexity due to drug interactions and medication adverse effects with antiretrovirals. We present a patient who suffered an acute deterioration in renal function from tenofovir, leading to an accumulation of co-administered ethambutol, thus resulting in optic neuritis.

Update on the safety of anesthesia in young children presenting for adenotonsillectomy

Tonsillectomy with and without adenoidectomy is a frequently performed surgical procedure in children.Although a common procedure,it is not without significant risk.It is critical for anesthesiologists to consider preoperative,intraoperative,and postoperative patient factors and events to optimize safety,especially in young children.In the majority of cases,the indication for adenotonsillectomy in young children is obstructive breathing.Preoperative evaluation for patient comorbidities,especially obstructive sleep apnea,risk factors for a difficult airway,and history of recent illness are crucial to prepare the patient for surgery and develop an anesthetic plan.Communication and collaboration with the otolaryngologist is key to prevent and treat intraoperative events such as airway fires or hemorrhage.Postoperative analgesia planning is critical for safe pain control especially for those patients with a history of obstructive sleep apnea and opioid sensitivity.In young children,it is important to also consider the impact of anesthetic medications on the developing brain.This is an area of continuing research but needs to be weighed when planning for surgical treatment and when discussing risks and benefits with patients’families.