Complete Blood Count Ratios Predict Adverse Events After Total Joint Arthroplasty.

INTRODUCTION: Complete blood count-based ratios (CBRs), including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are biomarkers associated with the proinflammatory surgical stress response. This study sought to determine whether preoperative CBRs are associated with postoperative complications, protracted hospital length of stay (LOS), and mortality after total joint arthroplasty, as well as establish threshold values for these outcomes for use in future investigations. METHODS: The Premier Healthcare Database was retrospectively queried for adult patients who underwent primary elective total hip arthroplasty or total knee arthroplasty (TKA). Approximate cut-point values for CBRs were identified by bootstrap simulation using the Youden index. Multivariable adjusted restricted cubic spline models using the predicted cut-point value as the threshold for odds of outcomes were created to identify a final threshold value associated with increased adjusted odds ratio (aOR) of study outcomes. RESULTS: A total of 32,868 total joint arthroplasties (THA: 12,807, TKA: 20,061) were identified. All measures predicted odds of aggregate postoperative complications (THA: NLR TV: 4.60 [aOR = 2.35], PLR TV: 163.4 [aOR = 1.32], MLR TV: 0.40 [aOR = 2.02], SII TV: 977.00 [aOR = 1.54]; TKA: NLR TV: 3.7 [aOR = 1.69], MLR TV: 0.41 [aOR = 1.62], PLR TV: 205.10 [aOR = 1.43], SII TV: 1,013.10 [aOR = 1.62]; all P < 0.05). A MLR > 0.40 [aOR = 1.54] P < 0.001) was associated with LOS ≥3 days after total hip arthroplasty while an NLR > 13.1 [aOR = 1.38] and an MLR > 0.41[aOR = 1.29] were associated with LOS ≥3 days after total knee arthroplasty (both P < 0.001). No association between inflammatory markers and inpatient mortality was observed. CONCLUSION: Given CBRs' ability to both predict outcomes and identify patients with a proinflammatory phenotype, the findings of this study provide a framework for future investigations aimed at identifying and treating high-risk patients with immune-modulating therapies. Continued work to validate these findings by applying TVs to interventional clinical trials is needed before wide clinical adoption.

Dexamethasone-Associated Hyperglycemia is Not Associated With Infectious Complications After Total Joint Arthroplasty in Diabetic Patients.

BACKGROUND: Postoperative infection is a devastating complication of total joint arthroplasty (TJA). Perioperative use of dexamethasone in patients who have diabetes mellitus (DM) remains controversial due to concern for increased infection risk. This study aimed to evaluate the association between dexamethasone and infection risk among patients who have DM undergoing TJA. METHODS: This was a retrospective cohort study conducted on adult patients who underwent primary, elective total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 2016 and December 2021 using a large national database. We identified 110,568 TJA patients (TKA: 66.6%; THA: 33.4%), 31.0% (34,298) of which had DM. Patients who received perioperative dexamethasone were compared to those who did not. The primary end points were the 90-day risk of postoperative periprosthetic joint infection, surgical site infection (SSI), and other non-SSI (urinary tract infection, pneumonia, sepsis). RESULTS: When modeling the association between dexamethasone exposure and study outcomes while accounting for the interaction between dexamethasone and morning blood glucose levels, dexamethasone administration conferred no increased odds of postoperative periprosthetic joint infection nor SSI in diabetics. However, dexamethasone significantly lowered the adjusted odds of other postoperative infections in diabetic patients (TKA: adjusted odds ratio = 09, 95% confidence interval = 0.8 to 1.0, P = .030; THA: adjusted odds ratio = 0.7, 95% confidence interval = 0.6 to 0.9, P = .001); specifically in patients with morning blood glucose levels between 110 to 248 mg/dL in TKA and ≤ 172 mg/dL in THA. CONCLUSIONS: This study provides strong evidence against withholding dexamethasone in diabetic patients undergoing TJA based on concern for infection. Instead, short-course perioperative dexamethasone reduced infection risk in select patients. The narrative surrounding dexamethasone should shift away from questions about whether dexamethasone is appropriate for diabetic patients, and instead focus on how best to optimize its use.

Orthopedic Resident and Patient Perception of Electronic Medical Record Use During the Clinic Visit.

Background The transition from paper charts to electronic medical records (EMRs) has resulted in greater efficiency and reduced medical errors. This study aimed to examine the perception of patients and orthopedic residents regarding computer use during the clinic visit. Methodology This study utilized a cross-sectional cluster design. Orthopedic resident physicians were given a one-time general pre-visit survey. Additional surveys were given to patients and resident physicians post-visit. Surveys included questions that assessed satisfaction and the perceived impact of computer usage on doctor-patient interactions. Logistic generalized estimating equations were run to determine if there was an association between patient response and clinician assessment, adjusting for repeated measures within clinicians. Results A total of 80 patients and 15 residents completed the surveys. Results from the physician pre-visit survey showed that more residents perceived the computer as having a "negative" (47%) than "positive" (26%) effect on their relationship with patients. According to the post-visit analysis, patients perceived the residents' use of the EMR as having an overall positive effect on their ability to establish a personal connection and having a positive effect on their ability to give them attention. Conclusions Overall, there was little correlation between patient and resident perception of the computer's effect on their relationship. Patients generally perceived the computer as having a positive effect on their interaction with the residents even when residents had a negative perception of the computer's effect on their interaction.

Knowledge Gaps in Anesthetic Gas Utilization in a Large Academic Hospital System: A Multicenter Survey.

Inhaled anesthetics account for a significant portion of the greenhouse gases generated by perioperative services within the healthcare systems. This cross-sectional study aimed to identify knowledge gaps and practice patterns related to carbon dioxide (CO2) absorbents and intraoperative delivery of fresh gas flows (FGF) for future sustainability endeavors. Secondary aims focused on differences in these knowledge gaps based on the level of training. Surveys were distributed at five large academic medical centers. In addition to site-specific CO2 absorbent use and practice volume and experience, respondents at each institution were queried about individual practice with FGF rates during anesthetic maintenance as well as the cost-effectiveness and environmental impact of different volatile anesthetics. Results were stratified and analyzed by the level of training. In total, 368 (44% physicians, 30% residents, and 26% nurse anesthetists) respondents completed surveys. Seventy-six percent of respondents were unaware or unsure about which type of CO2 absorbent was in use at their hospital. Fifty-nine percent and 48% of respondents used sevoflurane and desflurane with FGF ≥1 L/min, respectively. Most participants identified desflurane as the agent with the greatest environmental impact (89.9%) and a greater proportion of anesthesiologists correctly identified isoflurane as a cost-effective anesthetic (78.3%, p=0.02). Knowledge gaps about in-use CO2 absorbent and optimal FGF usage were identified within the anesthesia care team. Educational initiatives to increase awareness about the carbon emissions from anesthesia and newer CO2 absorbents will impact the environmental and economic cost per case and align anesthesia providers toward healthcare decarbonization.

A double-blinded, placebo-controlled, randomized study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain: a study protocol.

BACKGROUND: Pain management is a critical component of comprehensive postsurgical care, as it influences patient safety and outcomes, and inadequate control has been associated with the development of chronic pain syndromes. Despite recent improvements, the management of postoperative pain following total knee arthroplasty (TKA) remains a challenge. The use of opioid-sparing, multimodal analgesic regimens has broad support, but there is a paucity of high-quality evidence regarding optimal postoperative protocols and novel approaches are needed. Dextromethorphan stands out among both well-studied and emerging pharmacological adjuncts for postoperative pain due its robust safety profile and unique pharmacology. The purpose of this study is to evaluate the efficacy of multi-dose dextromethorphan for postoperative pain control following TKA. METHODS: This is a single-center, multi-dose, randomized, double-blinded, placebo-controlled trial. A total of 160 participants will be randomized 1:1 to receive either 60 mg oral dextromethorphan hydrobromide preoperatively, as well as 30 mg 8 h and 16 h postoperatively, or matching placebo. Outcome data will be obtained at baseline, during the first 48 h, and the first two follow-up visits. The primary outcome measure will be total opioid consumption at 24 h postoperatively. Secondary outcomes related to pain, function, and quality of life will be evaluated using standard pain scales, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) questionnaire, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, and clinical anchors. DISCUSSION: This study has a number of strengths including adequate power, a randomized controlled design, and an evidence-based dosing schedule. As such, it will provide the most robust evidence to date on dextromethorphan utilization for postoperative pain control following TKA. Limitations include not obtaining serum samples for pharmacokinetic analysis and the single-center study design. TRIAL REGISTRATION: This trial has been registered on the National Institute of Health's ClinicalTrials.gov (NCT number: NCT05278494). Registered on March 14, 2022.

Duloxetine for Postoperative Pain Control Following Knee or Hip Replacement: A Systematic Review and Meta-Analysis.

Background: Duloxetine is a Food and Drug Administration-approved selective norepinephrine reuptake inhibitor for treating depression, anxiety, fibromyalgia, and neuropathic and chronic musculoskeletal pain. This meta-analysis aims to evaluate the efficacy of duloxetine in reducing pain and postoperative opioid use following lower extremity total joint arthroplasty. Methods: A literature search was performed, identifying randomized controlled trials investigating duloxetine for pain management after total hip and total knee arthroplasty. Data from the visual analog scale (VAS) for pain during movement and at rest were extracted for postoperative days (PODs) 1, 3, 7, and 14, as well as postoperative week 6 and postoperative month 3. Opioid use data were obtained at 24, 48 and 72 hours. All data were analyzed using inverse variance with random effects and presented as weighted mean difference. Results: Eight unique studies were identified and included, 7 of which were analyzed quantitatively. Duloxetine decreased postoperative opioid consumption at 48 and 72 hours. For VAS for pain at rest, significantly reduced pain was reported by duloxetine-treated patients at POD 3, POD 7, and postoperative week 6. For VAS for pain at movement, significantly reduced pain was reported by duloxetine-treated patients at POD1, POD 3, POD 7, POD 14, postoperative week 6, and postoperative month 3. Conclusions: Duloxetine appears to decrease postoperative pain and opioid consumption following total joint arthroplasty. However, definitive conclusions are limited by small sample size and study heterogeneity. While there is a need for follow-up studies to determine the optimal dose, duration, and patient population, strong preliminary data provide robust support for future large-scale efficacy studies.

The impact of a mindfulness bracelet on emotional affect in medical students: a prospective cohort study.

BACKGROUND: There is concern that negative changes in emotional outlook among medical students may impair the behavior of students, diminish learning, and ultimately affect patient care. Although most medical students begin their professional education with idealism, enthusiasm, and attention to humanity, they often have difficulty balancing their happiness with social and professional responsibilities. The following study aimed to determine if a simple mindfulness reminder (in the form of a bracelet) will impact emotional affect in first-year medical students. The second aim is to better understand the changes in emotional affect as students start medical school. METHODS: First year medical students were invited to participate at the start of the academic year. Baseline survey data and demographic data were obtained prior to participants being given the mindfulness bracelet and a standardized presentation explaining its purpose. Follow-up surveys were obtained at one- and two-month intervals. Statistical analysis was based on sum score of the survey. Change of sum score over time was tested by using repeated measurement analysis. RESULTS: Data collection included 104 students at the initial distribution of the survey. Follow-up surveys were obtained from 78 and 69 students at the first- and second-month mark, respectively. No significant associations were detected between frequency of mindfulness bracelet usage and emotional affect. However, there was a significant decrease in positive affect over the first month of medical school (p < 0.01), followed by a significant recovery in positive affect in the second month of medical school (p < 0.01). Demographic data did not reveal statistically significant differences among demographic groups and progression of emotional affect. CONCLUSIONS: Although the mindfulness bracelet intervention did not yield significant improvement in emotional affect, our results are consistent with other studies demonstrating that the first year of medical school negatively impacts the emotional outlook of students. Future studies are needed to explore practical interventions and to better understand and address the negative effect that early medical school education has on student's emotional state.

A randomized, controlled study to assess if allopathic-osteopathic collaboration influences stereotypes, interprofessional readiness, and doctor-patient communication.

Despite the growing similarities between allopathic (MD) and osteopathic (DO) medical education, few studies have examined allopathic-osteopathic collaboration. The following study focused on stereotypes and student readiness for interprofessional learning. Patient perceptions were also evaluated. Osteopathic and allopathic students were randomly allocated 1:1:1 to work in pairs (MD/DO, MD/MD, DO/DO) at the start of each shift. A questionnaire evaluating student communication was collected from patients at the end of each encounter. Surveys assessing stereotypes and interprofessional readiness were obtained from students at the end of each workday. Data collection was stopped early due to Coronavirus-related safety measures. In the ITT analysis, there were a total of 126 participants (57 students 69 patients). A per-protocol analysis was performed to account for repeat clinic volunteers. No significant differences were detected between student pairs; however, the sensitivity analysis of the questionnaire assessing interprofessional readiness was 8 points higher in the DO/DO group compared to the MD/MD and MD/DO groups (P = 0.0503). In the content analysis of qualitative responses, the MD/DO group was more likely to respond with themes of enjoyment and less concern about stereotypes than the DO/DO group. The MD/DO group was also less likely to report concerns about differences in expectations, methods, and thinking than the MD/MD group. Early trends from this study suggest that DO students may be better positioned to engage in interprofessional learning than their MD counterparts. Additionally, the findings from our content analysis provide evidence that the collaborative experience improved feelings associated with professional legitimacy and credibility among DO students. Taken in aggregate, this study provides justification for a follow-up investigation, as well as a framework for how such studies could best be executed in the future.

Patient Perception Regarding the Safety of Elective Joint Arthroplasty Surgery During the COVID-19 Pandemic.

BACKGROUND: Total joint arthroplasty (TJA) practices have been dramatically impacted by the COVID-19 pandemic. To date, no study has assessed trends in patient perceptions regarding the safety of elective TJA. METHODS: A single-institution, prospective cohort study was conducted between May 11th and August 10th, 2020. All patients who underwent elective hip and knee arthroplasty were contacted via telephone or emailed surveys. Two-hundred and thirty-five consecutive patients were screened, and 158 agreed to participate. The average age was 65.9 ± 11.5 years, with 51.0% of patients being female. The percentage of participants who underwent total knee, total hip, and unicompartmental knee arthroplasty was 41.4%, 37.6%, and 21.0%, respectively. Survey components assessed demographic data, level of concern and specific concerns about the pandemic, and factors increasing patient comfort in proceeding with surgery. RESULTS: Older age (P = .029) and female sex (P = .004) independently predicted higher concern on multivariate analysis. Race (P = .343), surgical site (knee vs hip, P = .58), and procedure type (primary vs revision, P = .26) were not significantly related to degree of concern. Most participants (71.5%) disagreed that the pandemic would negatively affect the outcome of their surgery. Patient concern mirrored statewide COVID-19 cases and deaths, rather than local municipal trends. The most cited reassuring factors were preoperative COVID-19 testing, personal protective equipment usage by hospital staff, and surgeon support. CONCLUSIONS: Patient concern regarding the safety of elective TJA may follow broader policy-level events rather than local trends. Surgeons should note that universal preoperative COVID-19 testing, adequate personal protective equipment, and surgeon support were reassuring to patients. LEVEL OF EVIDENCE: Level IV Therapeutic.

The Efficacy of Platelet-Rich Plasma for Improving Pain and Function in Lateral Epicondylitis: A Systematic Review and Meta-analysis with Risk-of-Bias Assessment.

PURPOSE: To assess the efficacy of platelet-rich plasma (PRP) for lateral epicondylitis and evaluate its impact on pain and functional outcomes. METHODS: This study followed Preferred Reporting Items and Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted in September 2019 and repeated in April 2020 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Baseline and 3-, 6-, and 12-month data were extracted for visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH), and modified Mayo Clinic performance index for the elbow (MAYO) scores. Only level 1 studies with patients who had not undergone surgery were included. Outcomes data, study design, demographic variables, PRP formulation, and comparator treatments were recorded. Statistical analyses of pooled weighted mean differences (WMDs) were performed and compared with estimated minimal clinically important difference (MCID) values. The Coleman Methodology Score (CMS) was used to assess methodological quality, and the Cochrane risk-of-bias assessment was performed. RESULTS: This review included 16 level I studies, 9 of which (581 total patients, 281 receiving single injections of PRP) were quantitatively analyzed. The average age was 41.5 years, 56.8% of patients were female, and mean follow-up was 7.5 months. The mean CMS was 78.94 ± 12.74 (range 59 to 97), and 5 of 16 studies were at low risk for bias. Patients who received PRP had significantly improved VAS scores at 3 months (WMD -0.85; 95% confidence interval [CI] -1.03, -0.66; P < .01) and 6 months (WMD -0.74; 95% CI -0.98, -0.50; P < .01) compared with those who received autologous whole blood, though MAYO scores were statistically equivalent. Comparing PRP to corticosteroids, VAS and DASH scores were not significantly different at 3 months, although PRP was superior at 6 months for VAS (WMD -1.70; 95% CI -2.65, -0.75; P < .01) and DASH (WMD -6.23; 95% CI -10.78, -1.69; P < .01). Most differences in VAS and DASH scores exceeded the 5% absolute difference estimate for their respective MCIDs but fell short of the 10% estimate. CONCLUSION: Considering the small number of comparable studies, lack of quantification of specific PRP content, considerable heterogeneity between randomized control trials, and most effect sizes being equivocal within the framework of 2 estimated MCID values, the authors can neither scientifically support nor discourage the usage of PRP for lateral epicondylitis despite finding statistically significant improvements in pain and functional outcomes. LEVEL OF EVIDENCE: I, prognostic.

Evaluation of Knee Cartilage Diurnal, Activity, and BMI-Related Variations Using Quantitative T2 Mapping MRI and Fitbit Activity Tracking.

The aim of this study is to evaluate diurnal variation in knee cartilage 3 Tesla magnetic resonance imaging (MRI) T2 mapping relaxation times, as well as activity- and body mass index (BMI)-dependent variability, using quantitative analysis of T2 values from segmented regions of the weight-bearing articular surfaces of the medial and lateral femoral condyles and tibial plateaus. Ten healthy volunteers' daily activity (steps) were tracked with Fitbit pedometers. Sagittal MRI T2 maps were obtained in the morning and afternoon on days 2 and 3. Mean T2 values were analyzed for variation related to the number of steps taken (activity), time of day (diurnal variation), and BMI using mixed effect model. Significant (albeit small) differences in the medial femoral and medial tibial cartilage regions were identified between morning and afternoon scans (diurnal variation). Daily activity did not result in significant changes and increasing BMI only demonstrated a slight increase in T2 values for the lateral tibial plateau. These findings suggest that it may be necessary to control diurnal variation when using quantitative MRI T2 mapping to assess articular cartilage longitudinally in healthy participants. Further investigation is needed to confirm these findings and determine if they also apply to symptomatic patients.

Minimal clinically important difference (MCID) for patient-reported shoulder outcomes.

BACKGROUND: The minimal clinically important difference (MCID) is used when interpreting the importance of outcome data. However, a consensus regarding the MCID for commonly used patient-reported outcomes in shoulder surgery has not been established. The purpose of this systematic review was to evaluate the available literature on shoulder MCID to improve clinical interpretation of shoulder outcome data. METHODS: A systematic review of the literature was conducted to identify studies reporting anchor-based MCID values for the patient-reported outcomes recommended by the American Shoulder and Elbow Surgeons (ASES): Veterans Rand 12 score, ASES score, Single Assessment Numeric Evaluation (SANE) score, Western Ontario Rotator Cuff (WORC) score, Western Ontario Osteoarthritis Score (WOOS), Western Ontario Shoulder Instability Index (WOSI), Pennsylvania Shoulder Score, and Oxford Shoulder Score (OSS). RESULTS: A total of 14 articles reporting anchor-based MCID values were included in the final analysis. No studies reporting the Western Ontario Osteoarthritis Score (WOOS) were identified. The ASES score (6 studies), OSS (4 studies), and WORC score (2 studies) were the only instruments investigated in more than 1 study. The average reported MCID values for the ASES, OSS, and WORC scores were 15.5 (15% total difference), 275.7 (13% total difference), and 6 (13% total difference), respectively. The vast majority of studies failed to report information necessary to validate the credibility of these MCID values. DISCUSSION AND CONCLUSION: The current utility of the MCID for patient-report shoulder outcome instruments is limited by poor study methodology, inadequate reporting, and a lack of data. Further research is needed to more clearly define the MCID values for commonly used patient-reported outcomes in shoulder surgery.

Use of Platelet-Rich Plasma for the Improvement of Pain and Function in Rotator Cuff Tears: A Systematic Review and Meta-analysis With Bias Assessment.

BACKGROUND: Many clinical trials have investigated the use of platelet-rich plasma (PRP) to treat rotator cuff-related abnormalities. Several meta-analyses have been published, but none have focused exclusively on level 1 randomized controlled trials. PURPOSE: To assess the efficacy of PRP for rotator cuff-related abnormalities and evaluate how specific tendon involvement, the inclusion of leukocytes, and the use of gel/nongel formulations affect pain and functional outcomes. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The literature was screened following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Baseline, short-term, and long-term data were extracted for the Constant score, University of California, Los Angeles (UCLA) score, visual analog scale (VAS) for pain, retear rate, Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) score. The 100-point modified Coleman Methodology Score (CMS) was used to assess methodological quality. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers. RESULTS: A total of 18 level 1 studies were included in this review, 17 (1116 patients) of which could be included in quantitative analysis. The mean modified CMS was 79.4 ± 10.39. The Constant scores of patients who received PRP were significantly better short term (weighted mean difference [WMD], 2.89 [95% CI, 0.89-4.90]; P < .01) and long term (WMD, 2.66 [95% CI, 1.13-4.19]; P < .01). The VAS scores were significantly improved short term (WMD, -0.45 [95% CI, -0.75 to -0.15]; P < .01). Sugaya grade IV and V retears in PRP-treated patients were significantly reduced long term (odds ratio [OR], 0.34 [95% CI, 0.20-0.57]; P < .01). In PRP-treated patients with multiple tendons torn, there were reduced odds of retears (OR, 0.28 [95% CI, 0.13-0.60]; P < .01). Patients who received leukocyte-rich PRP had significantly better Constant scores compared with the leukocyte-poor PRP group, but there was no difference in VAS scores. Patients receiving PRP gel reported higher Constant scores compared with the controls, whereas those receiving nongel PRP treatments did not, although there was no difference in VAS scores. Long-term odds of retears were decreased, regardless of leukocyte content (leukocyte-poor PRP: OR, 0.36 [95% CI, 0.16-0.82]; leukocyte-rich PRP: OR, 0.32 [95% CI, 0.16-0.65]; all P < .05) or usage of gel (nongel: OR, 0.42 [95% CI, 0.23-0.76]; gel: OR, 0.17 [95% CI, 0.05-0.51]; all P < .01). CONCLUSION: Long-term retear rates were significantly decreased in patients with rotator cuff-related abnormalities who received PRP. Significant improvements in PRP-treated patients were noted for multiple functional outcomes, but none reached their respective minimal clinically important differences. Overall, our results suggest that PRP may positively affect clinical outcomes, but limited data, study heterogeneity, and poor methodological quality hinder firm conclusions.

Repair of Rotator Cuff Tendon Defects in Aged Rats Using a Growth Factor Injectable Gel Scaffold.

PURPOSE: To determine if the tendon-specific crosslinking gelatin (Col-Tgel) impregnated with growth factors promotes tendon healing at the bone interface and in a tendon window model. METHODS: Two different Col-Tgel formulations were first tested in vitro by evaluating cell morphology and tendogenic differentiation. After the optimum formulation was determined, the gel was mixed with either transforming growth factor-ß3 (TGF-ß3) or growth differentiation factor-7 (GDF-7) growth factor and prepared for injections. Window defects were induced in 12 animals, which were randomized into the following treatments: (1) sham, (2) empty Col-Tgel, (3) Col-Tgel containing TGF-ß3, or (4) Col-Tgel containing GDF-7. Based on these results, the sham, empty Col-Tgel, and Col-Tgel containing TGF-ß3 were applied to the supraspinatus repair interface. Tendons were analyzed biomechanically and histologically using hematoxylin and eosin and Masson's trichrome staining. RESULTS: In the window defect model, histologic scores were the best in rats treated with TGF-ß3 containing Col-Tgel, followed by the empty Col-Tgel scaffold, and finally the sham control. The GDF-7 Col-Tgel was not further tested because occasional ectopic cartilage and bone formation was found in the prior window defect model. In the supraspinatus repair model, there was no statistical difference (P > .05) in the biomechanical strength among the 3 treatment groups, but load-to-failure ratio improved when TGF-ß3 was added to the scaffold, suggesting improved tendon healing. CONCLUSIONS: This pilot study evaluated the performance of an injectable gel tendon graft in a population of retired breeder rats. The results suggest that Col-Tgel containing TGF-ß3 may be a useful adjunctive treatment for surgical repair of full-thickness rotator cuff tears. Histologic and biomechanical scores suggest that Col-Tgel containing TGF-ß3 promotes tendon healing. CLINICAL RELEVANCE: The results of this study suggest that shoulders injected with Col-Tgel may be a useful adjunctive treatment for repair of rotator cuff tears.

The association of smoking with ultrasound-measured kidney dimensions
.

PURPOSE: Ultrasound is considered a preferred first-line imaging technique for the assessment of kidney function. The potential relationship between tobacco smoke exposure and ultrasound-measured renal characteristics has yet to be explored. We hypothesized that exposure to tobacco smoke would be associated with reduced kidney dimensions. MATERIALS AND METHODS: This was a cross-sectional study that included all individuals over age 18 at a single site in Mojokerto, Indonesia. A questionnaire was used to assess prior history and environmental exposure, and blinded evaluators performed ultrasound assessments. Six kidney parameters (length, width, and parenchymal thickness of each kidney) were considered as dependent variables, and statistical relationships were assessed using multivariate analysis. Echogenicity was evaluated using a 5-point grading scale described previously. RESULTS: Of the 445 participants assessed, a total of 138 male and 269 female subjects were included in the final analysis. There was a statistically significant association between kidney measures and the following independent variables: pack years smoking (p < 0.001), height (p < 0.001), weight (p < 0.001), and beginning to smoke at the age of 25 or younger (p < 0.001). There was not a statistically significant association between kidney measures and hypertension (p > 0.05) or diabetes (p > 0.05). Echogenicity was similar among all smoking groups. CONCLUSION: Kidney dimensions were decreased in individuals with increased smoking history. This association is notable, particularly given that statistically significant associations were not observed between renal dimensions and hypertension or diabetes. The null findings using echogenicity are consistent with previous studies.

Fresh osteochondral grafting in the United States: the current status of tissue banking processing.

The use of musculoskeletal allografts has become increasingly popular among surgeons. The purpose of this review is to highlight the procurment and delievery process of fresh osteochondral allografts in the United States. The four distributors of fresh osteochondral allografts in the United States were contacted. Surveys containing quantitative and qualitative sections concerning the procurement and processing of osteochondral allograft tissue were obtained. Our results showed an average of 13 ± 4.24 years of experience with osteochondral allografts. The average donor age ranged from 13.5 ± 3 to 37.5 ± 5 years, with an average age of 27 ± 2.83 years. All donors were between ages 12 and 45 years old. The percentage of screened donors that were accepted for allograft transplant was consistent at 70-75% for 3 out of the 4 tissue banks. The percentage of grafts that expire without implantation ranged from 20% to 29%. Maximum shipping time varied between 24 and 96 hours. Each tissue bank used its own proprietary storage medium. The time from donor death to the harvest of allograft tissue was < 24 hours. The most commonly requested osteochondral allograft tissue for all banks was the medial femoral condyle. The market share of fresh allografts is as follows: Joint Restoration Foundation (JRF) 59.9%, Muskuloskeletal Transplant Foundation (MTF) 15.3%, LifeNet Health (LN) 14.5%, and Regeneration Technology Incorporated (RTI) 10.2%, with approximately 4700 fresh allografts distributed in 2018. This compiled data from the four tissue banks that supply fresh osteochondral allograft in the United States  provides important background information for patients and orthopaedic surgeons.

Nomenclature Inconsistency and Selective Outcome Reporting Hinder Understanding of Stem Cell Therapy for the Knee.

BACKGROUND: The prospect of treating knee cartilage injury/pathology with mesenchymal stem cells (MSCs) has garnered considerable attention in recent years, but study heterogeneity and a lack of randomized controlled trials (RCTs) preclude quantitative analysis. The purpose of this review was to provide clinicians with an overview of RCTs that addresses 2 key areas that have been largely overlooked: nomenclature inconsistency and selective outcome reporting. METHODS: RCTs that purported to use stem cells or MSCs to treat knee cartilage were identified with use of PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses). Study variables were compiled, and methodological quality was assessed. The cell treatments and the methods used to characterize them were recorded and compared. Clinical, radiographic, and arthroscopic outcomes were extracted and evaluated qualitatively. RESULTS: There was extensive variation among the treatments, adjuvant therapies, and outcome measures. Treatments did not coincide with terminology. Significant differences in clinical outcomes were reported infrequently, and intra-group improvements or inter-group subscore differences were consistently highlighted, particularly when inter-group comparisons were left unreported. CONCLUSIONS: Overall, there are isolated cases in which positive efficacy results have been published, but our results suggest that the generally positive efficacy conclusions concerning stem cell therapy for knee cartilage pathology may be overstated. Nevertheless, it is important to understand that the efficacy of stem cell therapies should not be considered in aggregate. Cells that are procured or processed differently produce entirely different drugs. When evaluating the efficacy of "stem cell" therapies, clinicians must consider the methodological quality, nomenclature, and inherent distinctness of each treatment.

Intra-articular treatment options for knee osteoarthritis.

Intra-articular drug delivery has a number of advantages over systemic administration; however, for the past 20 years, intra-articular treatment options for the management of knee osteoarthritis (OA) have been limited to analgesics, glucocorticoids, hyaluronic acid (HA) and a small number of unproven alternative therapies. Although HA and glucocorticoids can provide clinically meaningful benefits to an appreciable number of patients, emerging evidence indicates that the apparent effectiveness of these treatments is largely a result of other factors, including the placebo effect. Biologic drugs that target inflammatory processes are used to manage rheumatoid arthritis, but have not translated well into use in OA. A lack of high-level evidence and methodological limitations hinder our understanding of so-called 'stem' cell therapies and, although the off-label administration of intra-articular cell therapies (such as platelet-rich plasma and bone marrow aspirate concentrate) is common, high-quality clinical data are needed before these treatments can be recommended. A number of promising intra-articular treatments are currently in clinical development in the United States, including small-molecule and biologic therapies, devices and gene therapies. Although the prospect of new, non-surgical treatments for OA is exciting, the benefits of new treatments must be carefully weighed against their costs and potential risks.

A randomized, controlled study to evaluate the efficacy of intra-articular, autologous adipose tissue injections for the treatment of mild-to-moderate knee osteoarthritis compared to hyaluronic acid: a study protocol.

BACKGROUND: Osteoarthritis (OA) is a highly debilitating joint disease that causes progressive, irreversible damage to articular cartilage. OA takes a massive toll on society that has grown in recent decades, but no therapy has been shown to halt or reverse the progression of the disease. The critical need for better treatments and increased interest cellular therapies has spawned a new generation of "minimally manipulated" cell treatments. Autologous adipose tissue injections are among the most controversial of these new treatments. Despite a lack of clinical evidence, adipose tissue injections are often marketed as "stem cell" injections with wide-ranging regenerative benefits. The purpose of this study is to estimate the effect size of the treatment by comparing the efficacy of autologous fat to hyaluronic acid (HA). As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs. HA. METHODS: This is a prospective, single-center, parallel-group, randomized, controlled trial. Participants (n = 54) will receive either a single intra-articular, ultrasound-guided injection of autologous adipose tissue or a single intra-articular, ultrasound-guided injection of HA (1:1 ratio). Outcome data will be obtained at baseline, week-6 and month-6. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain domain (WOMAC-A) will be used as the primary outcome measure. Secondary clinical outcome measures include WOMAC (full), clinical anchors (pain, function, and stiffness), and the 29-point Patient-Reported Outcomes Measurement Information System (PROMIS®) profile. We will also take synovial fluid samples and assess sway velocity using a force plate, as well as analyze excess/discard adipose tissue to gain a better understanding of how intra-articular adipose tissue injections influence the biochemical environment of the joint. DISCUSSION: Given the widespread use of intra-articular fat injections in the United States, it is critical that randomized, controlled human studies evaluating efficacy and biological activity be performed. This study is the first step in addressing this unmet need, but it is not without limitations. The most notable limitations of this study are its small size and lack of blinding, which predisposes the study to both investigator and participant bias. TRIAL REGISTRATION: NCT03242707 // HS-17-00365 // Registration Date (First Posted): August 8, 2018.