Efficacy of hypertonic dextrose proliferation therapy in the treatment of rotator cuff lesions: a meta-analysis.

BACKGROUND: One of the most prevalent illnesses of the shoulder is rotator cuff tendinosis, which is also a major contributor to shoulder discomfort and shoulder joint dysfunction. According to statistics, rotator cuff tendinosis occurs in 0.3-5.5% of cases and affects 0.5-7.4% of people annually. It will be necessary to conduct a meta-analysis to evaluate the efficacy of hypertonic glucose proliferation therapy in the treatment of rotator cuff problems. METHODS: The databases Cochrane PubMed, Library, Web of Science and EMbase, are retrieved by the computer. Individuals with rotator cuff lesions in the intervention group were treated with hypertonic dextrose proliferation therapy, whereas individuals in the control condition were treated with a placebo. Outcome markers for rotator cuff lesions patients; Pursuant to studies, the visual analogue scale (VAS) score, the shoulder pain & disability index (SPADI), & other metrics are used to evaluate the effects of hypertonic dextrose proliferation treatment on individuals with rotator cuff diseases. After carefully evaluating the calibre of the literature, data analysis was performed utilising the RevMan 5.3 programme. RESULTS: Meta-analysis finally contained 6 papers. In six investigations, the test & control group's VAS scores improved, with the test team's score considerably outperforming the control team [standardized mean difference (SMD): 1.10; 95% Cl: 0.37,1.83; P < 0.01], shoulder pain and disability index (SPADI) score (SMD:8.13; 95% Cl: 5.34,10.91; P < 0.01), Flexion (SMD:5.73; 95% Cl: 0.99,10.47; P < 0.05), Abduction (SMD:6.49; 95% Cl: 0.66,12.31; P < 0.05), Internal rotation (SMD:-1.74; 95% Cl: -4.25,0.78; P = 0.176) and External rotation (SMD:2.78; 95% Cl: -0.13,5.69; P = 0.062). CONCLUSION: The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation treatment based on the visual analogue scale (VAS) score, the Shoulder Pain and Disability Index (SPADI) score, Flexion, & Abduction. These results must, nevertheless, be supported by high-caliber follow-up research.

Metformin mitigates adipogenesis of fibro-adipogenic progenitors after rotator cuff tears via activating mTOR/ULK1-mediated autophagy.

Muscular fatty infiltration is a common issue after rotator cuff tears (RCTs), which impair shoulder function. Females suffer a higher prevalence and a more severe degree of muscular fatty infiltration after RCT when compared with males, with the underlying mechanisms remaining unclear. Fibro-adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.NEW & NOTEWORTHY The current study demonstrated that gender-specific disparities in muscular fatty infiltration are attributed to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Moreover, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Therefore, metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.

Risk of rotator cuff tear and rotator cuff repair surgery comparison between sodium-glucose cotransporter 2 inhibitors and glucagon like peptide-1 receptor agonists: A real-world study.

AIM: Theoretically, sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of rotator cuff tear through an anti-inflammatory mechanism. To clarify this association, in this study, we compared SGLT2is users and glucagon-like peptide-1 receptor agonists (GLP-1RAs) users in terms of the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery. METHODS: A retrospective cohort analysis was conducted using data from the TriNetX platform. A target trial design was adopted to identify patients with type 2 diabetes mellitus who started receiving SGLT2is or GLP-1RAs. Propensity score matching was used to form two homogeneous groups. The study outcomes were the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated within the TriNetX platform. RESULTS: Initially, 351,800 SGLT2is users and 387,616 GLP-1RAs users were identified. After propensity score matching, each group comprised 274,026 patients. The mean age was 59.5 years in both groups; the proportions of women in the SGLT2is and GLP-1RAs groups were 46.9 % and 46.7 %, respectively. Compared with the GLP-1RAs group, the SGLT2is group had significantly reduced risks of rotator cuff tear (HR 0.812 [0.761;0.867]) and rotator cuff repair surgery (HR 0.900 [0.815;0.994]). CONCLUSION: SGLT2is appear to reduce the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery in patients with type 2 diabetes mellitus. Further prospective studies are needed to validate our findings.

Editorial Commentary: Postoperative Zoledronic Acid Improves Tendon Healing but Does Not Affect Outcomes in Rotator Cuff Repair Patients With Postmenopausal Osteoporosis.

Understanding the preoperative risk factors for successful rotator cuff repair (RCR) and ways to optimize these factors is an evolving area of study. The Rotator Cuff Healing Index and other proxy risk factors for failed rotator cuff healing have implicated significant fatty infiltration, muscular atrophy, advanced chronological age, tear size and retraction, and ultimately, osteoporosis. Although structural (or biological) augmentation and tendon transfer have been proposed as solutions for the alarmingly high rate of failure after primary RCR, other options may preferentially focus on the enthesis and underlying osseous footprint. Currently, bisphosphonates are frequently used in the treatment of osteoporosis and prevention of fragility fractures. However, burgeoning evidence suggests that postoperative zoledronic acid may have clinical utility after rotator cuff and other tendon repairs. In the cost-conscious world of evidence-based medicine, the added economic burden of additional medications and office visits may or may not improve patient outcomes-much less confer added value. Our advice to fellow shoulder surgeons: Wait for further information, but continue to holistically consider and optimize risk factors for poor soft-tissue healing. Although the addition of postoperative bisphosphonates may improve suture anchor fixation and promote a better foundation for healing, it will not immediately transform your RCR success rates.

Effect of tetrahedral framework nucleic acids on the reconstruction of tendon-to-bone injuries after rotator cuff tears.

Clinicians and researchers have always faced challenges in performing surgery for rotator cuff tears (RCT) due to the intricate nature of the tendon-bone gradient and the limited long-term effectiveness. At the same time, the occurrence of an inflammatory microenvironment further aggravates tissue damage, which has a negative impact on the regeneration process of mesenchymal stem cells (MSCs) and eventually leads to the production of scar tissue. Tetrahedral framework nucleic acids (tFNAs), novel nanomaterials, have shown great potential in biomedicine due to their strong biocompatibility, excellent cellular internalisation ability, and unparalleled programmability. The objective of this research was to examine if tFNAs have a positive effect on regeneration after RCTs. Experiments conducted in a controlled environment demonstrated that tFNAs hindered the assembly of inflammasomes in macrophages, resulting in a decrease in the release of inflammatory factors. Next, tFNAs were shown to exert a protective effect on the osteogenic and chondrogenic differentiation of bone marrow MSCs under inflammatory conditions. The in vitro results also demonstrated the regulatory effect of tFNAs on tendon-related protein expression levels in tenocytes after inflammatory stimulation. Finally, intra-articular injection of tFNAs into a rat RCT model showed that tFNAs improved tendon-to-bone healing, suggesting that tFNAs may be promising tendon-to-bone protective agents for the treatment of RCTs.

Editorial Commentary: Biocomposite Implant Combined With Local Human Recombinant Parathyroid Hormone Enhances the Histological Quality and Biomechanical Strength of Rotator Cuff Repairs.

Rates of rotator cuff repair retear remain unacceptably high and are frequently the source of diminished shoulder function and patient dissatisfaction. Endocrinopathies have been implicated in these processes. Parathyroid hormone (PTH) activates chondrogenesis and angiogenesis at the enthesis and prevents fatty infiltration and atrophy in rotator cuff musculature. These facts have spurred interest in the therapeutic benefits of PTH as a means to enhance tendon healing and strengthen the bone in and around tendon repairs. New research demonstrates that recombinant human PTH delivered locally through a process of coupling it to a bioengineered scaffold "sheath" may be beneficial. The growth factor, encased within polycaprolactone (PCL), is slowly released as the PCL degrades to extend drug delivery time. The augmentation of rotator cuff repairs with this biocomposite material improves short-term structural tissue integrity and promotes the formation of more organized and stronger tendon-to-bone interface in a rabbit model.

Dual Growth Factor Delivery Using Photo-Cross-Linkable Gelatin Hydrogels for Effectively Reinforced Regeneration of the Rotator Cuff Tendon.

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy32+) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.

Editorial Commentary: Corticosteroid Injections Administered Within 4 Weeks Before Shoulder Arthroscopy Are Associated With an Increased Risk of Infection.

Corticosteroid injections are a frequently used modality for addressing shoulder pain. The widespread utilization of corticosteroid injections is supported by clinical practice guidelines and consensus statements including the 2019 American Academy for Orthopaedic Surgeons (AAOS) guidelines for the management of rotator cuff injuries. However, steroids may be detrimental to healing potential following cuff repair and increase the risk of re-tear. In addition, corticosteroid injections administered within 4 weeks prior to shoulder arthroscopy are associated with an increased risk of infection. The degree of risk is dependent on the timing of surgery with longer time intervals between injection and shoulder arthroscopy being associated with less risk. The next version of the AAOS clinical practice guidelines for managing rotator cuff tears should incorporate commentary on the specific risk of surgical site infection following pre-operative corticosteroid injections, as well as on the timing of injections, with the aim of increasing awareness of these potentially devastating adverse effects.

Fibroblast Growth Factor Soaked Collagen Membrane Shows No Biomechanical or Histological Advantages in the Treatment of Chronic Rotator Cuff Tears in a Rabbit Model.

PURPOSE: To investigate the histological and biomechanical effects of a fibroblast growth factor (FGF-2)-soaked collagen membrane used to treat a full-thickness chronic rotator cuff (RC) rupture in a rabbit model. METHODS: Forty-eight shoulders from 24 rabbits were used. At the beginning of the procedure, 8 rabbits were killed to assess the control group (Group IT) with intact tendons. To establish a chronic RC tear model, a full-thickness subscapularis tear was created on both shoulders of the remaining 16 rabbits and left for 3 months. The transosseous mattress suture technique was used to repair tears in the left shoulder (Group R). The tears in the right shoulder (Group CM) were treated using the same approach, with an FGF-soaked collagen membrane inserted and sutured over the repair site. Three months after the procedure, all rabbits were killed. Biomechanical testing was performed on the tendons to determine failure load, linear stiffness, elongation intervals, and displacement. Histologically, the modified Watkins score was used to evaluate tendon-bone healing. RESULTS: There was no significant difference among the three groups in terms of failure load, displacement, linear stiffness, and elongation (P > .05). The total modified Watkins score was not affected by applying the FGF-soaked collagen membrane to the repair site (P > .05). Fibrocytes, parallel cells, large-diameter fibers, and the total modified Watkins score were significantly lower in both repair groups when compared to the intact tendon group (P < .05). CONCLUSIONS: In addition to tendon repair, FGF-2 soaked collagen membrane -application at the repair site provides neither biomechanical nor histological advantages in the treatment of chronic RC tears. CLINICAL RELEVANCE: FGF-soaked collagen membrane augmentation provides no impact on the chronic RC tear healing tissue. The need to investigate alternative methods that may have a positive effect on healing in chronic RC repairs continues.

Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

PURPOSE: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation. METHODS: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation. RESULTS: Part 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1. CONCLUSIONS: While there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.

Non-steroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors Do Not Affect Healing After Rotator Cuff Repair: A Systematic Review and Meta-analysis.

PURPOSE: To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors affect healing rate, functional outcomes, and patient satisfaction after rotator cuff repair. METHODS: Medline, EMBASE, PsychINFO and the Cochrane Library were searched for randomized controlled trials (RCTs) investigating the use of NSAIDs and COX-2 inhibitors after arthroscopic rotator cuff repair. Primary outcomes included healing and retear rate, determined by radiological imaging. Secondary outcomes included shoulder-specific outcome measures and the visual analog scale (VAS). Risk of bias was graded using the Cochrane risk-of-bias v2.0 tool. The GRADE framework was used to assess certainty of findings. RESULTS: Seven RCTs with a total of 507 patients were included (298 randomized to NSAID/COX-2 vs 209 randomized to control). NSAIDs use did not yield a difference in retear rate (P = .77). NSAIDs were shown to significantly reduce pain in the perioperative period (P = .01); however, no significant difference was present at a minimum of 6 months (P = .11). COX-2 inhibitors did not significantly reduce pain (P = .15). Quantitative analysis of ASES and UCLA scores showed NSAIDs significantly improved functional outcomes versus control (P = .004). COX-2 inhibitors did not significantly improve functional outcomes (P = .15). Two trials were deemed "low" risk of bias, four trials were graded to have "some concerns", and one trial was graded to have "high" risk of bias. Retear rate and functional PROMs were deemed to have "low" certainty. VAS pain scale was graded to have "moderate" certainty. CONCLUSIONS: This systematic review and meta-analysis indicates that NSAIDs do not affect healing rate after arthroscopic rotator cuff repair, but they do significantly improve postoperative pain and functional outcomes. No significant difference was seen in pain or functional outcomes with the use of COX-2 inhibitors. LEVEL OF EVIDENCE: Level I, meta-analysis of randomized controlled trials.

Local Injection of Rapamycin-Loaded Pcl-Peg Nanoparticles for Enhanced Tendon Healing in Rotator Cuff Tears via Simultaneously Reducing Fatty Infiltration and Drug Toxicity.

As a common cause of shoulder pain, rotator cuff tears (RCTs) are difficult to treat clinically because of their unsatisfactory prognosis due to the fatty infiltration caused by muscle-derived stem cells (MDSCs). Previous studies have found that rapamycin (RAPA) can inhibit fatty infiltration. However, systemic administration of RAPA may cause complications such as infection and nausea, while local administration of RAPA may lead to the cytotoxicity of tendon cells, affecting the healing of rotator cuffs. In this study, biocompatible and clinically approved polycaprolactone-polyethylene glycol (PCL-PEG) is formulated into an injectable nanoparticle for the sustained release of RAPA. The results indicate that the RAPA/PCL-PEG nanoparticles (NPs) can efficiently prolong the release of RAPA and significantly reduce the cytotoxicity of tendon cells caused by RAPA. The study of the fatty infiltration model in rats with delayed rotator cuff repair shows that weekly intraarticular injection of RAPA/PCL-PEG NPs can more effectively reduce the fatty infiltration and muscle atrophy of rat rotator cuffs and leads to better mechanical properties and gait improvements than a daily intraarticular injection of RAPA. These findings imply that local injection of RAPA/PCL-PEG NPs in the shoulder joints can be a potential clinical option for RCTs patients with fatty infiltration.

Estrogen and testosterone supplementation improves tendon healing and functional recovery after rotator cuff repair.

Failure of healing after rotator cuff repair (RCR) is common. The purpose of the current study was to evaluate the effect of systemic estrogen or testosterone supplementation on tendon healing after RCR. Seventy-two adult male mice were utilized for all experiments. The supraspinatus tendon was transected and repaired with 6-0 Prolene suture on the left shoulder of 51 animals. Mice were segregated into three groups postoperative: (1) vehicle group (VG; n = 18), (2) estrogen group (EST; n = 17), and (3) testosterone group (TST; n = 16). An unrepaired control group (unrepaired, n = 21) did not have surgery. Utilizing these animals, histological analysis, activity testing, biomechanical testing and RNA sequencing (RNA-seq) was performed. At 8 weeks post-RCR, TST, and EST supplementation improved the overall histologic structure of the repaired enthesis site. No differences in ultimate failure loads or stiffness were detected between VG, EST, and TST groups after biomechanical testing. RCR caused a reduction in wheel activity compared to unrepaired controls and supplementation with TST restored wheel activity. RNA-seq analysis indicated that estrogen and testosterone regulated different pathways associated with enthesis healing, including a suppression of inflammatory signaling. Supplementation with sex hormones improved the structure of the repaired tendon enthesis and significantly regulated expression of diverse pathways regulating multiple biological processes. Testosterone administration following RCR restored wheel activity without having a detrimental impact on biomechanical strength. Future human studies of sex hormone supplementation after RCR are warranted as supplementation in an animal model may improve tendon enthesis healing.

Postoperative Antiosteoporotic Treatment with Zoledronic Acid Improves Rotator Cuff Healing but Does Not Improve Outcomes in Female Patients with Postmenopausal Osteoporosis: A Prospective, Single-Blinded, Randomized Study.

PURPOSE: To investigate the effect of the antiosteoporotic agent zoledronic acid (ZA) on rotator cuff healing and clinical outcomes in patients with postmenopausal osteoporosis. METHODS: We prospectively enrolled 138 female patients with postmenopausal osteoporosis who were scheduled to undergo arthroscopic rotator cuff repair (ARCR) from March 2020 to March 2021. Patients were randomly allocated to the ZA group (ARCR followed by intravenous ZA infusions at postoperative Day 1 and 1 year later) and the control group (ARCR alone). All patients were followed up for 24 months. Tendon healing was evaluated by ultrasonography at 6 weeks and 24 months after surgery. The American Shoulder and Elbow Surgeons (ASES) score, Western Ontario Rotator Cuff (WORC) index, and Numeric Rating Scale (NRS) for pain were recorded at each follow-up, and the minimal clinically important difference (MCID) was calculated. RESULTS: A total of 124 patients were included in the final analysis, 61 in the ZA group and 63 in the control group. There was no statistically significant difference in participant characteristics between the 2 groups. The ZA group had a significantly higher tendon healing rate than the control group at 2 years after surgery (odds ratio = 5.0; 95% confidence interval [CI], 1.4-18.7; P = .014). Regarding clinical outcomes, 100% of patients exceeded the MCID in both groups, and no significant differences were found at 2 years after surgery between the 2 groups (ASES: 2.5 [95% CI, -2.2 to 7.2; P = .291]; WORC index: 4.5 [95% CI, -0.117 to 9.117; P = .056]; NRS: -0.1 [95% CI, -0.3 to 0.1; P = .394]). CONCLUSIONS: Antiosteoporotic treatment with ZA reduced the retear rate but did not significantly influence the clinical outcomes after ARCR in female patients with postmenopausal osteoporosis. Outcomes of ARCR showed good results in both groups and exceeded the MCID. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Editorial Commentary: Dasatinib With Quercetin Shows Promise in Decreasing Age-Related Senescence in the Rotator Cuff Tendon-Can It Work Elsewhere?

Cellular senescence is a fundamental mechanism seen in all age-related diseases. Human supraspinatus tendon and adjacent bursal specimens evaluated for cellular senescence by immunohistochemistry and gene expression show more senescent cells in older patients. This confirms the observation that older patients are more likely to have rotator cuff pathology, and older age is associated with lower rates of rotator cuff healing and more frequent tendon retears. Senolytic drugs can selectively eliminate senescent cells without a localized or systemic impact. Tendon and bursal specimens co-cultured and then incubated with dasatinib and quercetin for 48 hours show a significant decrease in senescent cells. This suggests that these drugs may slow biological aging in rotator cuff tendons and offer the possibility of a clinically effective treatment for the aging rotator cuff tendon. Moreover, this concept is promising for the development of future effective therapies addressing tissue senescence.

Current Research on the Influence of Statin Treatment on Rotator Cuff Healing.

Rotator cuff tears are a condition characterized by damage to the muscles and tendons that connect the scapula and humerus, which are responsible for shoulder rotation and arm lifting. Metabolic factors such as diabetes, thyroid disease, high cholesterol, vitamin D deficiency, obesity, and smoking have been associated with an increased risk of rotator cuff tears. Interestingly, patients with hyperlipidemia, a condition characterized by high levels of cholesterol and other fats in the blood, have been found to have a higher incidence of rotator cuff tears and breakdown of tendon matrix. As a result, statin therapy, which is commonly used to lower cholesterol levels in hyperlipidemia, has been explored as a potential treatment to improve clinical outcomes in rotator cuff tears. However, the results of preclinical and clinical studies on the effects of statins on tendon healing in rotator cuff tears are limited and not well-defined. Moreover, since hyperlipidemia and rotator cuff tears are more prevalent in older individuals, a literature review on the efficacy and safety of statin therapy in this population is needed.

Progress in studying the impact of hyperlipidemia and statins on rotator cuff injury and repair.

This review delves into the intersection of two prevalent conditions, hyperlipidemia and rotator cuff injuries, both of which bear substantial healthcare burdens. Our investigation begins with an exploration of rotator cuff injuries, common musculoskeletal disorders that severely impair shoulder functionality and quality of life. These injuries are notably pervasive among sports enthusiasts and the older adult, with an incidence rate estimated at 5-10% in the general population. Despite their widespread occurrence and the diverse, multifactorial etiological factors, effective treatment strategies remain elusive. We then examine hyperlipidemia, a metabolic disorder affecting approximately 40% of the global adult population. Characterized by elevated levels of cholesterol and triglycerides, hyperlipidemia can precipitate severe cardiovascular complications and presents a significant socioeconomic burden. Although current management strategies encompass lifestyle modifications and pharmacological interventions, the condition remains a formidable health challenge. Central to this review is the exploration of a potential association between hyperlipidemia and rotator cuff injuries. We aim to synthesize the current understanding of hyperlipidemia's role in the pathophysiology of rotator cuff injuries, thereby offering fresh insights into their common etiological underpinnings, potential therapeutic targets, and drugs, such as Statins. The influence of other lipid-lowering therapeutics on tendon health is also considered, and further research into the molecular pathways and potential therapeutic benefits of these drugs is required. This pursuit aligns with broader efforts to enhance patient outcomes, minimize healthcare burdens, and contribute to the global understanding of these prevalent conditions.

Management of partial-thickness rotator cuff tears with autologous adipose-derived regenerative cells is safe and more effective than injection of corticosteroid.

Symptomatic, partial-thickness rotator cuff tears (sPTRCT) are problematic. This study tested the hypothesis that management of sPTRCT with injection of fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) is safe and more effective than injection of corticosteroid even in the long run. To this end, subjects who had completed a former randomized controlled trial were enrolled in the present study. At baseline these subjects had not responded to physical therapy treatments for at least 6 weeks, and were randomly assigned to receive respectively a single injection of UA-ADRCs (n = 11) or a single injection of methylprednisolone (n = 5). Efficacy was assessed using the ASES Total score, pain visual analogue scale (VAS), RAND Short Form-36 Health Survey and range of motion at 33.2 ± 1.0 (mean ± SD) and 40.6 ± 1.9 months post-treatment. Proton density, fat-saturated, T2-weighted MRI of the index shoulder was performed at both study visits. There were no greater risks connected with injection of UA-ADRCs than those connected with injection of corticosteroid. The subjects in the UA-ADRCs group showed statistically significantly higher mean ASES Total scores than the subjects in the corticosteroid group. The MRI scans at 6 months post-treatment allowed to "watch the UA-ADRCs at work".

A multi-center, single-blinded, randomized, parallel-group, superiority study to compare the efficacy of manipulation under anesthesia versus intra-articular steroid injection in the treatment of patients with frozen shoulder and a diagnosis of rotator cuff injury or tear by MRI: study protocol for a randomized controlled trial.

BACKGROUND: Frozen shoulder (FS) is a common condition that can cause severe pain and limited range of motion in the shoulder joint. While intra-articular steroid injection has been shown to be an effective treatment for FS, manipulation under anesthesia (MUA) is an alternative treatment that has gained popularity in recent years. However, there is a lack of evidence regarding the effectiveness of MUA on FS patients with concomitant rotator cuff injury or tear. Though a few studies have shown that MUA is not associated with rotator cuff tears, and will not exacerbate the injury, more high-quality studies with bigger sample sizes are needed. Therefore, the aim of this multi-center, single-blinded, randomized, parallel-group, superiority study is to compare the efficacy of MUA versus intra-articular steroid injection in the treatment of FS patients with a diagnosis of rotator cuff injury or tear by MRI. METHODS: A parallel, single-blinded, multi-center randomized controlled trial of 320 patients will be conducted at three hospitals of China. Eligible patients with frozen shoulder and rotator cuff injury or tear diagnosed by MRI will be randomly assigned to, in equal proportions, the manipulation under anesthesia group and the intra-articular steroid injection group via a central randomization system, undergoing a corresponding operation on day one and a sequent physical exercise for 14 days. The primary outcome is the comprehensive efficacy evaluation (total effective rate) and the change of Constant-Murley Score. Outcome assessors and data analysts will be blinded, and participants will be asked not to reveal their allocation to assessors. DISCUSSION: This study aims to explore the superiority of manipulation under anesthesia in reducing pain and improving shoulder function in frozen shoulder patients accompanied with rotator cuff injury. To provide a scientific basis for the dissemination and application of manipulation under anesthesia, and a better knowledge for the role of MUA in the treatment of frozen shoulder accompanied with rotator cuff injury. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2200067122 . Registered on 27 December 2022. ChiCTR is a primary registry of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) network and includes all items from the WHO Trial Registration data set in Trial registration.

Editorial Commentary: Bone Marrow Stimulation and Losartan Augmentation of Shoulder Rotator Cuff Repair.

Rotator cuff retear rates after repair have been variously reported as ranging from 5% to 40% for small to mediums tears and as high as 40% to 94% for large to massive tears. Thus strategies to enhance structural healing are relevant. In rabbits, combining oral losartan (which has antifibrotic effects by downregulating transforming growth factor-ß1) and bone marrow stimulation (BMS) of the greater tuberosity, showed improved rotator cuff repair pull-out strength and highly organized tendon matrix in a chronic injury model, whereas BMS alone did not improve the mechanical properties. However, clinical studies show that BMS techniques have a positive impact on healing and retear rates. BMS stimulates migration of mesenchymal stem cells from bone marrow to the lesion, and this approach has been widely used to fill cartilage defects by fibrocartilage metaplasia. BMS is a straightforward and cost-effective technique; the use of multiple deeper bone tunnels is recommended.