Cell-Based Therapies for Rotator Cuff Injuries: An Updated Review of the Literature.

This review focuses on non-surgical treatment options for rotator cuff injuries and highlights the potential of mesenchymal stem cells (MSCs) as a potential regenerative approach. MSCs, sourced from various tissues like bone marrow and adipose tissue, exhibit promising mechanisms in vitro, influencing tendon-related gene expression and microenvironment modulation. Animal studies support this, showcasing MSCs' ability to reduce inflammation, improve tissue remodeling, and enhance repaired tendon strength. Human trials, while varied and limited, suggest that MSCs might lower retear rates and enhance post-repair outcomes, but randomized controlled trials yield mixed results, emphasizing the necessity for standardized investigations. Ultimately, while cell-based therapies demonstrate an excellent safety profile, more rigorous clinical trials are necessary to determine their efficacy in improving patient outcomes and achieving lasting structural changes in rotator cuff injuries.

Risk factors for degenerative, symptomatic rotator cuff tears: a case-control study.

BACKGROUND: Despite the considerable public health burden of rotator cuff tears, there is no consensus on risk factors associated with symptomatic rotator cuff tears. In this study, a large data source was used to identify factors associated with symptomatic rotator cuff tears. We defined cases of rotator cuff tears as those verified by imaging or operative reports and controls as symptomatic shoulders without rotator cuff tears as verified by imaging or operative reports. METHODS: We performed a case-control study of patients with and without symptomatic rotator cuff tears by use of the Vanderbilt University Medical Center de-identified electronic medical record system, the Synthetic Derivative, with records on >2.5 million patients from 1998 to 2017. Cases and controls were confirmed by individual chart review and review of imaging and/or operative notes. A final set of 11 variables were analyzed as potential risk factors for cuff tears: age, sex, body mass index (BMI), race, smoking history, hypertension, depression/anxiety, dyslipidemia, carpal tunnel syndrome, overhead activity, and affected side. Multivariable logistic regression was used to estimate the association between predictor variables and the risk of having a rotator cuff tear. RESULTS: A total of 2738 patients were selected from the Synthetic Derivative, which included 1731 patients with rotator cuff tears and 1007 patients without rotator cuff tears. Compared with individuals without tears, those with rotator cuff tears were more likely to be older (odds ratio [OR], 2.44; 95% confidence interval [CI], 2.12-2.89), to have a higher BMI (OR, 1.45; 95% CI, 1.24-1.69), to be of male sex (OR, 1.56; 95% CI, 1.32-1.85), and to have carpal tunnel syndrome (OR, 1.41; 95% CI, 1.03-1.93). Patients with rotator cuff tears were less likely to have left shoulder symptoms (OR, 0.68; 95% CI, 0.57-0.82) and to have depression/anxiety (OR, 0.77; 95% CI, 0.62-0.95) compared with the control group, which had symptomatic shoulder pain without rotator cuff tears. CONCLUSIONS: In a large imaging and operative report-verified case-control study, we identified advancing age, male sex, higher BMI, and diagnosis of carpal tunnel syndrome as risk factors significantly associated with an increased risk of rotator cuff tears. Left shoulder symptoms and depression/anxiety were less likely to be associated with rotator cuff tears compared with symptomatic shoulders without rotator cuff tears. Contrary to some prior reports in the literature, smoking was not associated with rotator cuff tears.

The role of familial predisposition in imaging-confirmed atraumatic rotator cuff tears.

BACKGROUND: The etiology of atraumatic rotator cuff tears is not completely understood. Limited data suggest the role of genetic and familial predisposition in the etiology of rotator cuff tears. The purpose of this study was to assess whether there is an increased likelihood of rotator cuff tears in family members of patients with rotator cuff tears vs. those without tears. This would provide evidence for whether there is an association between familial predisposition and rotator cuff tearing. METHODS: Patients presenting to a shoulder clinic were recruited in this study. They provided information on personal medical history, shoulder symptoms, and family history of rotator cuff tears. The diagnosis of rotator cuff tears was based on imaging (magnetic resonance imaging or computed tomography arthrogram) confirmation of a structural defect in the rotator cuff. The association between family history of rotator cuff problems and the likelihood of an imaging-confirmed rotator cuff tear diagnosis was evaluated using multivariate logistic regression, adjusting for age, sex, race/ethnicity, cigarette smoking, hypertension, diabetes, and depression. RESULTS: In our cohort of 2335 patients, 52.6% (n = 1229) of patients had a rotator cuff tear. Among patients with tears, 17.9% (n = 220) of patients reported a family history of rotator cuff issues vs. 11.1% (n = 123) in patients without tears. A family history of rotator cuff problems was significantly associated with the diagnosis of an imaging-confirmed rotator cuff tear (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.71, 2.95). Other confounding variables such as increasing age (OR 1.06, 95% CI 1.05, 1.07) and Hispanic race/ethnicity as compared to non-Hispanic white race/ethnicity (OR 1.48, 95% CI 1.07, 2.05) were significantly associated with rotator cuff tears. Sex, smoking, hypertension, diabetes, and depression were not significantly associated with rotator cuff tearing. CONCLUSION: Our study shows that individuals with rotator cuff tears were more than 2 times as likely to have a family member with a tear as compared to patients without tears. Increasing age and patients who identified as being of Hispanic ancestry were also significantly associated with higher odds of rotator cuff tears.

Obesity and sex influence fatty infiltration of the rotator cuff: the Rotator Cuff Outcomes Workgroup (ROW) and Multicenter Orthopaedic Outcomes Network (MOON) cohorts.

BACKGROUND: Fatty infiltration (FI) is one of the most important prognostic factors for outcomes after rotator cuff surgery. Established risk factors include advancing age, larger tear size, and increased tear chronicity. A growing body of evidence suggests that sex and obesity are associated with FI; however, data are limited. METHODS: We recruited 2 well-characterized multicenter cohorts of patients with rotator cuff tears (Multicenter Orthopaedic Outcomes Network [MOON] cohort [n = 80] and Rotator Cuff Outcomes Workgroup [ROW] cohort [n = 158]). We used multivariable logistic regression to evaluate the relationship between body mass index (BMI) and the presence of FI while adjusting for the participant's age at magnetic resonance imaging, sex, and duration of shoulder symptoms, as well as the cross-sectional area of the tear. We analyzed the 2 cohorts separately and performed a meta-analysis to combine estimates. RESULTS: A total of 27 patients (33.8%) in the Multicenter Orthopaedic Outcomes Network (MOON) cohort and 57 patients (36.1%) in the Rotator Cuff Outcomes Workgroup (ROW) cohort had FI. When BMI < 25 kg/m2 was used as the reference category, being overweight was associated with a 2.37-fold (95% confidence interval [CI], 0.77-7.29) increased odds of FI and being obese was associated with a 3.28-fold (95% CI, 1.16-9.25) increased odds of FI. Women were 4.9 times (95% CI, 2.06-11.69) as likely to have FI as men. CONCLUSIONS: Among patients with rotator cuff tears, obese patients had a substantially higher likelihood of FI. Further research is needed to assess whether modifying BMI can alter FI in patients with rotator cuff tears. This may have significant clinical implications for presurgical surgical management of rotator cuff tears. Sex was also significantly associated with FI, with women having higher odds of FI than men. Higher odds of FI in female patients may also explain previously reported early suboptimal outcomes of rotator cuff surgery and higher pain levels in female patients as compared with male patients.

Utilisation of skin blood flow as a precursor for pressure injury development in persons with acute spinal cord injury: A proof of concept.

People with spinal cord injury (SCI) are at high risk of developing a pressure injury. It is unclear why some people with SCI develop pressure injury while others with similar predisposing risk factors do not during acute hospitalisation. This may hinder healthcare utilisation to prevent pressure injuries. The purpose of the study was to examine the proof-of-concept objective bedside skin blood flow measurements before a pressure injury develops in spinal cord injured patients during acute hospitalisation. This was an observational study. All participants had acute traumatic SCI and were pressure injury-free upon enrollment. Skin blood flow patterns were collected at both heels under two circumstances: localised pressure for reactive hyperemia, and localised heating for heat hyperemia. Our results showed that reactive and heat hyperemia were successfully induced in all eleven participants. Two participants developed pressure injury and nine did not have pressure injury at discharge. Heat hyperemia was smaller in participants with pressure injury. No difference was observed in reactive hyperemia between the groups. In conclusion, skin blood flow measurements could be obtained at bedside during acute hospitalisation of SCI for the purpose of research. Further examination of a larger group is warranted to determine clinical use of heat hyperemia pattern as predictor for pressure injury development.

Surgery for rotator cuff tears.

BACKGROUND: This review is one in a series of Cochrane Reviews of interventions for shoulder disorders. OBJECTIVES: To synthesise the available evidence regarding the benefits and harms of rotator cuff repair with or without subacromial decompression in the treatment of rotator cuff tears of the shoulder. SEARCH METHODS: We searched the CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICRTP registry unrestricted by date or language until 8 January 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) including adults with full-thickness rotator cuff tears and assessing the effect of rotator cuff repair compared to placebo, no treatment, or any other treatment were included. As there were no trials comparing surgery with placebo, the primary comparison was rotator cuff repair with or without subacromial decompression versus non-operative treatment (exercises with or without glucocorticoid injection). Other comparisons were rotator cuff repair and acromioplasty versus rotator cuff repair alone, and rotator cuff repair and subacromial decompression versus subacromial decompression alone. Major outcomes were mean pain, shoulder function, quality of life, participant-rated global assessment of treatment success, adverse events and serious adverse events. The primary endpoint for this review was one year. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: We included nine trials with 1007 participants. Three trials compared rotator cuff repair with subacromial decompression followed by exercises with exercise alone. These trials included 339 participants with full-thickness rotator cuff tears diagnosed with magnetic resonance imaging (MRI) or ultrasound examination. One of the three trials also provided up to three glucocorticoid injections in the exercise group. All surgery groups received tendon repair with subacromial decompression and the postoperative exercises were similar to the exercises provided for the non-operative groups. Five trials (526 participants) compared repair with acromioplasty versus repair alone; and one trial (142 participants) compared repair with subacromial decompression versus subacromial decompression alone. The mean age of trial participants ranged between 56 and 68 years, and females comprised 29% to 56% of the participants. Symptom duration varied from a mean of 10 months up to 28 months. Two trials excluded tears with traumatic onset of symptoms. One trial defined a minimum duration of symptoms of six months and required a trial of conservative therapy before inclusion. The trials included mainly repairable full-thickness supraspinatus tears, six trials specifically excluded tears involving the subscapularis tendon. All trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding, but also for other reasons such as unclearly reported methods of random sequence generation or allocation concealment (six trials), incomplete outcome data (three trials), selective reporting (six trials), and other biases (six trials). Our main comparison was subacromial decompression versus non-operative treatment and results are reported for the 12 month follow up. At one year, moderate-certainty evidence (downgraded for bias) from 3 trials with 258 participants indicates that surgery probably provides little or no improvement in pain; mean pain (range 0 to 10, higher scores indicate more pain) was 1.6 points with non-operative treatment and 0.87 points better (0.43 better to 1.30 better) with surgery.. Mean function (zero to 100, higher score indicating better outcome) was 72 points with non-operative treatment and 6 points better (2.43 better to 9.54 better) with surgery (3 trials; 269 participants), low-certainty evidence (downgraded for bias and imprecision). Participant-rated global success rate was 873/1000 after non-operative treatment and 943/1000 after surgery corresponding to (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.96 to 1.22; low-certainty evidence (downgraded for bias and imprecision). Health-related quality of life was 57.5 points (SF-36 mental component score, 0 to 100, higher score indicating better quality of life) with non-operative treatment and 1.3 points worse (4.5 worse to 1.9 better) with surgery (1 trial; 103 participants), low-certainty evidence (downgraded for bias and imprecision). We were unable to estimate the risk of adverse events and serious adverse events as only one event was reported across the trials (very low-certainty evidence; downgraded once due to bias and twice due to very serious imprecision). AUTHORS' CONCLUSIONS: At the moment, we are uncertain whether rotator cuff repair surgery provides clinically meaningful benefits to people with symptomatic tears; it may provide little or no clinically important benefits with respect to pain, function, overall quality of life or participant-rated global assessment of treatment success when compared with non-operative treatment. Surgery may not improve shoulder pain or function compared with exercises, with or without glucocorticoid injections. The trials included have methodology concerns and none included a placebo control. They included participants with mostly small degenerative tears involving the supraspinatus tendon and the conclusions of this review may not be applicable to traumatic tears, large tears involving the subscapularis tendon or young people. Furthermore, the trials did not assess if surgery could prevent arthritic changes in long-term follow-up. Further well-designed trials in this area that include a placebo-surgery control group and long follow-up are needed to further increase certainty about the effects of surgery for rotator cuff tears.

Subacromial decompression surgery for rotator cuff disease.

BACKGROUND: Surgery for rotator cuff disease is usually used after non-operative interventions have failed, although our Cochrane Review, first published in 2007, found that there was uncertain clinical benefit following subacromial decompression surgery. OBJECTIVES: To synthesise the available evidence of the benefits and harms of subacromial decompression surgery compared with placebo, no intervention or non-surgical interventions in people with rotator cuff disease (excluding full thickness rotator cuff tears). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICRTP registry from 2006 until 22 October 2018, unrestricted by language. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) of adults with rotator cuff disease (excluding full-thickness tears), that compared subacromial decompression surgery with placebo, no treatment, or any other non-surgical interventions. As it is least prone to bias, subacromial decompression compared with placebo was the primary comparison. Other comparisons were subacromial decompression versus exercises or non-operative treatment. Major outcomes were mean pain scores, shoulder function, quality of life, participant global assessment of success, adverse events and serious adverse events. The primary endpoint for this review was one year. For serious adverse events, we also included data from prospective cohort studies designed to record harms that evaluated subacromial decompression surgery or shoulder arthroscopy. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. MAIN RESULTS: We included eight trials, with a total of 1062 randomised participants with rotator cuff disease, all with subacromial impingement. Two trials (506 participants) compared arthroscopic subacromial decompression with arthroscopy only (placebo surgery), with all groups receiving postoperative exercises. These trials included a third treatment group: no treatment (active monitoring) in one and exercises in the other. Six trials (556 participants) compared arthroscopic subacromial decompression followed by exercises with exercises alone. Two of these trials included a third arm: sham laser in one and open subacromial decompression in the other.Trial size varied from 42 to 313 participants. Participant mean age ranged between 42 and 65 years. Only two trials reported mean symptom duration (18 to 22 months in one trial and 30 to 31 months in the other), two did not report duration and four reported it categorically.Both placebo-controlled trials were at low risk of bias for the comparison of surgery versus placebo surgery. The other trials were at high risk of bias for several criteria, most notably at risk of performance or detection bias due to lack of participant and personnel blinding. We have restricted the reporting of results of benefits in the Abstract to the placebo-controlled trials.Compared with placebo, high-certainty evidence indicates that subacromial decompression provides no improvement in pain, shoulder function, or health-related quality of life up to one year, and probably no improvement in global success (moderate-certainty evidence, downgraded due to imprecision).At one year, mean pain (on a scale zero to 10, higher scores indicate more pain), was 2.9 points after placebo surgery and 0.26 better (0.84 better to 0.33 worse), after subacromial decompression (284 participants), an absolute difference of 3% (8% better to 3% worse), and relative difference of 4% (12% better to 5% worse). At one year, mean function (on a scale 0 to 100, higher score indicating better outcome), was 69 points after placebo surgery and 2.8 better (1.4 worse to 6.9 better), after surgery (274 participants), an absolute difference of 3% (7% better to 1% worse), and relative difference of 9% (22% better to 4% worse). Global success rate was 97/148 (or 655 per 1000), after placebo and 101/142 (or 708 per 1000) after surgery corresponding to RR 1.08 (95% CI 0.93 to 1.27). Health-related quality of life was 0.73 units (European Quality of Life EQ-5D, -0.59 to 1, higher score indicating better quality of life), after placebo and 0.03 units worse (0.011 units worse to 0.06 units better), after subacromial decompression (285 participants), an absolute difference of 1.3% (5% worse to 2.5% better), and relative difference of 4% (15% worse to 7% better).Adverse events including frozen shoulder or transient minor complications of surgery were reported in approximately 3% of participants across treatment groups in two randomised controlled trials, but due to low event rates we are uncertain if the risks differ between groups: 5/165 (37 per 1000) reported adverse events with subacromial decompression and 9/241 (34 per 1000) with placebo or non-operative treatment, RR 0.91 (95% CI 0.31 to 2.65) (moderate-certainty evidence, downgraded due to imprecision). The trials did not report serious adverse events.Based upon moderate-certainty evidence from two observational trials from the same prospective surgery registry, which also included other shoulder arthroscopic procedures (downgraded for indirectness), the incidence proportion of serious adverse events within 30 days following surgery was 0.5% (0.4% to 0.7%; data collected 2006 to 2011), or 0.6% (0.5 % to 0.7%; data collected 2011 to 2013). Serious adverse events such as deep infection, pulmonary embolism, nerve injury, and death have been observed in participants following shoulder surgery. AUTHORS' CONCLUSIONS: The data in this review do not support the use of subacromial decompression in the treatment of rotator cuff disease manifest as painful shoulder impingement. High-certainty evidence shows that subacromial decompression does not provide clinically important benefits over placebo in pain, function or health-related quality of life. Including results from open-label trials (with high risk of bias) did not change the estimates considerably. Due to imprecision, we downgraded the certainty of the evidence to moderate for global assessment of treatment success; there was probably no clinically important benefit in this outcome either compared with placebo, exercises or non-operative treatment.Adverse event rates were low, 3% or less across treatment groups in the trials, which is consistent with adverse event rates reported in the two observational studies. Although precise estimates are unknown, the risk of serious adverse events is likely less than 1%.

Which Is the Best Outcome Measure for Rotator Cuff Tears?

BACKGROUND: The American Shoulder and Elbow Surgeons Standardized Shoulder Form (ASES), the Shoulder Pain and Disability Index (SPADI), and the shortened Disability of the Arm, Shoulder, and Hand (quickDASH) are patient-reported upper extremity-specific outcome scales currently used to evaluate patients with rotator cuff tears. This heterogeneity does not allow for a uniform metric for research and patient care. QUESTIONS/PURPOSES: Our objective was to determine psychometric properties (reliability, convergent and discriminant validity, and responsiveness) of five commonly used outcome instruments (the ASES, the SPADI, the quickDASH, the SF-12, and the EuroQol-5D) in a longitudinal study of patients undergoing treatment for rotator cuff tears. METHODS: From February 2011 through June 2015, 120 patients completed a standardized history, the five outcome scales under study, a physical examination, and an MRI. Of these, 47 (39%) were lost to followup before 18 months, and another 24 (20%) were accounted for at 18 months but had missing data at one or more of the earlier prespecified followup intervals (3, 6, or 12 months). Reliability (the reproducibility of an outcome instrument between subjects; tested by Cronbach's alpha), convergent and discriminant validity (determining which outcome measures correlate most strongly with others; tested by Spearman's correlation coefficients), and responsiveness (the change in outcome scales over time based on percent improvement in shoulder functionality using the minimal clinically important difference [MCID] and the subjective shoulder value) were calculated. RESULTS: All outcomes measures had a Cronbach's alpha above 0.70 (range, 0.74-0.94) and therefore were considered reliable. Convergent validity was demonstrated as the upper extremity-specific measures (SPADI, ASES, and quickDASH) were more strongly correlated with each other (rho = 0.74-0.81; p < 0.001) than with any of the other measures. Discriminant validity was demonstrated because the Spearman's correlation coefficients were stronger for the relationships between upper extremity measures compared with the correlations between upper extremity measures and general health measures for 53 of the 54 correlations that were compared. Both internal and external responsiveness of the measures was supported. Patients who achieved the MCID and at least a 30% change on the subjective shoulder value had more positive change in scores over time compared with those who did not. Mixed model linear regressions revealed that all three upper extremity-specific measures had a group by time interaction for the MCID, indicating that patients who achieved the MCID had greater change over time compared with those who did not achieve the MCID. Results showed that the measure with the best discrimination between groups, or best internal responsiveness, was the ASES (beta = -8.26, 95% confidence interval [CI], -11.39 to -5.14; p < 0.001; η = 0.089) followed by the SPADI (beta = 6.88, 95% CI, 3.78-9.97; p < 0.001; η = 0.088) then the quickDASH (beta = 3.43, 95% CI, 0.86-6.01; p = 0.009, η = 0.027). Measures with the best external responsiveness followed the same pattern of results. CONCLUSIONS: All the upper extremity-specific scales had acceptable psychometric properties. Correlations were high and thus only one upper extremity-specific instrument is needed for outcome assessment. Given the overall psychometric assessment, we recommend SPADI be the shoulder-specific instrument used to assess outcomes in patients with rotator cuff tears. LEVEL OF EVIDENCE: Level III, diagnostic study.

Readmissions, revisions, and mortality after treatment for proximal humeral fractures in three large states.

BACKGROUND: Proximal humeral fractures can be treated non-operatively or operatively with open reduction and internal fixation (ORIF) and arthroplasty. Our objective was to assess practice patterns for operative and non-operative treatment of proximal humeral fractures. We also report on complications, readmissions, in-hospital mortality, and need for surgery after initial treatment of proximal humeral fractures in California, Florida, and New York. METHODS: The State Inpatient Databases and State Emergency Department Databases from the Healthcare Cost and Utilization Project, sponsored by the Agency for Healthcare Research and Quality, were used for the states of California (2005-2011), Florida (2005-2014), and New York (2008-2014). Data on patients with proximal humeral fractures was extracted. Patients underwent non-operative or operative (ORIF or arthroplasty) treatment at baseline and were followed for at least 4 years from the index presentation. If the patient needed subsequent surgery, time to event was calculated in days, and Kaplan-Meier survival curves were plotted. RESULTS: At the index visit, 90.3% of patients with proximal humeral fractures had non-operative treatment, 6.7% had ORIF, and 3.0% had arthroplasty. 7.6% of patients initially treated non-operatively, 6.6% initially treated with ORIF, and 7.2% initially treated with arthroplasty needed surgery during follow-up. Device complications were the primary reason for readmission in 5.3% of ORIF patients and 6.7% of arthroplasty patients (p < 0.0001). All-cause in-hospital mortality was 9.8% for patients managed non-operatively, 8.8% for ORIF, and 10.0% for arthroplasty (p = 0.003). CONCLUSIONS: A majority of patients with proximal humeral fractures underwent non-operative treatment. There was a relatively high all-cause in-hospital mortality irrespective of treatment. Given the recent debate on operative versus non-operative treatment for proximal humeral fractures, our study provides valuable information on the need for revision surgery after initial treatment. The differences in rates of revision surgery between patients treated non-operatively, with ORIF, and with arthroplasty were small in magnitude. At nine years of follow-up, ORIF had the lowest probability of needing follow-up surgery, and arthroplasty had the highest.

Physical therapy versus natural history in outcomes of rotator cuff tears: the Rotator Cuff Outcomes Workgroup (ROW) cohort study.

BACKGROUND: We compared the outcomes of patients who performed physical therapy versus those who did not in a longitudinal cohort of patients undergoing nonoperative treatment of rotator cuff tears. We also assessed whether there was a dose effect in which the pain and functional outcomes in patients performing physical therapy plateaued. METHODS: From February 2011 to June 2015, a multicenter cohort of patients with rotator cuff tears undergoing nonoperative treatment completed a detailed health and demographic questionnaire and the Shoulder Pain and Disability Index (SPADI) at baseline and 3, 6, 12, and 18 months. Longitudinal mixed models were used to assess whether physical therapy in the first 3 months predicted SPADI scores and dose effect. RESULTS: Among the 55 patients in our cohort, the performance of physical therapy within the first 3 months predicted better SPADI scores versus nonperformance of physical therapy at 3 months (P = .02). Scores were similar between groups at 6, 12, and 18 months. A threshold of 16 physical therapy sessions was observed for pain and functional improvement during follow-up, after which significant improvement was not seen. CONCLUSIONS: Patients who performed physical therapy within the first 3 months had statistically significant improvements in pain and function as measured by the SPADI score at 3 months compared with patients who did not report performing physical therapy. Depending on the minimal clinically important difference used for the SPADI score, our results could be interpreted as meeting the minimal clinically important difference threshold or not. Improvement in outcomes was observed up to 16 sessions of physical therapy, after which outcomes plateaued.

Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000.

BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival. METHODS: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of the 673 patients (13%) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets < 50 × 109 /L (P < .001), complex karyotype with ≥3 chromosomal abnormalities (P = .02), regimens that did not include cytarabine or hypomethylating agents (P = .014), and no prior CR lasting ≥12 months with frontline or salvage 1 therapies (P < .001). The independent adverse factors associated with worse survival were age ≥60 years (P = .01), platelets < 50 × 109 /L (P = .02), peripheral blasts ≥ 20% (P = .03), albumin ≤ 3 g/dL (P = .04), and complex karyotype (P = .003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. Cancer 2018;124:2534-40. © 2018 American Cancer Society.

Are Psychosocial Factors Associated With Patient-reported Outcome Measures in Patients With Rotator Cuff Tears? A Systematic Review.

BACKGROUND: Psychosocial factors are key determinants of health and can influence patient-reported outcomes after rotator cuff tears. However, to our knowledge, a systematic review of published studies has not been conducted to determine the degree of consistency and strength of the relationship between psychosocial factors and patient-reported outcomes in this patient population. QUESTIONS/PURPOSES: (1) Are psychosocial factors associated with patient-reported measures at initial clinical presentation in patients with rotator cuff tears? (2) Are psychosocial factors associated with patient-reported outcomes after treatment in patients with rotator cuff tears? METHODS: A systematic review of cross-sectional and prospective observational studies was performed in MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science from each database's inception to June 2016. We included studies examining associations between psychosocial factors and patient-reported measures in patients with rotator cuff tears. We excluded studies not reporting on this relationship, involving patients with nonspecific shoulder pain, and written in a language other than English. Two independent reviewers performed the search, extracted information, and assessed methodological quality. Study quality was assessed using the Methodological Items for Non-Randomized Studies (MINORS) criteria. The primary outcomes for the review were associations between each psychosocial factor and patient-reported measures of function or disability, pain, or quality of life. Associations were interpreted based on significance, strength, and direction of the relationship. A total of 10 studies (five cross-sectional and five prospective) in 1410 patients (age range, 46-62 years, 60% [571 of 958] men) were included in the review. Pooling of results for meta-analyses was not possible as a result of study heterogeneity. RESULTS: Weak to moderate cross-sectional associations were found for emotional or mental health with function or disability and pain in multiple studies. Lower emotional or mental health function was associated with greater pain or disability or lower physical function at initial evaluation. Only one psychosocial factor (patient expectation) was weak to moderately associated with patient-reported outcomes after treatment in more than one study. In the two studies that examined expectations, the higher the expectation of benefit, the greater the perceived benefit after surgical intervention. CONCLUSIONS: At the initial evaluation of patients with rotator cuff tear, there was an association between self-reported function and pain and emotional or mental health. However, these factors were not associated with patient-reported outcomes after intervention. This finding could be attributed to the lack of large prospective studies in this area or complex phenotypes within this patient population. Preoperative patient expectation is an important predictor of patient-reported outcomes in patients after rotator cuff surgery and may be a modifiable target for enhancing recovery. LEVEL OF EVIDENCE: Level III, therapeutic study.

Predictors of pain and functional outcomes after operative treatment for rotator cuff tears.

BACKGROUND: Optimal patient selection is key to success of operative treatment for cuff tears. We assessed predictors of pain and functional outcomes in a longitudinal cohort of patients undergoing operative treatment. METHODS: From March 2011 to January 2015, a cohort of patients with rotator cuff tears undergoing rotator cuff surgery was recruited. Patients completed a detailed health and demographic questionnaire, standardized shoulder questionnaires, including the Shoulder Pain and Disability Index (SPADI), and underwent a magnetic resonance imaging scan. Patients received follow-up questionnaires at 3, 6, 12, and 18 months. We assessed longitudinal predictors of SPADI using longitudinal mixed models. Interactions with follow-up duration after surgery were also assessed. RESULTS: In our analysis (n = 50), a lower Fear-Avoidance Beliefs Questionnaire physical activity score (P = .001) predicted a lower SPADI score (better shoulder pain and function). Those consuming alcohol 1 to 2 times per week or more had lower SPADI scores than those consuming alcohol 2 to 3 times per month or less (P = .017). Both of these variables had a significant interaction with duration of follow-up. Variables that were not significant predictors of SPADI included sociodemographic characteristics, magnetic resonance imaging characteristics, such as tear size and muscle quality, shoulder strength, and variations in surgical techniques/performance of adjuvant surgical procedures. CONCLUSIONS: Those with higher fear avoidance behavior and alcohol use of 1 to 2 times per week had worse shoulder pain and function at 18 months of follow-up. These data can be used to select optimal candidates for operative treatment of rotator cuff tears and assist with patient education and expectations before treatment.

Reliability of specific physical examination tests for the diagnosis of shoulder pathologies: a systematic review and meta-analysis.

BACKGROUND: Shoulder pain in the general population is common and to identify the aetiology of shoulder pain, history, motion and muscle testing, and physical examination tests are usually performed. OBJECTIVE: The aim of this systematic review was to summarise and evaluate intrarater and inter-rater reliability of physical examination tests in the diagnosis of shoulder pathologies. METHODS: A comprehensive systematic literature search was conducted using MEDLINE, EMBASE, Allied and Complementary Medicine Database (AMED) and Physiotherapy Evidence Database (PEDro) through 20 March 2015. Methodological quality was assessed using the Quality Appraisal of Reliability Studies (QAREL) tool by 2 independent reviewers. RESULTS: The search strategy revealed 3259 articles, of which 18 finally met the inclusion criteria. These studies evaluated the reliability of 62 test and test variations used for the specific physical examination tests for the diagnosis of shoulder pathologies. Methodological quality ranged from 2 to 7 positive criteria of the 11 items of the QAREL tool. CONCLUSIONS: This review identified a lack of high-quality studies evaluating inter-rater as well as intrarater reliability of specific physical examination tests for the diagnosis of shoulder pathologies. In addition, reliability measures differed between included studies hindering proper cross-study comparisons. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014009018.

Genetic and familial predisposition to rotator cuff disease: a systematic review.

BACKGROUND: Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and is likely to extend beyond repetitive microtrauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. METHODS: A literature search of PubMed and Embase databases identified 251 citations. After review of the titles, abstracts, and full articles, 7 met our inclusion and exclusion criteria. RESULTS: Four studies assessed familial predisposition to rotator cuff disease. One of these demonstrated that siblings of an individual with a rotator cuff tear were more likely to develop a full-thickness tear and more likely to be symptomatic. A 5-year follow-up showed that the relative risks were increased for the siblings to have a full-thickness tear, for a tear to progress in size, and for being symptomatic. Another study demonstrated that a significantly higher number of individuals with tears had family members with a history of tears or surgery than those without tears did. The other 3 studies investigated whether a genetic predisposition to rotator cuff disease exists and found significant association of haplotypes in DEFB1, FGFR1, FGF3, ESRRB, and FGF10 and 2 single-nucleotide polymorphisms within SAP30BP and SASH1. CONCLUSION: Prior studies provide preliminary evidence for genetic and familial predisposition to rotator cuff disease. However, there is a lack of large genome-wide studies that can provide more definitive information and guide early detection of individuals at risk, prophylactic rehabilitation, and potential gene therapies and regenerative medicine interventions.

Traumatic spinal cord injury in the United States, 1993-2012.

IMPORTANCE: Acute traumatic spinal cord injury results in disability and use of health care resources, yet data on contemporary national trends of traumatic spinal cord injury incidence and etiology are limited. OBJECTIVE: To assess trends in acute traumatic spinal cord injury incidence, etiology, mortality, and associated surgical procedures in the United States from 1993 to 2012. DESIGN, SETTING, AND PARTICIPANTS: Analysis of survey data from the US Nationwide Inpatient Sample databases for 1993-2012, including a total of 63,109 patients with acute traumatic spinal cord injury. MAIN OUTCOMES AND MEASURES: Age- and sex-stratified incidence of acute traumatic spinal cord injury; trends in etiology and in-hospital mortality of acute traumatic spinal cord injury. RESULTS: In 1993, the estimated incidence of acute spinal cord injury was 53 cases (95% CI, 52-54 cases) per 1 million persons based on 2659 actual cases. In 2012, the estimated incidence was 54 cases (95% CI, 53-55 cases) per 1 million population based on 3393 cases (average annual percentage change, 0.2%; 95% CI, -0.5% to 0.9%). Incidence rates among the younger male population declined from 1993 to 2012: for age 16 to 24 years, from 144 cases/million (2405 cases) to 87 cases/million (1770 cases) (average annual percentage change, -2.5%; 95% CI, -3.3% to -1.8%); for age 25 to 44 years, from 96 cases/million (3959 cases) to 71 cases/million persons (2930 cases), (average annual percentage change, -1.2%; 95% CI, -2.1% to -0.3%). A high rate of increase was observed in men aged 65 to 74 years (from 84 cases/million in 1993 [695 cases] to 131 cases/million [1465 cases]; average annual percentage change, 2.7%; 95% CI, 2.0%-3.5%). The percentage of spinal cord injury associated with falls increased significantly from 28% (95% CI, 26%-30%) in 1997-2000 to 66% (95% CI, 64%-68%) in 2010-2012 in those aged 65 years or older (P < .001). Although overall in-hospital mortality increased from 6.6% (95% CI, 6.1%-7.0%) in 1993-1996 to 7.5% (95% CI, 7.0%-8.0%) in 2010-2012 (P < .001), mortality decreased significantly from 24.2% (95% CI, 19.7%-28.7%) in 1993-1996 to 20.1% (95% CI, 17.0%-23.2%) in 2010-2012 (P = .003) among persons aged 85 years or older. CONCLUSIONS AND RELEVANCE: Between 1993 and 2012, the incidence rate of acute traumatic spinal cord injury remained relatively stable but, reflecting an increasing population, the total number of cases increased. The largest increase in incidence was observed in older patients, largely associated with an increase in falls, and in-hospital mortality remained high, especially among elderly persons.

Epidemiology of musculoskeletal upper extremity ambulatory surgery in the United States.

BACKGROUND: Musculoskeletal disorders of the upper extremity are common reasons for patients to seek care and undergo ambulatory surgery. The objective of our study was to assess the overall and age-adjusted utilization rates of rotator cuff repair, shoulder arthroscopy performed for indications other than rotator cuff repair, carpal tunnel release, and wrist arthroscopy performed for indications other than carpal tunnel release in the United States. We also compared demographics, indications, and operating room time for these procedures. METHODS: We used the 2006 National Survey of Ambulatory Surgery to estimate the number of procedures of interest performed in the United States in 2006. We combined these data with population size estimates from the 2006 U.S. Census Bureau to calculate rates per 10,000 persons. RESULTS: An estimated 272,148 (95% confidence intervals (CI) = 218,994, 325,302) rotator cuff repairs, 257,541 (95% CI = 185,268, 329,814) shoulder arthroscopies excluding those for cuff repairs, 576,924 (95% CI = 459,239, 694,609) carpal tunnel releases, and 25,250 (95% CI = 17,304, 33,196) wrist arthroscopies excluding those for carpal tunnel release were performed. Overall, carpal tunnel release had the highest utilization rate (37.3 per 10,000 persons in persons of age 45-64 years; 38.7 per 10,000 persons in 65-74 year olds, and; 44.2 per 10,000 persons in the age-group 75 years and older). Among those undergoing rotator cuff repairs, those in the age-group 65-74 had the highest utilization (28.3 per 10,000 persons). The most common indications for non-cuff repair related shoulder arthroscopy were impingement syndrome, periarthritis, bursitis, and instability/SLAP tears. Non-carpal tunnel release related wrist arthroscopy was most commonly performed for ligament sprains and diagnostic arthroscopies for pain and articular cartilage disorders. CONCLUSIONS: Our data shows substantial age and demographic differences in the utilization of these commonly performed upper extremity ambulatory procedures. While over one million upper extremity procedures of interest were performed, evidence-based clinical indications for these procedures remain poorly defined.

The contribution of reverse shoulder arthroplasty to utilization of primary shoulder arthroplasty.

BACKGROUND: We assessed the contribution of reverse shoulder arthroplasty to overall utilization of primary shoulder arthroplasty and present age- and sex-stratified national rates of shoulder arthroplasty. We also assessed contemporary complication rates, mortality rates, and indications for shoulder arthroplasty, as well as estimates and indications for revision arthroplasty. METHODS: We used the Nationwide Inpatient Samples for 2009 through 2011 to calculate estimates of shoulder arthroplasty and assessed trends using Joinpoint (National Cancer Institute, Bethesda, MD) regression. RESULTS: The cumulative estimated utilization of primary shoulder arthroplasty (anatomic total shoulder arthroplasty, hemiarthroplasty, and reverse shoulder arthroplasty) increased significantly from 52,397 procedures (95% confidence interval [CI], 47,093-57,701) in 2009 to 67,184 cases (95% CI, 60,638-73,731) in 2011. Reverse shoulder arthroplasty accounted for 42% of all primary shoulder arthroplasty procedures in 2011. The concomitant diagnosis of osteoarthritis and rotator cuff impairment was found in only 29.8% of reverse shoulder arthroplasty cases. The highest rate of reverse shoulder arthroplasty was in the 75- to 84-year-old female subgroup (77 per 100,000 persons; 95% CI, 67-87). Revision cases comprised 8.8% and 8.2% of all shoulder arthroplasties in 2009 and 2011, respectively, and 35% of revision cases were because of mechanical complications/loosening whereas 18% were because of dislocation. CONCLUSIONS: The utilization of primary shoulder arthroplasty significantly increased in just a 3-year time span, with a major contribution from reverse shoulder arthroplasty in 2011. Indications appear to have expanded because a large percentage of patients did not have rotator cuff pathology. The burden from revision arthroplasties was also substantial, and efforts to optimize outcomes and longevity of primary shoulder arthroplasty are needed.

Treatment choice affects inpatient adverse events and mortality in older aged inpatients with an isolated fracture of the proximal humerus.

BACKGROUND: This study tests the null hypothesis that, among patients aged 65 and older admitted to a United States hospital with an isolated fracture of the proximal humerus (no other injuries or fractures), there are no differences between operative (fixation or arthroplasty) and nonoperative treatments with respect to inpatient adverse events, inpatient mortality, and discharge to a long-term care facility rates accounting for comorbidities. METHODS: Using a large national database representing an estimated 132,005 patients aged 65 and older admitted to a US hospital with an isolated proximal humerus fracture between 2003 and 2007. Sixty-one percent did not have surgery, 22% were treated with open reduction and internal fixation (ORIF), and 17% were treated with arthroplasty. RESULTS: The risk of an in hospital adverse event was 21% overall and was 4.4 times greater with arthroplasty and 2.7 times greater with ORIF compared to nonoperative treatment. The risk of in hospital death was 1.8% overall and was 2.8 times greater with ORIF compared to nonoperative treatment. Patients treated operatively were less likely to be discharged to a long-term facility compared to patients treated nonoperatively. CONCLUSION: In spite of a tendency to treat the most infirm patients (those that are not discharged to home) nonoperatively, operative treatment (open reduction and internal fixation in particular) is an independent risk factor for inpatient adverse events and mortality in older-aged patients admitted to the hospital with an isolated fracture of the proximal humerus and should perhaps be offered more judiciously. LEVEL OF EVIDENCE: Level III, retrospective cohort study, treatment study.

Peripheral Nerve Stimulation of the Axillary Nerve Improves Chronic Shoulder Pain and Dysfunction Following Reverse Total Shoulder Arthroplasty: A Case Report.

ABSTRACT: Reverse total shoulder arthroplasty (rTSA) is an effective procedure to improve shoulder pain, range of motion, and function for a variety of conditions, including glenohumeral osteoarthritis and rotator cuff arthropathy. However, up to 22% of patients have persistent shoulder pain 12 to 24 months following rTSA, even in the absence of surgical complications. Currently, there are no widely accepted non-pharmacological treatments for persistent postoperative pain after rTSA. This case report details the successful management of a 64-year-old woman with chronic postoperative shoulder pain following rTSA. She was treated with single-lead percutaneous peripheral nerve stimulation to the right axillary nerve for eight weeks with 12 Hz motor-level stimulation. She demonstrated improvement in shoulder flexion active range of motion, shoulder flexion strength, and shoulder abduction strength. Her Shoulder Pain and Disability Index total score improved from 26.93% to 8.46% one year following treatment. She reported an overall Global Rating of Change of +7 one year following treatment. This case's success demonstrates that short term peripheral nerve stimulation may provide long-term improvement of persistent post-operative pain and dysfunction in patients with painful rTSA.