Understanding organization structures of the college, university, high school, clinical, and professional settings

Athletes participate at many different levels of competition--from amateur to professional, from backyard sandlot to Yankee Stadium. There are as many different organized structures involved in providing medical care to athletes as there are types of athletes themselves. Although the organizational structures involved in providing medical care for a little league team in a small town are different from those involved in providing care for a professional baseball team, the mission is the same-caring for athletes. This is the central theme of this article. Though there are different organizational structures, there are more common threads than differences in the mission of those who provide medical care for athletes at any level.     

Costimulatory receptors in jawed vertebrates: conserved CD28, odd CTLA4 and multiple BTLAs

CD28 family of costimulatory receptors is comprised of molecules with a single V-type extracellular Ig domain, a transmembrane and an intracytoplasmic region with signaling motifs. CD28 and cytotoxic T lymphocyte antigen-4 (CTLA4) homologs have been recently identified in rainbow trout. Other sequences similar to mammalian CD28 family members have now been identified using teleost, Xenopus and chicken databases. CD28- and CTLA4 homologs were found in all vertebrate classes whereas inducible costimulatory signal (ICOS) was restricted to tetrapods, and programmed cell death-1 (PD1) was limited to mammals and chicken. Multiple B and T Lymphocyte Attenuator (BTLA) sequences were found in teleosts, but not in Xenopus or in avian genomes. The intron/exon structure of btlas was different from that of cd28 and other members of the family. The Ig domain encoded in all the btla genes has features of the C-type structure, which suggests that BTLA does not belong to the CD28 family. The genomic localization of these genes in vertebrate genomes supports the split between the BTLA and CD28 families.     

Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients

There is a debate concerning the effects of antioxidant vitamins during radiation therapy: Can they reduce the adverse effects of therapy without reducing treatment efficacy? We examined whether dietary and plasma beta carotene and alpha tocopherol were related to severe acute adverse effects of radiation therapy and to cancer local recurrence. We conducted a prospective study of 540 head and neck cancer patients treated by radiation therapy. Dietary intakes of beta carotene and alpha tocopherol were measured by a validated food frequency questionnaire and plasma levels were determined. Acute adverse effects of radiation therapy and local recurrence were documented. A higher beta carotene dietary intake was associated with fewer severe acute adverse effects: odds ratio (OR) = 0.61 [95% confidence interval (CI) = 0.40-0.93]. There was a tendency for a similar effect for plasma beta carotene: OR = 0.73 (95% CI = 0.48-1.11). Participants with higher plasma beta carotene had a significantly lower rate of local recurrence (hazard ratio = 0.67; 95% CI = 0.45-0.99). Alpha tocopherol was not related to severe adverse effects or to cancer recurrence. This study suggests that a higher usual dietary beta carotene intake can reduce the occurrence of severe adverse effects of radiation therapy and decrease local cancer recurrence.     

CaxP and Ca/P in the parenteral feeding of preterm infants

Preterm infants requiring prolonged intravenous feeding frequently develop pathologic fractures and rickets. Infants who receive large amounts of calcium have fewer fractures. This observation led us to determine the maximal amounts of calcium and phosphate that can be added to parenteral nutrition solutions without the precipitation of calcium phosphate and to determine the optimal ratio of calcium to phosphate in these solutions. Clinical observations and in vitro experiments indicate that the product of calcium x phosphate (CaxP) in the dextrose-amino acid solution should not exceed 75 square millimolar (square millimole per square liter) to prevent calcium phosphate precipitation in barium-impregnated silicone rubber catheters and should not exceed 100 square millimolar in solutions administered through peripheral veins. Seven intake and output studies were performed in preterm infants to determine the ratio of calcium to phosphate (Ca/P) in the total parenteral nutrition solutions that minimized urinary losses. A Ca/P ratio of 5.0 minimized the sum of the calcium plus phosphate losses in the urine. However, experience with long-term total parenteral nutrition in preterm infants, awareness of the acute and life-threatening effects of body phosphate depletion, and an unmeasured endogenous enteric calcium secretion all suggest that a Ca/P ratio of approximately 3.0 provides a safer compromise between the acute and serious complications of phosphate deficiency and the chronic problems of fractures and rickets due to calcium deficiency.     

Safety and feasibility of motexafin gadolinium administration with whole brain radiation therapy and stereotactic radiosurgery boost in the treatment of ??6 brain metastases: a multi-institutional phase II trial

To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤ 6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥ 4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥ 3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.     

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3)

PURPOSE: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. METHODS AND MATERIALS: A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. RESULTS: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). CONCLUSION: In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.     

Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: a randomized trial among head and neck cancer patients

There has been concern that the efficacy of radiation therapy may be reduced when patients smoke or take antioxidant vitamins during treatment. Cancer prevention trials with beta carotene supplements documented adverse effects only among smokers. We conducted a randomized trial with alpha tocopherol (400 IU/day) and beta carotene (30 mg/day) supplements among 540 head and neck cancer (HNC) patients treated by radiation therapy. We examined whether smoking during radiation therapy modified the effects of the supplementation on HNC recurrence and on mortality. During the follow-up, 119 patients had a HNC recurrence and 179 died. Cox models were used to test the interaction between smoking and supplementation and to estimate the hazard ratios (HR) for HNC recurrence and death associated with the supplementation. Cigarette smoking either before or after radiation therapy did not modify the effects of the supplementation. In contrast, the interactions between supplementation and cigarette smoking during radiation therapy were statistically significant for HNC recurrence (p = 0.03), all-cause mortality (p = 0.02) and mortality from the initial HNC (p = 0.04). Among cigarette smokers, the HR were 2.41 (95% CI: 1.25-4.64) for recurrence, 2.26 (95% CI: 1.29-3.97) for all-cause mortality and 3.38 (95% CI: 1.11-10.34) for HNC mortality. All corresponding HR among nonsmokers were close to 1. These results could best be explained by the hypothesis that the combined exposures reduced the efficacy of radiation therapy. Particular attention should be devoted to prevent patients from both smoking and taking antioxidant supplements during radiation therapy.     

Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer

BACKGROUND:

The purpose of the study was to identify predictors of weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer.

METHODS:

This study was conducted as part of a phase 3 chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Their baseline characteristics, including lifestyle habits, diet, and quality of life, were assessed as potential predictors. Predictors were identified using multiple linear regressions. The reliability of the model was assessed by bootstrap resampling. A receiver operating characteristics curve was generated to estimate the model's accuracy in predicting critical weight loss (≥5%).

RESULTS:

The mean weight loss was 2.2 kg (standard deviation, 3.4). Five factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P<.001), higher pre‐RT body weight (P<.001), stage II disease (P = .002), dysphagia and/or odynophagia before RT (P = .001), and a lower Karnofsky performance score (P = .028). There was no association with pre‐RT lifestyle habits, diet, or quality of life. The bootstrapping method confirmed the reliability of this predictive model. The area under the curve was 71.3% (95% confidence interval, 65.8‐76.9), which represents an acceptable ability of the model to predict critical weight loss.

CONCLUSIONS:

These results could be useful to clinicians for screening patients with early stage HN cancer treated by RT who require special nutritional attention. Cancer 2010. © 2010 American Cancer Society.