Gregory Thomas

Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia

Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.

Pediatric oncology providers perceptions of barriers and facilitators to early integration of pediatric palliative care

Pediatric patients experience significant symptoms during cancer treatment. Symptom management is frequently inadequate. We studied perceptions of pediatric oncology care providers regarding early integration of palliative care (PC) for pediatric patients to identify barriers and facilitators that might assist in understanding how care could be improved.

Sustained engraftment post bone marrow transplant despite anti-platelet antibodies in Glanzmann thrombasthenia

Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life‐threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti‐platelet antibodies.

Preventive antibiotics in pediatric patients with acute myeloid leukemia (AML)

Treatment of acute myeloid leukemia (AML) comes with a significant risk of life‐threatening infection during periods of prolonged severe neutropenia. We studied the impact of preventive intravenous (IV) antibiotic administration at onset of absolute neutropenia on the incidence and outcome of life‐threatening infections during treatment of childhood AML.

Factors Associated With Efficacy of Nurse-led Bowel Training of Patients With Chronic Constipation

BACKGROUND & AIMS It is not clear whether nurse-led bowel training (NBT), an individually tailored biofeedback strategy designed to improve the physiological process of defecation by operant conditioning and trial and error learning, is effective for patients with chronic constipation. We assessed the ability of NBT to reduce symptoms and increase quality of life in patients with constipation at a large tertiary medical center. METHODS We performed a retrospective analysis of data from 347 patients (median age, 50 years) who underwent a median 3 sessions of NBT for chronic constipation from January 2011 through December 2013 at St Marks Hospital in the United Kingdom. The NBT comprised a combination of sensory retraining, pelvic floor conditioning, and advice on diet and toileting behavior. Data on patient demographics (age, sex, type of constipation) were collected alongside their assessments of constipation, which were based on Patient Assessment of Constipation Quality of Life (PAC-QoL) and patient satisfaction scores. We performed binary logistic regression analysis. Each variable was tested first at the univariate level; those with significance (P < .10) were included in a multivariate model. RESULTS At the end of NBT, 62.5% of the patients (217/347) reported reduced symptoms, and 40.2% of the patients (41/102) reported a reduction of at least 1 point on the PAC-QoL score. The mean PAC-QoL scores before and after NBT were 2.42 and 1.41, respectively (P = .001). Multivariate analysis demonstrated that increasing age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.02-2.87; P = .042), greater number of sessions (OR, 4.14; 95% CI, 2.09-8.20; P < .001), and non-irrigation (OR, 4.39; 95% CI, 1.89-10.19; P = .001) were independent predictors of patient satisfaction. CONCLUSIONS Data collected immediately after patients with chronic constipation received NBT indicate that it is an effective treatment for most patients. Older patients with dyssynergic defecation benefit most from at least 4 sessions.

Invasive High-grade Upper Tract Urothelial Carcinoma in a 14-Year-Old Girl.

We present an unusual pediatric case of invasive upper tract urothelial carcinoma with an associated genetic predisposition. A 14-year-old female presented with intermittent right flank pain, and was found to have a poorly functioning hydronephrotic right kidney. Laparoscopic nephrectomy was performed. Pathology demonstrated upper tract urothelial carcinoma, and she subsequently underwent completion ureterectomy. Genetic studies demonstrated a double-hit constitutional deletion of a DNA mismatch repair protein, revealing a rare Lynch syndrome variant known as Constitutional Mismatch Repair Deficiency Syndrome. This disease places her at high risk for multiple malignancies, including upper tract urothelial carcinoma.