Citations

ABSTRACTObjective:Differentiation between the common etiologies of dense esophageal eosinophilia such as gastroesophageal reflux disease (GERD) and eosinophilic esophagitis can be difficult. We hypothesized that histologic features may provide diagnostic clues concerning the etiology of esophageal eosinophilia.Methods:We performed a retrospective chart review of 204 children with the diagnosis of esophagitis characterized by ≥15 eosinophils (eos) per high‐power field (HPF) in at least 1 biopsy. We then restricted our analysis to subjects who had received at least 8 weeks of only proton pump inhibitors (PPIs) followed by endoscopy and who had a clinicopathologic response to this treatment. Symptoms, endoscopic findings, and pathologic descriptions were reviewed and an eosinophil peroxidase (EPX) index was determined to assess for degranulation/eosinophil activation.Results:Of the 204 identified charts, 7 subjects identified met the inclusion criteria. Five of these 7 patients showed a clinicopathologic response to PPIs after their follow‐up endoscopy, (mean peak eosinophil count: 92 vs 5 eos/HPF, and EPX index: 39.2 vs 14.6, pre‐ and posttreatment, respectively). Two patients experienced initial resolution of symptoms and esophageal eosinophilia with PPI therapy; however, within 17–23 months they redeveloped symptoms and esophageal eosinophilia while receiving PPI therapy at the time of a third endoscopy (mean peak eosinophil count: 40 vs 11 vs 36 eos/HPF, and EPX index: 44 vs 21 vs 36.5, pre‐, post‐ and posttreatment, respectively). No clinicopathologic features or degranulation patterns differentiated subjects with GERD/PPI responsive esophageal eosinophilia from those who had transient response to PPI treatment.Conclusions:No clinicopathologic features differentiated subjects who responded to PPI treatment. PPI treatment can be helpful to exclude GERD and PPI responsive esophageal eosinophilia but long‐term follow‐up is critical in the management of esophagitis.

BackgroundTo evaluate the impact of adjuvant hormonal therapy after radical prostatectomy on overall survival in high‐risk prostate cancer patients, stratified by comorbidity status.MethodsWe identified 1247 patients who underwent radical prostatectomy from 1988 to 2004 for high‐risk prostate cancer, as defined by National Comprehensive Cancer Network classification. Comorbidity status was stratified by Charlson Comorbidity Index as 0, 1 or >2, as well as by the presence or absence of cardiovascular disease. Overall survival was estimated by the Kaplan–Meier method, and compared within each comorbidity category/adjuvant hormonal therapy strata with the log–rank test.ResultsMedian patient age was 65 years, and the median postoperative follow up was 11.2 years. In total, 419 patients (34%) received adjuvant hormonal therapy. The distribution of Charlson Comorbidity Index was 0, 1 and ≥2 in 861 (69%), 244 (20%) and 142 (11%) patients, respectively. The 10‐year overall survival for patients who received adjuvant hormonal therapy versus those who did not was 75% versus 82% (P = 0.54) for patients with Charlson Comorbidity Index = 0, 72% versus 76% (P = 0.83) with Charlson Comorbidity Index = 1, and 70% versus 68% (P = 0.33) with Charlson Comorbidity Index ≥2. Meanwhile, 155 (12%) patients had cardiovascular disease, and the 10‐year overall survival for patients with cardiovascular disease who received adjuvant hormonal therapy was 72%, compared with 76% without adjuvant hormonal therapy (P = 0.97). On multivariate analysis, receipt of adjuvant hormonal therapy was not associated with non‐prostate cancer mortality (P = 0.24).ConclusionsAdjuvant hormonal therapy after radical prostatectomy for high‐risk prostate cancer does not increase non‐prostate cancer mortality, even among patients with multiple comorbidities. Additional studies are warranted to determine optimal multimodal treatment approach for high‐risk patients.

R231H Causes a High Penetrance for Familial AFBackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease.Method and ResultsCandidate gene sequencing in 5 unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage‐gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage‐dependent gating.ConclusionsThe R231H variant causes a high penetrance for interfamilial early‐onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF.

ABSTRACTObjectives:Children with nonalcoholic fatty liver disease (NAFLD) experience compromised quality of life (QOL) akin to those with other chronic disease. Our objectives were to examine the association between NAFLD and QOL as well as other psychosocial outcomes, to compare psychosocial outcomes to obese children without known NAFLD, and to determine whether present standard care for NAFLD results in weight loss and improvement in psychosocial outcomes longitudinally.Methods:Children with NAFLD between 8 and 18 years and obese control children without known NAFLD were consented to complete a brief psychosocial battery examining depression (Children's Depression Inventory), QOL (Pediatric Quality of Life Inventory; PedsQL), and effect of weight on self‐esteem (Body‐Esteem Scale for Adolescents and Adults) at baseline; and additionally for the NAFLD group after at least 6 months.Results:A total of 48 children with NAFLD and 40 obese control children were enrolled. The PedsQL scores were not significantly different but the CDI total score and subscales of negative mood, ineffectiveness, and negative self‐esteem as well as all of the 3 subscales of BESAA, appearance, attribution, and weight were worse in the NAFLD group compared with obese controls. The PedsQL scores also did not change after standard care in the 33 patients with NAFLD who completed the follow‐up evaluations, but the CDI score differed between those whose body mass index improved or not.Conclusions:Children with NAFLD have higher levels of depression than obese controls. Outcomes did not improve with standard care. Larger longitudinal studies and appropriate interventions are required in this area.

Objectives To quantify the occurrence of myocardial infarction ( MI ) occurring in the early postoperative period after surgical hip fracture repair and estimate the effect on 1‐year mortality. Design A population‐based, historical cohort study of individuals who underwent surgical repair of a hip fracture that used the computerized medical record linkage system of the R ochester E pidemiology P roject. Setting Academic and community hospitals, outpatient offices, and nursing homes in O lmsted C ounty, M innesota. Participants Over the 15‐year study period (1988–2002), 1,116 elderly adults underwent surgical repair of a hip fracture. Measurements At the end of the first 7 days after hip fracture repair, participants were classified into one of three groups: clinically verified MI (cv‐ MI ), subclinical myocardial ischemia, and no myocardial ischemia. One‐year mortality was compared between these groups. Multivariate models assessed risk factors for early postoperative cv‐ MI and 1‐year mortality. Results Within the first 7 days after hip fracture repair, 116 (10.4%) participants experienced cv‐ MI and 41 (3.7%) subclinical myocardial ischemia. Overall 1‐year mortality was 22%, with no difference between those with subclinical myocardial ischemia and those with no myocardial ischemia. One‐year mortality for those with cv‐ MI (35.8%) was significantly higher than for the other two groups. Occurrence of early postoperative cv‐ MI , male sex, and history of heart failure or dementia were independently associated with greater 1‐year mortality, whereas prefracture home residence and preoperative higher hemoglobin were protective. Conclusion Rates of early postoperative, cv‐ MI after hip fracture repair exceed rates after other major orthopedic surgeries and are independently associated with greater 1‐year mortality.