High variability among surgeons in evaluation, treatment, and rehabilitation of medial ulnar collateral ligament injuries.

Hypothesis and/or Background: The incidence of elbow medial ulnar collateral ligament (MUCL) injuries has been increasing, leading to advances in surgical treatments. However, it is not clear that there is consensus among surgeons regarding diagnostic imaging, the indications for acute surgery and postoperative rehabilitation. The purpose of this study is evaluate surgeon variability in the presurgical, surgical, and postsurgical treatment of MUCL injuries regarding the imaging modalities used for diagnosis, indications for acute surgical treatment, and postoperative treatment recommendations for rehabilitation and return to play (RTP). Our hypothesis is that indications for acute surgical treatment will be highly variable based on MUCL tear patterns and that agreement on the time to RTP will be consistent for throwing athletes and inconsistent for nonthrowing athletes. Methods: A survey developed by 6 orthopedic surgeons with expertise in throwing athlete elbow injuries was distributed to 31 orthopedic surgeons who routinely treat MUCL injuries. The survey evaluated diagnostic and treatment topics related to MUCL injuries, and responses reaching 75% agreement were considered as high-level agreement. Results: Twenty-four surgeons responded to the survey, resulting in a 77% response rate. There is 75% or better agreement among surveyed surgeons regarding acute surgical treatment for distal full thickness tears, ulnar nerve transposition in symptomatic patients or with ulnar nerve subluxation, postoperative splinting for 1-2 weeks with initiation of rehabilitation within 2 weeks, the use of bracing after surgery and the initiation of a throwing program at 3 months after MUCL repair with internal brace by surgeons performing 20 or more MUCL surgeries per year. There were a considerable number of survey topics without high-level agreement, particularly regarding the indications for acute surgical treatment, the time to return to throwing and time RTP in both throwing and nonthrowing athletes. Discussion and/or Conclusion: The study reveals that there is agreement for the indication of acute surgical treatment of distal MUCL tears, duration of bracing after surgery, and the time to initiate physical therapy after surgery. There is not clear agreement on indications for surgical treatment for every MUCL tear pattern, RTP time for throwing, hitting and participation in nonthrowing sports.

Interval Throwing Programs for Baseball Players: Methodological Assessment of the Quality and Construct of Publicly Available Programs.

CONTEXT: The quality and interprogram variability of publicly available throwing programs have not been assessed. OBJECTIVE: To (1) identify publicly available interval throwing programs, (2) describe their components and structure, and (3) evaluate their quality, variability, and completeness. DATA SOURCES: Google, Bing, Yahoo; keyword: "interval throwing program." STUDY SELECTION: Baseball-specific publicly available programs. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Independent evaluation by 2 authors using a novel 21-item Quality Assessment Rubric (QAR). RESULTS: Of the 99 included programs, 54% were designed for return from injury/surgery; 42% explicitly stated no expected timeline for completion, and approximately 40% did not provide criteria to initiate the program. Program construction was highly variable. There were broad-ranging shortest (mean: 40±8 ft, range: 20-45 ft) and longest (mean: 150±33 ft, range: 90-250 ft) long toss distances, and variable maximum numbers of mound pitches thrown before returning to game play (range: 40-120, mean: 85). Only 63% of programs provided guidelines for handling setbacks, and standardized warm-ups, arm care, and concomitant training were absent in 32%, 63%, and 47% of programs, respectively. Mean QAR completion rate and QAR item response rate were low (62 ± 4% [range, 24-91%], 62 ± 24% [range, 7-99%], respectively). Finally, only 20 (20%) programs provided at least 1 peer-reviewed reference, most of which were published >10 years ago. CONCLUSION: Publicly available interval throwing programs are readily available but demonstrate significant interprogram heterogeneity across multiple areas including target audience, program construction, progression, and execution. The quality and consistency of publicly available interval throwing programs is poor at this time, which may limit their utility and effectiveness for baseball players attempting to return to competition. This work identifies a multitude of deficiencies in currently available throwing programs that should be targets of future improvement efforts.

Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function.

Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates ("calmodulinopathy"). As CaM regulates many key cardiac ion channels, an understanding of disease mechanism associated with CaM variant arrhythmias requires elucidating individual CaM variant effects on distinct channels. One key CaM regulatory target is the KCNQ1 (KV7.1) voltage-gated potassium channel that carries the IKs current. Yet, relatively little is known as to how CaM variants interact with KCNQ1 or affect its function. Here, we take a multipronged approach employing a live-cell fluorescence resonance energy transfer binding assay, fluorescence trafficking assay, and functional electrophysiology to characterize >10 arrhythmia-associated CaM variants for effect on KCNQ1 CaM binding, membrane trafficking, and channel function. We identify one variant (G114W) that exhibits severely weakened binding to KCNQ1 but find that most other CaM variants interact with similar binding affinity to KCNQ1 when compared with CaM wild-type over physiological Ca2+ ranges. We further identify several CaM variants that affect KCNQ1 and IKs membrane trafficking and/or baseline current activation kinetics, thereby delineating KCNQ1 dysfunction in calmodulinopathy. Lastly, we identify CaM variants with no effect on KCNQ1 function. This study provides extensive functional data that reveal how CaM variants contribute to creating a proarrhythmic substrate by causing abnormal KCNQ1 membrane trafficking and current conduction. We find that CaM variant regulation of KCNQ1 is not uniform with effects varying from benign to significant loss of function, suggesting how CaM variants predispose patients to arrhythmia via the dysregulation of multiple cardiac ion channels. Classification: Biological, Health, and Medical Sciences, Physiology.

Arrhythmia-associated Calmodulin Variants Interact with KCNQ1 to Confer Aberrant Membrane Trafficking and Function.

Rationale: Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates. As CaM regulates several key cardiac ion channels, a mechanistic understanding of CaM variant-associated arrhythmias requires elucidating individual CaM variant effect on distinct channels. One key CaM regulatory target is the KCNQ1 (K V 7.1) voltage-gated potassium channel that underlie the I Ks current. Yet, relatively little is known as to how CaM variants interact with KCNQ1 or affect its function. Objective: To observe how arrhythmia-associated CaM variants affect binding to KCNQ1, channel membrane trafficking, and KCNQ1 function. Methods and Results: We combine a live-cell FRET binding assay, fluorescence trafficking assay, and functional electrophysiology to characterize >10 arrhythmia-associated CaM variants effect on KCNQ1. We identify one variant (G114W) that exhibits severely weakened binding to KCNQ1 but find that most other CaM variants interact with similar binding affinity to KCNQ1 when compared to CaM wild-type over physiological Ca 2+ ranges. We further identify several CaM variants that affect KCNQ1 and I Ks membrane trafficking and/or baseline current activation kinetics, thereby contextualizing KCNQ1 dysfunction in calmodulinopathy. Lastly, we delineate CaM variants with no effect on KCNQ1 function. Conclusions: This study provides comprehensive functional data that reveal how CaM variants contribute to creating a pro-arrhythmic substrate by causing abnormal KCNQ1 membrane trafficking and current conduction. We find that CaM variant regulation of KCNQ1 is not uniform with effects varying from benign to significant loss of function. This study provides a new approach to collecting details of CaM binding that are key for understanding how CaM variants predispose patients to arrhythmia via the dysregulation of multiple cardiac ion channels.