Citations

Purpose The purposes of this study were to determine whether delayed‐onset ulnar neuritis (DOUN) after elbow contracture release can be prevented and to compare the efficacy of ulnar nerve decompression versus subcutaneous transposition. Methods A retrospective study of 563 consecutive arthroscopic elbow contracture releases was conducted. The prophylactic efficacy of (1) subcutaneous transposition, (2) ulnar nerve decompression, (3) limited ulnar nerve decompression (7 to 8 cm), and (4) mini‐decompression (4 to 6 cm) was assessed prospectively. The efficacy of prophylactic strategies (transposition, decompression, limited decompression, or mini‐decompression) in preventing DOUN was compared by univariate survival analysis. Patients who underwent a subcutaneous transposition were matched with patients who underwent a standard open decompression or a limited decompression, according to gender, age (±10 years), diagnosis, and preoperative motion. This analysis was repeated after we excluded the patients who underwent associated open procedures (e.g., hardware removal). Results DOUN occurred in 26 of 235 patients (11%) who did not undergo any prophylactic procedure versus 8 of 295 patients (3%) who underwent a prophylactic ulnar nerve decompression or transposition at the time of contracture release ( P < .001). The neurologic impairment was significantly less severe after prophylactic decompression compared with patients without any prophylactic intervention (grade on Neuropathy Grading Scale, 2 v 4; P = .03). Ulnar nerve transposition and decompression were equally protective. The decompression length was the only factor significantly related to the failure of the prophylactic intervention (odds ratio, 0.19; P = .02). A mini‐decompression was not as effective as a prophylactic procedure, whereas a limited decompression was equal to a standard decompression. The case‐control analysis showed that the decompression and transposition had equal preventive effects but the transposition was associated with a higher rate of wound complications (19% v 4%, P = .03). Conclusions DOUN is a complication of arthroscopic elbow contracture release. Its incidence and severity can be reduced by limited open ulnar nerve decompression or transposition. Level of Evidence Level II, prospective comparative study with retrospective analysis.

AbstractBackgroundBasosquamous carcinoma (BSC) and metatypical basal cell carcinoma (MBCC) are uncommon tumors poorly defined in the literature. Available studies suggest these tumors carry a greater risk of recurrence and metastases than basal cell carcinomas (BCCs) and, in some studies, squamous cell carcinomas. Formal treatment recommendations are not fully established.ObjectiveTo analyze BSC and MBCC separately, evaluate whether they are distinct tumor subtypes, and analyze Mohs micrographic surgery (MMS) efficacy for BSC and MBCC.MethodsRetrospective review of medical records and histologic specimens was conducted for 293 patients with 303 biopsy‐proven BSCs or MBCCs treated with MMS between 1996 and 2004. In total, 32 BSCs and 128 MBCCs were identified. Surgical and follow‐up data were analyzed.ResultsKaplan–Meier estimates of recurrence‐free survival after MMS were 100% at one year for both tumor subtypes and were 100% for BSC and 93.8% for MBCC at 5 years. Initial mean sizes were 1.5 cm for BSC and 1.3 cm for MBCC. Approximately 7% represented recurrent tumors at surgery. Of six patients with recurrences, none had known metastatic disease.LimitationsLimitations include retrospective design, analysis of only head and neck sites, and small sample sizes.ConclusionBSC and MBCC showed no significant distinguishing characteristics to separate them into two BCC subtypes. Reported recurrence rates for BSC and MBCC are 12–45% with wide local excision; estimated recurrence rates are 4.1% with MMS. Our study showed recurrence‐free survival of 95.1% at five years. Hence, MMS is effective in treating these BCC subtypes.

Abstract Inflammation is a facilitating process for multiple cancer types. It is believed to affect cancer development and progression through several etiologic pathways, including increased levels of DNA adduct formation, increased angiogenesis, and altered antiapoptotic signaling. This review highlights the application of inflammatory biomarkers in epidemiologic studies and discusses the various cellular mediators of inflammation characterizing the innate immune system response to infection and chronic insult from environmental factors. Included is a review of six classes of inflammation-related biomarkers: cytokines/chemokines, immune-related effectors, acute-phase proteins, reactive oxygen and nitrogen species, prostaglandins and cyclooxygenase-related factors, and mediators such as transcription factors and growth factors. For each of these biomarkers, we provide a brief overview of the etiologic role in the inflammation response and how they have been related to cancer etiology and progression within the literature. We provide a discussion of the common techniques available for quantification of each marker, including strengths, weaknesses, and potential pitfalls. Subsequently, we highlight a few under-studied measures to characterize the inflammatory response and their potential utility in epidemiologic studies of cancer. Finally, we suggest integrative methods for future studies to apply multifaceted approaches to examine the relationship between inflammatory markers and their roles in cancer development. Cancer Epidemiol Biomarkers Prev; 23(9); 1729–51. ©2014 AACR.

SummaryBackgroundThe ideal means of identifying obesity in children and adolescents has not been determined although body mass index (BMI) is the most widely used screening tool.ObjectiveWe performed a systematic review and meta‐analysis of studies assessing the diagnostic performance of BMI to detect adiposity in children up to 18 years.MethodsData sources were EMBASE, MEDLINE, Cochrane, Database of Systematic Reviews Cochrane CENTRAL, Web of Science and SCOPUS up to March 2013. Studies providing measures of diagnostic performance of BMI and using body composition technique for body fat percentage measurement were included.ResultsThirty‐seven eligible studies that evaluated 53 521 patients, with mean age ranging from 4 to 18 years were included in the meta‐analysis. Commonly used BMI cut‐offs for obesity showed pooled sensitivity to detect high adiposity of 0.73 (confidence interval [CI] 0.67–0.79), specificity of 0.93 (CI 0.88–0.96) and diagnostic odds ratio of 36.93 (CI 20.75–65.71). Males had lower sensitivity. Moderate heterogeneity was observed (I2 = 48%) explained in meta‐regression by differences across studies in race, BMI cut‐off, BMI reference criteria (Center for Disease Control vs. International Obesity Task Force) and reference standard method assessing adiposity.ConclusionBMI has high specificity but low sensitivity to detect excess adiposity and fails to identify over a quarter of children with excess body fat percentage.

Abstract Background: Allergic diseases signify immune dysregulation attributable to underlying genetics and environmental exposures. Associations between various allergies and hematopoietic cancers have been observed, albeit inconsistently; however, few prospective studies have examined the risk, and even fewer among older adults. Methods: We examined risk of incident hematopoietic cancers in those reporting allergic diseases in a population-based cohort of 22,601 older women (Iowa Women's Health Study). Self-reported allergic status, including asthma, hay fever, eczema, and/or other allergies, was determined via questionnaire in 1997 (mean age, 72 years; range, 63–81 years). Incident cancers were ascertained by linkage with the Iowa Cancer Registry from 1997 to 2011. Cox proportional hazards regression was performed to estimate multivariate-adjusted HR and 95% confidence intervals (CI) for myeloid (N = 177) and lymphoid (N = 437) malignancies, respectively. Results: Allergic diseases were not associated with risk of myeloid (HR, 1.00; 95% CI, 0.72–1.37) or lymphoid (HR, 0.99; 95% CI, 0.81–1.22) malignancies overall, or for most allergic and malignant subtypes examined. Self-reported asthma was positively associated with development of myelodysplastic syndrome (MDS; HR, 2.00; 95% CI, 0.93–4.32). In addition, there was a 30% to 40% decrease in risk of both lymphoid and myeloid cancers in those reporting rural residences but no association in those reporting urban residences; the interaction between residence and allergy was statistically significant for lymphoid malignancies (Pinteraction = 0.05). Conclusions and Impact: These results suggest that asthma may contribute to the pathogenesis of MDS, a finding consistent with the chronic antigen stimulation hypothesis. Susceptibility differences by location of residence are concordant with the hygiene hypothesis and merit additional exploration. Cancer Epidemiol Biomarkers Prev; 23(9); 1903–12. ©2014 AACR.

Rationale : Semaphorin 3A ( SEMA3A )-encoded semaphorin is a chemorepellent that disrupts neural patterning in the nervous and cardiac systems. In addition, SEMA3A has an amino acid motif that is analogous to hanatoxin, an inhibitor of voltage-gated K + channels. SEMA3A -knockout mice exhibit an abnormal ECG pattern and are prone to ventricular arrhythmias and sudden cardiac death. Objective : Our aim was to determine whether SEMA3A is a naturally occurring protein inhibitor of K v 4.3 (I to ) channels and its potential contribution to Brugada syndrome. Methods and Results : K v 4.3, Na v 1.5, Ca v 1.2, or K v 4.2 were coexpressed or perfused with SEMA3A in HEK293 cells, and electrophysiological properties were examined via whole-cell patch clamp technique. SEMA3A selectively altered K v 4.3 by significantly reducing peak current density without perturbing K v 4.3 cell surface protein expression. SEMA3A also reduced I to current density in cardiomyocytes derived from human-induced pluripotent stem cells. Disruption of a putative toxin binding domain on K v 4.3 was used to assess physical interactions between SEMA3A and K v 4.3. These findings in combination with coimmunoprecipitations of SEMA3A and K v 4.3 revealed a potential direct binding interaction between these proteins. Comprehensive mutational analysis of SEMA3A was performed on 198 unrelated SCN5A genotype–negative patients with Brugada syndrome, and 2 rare SEMA3A missense mutations were identified. The SEMA3A mutations disrupted SEMA3A’s ability to inhibit K v 4.3 channels, resulting in a significant gain of K v 4.3 current compared with wild-type SEMA3A. Conclusions : This study is the first to demonstrate SEMA3A as a naturally occurring protein that selectively inhibits K v 4.3 and SEMA3A as a possible Brugada syndrome susceptibility gene through a K v 4.3 gain-of-function mechanism.

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however, the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is overexpressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for patients with ccRCC diagnosed with or at risk of developing metastatic disease. Cancer Res; 74(17); 4796–810. ©2014 AACR.

SummaryThe role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil‐deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodelling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil‐deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) the initiating phase of events leading to Th2‐polarized pulmonary inflammation, (ii) the suppression Th1/Th17 pathways in lung‐draining lymph nodes, (iii) the recruitment of effector Th2 T cells to the lung, and finally, (iv) mechanisms of inflammatory resolution that re‐establish pulmonary homoeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil‐deficient strain of mice (iPHIL) that demonstrated an eosinophil‐dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC) and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re‐establishment of homoeostatic baseline. In this review, we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung following allergen provocation.