Utilizing a novel hybrid brachytherapy technique FINITO (Freehand Interstitial Needles in addition to Tandem and Ovoid) for locally advanced cervical cancer.

PURPOSE: We aimed to assess the clinical feasibility and advantages of using a novel hybrid brachytherapy technique by placing Freehand Interstitial Needles in addition to the Tandem and Ovoid applicator (FINITO) for the treatment of locally advanced cervical cancer (LAC). METHODS AND MATERIALS: A retrospective analysis was performed on two cohorts of patients with LACC treated at our institution: 29 patients in the FINITO group and 17 patients in the control group using T&O only approach. Clinical outcomes of interest included local control (LC), progression-free survival (PFS), overall survival (OS), and rates of acute and late toxicities. Kaplan-Meier methodology was used to estimate OS, PFS, and LC. Wilcoxon signed-rank test was used to compare the median values for dosimetry parameters. A p-value of ≤ 0.05 was considered statistically significant. All statistical analyses were performed using RStudio. RESULTS: At a median of 2 years there was no difference in rates of OS, PFS or LC between the FINITO and the control group of patients. The 2-year OS, PFS, and LC for the FINITO group were 59% (95% CI 34%-100%), 58% (95% CI 38%-89%), and 84% (95% CI 69%-100%), respectively. Late toxicities were significantly lower in the FINITO group for both gastrointestinal and genitourinary symptoms (p = 0.001 and 0.01, respectively) as compared to the T&O group. CONCLUSION: Based on the equivalent LC rate and lower toxicity profile, our FINITO technique appears to be an excellent alternative to the standard intracavitary brachytherapy in patients with advanced disease, especially in resource-limited settings.

Change in vaginal length and sexual function in women who undergo surgery ± radiation therapy for endometrial cancer.

PURPOSE: Endometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT. METHODS AND MATERIALS: Enrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function. RESULTS: Forty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (p = 0.02) while RT without dilation showed a significant decrease (p = 0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (p = 0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (p = 0.14). CONCLUSION: This data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.

Automated Lung Cancer Segmentation Using a PET and CT Dual-Modality Deep Learning Neural Network.

PURPOSE: To develop an automated lung tumor segmentation method for radiation therapy planning based on deep learning and dual-modality positron emission tomography (PET) and computed tomography (CT) images. METHODS AND MATERIALS: A 3-dimensional (3D) convolutional neural network using inputs from diagnostic PETs and simulation CTs was constructed with 2 parallel convolution paths for independent feature extraction at multiple resolution levels and a single deconvolution path. At each resolution level, the extracted features from the convolution arms were concatenated and fed through the skip connections into the deconvolution path that produced the tumor segmentation. Our network was trained/validated/tested by a 3:1:1 split on 290 pairs of PET and CT images from patients with lung cancer treated at our clinic, with manual physician contours as the ground truth. A stratified training strategy based on the magnitude of the gross tumor volume (GTV) was investigated to improve performance, especially for small tumors. Multiple radiation oncologists assessed the clinical acceptability of the network-produced segmentations. RESULTS: The mean Dice similarity coefficient, Hausdorff distance, and bidirectional local distance comparing manual versus automated contours were 0.79 ± 0.10, 5.8 ± 3.2 mm, and 2.8 ± 1.5 mm for the unstratified 3D dual-modality model. Stratification delivered the best results when the model for the large GTVs (>25 mL) was trained with all-size GTVs and the model for the small GTVs (<25 mL) was trained with small GTVs only. The best combined Dice similarity coefficient, Hausdorff distance, and bidirectional local distance from the 2 stratified models on their corresponding test data sets were 0.83 ± 0.07, 5.9 ± 2.5 mm, and 2.8 ± 1.4 mm, respectively. In the multiobserver review, 91.25% manual versus 88.75% automatic contours were accepted or accepted with modifications. CONCLUSIONS: By using an expansive clinical PET and CT image database and a dual-modality architecture, the proposed 3D network with a novel GTVbased stratification strategy generated clinically useful lung cancer contours that were highly acceptable on physician review.

Radiation induces ESCRT pathway dependent CD44v3+ extracellular vesicle production stimulating pro-tumor fibroblast activity in breast cancer.

Despite recent advances in radiotherapeutic strategies, acquired resistance remains a major obstacle, leading to tumor recurrence for many patients. Once thought to be a strictly cancer cell intrinsic property, it is becoming increasingly clear that treatment-resistance is driven in part by complex interactions between cancer cells and non-transformed cells of the tumor microenvironment. Herein, we report that radiotherapy induces the production of extracellular vesicles by breast cancer cells capable of stimulating tumor-supporting fibroblast activity, facilitating tumor survival and promoting cancer stem-like cell expansion. This pro-tumor activity was associated with fibroblast production of the paracrine signaling factor IL-6 and was dependent on the expression of the heparan sulfate proteoglycan CD44v3 on the vesicle surface. Enzymatic removal or pharmaceutical inhibition of its heparan sulfate side chains disrupted this tumor-fibroblast crosstalk. Additionally, we show that the radiation-induced production of CD44v3+ vesicles is effectively silenced by blocking the ESCRT pathway using a soluble pharmacological inhibitor of MDA-9/Syntenin/SDCBP PDZ1 domain activity, PDZ1i. This population of vesicles was also detected in the sera of human patients undergoing radiotherapy, therefore representing a potential biomarker for radiation therapy and providing an opportunity for clinical intervention to improve treatment outcomes.

Platelet rich plasma for hallux sesamoid injuries: a case series.

OBJECTIVE: Hallux sesamoid injuries are well described and can be debilitating and chronically disabling. The role of orthobiologics such as platelet-rich plasma (PRP) in sesamoid injuries has not been reported. This study describes three cases of recalcitrant hallux sesamoid injuries in teenage athletes who returned to impact activities, pain free, following one treatment of PRP. METHODS: This is a case-series study describing three teenage athletes presenting to a tertiary level pediatric sports medicine practice with chronic hallux sesamoid injuries. RESULTS: The three patients (two female, one male) described in this case series were 13-, 16-, and 17-year-old athletes. Their primary sports were ballet, basketball, and Irish step dance, respectively. All three athletes received PRP: two received unilateral treatment (one tibial sesamoid, one fibular sesamoid) and one received treatment to bilateral tibial sesamoids. The average duration of symptoms prior to PRP was 52.5 weeks (14-128 weeks). The average time out of their primary sport was 48.7 weeks (20-78 weeks). Three of the 4 sesamoids treated with PRP were tibial sesamoids. Each site of injury was treated with one treatment of leukocyte-rich PRP. All three athletes were cleared to return to impact activities such as running and jumping at 6-9 weeks following PRP, specifically 9 weeks after the final PRP injection for the patient who underwent bilateral treatments. CONCLUSION: In the three cases provided of sesamoid injuries treated with PRP, the time to return to impact activities was less than reported for athletes not treated with PRP. Acknowledging that other management factors likely contributed to return to impact activities, this case series sets the groundwork for future research investigating the role of PRP with needle fenestration in the treatment of sesamoid injuries.

Hallux Sesamoid Injury Characteristics in Young Athletes Presented to the Sports Medicine Clinic.

OBJECTIVE: To investigate clinical diagnoses, sports participation, and return to sport timeline associated with hallux sesamoid injuries with sex comparisons. DESIGN: Descriptive epidemiology study. SETTING: Sports medicine clinics at a tertiary-level pediatric medical center. PATIENTS: Six hundred eighty-three young athletes (546 women and 137 men). INDEPENDENT VARIABLES: Sex (women vs men). MAIN OUTCOME MEASURES: Clinical diagnoses, participating sports, and injury timeline. RESULTS: The most common diagnosis was sesamoiditis (62.6%). The top 3 primary sports were dance (34.6%), running (13.7%), and soccer (11.7%). When stratified by sex, dance (40.1%), running (13.6%), and soccer (10.7%) were the top primary sports for women while running (19.4%), soccer (18.5%), and basketball (11.3%) were the leading diagnoses for male athletes. The mean time between injury occurrence and first clinic visit was 135.5 ± 229.3 days. The mean time between the first clinic visit and return to sport was 104.3 ± 128.2 days. Comparison by sex showed that women had a longer mean time than men (women: 111.5 ± 132.5 days, men: 67.2 ± 96.3 days, P = 0.001). The mean time from injury occurrence to return to sport was 235.2 ± 281.0 days. Women showed a longer mean timeline for return to sport compared with men (women: 245.2 ± 288.2 days, men: 179.3 ± 231.9 days, P = 0.014). CONCLUSION: Sesamoiditis was the most common diagnosis, and dance, running, and soccer were top 3 sports. The most salient finding was that women taking almost twice as long to return the sport or activity compared with men, which likely stems from delay of reporting symptom onset to clinics.

Special Considerations for Growing Dancers.

Care of young dancers requires a unique approach during a critical time of growth and development. Young dancers' well-being depends on factors including sleep, mental health, growth-associated musculoskeletal imbalances, and nutrition. Puberty is a particularly important time for young dancers. It coincides with an increased commitment to their art form and physical/psychosocial changes. It is imperative for practitioners to understand these various factors in order to optimize young dancers' health and allow them to safely train and perform.

Part I: Crossfit-Related Injury Characteristics Presenting to Sports Medicine Clinic.

OBJECTIVE: To investigate CrossFit-related injuries presenting to a pediatric sports medicine clinic. DESIGN: Retrospective review of pediatric CrossFit-related injuries from between January 1, 2003, and June 31, 2016. SETTING: Pediatric sports medicine clinic at a tertiary-level academic medical center. PATIENTS: Patients with injury related to CrossFit participation. INDEPENDENT VARIABLES: Sex, age, injury site, diagnosis, diagnostic imaging, and treatment. MAIN OUTCOME MEASURES: Annual CrossFit-related injury proportion (%) over time. RESULTS: One hundred fifteen medical identified (N = 55 female; mean age, 25.2 ± 10.4 years). Proportion of CrossFit-related injuries presenting to clinic relative to overall clinic volume consistently increased over time (Pearson r = 0.825; P = 0.022). Injury location included head (0.08%), trunk/spine (25.2%), upper extremity (27.0%), and lower extremity (47.0%). Common injured joints included knee (27%), spine (24.3%), and shoulder (16.5%). Nearly half of patients had a single diagnostic imaging (49.6%; 57 of 115). Most common diagnostics included magnetic resonance imaging (60.0%; 69 of 115), plain radiographs (51.3%; 59 of 115), ultrasound (10.4%; 12 of 115), and computerized tomographic scan (9.6%; 11 of 115). Most commonly prescribed treatments included physical/occupational therapy (38.3%; 44 of 115), activity modification (19.1%; 22 of 115), crutches/brace/splinting/compression sleeve (13.0%; 15 of 115), and non-steroidal anti-inflammatory medications (10.4%; 12 of 115). CONCLUSIONS: CrossFit-related injury proportion presenting to a pediatric sports medicine clinic increased over time. A notable proportion of injuries occurred to the trunk and spine. Advanced imaging was obtained in approximately half of these youth athletes. Further research in youth CrossFit athletes is required surrounding mechanism of injury to prevent future injury in this mode of training for youth athletes.

Part II: Comparison of Crossfit-Related Injury Presenting to Sports Medicine Clinic by Sex and Age.

OBJECTIVE: To examine CrossFit-related injuries based on sex and age. DESIGN: Retrospective case series. SETTING: A tertiary-level pediatric sports medicine clinic. PARTICIPANTS: CrossFit athletes. MAIN OUTCOME MEASURES: CrossFit-related injuries by sex (males vs females) and age groups (≤19 years vs >19 years) using a χ analysis with P = 0.05, odds ratio (OR), and 95% confidence interval (95% CI). RESULTS: Among injured CrossFit athletes, female athletes sustained lower extremity injuries more frequently than male athletes (P = 0.011; OR, 2.65; 95% CI, 1.25-5.65). In observed CrossFit injuries, shoulder injuries were more frequently observed in male athletes compared with female athletes (P = 0.049; OR, 2.79; 95% CI, 0.98-7.95). Additionally, a greater proportion of CrossFit athletes aged 19 years and younger suffered trunk/spine injuries than those older than 19 years (P = 0.027; OR, 2.61; 95% CI, 1.10-6.21) in injured CrossFit athletes. CONCLUSIONS: The current results indicated sex- and age-specific susceptibility to CrossFit-related injuries based on body parts and diagnoses. The presented information may be useful to develop a safer exercise program, especially for pediatric and adolescent CrossFit participants.

The vaginal cylinder: Misunderstood, misused, or trivial? An in-depth dosimetric and multiinstitutional outcome investigation.

PURPOSE: The purpose of the study was to investigate the impact on dose distribution and radiobiological metrics of common high-dose-rate vaginal brachytherapy treatment parameters and to analyze multiinstitutional data for clinically significant impact on outcomes in early-stage endometrial cancer. METHODS AND MATERIALS: Treatment plans were created for all combinations of prescription parameters and used to quantify the dosimetric impact of each parameter and to estimate the dose delivered using common voxel-integrated radiobiological metrics. A rating system, based on risk grouping from GOG and PORTEC trials, was used to consolidate staging information into a cancer "aggressiveness" measure. Correlations between the rating, toxicity, disease recurrence, and plan parameters were investigated. RESULTS: When prescribing to 5 mm depth, the variation caused by the diameter was very large across all dose metrics, ranging from 51% to 175% increase with the most divergence in BEDmax. For surface prescription, changing the cylinder diameter from 4 cm to 2 cm caused the dose metrics of BEDmin, Dmin, and gBEUD (a = -3) to increase by 117%, 67%, and 52%, respectively. Prescription to 5-mm depth caused changes across all dose metrics of 260% compared with surface prescription for a 2-cm cylinder. Deeper prescription point (p = 0.005) and longer treatment length (p = 0.01) were correlated with increased stenosis rates. No correlation between recurrence and any plan parameter was found. CONCLUSIONS: Dramatic differences in dose distributions arise by small variations of plan parameters, with large impact on rates of vaginal stenosis, but no clear relation with local recurrence. To help radiation oncologists interpret the magnitude of these effects for their patients, we created a tool that allows comparison between dose and fractionation parameters.

The Evaluation of Strength, Flexibility, and Functional Performance in the Adolescent Ballet Dancer During Intensive Dance Training.

BACKGROUND: Adolescent ballet dancers have a higher incidence of injury than adult professional dancers. It is unclear which factors, including biomechanical changes related to intense dance training and/or the growth process itself, contribute to increased injury risk in this population. OBJECTIVE: To assess changes in strength, flexibility, and functional performance in adolescent ballet dancers during a summer intensive dance program. DESIGN: Prospective cohort study. SETTING: Performing arts school in a suburb of Massachusetts. PARTICIPANTS: A convenience sample of 58 male and female ballet dancers, 12 to 17 years old, was enrolled. One dancer did not have functional testing due to injury, but strength and range of motion results were included. METHODS: Paired sample t-test was used to evaluate changes in (1) strength: lower abdominal muscle strength evaluated by the Kendall double leg lowering test; (2) flexibility: passive range of motion in hip extensibility, hip internal rotation, hip external rotation, hip turnout, and ankle dorsiflexion; and (3) functional athletic and dance assessment: the star excursion balance test (SEBT), vertical jump test, and dance technique performing demi-plié and passé dance positions. MAIN OUTCOME MEASUREMENTS: Change in strength, flexibility, and functional dance measurements pre- and postsummer intensive dance training. RESULTS: Lower abdominal strength testing improved 11° on the Kendall test (P < .001); lower extremity passive flexibility was reduced in all tested ranges bilaterally. Dance technique, in performing demi-plié and passé dance positions, improved. More dancers demonstrated correct knee alignment during demi-plié (P < .001-.002) and hip alignment during plié (P = .01-.04). Dancers also had greater active hip turnout in first position passé of 2 to 3° (P = .02-.05). No significant change was found in functional athletic performance as measured by the SEBT and vertical jump test. CONCLUSION: Adolescent dancers in this study cohort who participated in a summer intensive dance program improved lower abdominal muscle strength as well as functional dance technique in demonstrating correct alignment performing demi-plié and passé dance positions despite a decrease in passive lower extremity range of motion. Further research is needed to clarify the role of these findings in training for young dancers in order to move forward injury prevention efforts. LEVEL OF EVIDENCE: II.

Increasing age predicts poor cervical cancer prognosis with subsequent effect on treatment and overall survival.

PURPOSE: Stage and histology are well-established prognostic factors for cervical cancer, but the importance of age has been controversial and a clear role for this factor has not yet been defined. Thus, we aim with this study to evaluate the significance of age as an independent prognostic factor in women with cervical cancer and evaluate the therapeutic consequences and survival outcomes as they relate to this factor. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results (SEER) database was used to retrospectively analyze patients diagnosed with cervical cancer from 1973 to 2013 in the United States. Data collected included demographics, tumor histology and stage, treatment details, and survival outcomes. Age was grouped into 20-49, 50-69, ≥70 years. Stage was localized (FIGO IA-IB1), regional (IB2-IVA), and distant (IVB). Treatments were classified as "aggressive" (surgery, external beam radiation therapy [XRT] + brachytherapy [BT], surgery + BT, surgery + XRT, or surgery + XRT + BT) or "nonaggressive" (XRT alone, BT alone, or no treatment). Statistical analysis performed on these data included the use of the Log-Rank test, χ2 analysis, and the Cox proportional hazards model. RESULTS: Forty-six thousand three hundred fifty women with cervical cancer were identified using the SEER database. 54% were aged <50 years, 33% 50-69 years, and 13% ≥70 years. Older women, particular those over age 70 years, show significantly decreased survival trends when stratified by stage and histology (p < 0.0001). Furthermore, taking stage, histology, race, and treatment into account, increasing age demonstrates negative prognostic significance with a hazard ratio of 2.87 for women over age 70 years and 1.46 for women aged 50-69 years. In addition, women over 70 years, regardless of stage, are significantly more likely to receive nonaggressive treatment regimens (<0.0001), or no treatment at all (p < 0.0001). Finally, older women gain a significant survival advantage from treatment, even with less-aggressive regimens, as compared with no treatment at all (p < 0.0001), with BT alone showing the greatest survival benefit (p < 0.0001 vs no treatment; p < 0.0087 vs XRT) among less-aggressive therapies. When evaluated by stage, BT continues to hold a significant survival advantage for localized, regional, and distant disease in individuals over age 70 years (localized: p = 0.0009 vs no treatment; regional and distant: p < 0.0001 vs no treatment), with both an overall survival and disease-specific survival benefit over XRT seen as well for women with distant disease (p < 0.0001). CONCLUSIONS: Older women with cervical cancer show a poor overall survival trend that remains consistent among various stages and histologic subtypes. Risk analysis of this study population supports that age is an independent negative prognostic factor, even when accounting for stage, histology, and race. Furthermore, older women receive less-aggressive treatment as compared with their younger counterparts, with a significant number receiving no treatment at all. Despite this, older women still obtain a significant survival benefit with less-aggressive therapies, particularly with BT alone. Most interesting is that BT shows a survival benefit for older women among all cervical cancer stages, supporting the immense potential clinical benefit. In fact, women over 70 years with more advanced stage disease showed a significant survival benefit, both overall survival and disease-specific survival, with BT over external beam radiotherapy as well. Previous studies have created a foundation of literature, which shows that inclusion of BT in treatment regimens among all age groups improves survival and that older women in general are less likely to be adequately treated for cervical cancer. The novelty of this study lies in the fact that it demonstrates that older women, who we show are at risk for a poorer overall prognosis because of their age, are not only receiving appropriate treatment less often, they are also dying more frequently because of it. Our data support that older women are a high-risk group of patients who would benefit significantly from treatment, even if that treatment is BT alone. BT for cervical cancer is a tolerable procedure, even for most elderly women, and should, therefore, remain a standard clinical option for this population, regardless of their stage or histology at diagnosis.

Body Mass Index and Menstrual Patterns in Dancers.

Questionnaires were distributed to investigate body mass index (BMI) and menstrual patterns in female dancers aged 12 to 17 years. The study cohort consisted of 105 dancers, mean age 14.8 ± 1.1 years, and mean BMI 19.5 ± 2.3 kg/m2. In all, 92% were healthy weight for height. First menses age ranged from 10 to 15 years (mean 12.9 ± 1.1 years). A total of 44% reported irregular menses; of those, 14% described irregularity as "every other month," 37% as "every 3 months," and 49% as "skips a month occasionally." A total of 36% of the dancers stop getting their menses during times of increased activity/dance, and 30% have gone >3 months at any time without getting their menses. A significant negative correlation between BMI and age of first menses was found with lower BMI associated with increased age of first menses (linear regression, ß = -0.49, P = .021). This study supports an association between BMI and age of menarche among young female dancers. Given bone health reliance on hormonal milieu in female dancers, future research is warranted.

Femoral Neck Stress Fractures in Children Younger Than 10 Years of Age.

BACKGROUND: Femoral neck stress fractures are rare in healthy children, with only 9 cases previously reported. The present article reviews our institutional experience with femoral neck stress fractures in children younger than 10 years of age, to highlight the unique features of this condition. METHODS: We undertook a retrospective review of clinical records of patients who had been treated at our institution for an idiopathic femoral neck stress fracture between 2000 and 2014. To focus on children rather than adolescents, the World Health Organization's definition of adolescent as a person between 10 and 19 years of age was used; we thereby limited our analysis to patients younger than 10 years of age. RESULTS: The study included 6 patients (3 males, 3 females) treated for an idiopathic femoral neck stress fracture, with a mean age at diagnosis of 7.7 years (range, 5.2 to 8.9 y). All patients presented with a limp, which worsened with activity and had persisted for a mean of 5 weeks (range, 2 to 9 wk). None of the patients had experienced an increase in activity level or sporting volume before symptom onset. On examination, 3 patients experienced pain with terminal hip flexion and 3 patients demonstrated pain-free hip range of motion. Plain radiography demonstrated inferior femoral neck cortical disruption, suggesting a compression-type stress fracture mechanism. The diagnosis was confirmed by cross-sectional imaging in all cases. All patients were initially treated with 6 to 8 weeks of non-weight-bearing followed by 4 to 6 weeks of partial weight-bearing, leading to complete healing in 4 patients. Two patients demonstrated incomplete healing and were managed with spica casting for an additional 6 weeks. CONCLUSIONS: Our case series illustrates the unique features of this rare condition in children, with a history and examination profile distinct from those of adolescents and adults. Compliance with weight-bearing restrictions is difficult in this population and hip spica casting may be required to permit complete healing. LEVEL OF EVIDENCE: Level IV-case series.

Therapy of pancreatic cancer via an EphA2 receptor-targeted delivery of gemcitabine.

First line treatment for pancreatic cancer consists of surgical resection, if possible, and a subsequent course of chemotherapy using the nucleoside analogue gemcitabine. In some patients, an active transport mechanism allows gemcitabine to enter efficiently into the tumor cells, resulting in a significant clinical benefit. However, in most patients, low expression of gemcitabine transporters limits the efficacy of the drug to marginal levels, and patients need frequent administration of the drug at high doses, significantly increasing systemic drug toxicity. In this article we focus on a novel targeted delivery approach for gemcitabine consisting of conjugating the drug with an EphA2 targeting agent. We show that the EphA2 receptor is highly expressed in pancreatic cancers, and accordingly, the drug-conjugate is more effective than gemcitabine alone in targeting pancreatic tumors. Our preliminary observations suggest that this approach may provide a general benefit to pancreatic cancer patients and offers a comprehensive strategy for enhancing delivery of diverse therapeutic agents to a wide range of cancers overexpressing EphA2, thereby potentially reducing toxicity while enhancing therapeutic efficacy.

Physical Activity Level and Symptom Duration Are Not Associated After Concussion.

BACKGROUND: Physical rest after a concussion has been described as a key component in the management of the injury. Evidence supporting this recommendation, however, is limited. PURPOSE: To examine the association between physical activity and symptom duration in a cohort of patients after a concussion. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This study included 364 patients who were diagnosed with a concussion, were seen by a physician within 3 weeks of injury, and completed a questionnaire at the initial clinic visit. The questionnaire assessed the postconcussion symptom scale (PCSS) score, previous number of concussions, presence of the loss of consciousness or amnesia at the time of injury, and prior treatment for headaches. During each follow-up clinic visit, physical activity level was self-reported. A Cox proportional hazard model was constructed to determine the association between symptom duration, initial clinic visit responses, and self-reported physical activity level after the injury. RESULTS: Study participants ranged in age from 8 to 27 years (mean age, 15.0 years) and had sustained a mean of 0.8 prior concussions; 222 patients (61%) were male. On initial examination, the mean PCSS score was 34.7. The mean symptom duration was 48.9 days after the injury. Among the variables included in the model, initial PCSS score and female sex were independently associated with symptom duration, while physical activity level after the injury was not. For participants aged between 13 and 18 years, however, higher levels of physical activity after the injury were associated with a shorter symptom duration. CONCLUSION: Results from this study indicate that physical activity after the injury may not be universally detrimental to the recovery of concussion symptoms.

Athletes Doing Arabesques: Important Considerations in the Care of Young Dancers.

Dance is as much a sport as an art form. Sports medicine clinicians seeing dancers in their practice will need to be familiar with the unique characteristics of dance in order to provide proper care. Dance encompasses different forms, which vary in equipment and terminology. The epidemiology of dance injuries has historically focused on ballet, but there is increasing research on other dance forms. Lower extremity and back injuries predominate. Injury prevention, both primary and secondary, is at the heart of dance medicine. Primary prevention includes preseason conditioning, identifying risk factors for injury, and recognizing the female athlete triad. Secondary prevention includes a comprehensive approach to injury rehabilitation, an appreciation for the unique demands of dance, and an understanding of the particulars of the injury being treated. Dancers may have difficulty accessing medical care or following prescribed advice; the proactive clinician will anticipate these situations.

"Nutcracker Fracture" in a Ballet Dancer Performing in The Nutcracker.

A 26-year-old female professional dancer sustained an acute injury to her mid-foot during a performance of The Nutcracker. An intra-articular, comminuted, minimally displaced fracture of the cuboid was found. The patient was treated non-operatively with cast and boot immobilization, modified weightbearing, and progressive rehabilitation. She was able to return to professional dance at 6 months post-injury and continues to dance professionally over 1 year out from injury without issue. The unique demands of classical ballet, especially dancing en pointe, increase the risk for mid-foot fractures, and clinicians should have a high-index of suspicion in dancers suffering an acute injury to the foot and ankle with greater than expected pain or swelling. Multiple imaging modalities can be used to make the diagnosis, to include plain film radiographs, MRI, and CT scan. Fracture characteristics and patient-specific factors should be taken into account when deciding on a treatment plan.

Design and Characterization of Novel EphA2 Agonists for Targeted Delivery of Chemotherapy to Cancer Cells.

The development of novel, targeted delivery agents for anti-cancer therapies requires the design and optimization of potent and selective tumor-targeting agents that are stable and amenable to conjugation with chemotherapeutic drugs. While short peptides represent potentially an excellent platform for these purposes, they often get degraded and are eliminated too rapidly in vivo. In this study, we used a combination of nuclear magnetic resonance-guided structure-activity relationships along with biochemical and cellular studies to derive a novel tumor-homing agent, named 123B9, targeting the EphA2 tyrosine kinase receptor ligand-binding domain. Conjugating 123B9 to the chemotherapeutic drug paclitaxel (PTX) via a stable linker results in an agent that is significantly more effective than the unconjugated drug in both a pancreatic cancer xenograft model and a melanoma lung colonization and metastases model. Hence, 123B9 could represent a promising strategy for the development of novel targeted therapies for cancer.

Pancreatic Cancer Combination Therapy Using a BH3 Mimetic and a Synthetic Tetracycline.

Improved treatments for pancreatic cancer remain a clinical imperative. Sabutoclax, a small-molecule BH3 mimetic, inhibits the function of antiapoptotic Bcl-2 proteins. Minocycline, a synthetic tetracycline, displays antitumor activity. Here, we offer evidence of the combinatorial antitumor potency of these agents in several preclinical models of pancreatic cancer. Sabutoclax induced growth arrest and apoptosis in pancreatic cancer cells and synergized with minocycline to yield a robust mitochondria-mediated caspase-dependent cytotoxicity. This combinatorial property relied upon loss of phosphorylated Stat3 insofar as reintroduction of activated Stat3-rescued cells from toxicity. Tumor growth was inhibited potently in both immune-deficient and immune-competent models with evidence of extended survival. Overall, our results showed that the combination of sabutoclax and minocycline was highly cytotoxic to pancreatic cancer cells and safely efficacious in vivo.