Neuropsychiatric Effects Associated with Opioid-Based Management for Palliative Care Patients.

PURPOSE OF REVIEW: The abundance of opioids administered in the palliative care setting that was once considered a standard of care is at present necessitating that providers evaluate patients for unintentional and deleterious symptomology related to aberrant opioid use and addiction. Polypharmacy with opioids is dynamic in affecting patients neurologically, and increased amounts of prescriptions have had inimical effects, not only for the individual, but also for their families and healthcare providers. The purpose of this review is to widen the perspective of opioid consequences and bring awareness to the numerous neuropsychiatric effects associated with the most commonly prescribed opioids for patients receiving palliative care. RECENT FINDINGS: Numerous clinical and research studies have found evidence in support for increased incidence of opioid usage and abuse as well as undesirable neurological outcomes. The most common and concerning effects of opioid usage in this setting are delirium and problematic drug-related behavioral changes such as deceitful behavior towards family and physicians, anger outbursts, overtaking of medications, and early prescription refill requests. Other neuropsychiatric effects detailed by recent studies include drug-seeking behavior, tolerance, dependence, addictive disorder, anxiety, substance use disorder, emotional distress, continuation of opioids to avoid opioid withdrawal syndrome, depression, and suicidal ideation. Opioid usage has detrimental and confounding effects that have been overlooked for many years by palliative care providers and patients receiving palliative care. It is necessary, even lifesaving, to be cognizant of potential neuropsychiatric effects that opioids can have on an individual, especially for those under palliative care. By having an increased understanding and awareness of potential opioid neuropsychiatric effects, patient quality of life can be improved, healthcare system costs can be decreased, and patient outcomes can be met and exceeded.

Efficacy and Safety of Intrathecal Morphine for Cesarean Delivery: A Narrative Review.

PURPOSE OF REVIEW: Pain management is a critical aspect of care during and following a cesarean delivery. Without proper control of pain, individuals can experience poor mobility, increased thromboembolic events, and difficulty caring for the neonate in the postpartum period. There have been multiple methods for pain management for cesarean delivery and intrathecal morphine (ITM) has emerged as a prominent option for post-operative analgesia due to its efficacy, safety, and potential benefits over other treatments. This review analyzes data on efficacy, side effects, and safety of ITM and the pain control alternatives. RECENT FINDINGS: A comprehensive literature review was conducted to compare ITM with other analgesic techniques in post-cesarean patients. ITM was found to be as effective or better than other analgesic options, including bilateral quadratus lumborum block (QLB), opioid-free epidural analgesia (CSEA-EDA), and intravenous fentanyl. One study found that both ITM and oral analgesia were effective in pain control and that ITM caused fewer breakthrough pain events but had a longer duration and a greater rate of side effects than oral opioid analgesia. Commonly observed side effects of intrathecal opioids include nausea, vomiting, pruritus, and urinary retention, and it is thought that the adverse effects from intrathecal administration of opioids are short-lived. ITM may provide a decreased risk of DVT and coagulation by decreasing lower extremity weakness and numbness, thereby decreasing recovery time and increasing mobility. ITM is a safe and effective option for post-cesarean analgesia, with comparable pain relief to alternative forms of pain control, and side effects that are generally manageable. Further research is warranted to explore beneficial combinations with other methods of pain management and optimal dosing strategies.

Glycoengineering of Esterase Activity through Metabolic Flux-Based Modulation of Sialic Acid.

This report describes the metabolic glycoengineering (MGE) of intracellular esterase activity in human colon cancer (LS174T) and Chinese hamster ovary (CHO) cells. In silico analysis of carboxylesterases CES1 and CES2 suggested that these enzymes are modified with sialylated N-glycans, which are proposed to stabilize the active multimeric forms of these enzymes. This premise was supported by treating cells with butanolylated ManNAc to increase sialylation, which in turn increased esterase activity. By contrast, hexosamine analogues not targeted to sialic acid biosynthesis (e.g., butanoylated GlcNAc or GalNAc) had minimal impact. Measurement of mRNA and protein confirmed that esterase activity was controlled through glycosylation and not through transcription or translation. Azide-modified ManNAc analogues widely used in MGE also enhanced esterase activity and provided a way to enrich targeted glycoengineered proteins (such as CES2), thereby providing unambiguous evidence that the compounds were converted to sialosides and installed into the glycan structures of esterases as intended. Overall, this study provides a pioneering example of the modulation of intracellular enzyme activity through MGE, which expands the value of this technology from its current status as a labeling strategy and modulator of cell surface biological events.

Radiology medical malpractice suits in gastrointestinal radiology: prevalence, causes, and outcomes.

The purpose of this study is to determine the prevalence, causes, and outcomes of GI malpractice suits in a survey of 8,401 radiologists. The malpractice histories of 8,401 radiologists from 47 states were evaluated from credentialing data of all radiologists participating in the network of One Call Medical Inc. Thirty-two percent of radiologists were defendants in at least one malpractice suit. Of the 4,073 total claims, 346 (8.49 %) were related to the gastrointestinal system. The most frequent primary allegations were failure to diagnose, 65.9 %, and procedural complications, 17.1 %. The commonest missed diagnoses were malignancy, 31.6 %; pneumoperitoneum, 19.3 %; and appendicitis, 14.5 %. Payment to the plaintiff occurred in 75.8 % of claims pertinent to cancer, 73.2 % for missed pneumoperitoneum, and 62.5 % related to appendicitis. Of cases in which a ruling was made in favor of the plaintiff, median payments for pneumoperitoneum was $215,000, for primary cancer $200,000, and for appendicitis $60,000. Among procedurally related errors resulting in judgment against a defending radiologist, 78.6 % of claims regarding retained foreign body, 75 % of barium enema cases, and 62.5 % of liver biopsy resulted in a payment to the plaintiff. Among all resolved cases, the median award was $30,000 for unrecognized foreign body retention, $100,000 for barium enema complications, and $400,000 for liver biopsy complication. Of all GI malpractice claims, failure to diagnose was the most prevalent. Among them, approximately three fourths of claims related to either the diagnosis of primary cancer or for detection of a pneumoperitoneum.

Prostate cancer: diffusion-weighted imaging versus dynamic-contrast enhanced imaging for tumor localization-a meta-analysis.

PURPOSE: The purpose of this study was to compare the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging for prostate cancer (PCa) detection by performing a meta-analysis of studies evaluating these techniques within the same patient cohort. METHODS: Evidence-based online databases were searched for studies reporting the performance of DWI and DCE in PCa detection in the same patient cohorts using histopathology as reference standard and providing sufficient data to construct 2 × 2 contingency tables. Pooled estimates of diagnostic performance were computed across included studies. RESULTS: Of 80 initial studies identified, 5 studies (total of 265 patients and 1730 prostatic regions) met criteria for inclusion in the meta-analysis. Pooled sensitivity was 58.4% (95% confidence interval [CI], 53.5%-63.1%) for DWI and 55.3% (95% CI, 50.4%-60.1%) for DCE. Pooled specificity was 89.0% (95% CI, 87.2%-0.7%) for DWI and 87.9% (95% CI, 86.0%-89.6%) for DCE. At summary receiver-operating-characteristic analysis, area-under-the-curve was 0.810 (0.059) for DWI and 0.786 (0.079) for DCE. Heterogeneity across studies was high for sensitivity and specificity [inconsistency index (I), >90%], although heterogeneity of specificity was substantially improved after excluding an outlier study in terms of diagnostic threshold (I = 0.0%-68.8%). Relative performance of DWI and DCE remained similar after this exclusion CONCLUSIONS: There was a paucity of studies comparing DWI and DCE in the same patient cohorts, and heterogeneity among these studies was substantial. Nevertheless, performance of DWI and DCE was similar across identified studies, with both techniques showing substantially better specificity than sensitivity. Larger studies with uniform methodology are warranted to further understand relative merits of the 2 techniques.

A Rare Presentation of Multiple Hepatic Masses Due to Hepatic Adenoma: A Case Report.

Hepatic adenomas (HAs) are rare but benign neoplasms of the liver which predominantly present as solitary lesions in women of reproductive age. The incidence of HAs has increased dramatically since the introduction of oral contraceptive pills (OCPs) along with the rising incidence of obesity. Discontinuation of OCPs and lifestyle modifications, including weight loss regimens, are considered as conservative treatment options for HAs. Large lesions may result in malignant transformation with a higher propensity for hemorrhage. Importantly, larger lesions that do not respond to conservative management require surgical excision. We report a case of a patient presenting with multiple hepatic lesions that were subsequently confirmed as HAs.

Parvovirus in Kidney Transplant Recipients: A Single-Center Experience.

OBJECTIVES: Parvovirus testing is not done in routine clinical practice; thus, it is possible that reported parvovirus cases are just the tip of the iceberg of total prevalence. We present a single-center retrospective analysis of 22 events of parvovirus B19 anemia in 20 renal transplant recipients, among which 2 patients had recurrence. MATERIALS AND METHODS: For this descriptive analytical study, parvovirus B19 disease was defined as parvovirus infection (detection by real-time polymerase chain reaction) in the presence of anemia with clinical symptoms or bone marrow biopsy findings consistent with the diagnosis. Study duration was 18 months, from June 2021 through December 2022, and patients were enrolled from a single center. RESULTS: All patients detected with the virus had received induction with thymocyte globulin and were on standard triple drug immunosuppression. Mean age was 32 ± 12 years with median time to diagnosis of 2 months after transplant. Anemia was observed in all patients with mean hemoglobin level at presentation of 6.02 ± 1.28 g/dL. Creatinine at presentation was 1.49 mg/dL (interquartile range, 0.92-2.69 mg/dL). The most common presentation was asymptomatic patient with evaluation for anemia. During therapy, the highest median creatinine level was 2.0 mg/dL (interquartile range, 1.38-3.2 mg/dL), which was significantly higher than that at presentation (P < .018). After therapy, median creatinine level was 1.3 mg/dL, which was not significantly higher than the baseline level, demonstrating a mostly transient graft dysfunction. CONCLUSIONS: Parvovirus B19 is a relatively underreported disease in renal transplant recipients, with patients presenting with anemia and the disease causing transient graft dysfunction. Parvovirus B19 infection responds well to a decrease in immunosuppression and intravenous immunoglobulin therapy.

Metabolic oligosaccharide engineering with N-Acyl functionalized ManNAc analogs: cytotoxicity, metabolic flux, and glycan-display considerations.

Metabolic oligosaccharide engineering (MOE) is a maturing technology capable of modifying cell surface sugars in living cells and animals through the biosynthetic installation of non-natural monosaccharides into the glycocalyx. A particularly robust area of investigation involves the incorporation of azide functional groups onto the cell surface, which can then be further derivatized using "click chemistry." While considerable effort has gone into optimizing the reagents used for the azide ligation reactions, less optimization of the monosaccharide analogs used in the preceding metabolic incorporation steps has been done. This study fills this void by reporting novel butanoylated ManNAc analogs that are used by cells with greater efficiency and less cytotoxicity than the current "gold standard," which are peracetylated compounds such as Ac4 ManNAz. In particular, tributanoylated, N-acetyl, N-azido, and N-levulinoyl ManNAc analogs with the high flux 1,3,4-O-hydroxyl pattern of butanoylation were compared with their counterparts having the pro-apoptotic 3,4,6-O-butanoylation pattern. The results reveal that the ketone-bearing N-levulinoyl analog 3,4,6-O-Bu3 ManNLev is highly apoptotic, and thus is a promising anti-cancer drug candidate. By contrast, the azide-bearing analog 1,3,4-O-Bu3 ManNAz effectively labeled cellular sialoglycans at concentrations ∼3- to 5-fold lower (e.g., at 12.5-25 µM) than Ac4 ManNAz (50-150 µM) and exhibited no indications of apoptosis even at concentrations up to 400 µM. In summary, this work extends emerging structure activity relationships that predict the effects of short chain fatty acid modified monosaccharides on mammalian cells and also provides a tangible advance in efforts to make MOE a practical technology for the medical and biotechnology communities.

Extracellular and intracellular esterase processing of SCFA-hexosamine analogs: implications for metabolic glycoengineering and drug delivery.

This report provides a synopsis of the esterase processing of short chain fatty acid (SCFA)-derivatized hexosamine analogs used in metabolic glycoengineering by demonstrating that the extracellular hydrolysis of these compounds is comparatively slow (e.g., with a t(1/2) of ∼4 h to several days) in normal cell culture as well as in high serum concentrations intended to mimic in vivo conditions. Structure-activity relationship (SAR) analysis of common sugar analogs revealed that O-acetylated and N-azido ManNAc derivatives were more refractory against extracellular inactivation by FBS than their butanoylated counterparts consistent with in silico docking simulations of Ac(4)ManNAc and Bu(4)ManNAc to human carboxylesterase 1 (hCE1). By contrast, all analogs tested supported increased intracellular sialic acid production within 2h establishing that esterase processing once the analogs are taken up by cells is not rate limiting.

A Rare Case of Habitual Dislocation of the Fourth Metatarsophalangeal Joint.

Introduction: Dislocations of lesser metatarsophalangeal joints (MTPJs) following trauma, inflammatory arthritis, and synovitis are not uncommon. Closed reduction is sufficient in most instances. However, if it is not addressed scientifically in the first instance; rarely, a habitual dislocation may result. Case Report: We present a case of a 43-year-old male patient with painful habitual dorsal dislocation of the fourth MTPJ following a trivial trauma 2 years back, resulting in an inability to wear closed footwear. The patient was managed with the repair of the plantar plate, excision of the neuroma, and transfer of long flexor to dorsum to act as dynamic check rein. At 3 months, he was able to wear shoes and returned to normal activities. There was no radiographic evidence of arthritis or avascular necrosis at 2 years follow-up, and he was comfortably using closed footwear. Conclusion: Isolated dislocation of the lesser MTPJs is an uncommon entity. Traditional practice is closed reduction. However, if the reduction is inadequate, open reduction should be performed to prevent chances of recurrence.

Insight into resident burnout, mental wellness, and coping mechanisms early in the COVID-19 pandemic.

BACKGROUND: Acute augmentation of stress and disruption of training, such as during the COVID-19 pandemic, may impact resident wellbeing. OBJECTIVES: We investigated how residents in various specialties in the United States were impacted by COVID-19 on mental wellbeing and resilience levels, and the methodology for coping with the stress incurred. METHODS: In April 2020, the authors electronically surveyed 200 residency programs of all specialties nationally. The survey utilized two validated questionnaires to assess wellbeing and resilience, while investigating demographics and coping mechanisms. The authors used student t-test and ANOVA to quantitatively analyze the data. RESULTS: The sample consisted of 1115 respondents (with an 18% response rate). Male gender & Age >39 years were associated with more favorable average well-being indices (both p<0.01). Regarding resources, institutional support (IS) appeared favorable for resident well-being (IS 2.74, SD1.96 vs NoIS 3.71, SD2.29, p<0.01) & resilience (IS 3.72, SD0.70 vs NoIS 3.53, SD0.73, p = 0.05). The effects of mindfulness practices (MP) were not statistically significant for improvement of wellness (MP 2.87, SD 1.99 vs No MP 2.76, SD 2.15, p = 0.85) or resilience (MP 3.71, SD 0.70 vs No MP 3.72, SD 0.68, p = 0.87). CONCLUSIONS: Findings highlight the critical importance of resident mental status in cases of augmented stress situations. Institutional support may contribute to promotion of resident wellbeing.

A Rare Case of Bilateral Fracture Neck Femur Treated with Bilateral Distal Loading Stem Total Hip Arthroplasty, in a Single Sitting.

INTRODUCTION: Bilateral intracapsular neck of femur fractures is rare and has been reported in patients with metabolic bone diseases, after electroconvulsive therapy and due to stress fractures. Total hip arthroplasty (THA) is considered as a treatment of choice for old aged patients. Surgery done in a single sitting for such patients helps in early mobilization. CASE REPORT: A 60-year-old male, known case of epilepsy and chronic renal disease, presented to us with bilateral intracapsular fracture of neck of femur following episode of convulsion. The patient was operated for a distal loading stem THA on both sides in a single sitting. Proximally deficient hip was managed with screw and cerclage looping fixation of greater trochanter on both sides. The post-operative course was uneventful. At 2 weeks, the patient was allowed protected weight-bearing with a walker. At 8 weeks, the patient was doing full weight-bearing, while at 4 months, the patient was carrying out all activities of daily living. Mean Harris hip score was 86 at the end of 6 months. CONCLUSION: Bilateral long stem distal loading THA can give good clinical and functional outcomes in a case of the bilateral neck of femur fracture with a deficit of proximal femur. The patient can safely be operated for arthroplasty on both sides in a single sitting. Single sitting surgery will help in early mobilization and better functional outcomes.

A Rare Case of Symptomatic Planovalgus Foot with Triple Coalition.

INTRODUCTION: Tarsal coalitions in the general population are low, possibly due to the asymptomatic nature. In the symptomatic group, however, the presentation is usually during adolescence or early adulthood. The occurrence of a triple tarsal coalition is extremely rare, especially if not associated with a syndrome. CASE REPORT: We report a case that has the unique configuration of talocalcaneal, talonavicular, and calcaneocuboid coalitions with a planovalgus foot. We review the available literature on this rare occurrence and outline our management in this case to achieve a plantigrade, painless functional foot. CONCLUSION: Symptomatic triple coalition planovlagoid cases, require a surgical corrective procedure in order to achieve a plantigrade foot.

Variation of stress levels, burnout, and resilience throughout the academic year in first-year medical students.

Medical student wellness is of great concern in the health care field. A growing number of studies point to increases in suicide, depression, anxiety, mood disorders, and burnout related to physician lifestyles. Mental health issues commencing in medical school have been suggested to have a significant impact on future physician lifestyle and burnout. Tracking the mental health of medical students at the University of Toledo College of Medicine and Life Sciences (UTCOMLS) with standardized indices will help elucidate triggers of poor mental health. Anonymous surveys were developed and distributed to preclinical medical students at five strategic time points throughout the 2018 2019 academic year. Surveys collected basic demographic information as well as inventories measuring perceived stress, burnout, resilience, and mindfulness. 172 M1s (83 males and 89 females) were included in the study and average response rate for the first 4 (out of 5) surveys averaged 74.8%. M1 males and females had on average increased personal burnout over time with females consistently scoring higher. Both males and females had an increase in stress from August to each subsequent month (p<0.05). Females reported a higher level of perceived stress than males in the beginning and middle of the academic year (p<0.05). Both males and females report a gradual decrease in resiliency throughout the academic year. These surveys demonstrated over half of males and females in medical school reported higher perceived stress scores than their gender-matched peers in the general United States population. Our study strengthens documented trends in resiliency, perceived stress, and burnout amongst medical students. More study in designing targeted approaches to ameliorate these findings in the medical student population is warranted.

Targeting the NF-κB signaling pathway in chronic tendon disease.

Tendon disorders represent the most common musculoskeletal complaint for which patients seek medical attention; inflammation drives tendon degeneration before tearing and impairs healing after repair. Clinical evidence has implicated the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway as a correlate of pain-free return to function after surgical repair. However, it is currently unknown whether this response is a reaction to or a driver of pathology. Therefore, we aimed to understand the clinically relevant involvement of the NF-κB pathway in tendinopathy, to determine its potential causative roles in tendon degeneration, and to test its potential as a therapeutic candidate. Transcriptional profiling of early rotator cuff tendinopathy identified increases in NF-κB signaling, including increased expression of the regulatory serine kinase subunit IKKß, which plays an essential role in inflammation. Using cre-mediated overexpression of IKKß in tendon fibroblasts, we observed degeneration of mouse rotator cuff tendons and the adjacent humeral head. These changes were associated with increases in proinflammatory cytokines and innate immune cells within the joint. Conversely, genetic deletion of IKKß in tendon fibroblasts partially protected mice from chronic overuse-induced tendinopathy. Furthermore, conditional knockout of IKKß improved outcomes after surgical repair, whereas overexpression impaired tendon healing. Accordingly, targeting of the IKKß/NF-κB pathway in tendon stromal cells may offer previously unidentified therapeutic approaches in the management of human tendon disorders.

Unusual Presentation of Tuberculosis of Subtalar Joint.

INTRODUCTION: A case of seronegative variety of subtalar joint arthritis was treated with subtalar joint fusion surgery. In spite of perfect execution of surgery, fusion did not occur. It was only at a revision surgery that case could be diagnosed as a case of tuberculosis of subtalar joint. CASE REPORT: Elderly female was operated for seronegative subtalar joint arthritis with fusion plus primary bone grafting. Fusion did not progress in spite of every added efforts such as extended immobilization, calcium supplements, and antibiotic therapy. Revision surgery was undertaken considering the reason of failure being a low-grade infection. At a revision surgery, case was diagnosed as a case of tuberculosis of subtalar joint, a very rare presentation. Fusion succeeded just with addition of antituberculous therapy supported with short-term immobilization. CONCLUSION: Tuberculosis of the foot and ankle joints, though are rare, they can mimic like many other disorders. In developing countries, a high index of suspicion is warranted to early diagnose it.

Delayed presentation or delayed diagnosis? A retrospective study of prospectively collected data of 482 foot and ankle injuries.

BACKGROUND: Delayed presentation of injury cases is common in developing countries like India. It is prudent to study reasons for delayed presentations to focus preventive measures towards responsible factors. Since foot and ankle orthopaedics is in its infancy in India, it was deemed to be worthwhile to study reasons for delayed presentations of foot and ankle injuries. METHODS: Retrospective analysis of prospectively collected data from 482 foot and ankle injuries treated at our three foot and ankle centres over past three years was undertaken. Delayed presentation was defined as cases presenting to us at or after 3 weeks of injury, but with complete records. Reasons for delayed presentations were analysed. RESULTS: There were ninety eight such cases who fulfilled the delayed presentation criteria and within this group there were twenty different varieties of foot and ankle injuries. Of these twenty six cases were never treated by qualified orthopaedic surgeons and were labelled as direct delayed presentations, and the remaining 72 cases who were treated by qualified orthopaedic surgeons, but could not be diagnosed and presented late, were labelled as indirect delayed presentations. Failure to suspect injury (5 cases) or failure to diagnose injury (67 cases) were reasons for indirect delayed presentations. Failure to diagnose injury on part of clinicians was either due to failure of clinical and radiological analysis (analytical failure - 15 cases) or due to failure to investigate case with further radiological investigations (investigative failure - 10 cases). Forty-two cases had combined failures. CONCLUSIONS: In developing countries like India, patients did neglect their foot and ankle injuries and presented late. In fact, by way of delayed diagnosis, clinicians were more responsible for indirect delayed presentations of foot and ankle injuries. This is contrary to the common belief that in developing countries like India, only patients would be solely responsible for delayed presentations after injury. Because delayed diagnosis by clinicians seemed more alarming than delayed presentation by patients, focus of prevention of foot and ankle injuries in developing countries should shift more towards educating clinicians than patients.

Targeting Inflammation in Rotator Cuff Tendon Degeneration and Repair.

Rotator cuff degeneration is a common affliction that results in pain and disability. Tendinopathy was historically classified with or without the involvement of the immune system. However, technological advancements in screening have shown that the immune system is both present and active in all forms of tendinopathy. During injury and healing, the coordinated effort of numerous immune cell populations work with the resident stromal cells to break down damaged tissues and stimulate remodeling. These cells deploy a wide array of tools, including phagocytosis, enzyme secretion, and chemotactic gradients to direct these processes. Yet, there remains a knowledge gap in our understanding of the sequence of critical events and regulatory factors that mediate this is process in injury and healing. Furthermore, current treatments do not specifically target inflammation at the molecular level. Typical regimens include non-steroidal anti-inflammatory drugs or corticosteroids; however, researchers have found irrevocable functional deficits following treatment, and have disputed their long-term efficacy. Therefore, developing therapeutics that specifically consider the nuances of the immune system are necessary to improve patient outcomes.

Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model.

BACKGROUND: Rotator cuff tears are a common source of pain and disability, and poor healing after repair leads to high retear rates. Bone loss in the humeral head before and after repair has been associated with poor healing. The purpose of the current study was to mitigate bone loss near the repaired cuff and improve healing outcomes. METHODS: Sclerostin antibody (Scl-Ab) treatment, previously shown to increase bone formation and strength in the setting of osteoporosis, was used in the current study to address bone loss and enhance rotator cuff healing in an animal model. Scl-Ab was administered subcutaneously at the time of rotator cuff repair and every 2 weeks until the animals were sacrificed. The effect of Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone morphometric analysis, biomechanical evaluation, histological analysis, and gene expression outcomes. RESULTS: Injury and repair led to a reduction in bone mineral density after 2 and 4 weeks of healing in the control and Scl-Ab treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment had 30% greater bone mineral density than the controls. A decrease in biomechanical properties was observed in both groups after 4 weeks of healing compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl-Ab-treated animals had improved strength (38%) and stiffness (43%) compared with control animals. Histological assessment showed that Scl-Ab promoted better integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant effects on gene expression in bone, indicative of enhanced bone formation, and no effect on the expression of genes in tendon. CONCLUSIONS: This study provides evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator cuff by increasing attachment-site bone mineral density, leading to improved biomechanical properties. CLINICAL RELEVANCE: Scl-Ab treatment may improve outcomes after rotator cuff repair.