Citations

Context: Baseball throwing injuries are common. Emphasis on injury prevention and rehabilitation is made in an attempt to keep athletes on the field of competition. Interval throwing programs are an integral part of training, conditioning, and returning an injured baseball player to the game. Evidence Acquisition: Development of data-driven programs was based on the number, type, distance, and intensity of throws during games, across the spectrum of ages and positions for baseball athletes at all levels of play. Statistical analysis by age, position, and level of play determined the need for separate throwing programs. Means, the high range, game rules, and practical considerations were used to develop each data-based interval throwing program. Results: Data-based age and level-of-play interval throwing programs for pitchers, catchers, infielders, and outfielders have been developed, tested, and implemented for more than 10 years. Progression is based on type and location of injury, symptoms in response to throwing, and preinjury performance profile. Although the throwing programs are highly structured, there is ample opportunity to modify them to meet the needs of individual athletes. Conclusion: Data-based interval throwing programs for baseball athletes are an integral training and conditioning element for both injured and uninjured athletes who are preparing for sports participation. Medical team members should equip themselves with an understanding of how to use the programs for safe training, conditioning, and return to play.

Abstract Purpose: Immunotherapeutic modalities are commonly used for treatment of patients with melanoma. The therapeutic success in preclinical models has not yielded the expected clinical results. To understand this discrepancy, we attempted to define immune homeostasis of 209 patients with melanoma across stages of disease relative to normal controls. Experimental Design: Peripheral blood mononuclear cells (PBMC) and plasma were collected from patients and healthy donors. PBMC were analyzed for frequencies of natural killer, dendritic, and T cells and their functional status. Matched plasma samples were analyzed for the concentrations of 27 cytokines, chemokines, and growth factors. RNA was isolated from 24 metastatic melanoma tumor biopsies and profiled by microarray analysis. Results: The frequency of natural killer, T, and dendritic cells in patients does not significantly change across stages of melanoma. However, plasma concentrations of Th2 cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] in tumor-bearing patients were significantly higher than those with resected melanoma. Expression array analysis of metastatic melanoma revealed that the malignant melanocytes were not the source of the Th2 cytokines but did highly up-regulate vascular endothelial growth factor (VEGF) transcripts, consistent with plasma VEGF concentrations. In vitro VEGF exposure of normal PBMC lead to repolarization from Th1 to Th2 emulating the state of metastatic melanoma. Conclusions: Patients with metastatic melanoma exist in a state of Th2-mediated “chronic inflammation” as a result of at least VEGF overproduction by malignant tumors. These data support prior observations regarding the effect of VEGF on immune cell function and suggests consideration of VEGF inhibitors in future cancer immunotherapy clinical studies in metastatic melanoma.

Background: Identification of highly active individuals early after acute anterior cruciate ligament deficiency who are good candidates for nonoperative management is a clinical challenge. The University of Delaware has developed and validated a treatment algorithm and screening examination to distinguish between nonoperative and surgical candidates. Study Design: Review. Evidence Acquisition: A description of the decision-making rules and rehabilitation protocol for highly active individuals with anterior cruciate ligament deficiency is provided. Results from clinical trials, outcome studies, and biomechanical investigations conducted using the treatment algorithm and screening examination are also reviewed. Results: Patients identified as nonoperative rehabilitation candidates using these clinical guidelines have a far greater success rate than what has been reported when patients self-select nonoperative management. Furthermore, nonoperative outcomes are improved when patients participate in a perturbation-enhanced rehabilitation protocol. Divergent lower extremity movement patterns are consistent with the different functional abilities of the dichotomous patient groups identified with the screening examination. Conclusion: Given the differential patient response to anterior cruciate ligament injury, implementation of the decision-making guidelines discussed in this review offers clinicians the opportunity to provide individualized patient care rather than continuing with a blanket surgical treatment strategy.

AbstractEarly‐onset Alzheimer's disease (EOAD) is an increasingly diagnosed condition and is associated with genetic risk factors. This is one of the first studies exploring the lived experience of siblings of individuals with EOAD. We used structured questionnaires and semi‐structured interviews to assess a broad range of siblings’ experiences with and beliefs about EOAD, including knowledge, perceptions of personal risk, level of worry, and effects on life decisions. Participants (n = 24) were predominantly female (62.5%) and middle‐aged (mean = 56.8 years; range 37–83). When asked about risk factors, genetics was cited most frequently (62.5%). Several potential means of reducing AD risk were endorsed, with 54% reporting engagement in behaviors for this purpose (e.g., keeping mentally active). Participants ranged widely in their perceived personal risk of AD (range: 0–100; mean = 35.6%), with higher perceived risk associated with worry about AD (p < 0.01). Understanding siblings’ experiences with EOAD can inform how genetic counselors and healthcare professionals work with this population to facilitate risk communication and decision‐making about testing and healthcare.

A retrospective case review was carried out to report the outcomes in a contemporary case series of Ewing’s sarcoma originating in the hand. We identified five patients treated since 1995. All five had wide surgical excision, one by ray amputation. All were treated with chemotherapy. Four patients also received radiation therapy, two to treat metastases and two as an adjunct to local excision. There were no local recurrences. Two patients developed metastases. Both died of their disease. Neither of these two patients had received local postoperative radiation therapy; one did not receive chemotherapy before definitive surgery. The other three patients were alive and free of disease at last follow-up, 4 to 12 years after initial presentation.

Organochlorine exposure was linked to non-Hodgkin lymphoma (NHL) risk. To determine whether this relation is modified by immune gene variation, we genotyped 61 polymorphisms in 36 immune genes in 1172 NHL cases and 982 controls from the National Cancer Institute–Surveillance, Epidemiology, and End Results (NCI-SEER) study. We examined 3 exposures with elevated risk in this study: PCB180 (plasma, dust measurements), the toxic equivalency quotient (an integrated functional measure of several organochlorines) in plasma, and α-chlordane (dust measurements, self-reported termiticide use). Plasma (100 cases, 100 controls) and dust (682 cases, 513 controls) levels were treated as natural log-transformed continuous variables. Unconditional logistic regression was used to calculate β coefficients and odds ratios, stratified by genotype. Associations between all 3 exposures and NHL risk were limited to the same genotypes for IFNG (C−1615T) TT and IL4 (5′-UTR, Ex1-168C>T) CC. Associations between PCB180 in plasma and dust and NHL risk were limited to the same genotypes for IL16 (3′-UTR, Ex22+871A>G) AA, IL8 (T−251A) TT, and IL10 (A−1082G) AG/GG. This shows that the relation between organochlorine exposure and NHL risk may be modified by particular variants in immune genes and provides one of the first examples of a potential gene-environment interaction for NHL.

AbstractOver 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a &lt;25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567–72)

Subcutaneous nodules occur in approximately 20–25% of rheumatoid factor (RF)-positive rheumatoid patients. In this paper, we present a unique case of a 47-year-old healthy RF-negative woman with a 3-year history of necrobiotic nodules over the dorsum of her hands, extensor forearms, and lower extremities. This may represent an atypical presentation or a new rheumatoid variant.