The effect of tenotomy, neurotomy, and dual injury on mouse rotator cuff muscles: Consequences for the mouse as a preclinical model.

A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time-series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration-regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically.

Occipital Headache Evaluation and Rates of Migraine Assessment, Diagnosis, and Treatment in Patients Receiving Greater Occipital Nerve Blocks in an Academic Pain Clinic.

OBJECTIVE: Diagnosis of patients with occipital headache can be challenging, as both primary and secondary causes must be considered. Our study assessed how often migraine is screened for, diagnosed, and treated in patients receiving greater occipital nerve blocks (GONBs) in a pain clinic. DESIGN: Institutional review board-approved, retrospective observational study. SETTING: Academic multidisciplinary pain clinic. SUBJECTS: One hundred forty-three consecutive patients who received GONBs. RESULTS: About 75% of patients had been evaluated by neurologists and about 25% by non-neurologist pain specialists only, and 62.2% of patients had photophobia, phonophobia, and nausea assessed. Compared with patients who had been evaluated by non-neurologists, patients who had been evaluated by a neurologist were more likely to have photophobia, phonophobia, and nausea assessed (75.9% vs 20.0%, odds ratio [OR] 12.6, 95% confidence interval [CI] 4.90 to 32.2); more likely to be diagnosed with migraine (48.1% vs 14.3%, OR 5.6, 95% CI 2.0 to 15); less likely to be diagnosed with occipital neuralgia (39.8% vs 65.7%, OR 0.3, 95% CI 0.2 to 0.8); and equally likely to be diagnosed with cervicogenic headache (21.3% vs 25.7%, OR 0.8, 95% CI 0.3 to 1.9). Among patients diagnosed with migraine, 82.5% received acute migraine treatment, 89.5% received preventive migraine treatment, and 52.6% were documented as receiving migraine lifestyle counseling. CONCLUSIONS: Of the patients in this study who had occipital headache and received GONBs, 62.2% were assessed for migraine, and most received appropriate acute, preventive, and lifestyle treatments when diagnosed. Patients seen by neurologists were significantly more likely to be screened for and diagnosed with migraine than were those evaluated by non-neurologist pain medicine specialists only. All clinicians should remain vigilant for migraine in patients with occipital headache.

Patient Satisfaction Ratings of Male and Female Residents Across Subspecialties.

BACKGROUND: Females currently comprise approximately 50% of incoming medical students yet continue to be underrepresented in certain medical subspecialties. OBJECTIVE: To assess whether gender plays a role in patients' perception of physician competency among different specialties. METHODS: We administered surveys at 2 academic medical centers to patients who were stable, cognitively aware, and indicated English as their primary language. Survey questions evaluated communication, medical expertise, and quality of care. RESULTS: A total of 4222 surveys were collected. Females comprised around half (n = 2133, 50.7%) of evaluated residents. First-year (n = 1647, 39%) and second-year (n = 1416, 33.5%) residents were assessed most frequently. Internal medicine conducted the most surveys (n = 1111, 23.6%), whereas head and neck surgery conducted the least (n = 137, 3.24%). There was no statistically significant difference between patients' perception of male and female residents of the same year in overall communication skills, medical expertise, and quality of medical care. Female residents outperformed their male counterparts on specific questions evaluating the communication of treatment plans, patient education, and patient satisfaction (P < .001, P = .03, P = .04, respectively). Unsurprisingly, patients' perceptions of residents' overall communication skills, medical expertise, and quality of medical care significantly improved when comparing more experienced residents to newer residents. CONCLUSION: There is no difference between overall communication, medical expertise, and quality of care between sexes, and across subspecialties. Though gender inequalities currently exist most starkly in practitioners in surgical subspecialties, women in surgical residencies were much better communicators than their male counterparts, but still perceived to have similar levels of medical expertise and quality of care.

Preoperative multimodal analgesia decreases 24-hour postoperative narcotic consumption in elective spinal fusion patients.

BACKGROUND CONTEXT: Effective postoperative pain management in patients undergoing elective spinal fusion surgery has been associated with shorter hospital stays, reduced rates of hospital readmissions due to pain, and decreased cost of care. Furthermore, preoperative multimodal analgesia regimens have been shown to decrease postoperative subjective pain measurements and narcotic consumption in patients undergoing spinal fusion and total arthroplasty surgeries. PURPOSE: Compare the difference in effects on 24-hour postoperative narcotic consumption, reported pain, and early mobility with administration of preoperative celecoxib plus gabapentin, gabapentin alone, and a nonstandardized analgesia regimen in patients undergoing elective spinal fusion surgery involving ≤5 levels. STUDY DESIGN: Retrospective review, Level of Evidence III. PATIENT SAMPLE: A total of 185 adult patients undergoing elective spinal fusion surgery involving ≤5 levels from 2013 to 2017 at one academic institution. Patients were excluded if the surgery was nonelective, for oncological purposes, or the patient was younger than 17 years old. OUTCOME MEASURES: Twenty-four-hour postoperative morphine equivalent consumption, 24-hour postoperative visual analogue scale (VAS) pain scores, postoperative day to ambulate, and postoperative day to clear physical therapy. METHODS: A single-institution retrospective chart review was conducted. Patients meeting inclusion criteria were grouped by whether they had received preoperative celecoxib plus gabapentin, gabapentin alone, or neither of these medications. Opioid medication intake for the first 24 hours after the surgery end time was tabulated and converted to morphine equivalents. Visual analogue scale (VAS) pain scores were also averaged over the first 24 hours. Finally, physical therapy notes were reviewed to determine the time taken for the patient to first ambulate and to clear physical therapy. No external funding was procured for this research and the authors' conflicts of interest are not pertinent to the present work. RESULTS: Twenty-four-hour postoperative morphine equivalent consumption was significantly lower in the celecoxib plus gabapentin group compared with control (p=.004). Patients in the celecoxib plus gabapentin group had significantly lower mean VAS scores (p=.002) and had earlier mobility postoperatively (p=.012) than those in the control group. Early mobility and time to physical therapy clearance did differ between the celecoxib + gabapentin group compared with the gabapentin alone group. The gabapentin group had a significantly higher 24-hour morphine dose equivalent (p=.013) and a significantly higher VAS average (p=.009) compared with the celecoxib + gabapentin group. Gabapentin given alone compared with control did not show statistically significant improved outcomes in postoperative morphine equivalent consumption, pain scores or physical therapy goals. CONCLUSIONS: This study demonstrates that administering a selective COX-2 inhibitor and GABA-analogue preoperatively can significantly decrease 24-hour postoperative opioid consumption, VAS pain scores, and elapsed time to postoperative mobility in patients undergoing elective spine fusion surgery of ≤5 levels. Optimal standardized dosing and drug combination for preoperative multimodal analgesia remains to be elucidated.

Topical Administration of Ibuprofen for Injured Athletes: Considerations, Formulations, and Comparison to Oral Delivery.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs commonly used to treat both the acute and chronic injuries sustained by athletes during training and competition. In many parts of the world, NSAIDs can be purchased over-the-counter and used without any physician oversight. However, the chronic nature of overuse injuries requires NSAIDs to be taken orally for an extended period of time. As a result, they can have significant adverse effects on athletes, namely gastrointestinal (GI), renal, and cardiovascular damage. Dyspepsia and upper GI ulceration and bleeding are of great concern in chronic NSAID use, and as such oral NSAIDs are generally contraindicated in those with a history of peptic ulcers or irritable bowel disease. In the setting of chronic overuse soft tissue or joint disease, topically administered NSAIDs offer an alternate route of administration that has the potential to deliver a similar level of pain and anti-inflammatory relief while bypassing the harmful side effects associated with oral intake. Topically applied NSAIDs are able to achieve high concentrations within the targeted site of action while simultaneously keeping plasma concentrations low, offering several advantages over oral administration. One commonly used generic NSAID is ibuprofen (2-(4-isobutylphenyl)propanoic acid). First synthesized in the 1960s, ibuprofen has since become widely available as an over-the-counter pharmaceutical. In this review, we outline new and different techniques that have been used to deliver ibuprofen into diseased tissues, including supersaturations, microemulsions, gels, nanosystems, and microneedles. We also review relevant clinical trials comparing transdermally delivered ibuprofen to placebo and orally administered ibuprofen.

Paper #14: Curve Reduction, Radiation Exposure, and Anesthesia Exposure in Serial Elongation De-Rotation Flexion Casting.

We present our experience with serial elongation de-rotation flexion (EDF) casting at a single center, focusing on reduction of primary coronal curve angle and the cumulative exposure to general anesthetics and diagnostic radiographs.

Paper #7: Repeated Anesthetics and Radiographic Imaging during Traditional Growing Rod Management.

We provide a risk -benefit analysis of each traditional growing rod instrumentation (TGR) procedure that can aid in shared decision-making of initiating, continuing, and completing treatment with TGR.

p300 is not required for metabolic adaptation to endurance exercise training.

The acetyltransferase, E1a-binding protein (p300), is proposed to regulate various aspects of skeletal muscle development, metabolism, and mitochondrial function,viaits interaction with numerous transcriptional regulators and other proteins. Remarkably, however, the contribution of p300 to skeletal muscle function and metabolism,in vivo, is poorly understood. To address this, we used Cre-LoxP methodology to generate mice with skeletal muscle-specific knockout of E1a-binding protein (mKO). mKO mice were indistinguishable from their wild-type/floxed littermates, with no differences in lean mass, skeletal muscle structure, fiber type, respirometry flux, or metabolites of fatty acid and amino acid metabolism.Ex vivomuscle function in extensor digitorum longus and soleus muscles, including peak stress and time to fatigue, as well asin vivorunning capacity were also comparable. Moreover, expected adaptations to a 20 d voluntary wheel running regime were not compromised in mKO mice. Taken together, these findings demonstrate that p300 is not required for the normal development or functioning of adult skeletal muscle, nor is it required for endurance exercise-mediated mitochondrial adaptations.-LaBarge, S. A., Migdal, C. W., Buckner, E. H., Okuno, H., Gertsman, I., Stocks, B., Barshop, B. A., Nalbandian, S. R., Philp, A., McCurdy, C. E., Schenk, S. p300 is not required for metabolic adaptation to endurance exercise training.

Is acetylation a metabolic rheostat that regulates skeletal muscle insulin action?

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale "omics" studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle.

Impact of electronic health records on the patient experience in a hospital setting.

BACKGROUND: The impact of electronic health records (EHRs) and their effects on optimizing the patient experience has been debated nationally. Currently, there is a paucity of data in this area, and existing research offers conflicting results. Since 2006, the Assessing Residents' CI-CARE (ARC) program has evaluated the physician-patient interaction of resident physicians at University of California, Los Angeles (UCLA) Health utilizing a 20-item questionnaire administered through facilitator-patient interviews. OBJECTIVE: To evaluate the impact of EHR implementation on the patient experience. DESIGN: Retrospective cohort study. SETTING: Two academic medical campuses: Ronald Reagan UCLA Medical Center and UCLA Medical Center, Santa Monica. METHODS: A total of 3417 surveys, spanning December 1, 2012 to May 30, 2013, were assessed. This included patient representation from 9 departments within UCLA Health. Surveys were analyzed to assess physician-patient communication. Statistical comparisons were made using χ analysis. RESULTS: All 16 questions assessing physician-patient communication received better responses in the 3 months following EHR implementation, compared to the 3 months prior to implementation. Of these, 9 questions illustrated statistically significant improvement, whereas the improvement in the remaining 7 questions was not statistically significant. DISCUSSION: These results suggest that EHRs may improve physician-patient communication. The ARC infrastructure allowed for observation of this trend; however, future research should aim to further validate and understand the etiologies of this improvement.

ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic characterization.

PURPOSE: To present a radiogenomic computed tomographic (CT) characterization of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) (ALK+). MATERIALS AND METHODS: In this HIPAA-compliant institutional review board-approved retrospective study, CT studies, ALK status, and clinical-pathologic data in 172 patients with NSCLC from three institutions were analyzed. A screen of 24 CT image traits was performed in a training set of 59 patients, followed by random forest variable selection incorporating 24 CT traits plus six clinical-pathologic covariates to identify a radiogenomic predictor of ALK+ status. This predictor was then validated in an independent cohort (n = 113). Test-for-accuracy and subset analyses were performed. A similar analysis was performed to identify a biomarker associated with shorter progression-free survival (PFS) after therapy with the ALK inhibitor crizotinib. RESULTS: ALK+ status was associated with central tumor location, absence of pleural tail, and large pleural effusion. An ALK+ radiogenomic CT status biomarker consisting of these three imaging traits with patient age of younger than 60 years showed strong discriminatory power for ALK+ status, with a sensitivity of 83.3% (15 of 18), a specificity of 77.9% (74 of 95), and an accuracy of 78.8% (89 of 113) in independent testing. The discriminatory power was particularly strong in patients with operable disease (stage IIIA or lower), with a sensitivity of 100.0% (five of five), a specificity of 88.1% (37 of 42), and an accuracy of 89.4% (42 of 47). Tumors with a disorganized vessel pattern had a shorter PFS with crizotinib therapy than tumors without this trait (11.4 vs 20.2 months, P = .041). CONCLUSION: ALK+ NSCLC has distinct characteristics at CT imaging that, when combined with clinical covariates, discriminate ALK+ from non-ALK tumors and can potentially identify patients with a shorter durable response to crizotinib.