Citations

Constitutively active nuclear factor-κB (NF-κB) is integral to the survival of Hodgkin/Reed-Sternberg cells (H/RS) in Hodgkin lymphoma (HL). To investigate NF-κB pathway proteins in pediatric HL, we utilized a tissue microarray compiled from 102 children enrolled in the Children's Oncology Group intermediate-risk clinical trial AHOD0031 (56 male, 78 Caucasian, median age 15 years (range 1–20 years), 85 nodular sclerosing subtype, 23 Epstein-Barr virus (EBV) positive, and 24 refractory/relapsed disease). We examined the intensity, localization, and pathway correlations of NF-κB pathway proteins (Rel-A/p65, Rel-B, c-Rel, NF-κB1, NF-κB2, IκB-α, IKK-α, IKK-β, IKK-γ/NEMO, NIK, and A20), as well as their associations with EBV status and clinical outcome. NF-κB pathway proteins were overexpressed in pediatric HL patients compared to controls. Patients with EBV− tumors, or with rapid early therapy response, had tightly coordinated regulation of NF-κB pathway proteins, whereas patients with EBV+ tumors, or slow early therapy response, had little coordinated NF-κB pathway regulation. High NIK expression was associated with a slow response to therapy and decreased EFS. Elevated Rel-B, NIK, and the NF-κB inhibitor A20 were associated with decreased EFS in multivariate analysis. These studies suggest a pivotal role for the NF-κB pathway in therapy response and patient survival in Hodgkin lymphoma.

Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase–generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.

PurposeIn this article, the authors report reliability and validity evidence for the Dynamic Evaluation of Motor Speech Skill (DEMSS), a new test that uses dynamic assessment to aid in the differential diagnosis of childhood apraxia of speech (CAS).MethodParticipants were 81 children between 36 and 79 months of age who were referred to the Mayo Clinic for diagnosis of speech sound disorders. Children were given the DEMSS and a standard speech and language test battery as part of routine evaluations. Subsequently, intrajudge, interjudge, and test–retest reliability were evaluated for a subset of participants. Construct validity was explored for all 81 participants through the use of agglomerative cluster analysis, sensitivity measures, and likelihood ratios.ResultsThe mean percentage of agreement for 171 judgments was 89% for test–retest reliability, 89% for intrajudge reliability, and 91% for interjudge reliability. Agglomerative hierarchical cluster analysis showed that total DEMSS scores largely differentiated clusters of children with CAS vs. mild CAS vs. other speech disorders. Positive and negative likelihood ratios and measures of sensitivity and specificity suggested that the DEMSS does not overdiagnose CAS but sometimes fails to identify children with CAS.ConclusionsThe value of the DEMSS in differential diagnosis of severe speech impairments was supported on the basis of evidence of reliability and validity.

Purpose The purpose of this prospective randomized study was to compare the outcomes of arthroscopic labral repair and selective labral debridement in female patients undergoing arthroscopy for the treatment of pincer‐type or combined pincer‐ and cam‐type femoroacetabular impingement. Methods Between June 2007 and June 2009, 36 female patients undergoing arthroscopic hip treatment for pincer‐ or combined‐type femoroacetabular impingement were randomized to 2 treatment groups at the time of surgery: labral repair or labral debridement. The repair group comprised 18 patients with a mean age of 38; the debridement group comprised 18 patients with a mean age of 39. All patients underwent the same rehabilitation protocol postoperatively. At a minimum of 1 year, all patients were assessed using a validated Hip Outcome Score (HOS) to determine hip function, and also completed a simple subjective outcome measure. Results All 36 patients were available for follow‐up at an average time of 32 months (range, 12 to 48). In both groups, HOSs for activities of daily living (ADL) and sports improved significantly from before surgery to the final follow‐up ( P < .05). The postoperative ADL HOS was significantly better in the repair group (91.2; range, 73 to 100) compared with the debridement group (80.9; range, 42.6 to 100; P < .05). Similarly, the postoperative sports HOS was significantly greater in the repair group (88.7; range, 28.6 to 100) than in the debridement group (76.3; range, 28.6 to 100; P < .05). Additionally, patient subjective outcome was significantly better in the labral repair group ( P = .046). Conclusions Arthroscopic treatment of femoroacetabular impingement with labral repair in female patients resulted in superior improvement in hip functional outcomes compared with labral debridement. In addition, a greater number of patients in the repair group subjectively rated their hip function as normal or nearly normal after surgery compared with the labral debridement group. Level of Evidence Level I, prospective randomized study.

Abstract This article reviews the current status of healthcare provision in the US with regards to reconstructive surgery affecting physical appearance and suggests future directions for outcomes research and patient advocacy. It discusses surgery for children born with congenital anomalies, breast surgery, body contouring surgery, and the provision of psychosocial services in the United States.

AbstractFollicular mucinosis (FM) and folliculotropic mycosis fungoides (MF) are rare in children, and data regarding long‐term outcomes are limited. We sought to describe clinical and histopathologic findings of children with FM with and without MF, as well as treatments administered and clinical outcomes. We conducted a retrospective chart review of patients younger than 22 years (at time of diagnosis) with a biopsy demonstrating FM who were seen in the Dermatology Department at the Mayo Clinic from September 1, 1999, to September 1, 2010. Eleven patients (six male, five female) ages 11 to 19 years at the time of diagnosis met the inclusion criteria. Follow‐up data were available for 10 patients, with a mean duration of 4.9 years. The head, neck, and extremities were the most common sites of involvement, and lesions were follicular‐based papules (18%), scaly alopecic patches and plaques (45%), or a combination of the two (36%). Overall, three patients were confirmed to have MF. T‐cell receptor gene rearrangement demonstrated clonality in two cases and was equivocal in one case. Treatments included topical corticosteroids, topical retinoids, oral minocycline, and, in patients with MF, ultraviolet light and topical bexarotene. Lesions resolved completely in seven patients, partially in one, and not at all in two (no follow‐up data on one patient). Of the three patients with MF, two had complete resolution, and one has intermittent flares. To our knowledge, no patients developed other lymphoproliferative disorders. FM in children is rare. A histopathologic diagnosis of FM does not equate to folliculotropic MF in all cases. Most patients responded to treatment with topical steroids, topical retinoids, or phototherapy. In our series of patients, the disease ran a benign course.

Abstract Background Although many probiotic products are currently available in yogurt or pill form in the United States ( US ), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population. Objective This study examined how patients with chronic gastrointestinal ( GI ) diseases view the regulation of probiotics. Design We conducted a multi‐site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review]. Results We conducted 22 focus groups with 136 patients with major gastrointestinal ( GI ) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs. Discussion and conclusion If GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.

Abstract Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face‐to‐face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference.