Youth Pitcher Fatigue: Medial Elbow Laxity, Ultrasonographic Assessment of Flexor-Pronator Mass Energy Depletion, and Association With Pitch Count.

Background: Ulnar collateral ligament (UCL) injuries in youth pitchers continue to be concerning despite the institution of pitch count limits. Flexor-pronator mass fatigue can lead to diminished dynamic stability, resulting in greater stress on the UCL. Purpose/Hypothesis: To evaluate fatigue of the flexor-pronator mass by assessing changes in medial elbow laxity; noninvasively characterizing alterations in muscle glycogen; and identifying changes in subjective fatigue, strength, range of motion (ROM), pitching velocity, and accuracy with increasing pitches thrown by youth pitchers to their recommended 75-pitch count limit. It was hypothesized that, with increased pitches, medial elbow laxity would increase and that the glycogen content of the flexor-pronator mass would decrease. Study Design: Descriptive laboratory study. Methods: Healthy male pitchers aged 10 years (n = 22) threw 3 sets of 25 pitches with 12 minutes between sets (3 timepoints). Bilateral ulnohumeral joint gapping was measured by applying a standardized valgus force and utilizing ultrasound imaging. Relative changes in muscle glycogen in the bilateral flexor carpi radialis (FCR), and the flexor digitorum superficialis/flexor carpi ulnaris (FDS/FCU) muscles were measured with ultrasound software and recorded as fuel percentiles. Additional measures obtained included subjective fatigue, strength, ROM, velocity, and accuracy. Results: There were no differences in medial elbow joint-line gapping between the throwing and nonthrowing arms or between timepoints. The throwing arm demonstrated a significant decline in fuel percentile of the FCR from baseline to after 75 pitches (P = .05). There were no differences across timepoints for FDS/FCU fuel percentile values. Fatigue measurements for both arms were significantly higher at all timepoints compared with baseline (P≤ .03). Grip strength of the dominant arm after 75 pitches was decreased significantly compared with after 25 pitches (P = .02). Conclusion: Although an increase in medial elbow joint gapping was not demonstrated within the recommended 75 pitch count limit in 10-year-olds, a relative decrease in glycogen stores of the flexor-pronator mass did occur, as well as a decrease in grip strength, with increasing subjective fatigue. Clinical Relevance: This study provides a foundation for further objective testing of physiologic changes that occur with pitching to better guide pitch count limits and improve the safety of young athletes.

Regulatory and Ethical Aspects of Orthobiologic Therapies.

Orthobiologic therapies show significant promise to improve outcomes for patients with musculoskeletal pathology. There are considerable research efforts to develop strategies that seek to modulate the biological environment to promote tissue regeneration and healing and/or provide symptomatic relief. However, the regulatory pathways overseeing the clinical translation of these therapies are complex, with considerable worldwide variation. The introduction of novel biologic treatments into clinical practice raises several ethical dilemmas. In this review, we describe the process for seeking approval for biologic therapies in the United States, Europe, and Japan. We highlight a number of ethical issues raised by the clinical translation of these treatments, including the design of clinical trials, monitoring outcomes, biobanking, "off-label" use, engagement with the public, marketing of unproven therapies, and scientific integrity.

A robust prediction model for evaluation of plastic limit based on sieve # 200 passing material using gene expression programming.

This study aims to propose a novel and high-accuracy prediction model of plastic limit (PL) based on soil particles passing through sieve # 200 (0.075 mm) using gene expression programming (GEP). PL is used for the classification of fine-grained soils which are particles passing from sieve # 200. However, it is conventionally evaluated using sieve # 40 passing material. According to literature, PL should be determined using sieve # 200 passing material. Although, PL200 is considered the accurate representation of plasticity of soil, its' determination in laboratory is time consuming and difficult task. Additionally, it is influenced by clay and silt content along with sand particles. Thus, artificial intelligence-based techniques are considered viable solution to propose the prediction model which can incorporate multiple influencing parameters. In this regard, the laboratory experimental data was utilized to develop prediction model for PL200 using gene expression programming considering sand, clay, silt and PL using sieve 40 material (PL40) as input parameters. The prediction model was validated through multiple statistical checks such as correlation coefficient (R2), root mean square error (RMSE), mean absolute error (MAE) and relatively squared error (RSE). The sensitivity and parametric studies were also performed to further justify the accuracy and reliability of the proposed model. The results show that the model meets all of the criteria and can be used in the field.

American Medical Society for Sports Medicine Position Statement: Principles for the Responsible Use of Regenerative Medicine in Sports Medicine.

ABSTRACT: Many sports medicine physicians are currently considering introducing regenerative medicine into their practice. Regenerative medicine and the subclassification of orthobiologics are a complicated topic and have produced widely varying opinions. Although there is concern by government regulators, clinicians, scientists, patient advocacy organizations, and the media regarding the use of regenerative medicine products, there is also excitement about the potential benefits with growing evidence that certain regenerative medicine products are safe and potentially efficacious in treating musculoskeletal conditions. Sports medicine physicians would benefit from decision-making guidance about whether to introduce orthobiologics into their practice and how to do it responsibly. The purpose of this position statement is to provide sports medicine physicians with information regarding regenerative medicine terminology, a brief review of basic science and clinical studies within the subclassification of orthobiologics, regulatory considerations, and best practices for introducing regenerative medicine into clinical practice. This information will help sports medicine physicians make informed and responsible decisions about the role of regenerative medicine and orthobiologics in their practice.

Autologous fat grafting for nerve regeneration and neuropathic pain: current state from bench-to-bedside.

Despite recent advances in microsurgical techniques, functional recovery following peripheral nerve injury remains slow and inadequate. Poor peripheral nerve regeneration not only leaves patients with significant impairments, but also commonly leads to the development of debilitating neuropathic pain. Recent research has demonstrated the potential therapeutic benefits of adipose-derived stem cells, to enhance nerve regeneration. However, clinical translation remains limited due to the current regulatory burdens of the US FDA. A reliable and immediately translatable alternative is autologous fat grafting, where native adipose-derived stem cells present in the transferred tissue can potentially act upon regenerating axons. This review presents the scope of adipose tissue-based therapies to enhance outcomes following peripheral nerve injury, specifically focusing on their role in regeneration and ameliorating neuropathic pain.

The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial.

BACKGROUND: Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR. HYPOTHESIS: Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strength and volume, patient-reported outcome scores, and circulating biomarkers were measured at several time points through 6 months after surgery. Mixed-effects models were used to evaluate differences between treatment groups and time points, and as this was a pilot study, significance was set at P < .10. The Cohen d was calculated to determine the effect size. RESULTS: HGH was well-tolerated, and no differences in adverse events between the groups were observed. The HGH group had a 2.1-fold increase in circulating insulin-like growth factor 1 over the course of the treatment period (P < .05; d = 2.93). The primary outcome measure was knee extension strength, and HGH treatment increased normalized peak isokinetic knee extension torque by 29% compared with the placebo group (P = .05; d = 0.80). Matrix metalloproteinase-3 (MMP3), which was used as an indirect biomarker of cartilage degradation, was 36% lower in the HGH group (P = .05; d = -1.34). HGH did not appear to be associated with changes in muscle volume or patient-reported outcome scores. CONCLUSION: HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted. REGISTRATION: NCT02420353 ( ClinicalTrials.gov identifier).

Whole-Body Cryotherapy in Sports Medicine.

Cryotherapy has gained popularity among athletes across many sports. The main goals of cryotherapy, and specifically whole-body cryotherapy, are for injury prevention and counteracting negative inflammatory symptoms following athletic performance in hopes of improving recovery.

Minimally Invasive Ultrasound-Guided Carpal Tunnel Release: Preliminary Clinical Results.

Ultrasound-guided carpal tunnel release was performed on 14 patients (18 wrists) using dynamic expansion of the transverse safe zone. Our patient population included able-bodied patients and those with impairments. The first 8 cases (12 wrists) underwent the procedure in an operating room, the remainder in an outpatient setting. No complications occurred, and all patients were able to immediately resume use of their hands without therapy. Improvements in the Quick Form of the Disabilities of the Arm, Shoulder, and Hand Index and Boston Carpal Tunnel Questionnaire at 3 months were comparable to results reported with mini-open and endoscopic release. Our results show that ultrasound-guided carpal tunnel release can be safely and effectively performed in an outpatient setting.

Pathogenesis and Management of Tendinopathies in Sports Medicine.

OBJECTIVE: Tendinopathy is a major clinical problem in sports medicine and is often difficult to treat. Traditional therapeutic approaches have focused on reducing inflammation, yet research suggests that little to no inflammation is present in the tendons that fail to heal. The purpose of this review was to evaluate the effectiveness of the available treatment options for tendinopathy and to inform best clinical practices. DESIGN: A narrative review. METHODS: A comprehensive search of electronic databases (PubMed, Google Scholar and Web of Science) was conducted to identify relevant studies through June 2016. Studies were deemed relevant if they were published in English and contained original research on the management of tendinopathy in humans. RESULTS: Studies varied in methodological quality and were often limited by small sample size and lack of sufficient control groups. Critical evaluation of the literature suggests that physical therapy with or without eccentric exercise should be considered a first-line treatment. Corticosteroids and nonsteroidal anti-inflammatory drugs provide short-term symptomatic relief, but long-term efficacy has not been demonstrated. Inconsistent results do not support the routine use of prolotherapy, platelet-rich plasma injections and topical nitric oxide patches. Operative intervention should be reserved until conservative measures fail or an obvious operative lesion is present. CONCLUSIONS: While numerous therapeutic modalities exist for tendinopathy in the athlete, the ideal treatment protocol has not been clearly defined. The development of new targeted therapies for tendinopathy is likely to follow a greater understanding of the cellular and molecular mechanisms that underlie its pathogenesis.

Single- Versus Multiple-Site Harvesting Techniques for Bone Marrow Concentrate: Evaluation of Aspirate Quality and Pain.

BACKGROUND: Bone marrow concentrate (BMC) is growing in popularity as an alternative treatment option in orthopaedics. The regenerative capacity of BMC has been linked to the number of mesenchymal stem cells (MSCs) present in the graft at the time of its clinical application. MSC counts in bone marrow aspirate (BMA) are affected by harvest technique, but controversy exists over which aspiration method optimizes cellular yield while taking patient comfort and risk into consideration. PURPOSE: To compare a single- versus multiple-site bone marrow aspiration technique to determine which would generate a sufficient volume of high-quality BMA for concentration into a BMC graft. The level of pain experienced by the patient was monitored, since patient comfort should be included in the determination of a safe and effective aspiration technique. STUDY DESIGN: Controlled laboratory study and cohort study; Level of evidence, 2. METHODS: BMC samples from 6 patients were sent to an outside source for laboratory analysis. All 6 participants underwent bilateral bone marrow aspiration. Each patient received both techniques at the posterior iliac crest: one side underwent a multiple-site aspiration technique, and the contralateral side underwent a single-site technique with needle redirection. BMA and BMC samples were analyzed for concentrations white blood cells, total nucleated cells, red blood cells, neutrophils, and hematopoietic stem cells. One BMC sample was cultured, and MSC analysis was performed via flow cytometry. All patients underwent monitoring of pain scores during and after the procedure through a visual analog pain scale at 24 hours, 72 hours, and 7 days after BMA. RESULTS: No significant difference was found between the cell ratios of the single- and multiple-site groups. Both aspiration techniques were found to provide ample colony-forming units without a marked difference in appearance. Additionally, no significant difference was found between groups with regard to MSC numbers. Pain during and 24 hours after the procedure was significantly greater with the multiple-site method than the single-insertion method. CONCLUSION: The single-insertion method produced final cellular concentrations and culture results that were not significantly different from those of a multiple-insertion method. Additionally, the single-insertion site technique was significantly less painful to the patient at the time of the procedure as well as 24 hours after aspiration. CLINICAL RELEVANCE: The results of this study indicated that a high-quality bone marrow aspirate is possible with a single-stick aspiration method.

Local cryotherapy minimally impacts the metabolome and transcriptome of human skeletal muscle.

Cryotherapy is commonly used in the treatment of skeletal muscle injuries. However, the data to support the use of cryotherapy is inconclusive, and the biochemical etiology of cryotherapy in human skeletal muscle remains largely unknown. We therefore sought to determine how a clinically-relevant dose of cryotherapy would impact the transcriptome and metabolome of skeletal muscle. Eight healthy male subjects (age 24.7 ± 4.5 years, BMI 22.2 ± 1.6) received a 15 minute bout of local cryotherapy, delivered via ice cup massage over the anterolateral thigh. This resulted in an 85% decrease in skin temperature and a predicted 27% reduction in intramuscular temperature. The contralateral side served as a non-treated control. Two hours after cryotherapy, muscle biopsies were obtained to analyze changes in the transcriptome, metabolome, and activation of p38 MAPK, ERK1/2, Akt, and p70S6K proteins. No changes were detected in the transcriptome between control and cooled muscles. Cryotherapy reduced levels of hexose sugars and hypoxanthine by 1.3%, but no statistically different changes were observed in 60 additional metabolites. Overall, no differences in phosphorylated p38 MAPK, ERK1/2, Akt, and p70S6K were observed. A clinically relevant dose of cryotherapy produced negligible acute biochemical and molecular changes in the skeletal muscle of human subjects.

Regeneration of Skeletal Muscle After Eccentric Injury.

Eccentric-contraction-induced skeletal muscle injuries, included in what is clinically referred to as muscle strains, are among the most common injuries treated in the sports medicine setting. Although patients with mild injuries often fully recover to their preinjury levels, patients who suffer moderate or severe injuries can have a persistent weakness and loss of function that is refractory to rehabilitation exercises and currently available therapeutic interventions. The objectives of this review were to describe the fundamental biophysics of force transmission in muscle and the mechanism of muscle-strain injuries, as well as the cellular and molecular processes that underlie the repair and regeneration of injured muscle tissue. The review also summarizes how commonly used therapeutic modalities affect muscle regeneration and opportunities to further improve our treatment of skeletal muscle strain injuries.

High growth hormone levels in clinically short stature children.

BACKGROUND: Growth Hormone (GH) is secreted from the anterior pituitary gland. It binds to receptors on the surface of target cells, stimulates production of Insulin-like growth factor-I (IGF-I) leading to growth of almost all tissues of the body capable of growing. Growth failure (height below 3rd centile) occurs in children who do not secrete sufficient amount of GH. In some children, however, short stature is present in the presence of high levels of GH in their blood and they also secrete normal to increased amounts of GH in response to stimulation tests when tested for possible deficiency of GH. This condition is known as GH resistance syndrome or Larons syndrome (LS). METHODS: All patients after a thorough clinical evaluation underwent GH evaluation protocol as follows. On arrival in the lab a blood sample was collected for basal GH level in each patient. Screening was performed by subjecting the patients to exercise stimulation test and/or L-dopa stimulation test. Patients with GH deficiency underwent insulin tolerance test (ITT) after one week for confirmation. All the basal and post-stimulation samples were analyzed for GH levels. A level below 10mIU/L indicated GH deficiency, between 10-20mIU/L as borderline and an adequate response was defined as a GH >20mIU/L. Patients with a basal GH level of >20mIU/L and/or a post-stimulation level of >40mIU/L were arbitrarily considered as having exaggerated GH levels. This article evaluates the high plasma growth hormone levels among clinically short stature children undergoing growth hormone stimulation tests. RESULTS: Two hundred ninty-three patients reported for GH evaluation. Twenty were excluded for various reasons. Thus 273 patients were included for GH evaluation out of which 66(24.2%) showed GH deficiency, 89(32.6%) were borderline while 118(43.2%) patients exhibited adequate response, with GH levels of >20mIU/L. A number of patients unexpectedly showed very high GH levels on screening tests. Out of 118 patients, 21 showed either very high basal levels of >20mIU/L and/or a much-exaggerated response to stimulation tests with levels more than about 40mIU/L. Close consanguinity was found in 67% of patients showing very high GH levels. CONCLUSION: Some children with idiopathic short stature may show high levels of GH during their evaluation for GH deficiency. We identified a considerable number of such patients. These patients require further investigations.

Frequency of growth hormone deficiency in short statured children.

OBJECTIVE: To determine the frequency of growth hormone deficiency among short stature children referred for growth hormone evaluation. DESIGN: A cross-sectional survey. PLACE AND DURATION OF STUDY: The study was conducted in the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from June 1999 to July 2000. PATIENTS AND METHODS: A total of 293 children were referred for growth hormone evaluation. All the patients underwent thorough clinical evaluation including recording of height, weight, presence of chronic diseases and malnutrition. Twenty children were excluded for various reasons. Screening for GH deficiency was carried out by exercise stimulation test and/or L-dopa stimulation test. The children with GH level < 10 mIU/L on screening tests were provisionally considered to have GH deficiency. These children underwent insulin tolerance test (ITT). RESULTS: Out of 273 children, 189 were subjected to both exercise and L-dopa stimulation test, while 60 patients underwent only exercise stimulation test. The remaining 24 patients were subjected to L-dopa administration alone because of their physical weakness or inability to perform exercise. Sixty-six patients exhibited GH levels < 10 mIU/L on screening tests. The frequency of GH deficiency was found to be 24.17% on screening. Out of these 66 patients, 54 underwent an ITT, while 12 patients did not report back for the test. Thirty-eight children showed lack of response on ITT, therefore, after ITT, the frequency of GH deficiency was revealed to be 13.9%. CONCLUSION: GH deficiency is responsible for about 14% cases of short stature in a hospital setting. Screening tests showed a positive predictive value of 70.4% and a false positivity of 6.8%.