Editorial Commentary: Predictors of Best Outcomes After Latissimus Dorsi Transfer for Irreparable Rotator Cuff Tear.

The management of patients with massive posterosuperior rotator cuff tears without glenohumeral arthritis remains a challenge to arthroscopic surgeons. A wide variety of treatment options have been described, including latissimus dorsi tendon transfer (LDTT) and lower trapezius tendon transfer. These tendon transfers have been utilized to rebalance the glenohumeral force couple for patients with massive or irreparable posterosuperior rotator cuff tears. Proponents of the latissimus dorsi tendon transfer have touted several theoretical advantages, including improvement of the shoulder fulcrum, optimization of the deltoid function, improved humeral head depression, and restoration of shoulder motion. Currently accepted contra-indications to LDTT include glenohumeral arthritis, irreparable subscapularis tear, axillary nerve palsy and/or deltoid insufficiency. However, few studies have investigated the ideal patient selection for LDTT, particularly as it relates to clinically significant outcomes. Recent literature suggests a high rate of complications and re-tear following LDTT, and studies suggest that older age, previous surgery, true pseuoparalysis, lower low pre-operative acromiohumeral interval (AHI) or AHI reversibility negatively impact results. Ultimately, candidates for tendon transfer should be carefully stratified according to their modifiable and non-modifiable risk factors, and surgeons should understand how pre-operative patient characteristics may affect the treatment options available for this unique patient population. In the setting of supraspinatus and infraspinatus deficiency, we prefer to utilize the lower trapezius tendon transfer, given its more predictable handling characteristics, ease of harvest, and greater function consistency compared to LDTT.

l-Fucose prevention of renal ischaemia/reperfusion injury in Mice.

In a recent study, we identified a fucosylated damage-associated ligand exposed by ischemia on renal tubule epithelial cells, which after recognition by collectin-11 (CL-11 or collectin kidney 1 (CL-K1)), initiates complement activation and acute kidney injury. We exploited the ability to increase the local tissue concentration of free l-fucose following systemic administration, in order to block ligand binding by local CL-11 and prevent complement activation. We achieved a thirty-five-fold increase in the intrarenal concentration of l-fucose following an IP bolus given before the ischemia induction procedure - a concentration found to significantly block in vitro binding of CL-11 on hypoxia-stressed renal tubule cells. At this l-fucose dose, complement activation and acute post-ischemic kidney injury are prevented, with additional protection achieved by a second bolus after the induction procedure. CL-11-/- mice gained no additional protection from l-fucose administration, indicating that the mechanism of l-fucose therapy was largely CL-11-dependent. The hypothesis is that a high dose of l-fucose delivered to the kidney obstructs the carbohydrate recognition site on CL-11 thereby reducing complement-mediated damage following ischemic insult. Further work will examine the utility in preventing post-ischemic injury during renal transplantation, where acute kidney injury is known to correlate with poor graft survival.

Fucose as a new therapeutic target in renal transplantation.

Ischaemia/reperfusion injury (IRI) is an inevitable and damaging consequence of the process of kidney transplantation, ultimately leading to delayed graft function and increased risk of graft loss. A key driver of this adverse reaction in kidneys is activation of the complement system, an important part of the innate immune system. This activation causes deposition of complement C3 on renal tubules as well as infiltration of immune cells and ultimately damage to the tubules resulting in reduced kidney function. Collectin-11 (CL-11) is a pattern recognition molecule of the lectin pathway of complement. CL-11 binds to a ligand that is exposed on the renal tubules by the stress caused by IRI, and through attached proteases, CL-11 activates complement and this contributes to the consequences outlined above. Recent work in our lab has shown that this damage-associated ligand contains a fucose residue that aids CL-11 binding and promotes complement activation. In this review, we will discuss the clinical context of renal transplantation, the relevance of the complement system in IRI, and outline the evidence for the role of CL-11 binding to a fucosylated ligand in IRI as well as its downstream effects. Finally, we will detail the simple but elegant theory that increasing the level of free fucose in the kidney acts as a decoy molecule, greatly reducing the clinical consequences of IRI mediated by CL-11.

Editorial Commentary: Repairing Retracted Rotator Cuff Tears: Histologically Different, but Success Still Achievable With "Failure in Continuity".

Failure after rotator cuff repair continues to occur despite advances in our understanding of the native tendon enthesis. Recurrent postoperative tendon defects are common, and the impact of nonhealing on postoperative outcomes remains controversial. Rotator cuff tears (RCT) of all patterns commonly present with some degree of retraction, and it is, therefore, critical to understand and examine the biology and biomechanics of the retracted RCT to address why a repaired tendon may fail. An article in this issue reports on retracted tears forming more disorganized fibrous tissue with similar biomechanical properties compared to nonretracted tear tissue. It provides insight into what lies "beneath the surface" after retracted rotator cuff repair, but it is unclear whether the fibrous tissue formed after their acute partial tendon excision adequately reflects the tissue found in more chronic, retracted human rotator cuff tears, particularly with varying degrees of retraction. Facilitating a more favorable "scar-forming" environment and optimizing this postoperative fibrous tissue may be crucial to improving rotator cuff repairs in the future.

Optimizing Outcomes After Reverse Total Shoulder Arthroplasty: Rehabilitation, Expected Outcomes, and Maximizing Return to Activities.

PURPOSE OF REVIEW: Given the touted clinical and patient-reported outcomes of reverse shoulder arthroplasty (RTSA) in improving pain and restoring function, shoulder surgeons are rapidly expanding the indications and utilization of RTSA. Despite its increasing use, the ideal post-operative management ensuring the best patient outcomes is still debated. This review synthesizes the current literature regarding the impact of post-operative immobilization and rehabilitation on clinical outcomes following RTSA including return to sport. RECENT FINDINGS: Literature regarding the various facets of post-operative rehabilitation is heterogeneous in both methodology and quality. While most surgeons recommend 4-6 weeks of immobilization post-operatively, two recent prospective studies have shown that early motion following RTSA is both safe and effective with low complication rates and significant improvements in patient-reported outcome scores. Furthermore, no studies currently exist assessing the use of home-based therapy following RTSA. However, there is an ongoing prospective, randomized control trial assessing patient-reported and clinical outcomes which will help shed light on the clinical and economic value of home therapy. Finally, surgeons have varying opinions regarding return to higher level activities following RTSA. Despite no clear consensus, there is growing evidence that elderly patients are able to return to sport (e.g., golf, tennis) safely, though caution must be taken with younger or more high-functioning patients. While post-operative rehabilitation is believed to be essential to maximize outcomes following RTSA, there is a paucity of high-quality evidence that guides current rehabilitation protocols. There is no consensus regarding type of immobilization, timing of rehabilitation, or need for formal therapist-directed rehabilitation versus physician-guided home exercise. Additionally, surgeons have varied opinions regarding return to higher level activities and sports following RTSA. There is burgeoning evidence that elderly patients can return to sport safely, though caution must be taken with younger patients. Further research is needed to clarify the optimal rehabilitation protocols and return to sport guidelines.

Complement in ischaemia-reperfusion injury and transplantation.

Until recently, the only known condition in which complement could mediate transplant injury was the rare occurrence of antibody-mediated rejection, in which the original concept of antibody immunity against the transplant was supported by complementary proteins present in the serum. This has changed within the last two decades because of evidence that the processes of ischaemia-reperfusion injury followed by T cell-mediated rejection are also critically dependent on components generated by the complement system. We now have a clearer understanding of the complement triggers and effectors that mediate injury, and a detailed map of their local sites of production and activation in the kidney. This is providing helpful guidelines as to how these harmful processes that restrict transplant outcomes can be targeted for therapeutic benefit. Here we review some of the recent advances highlighting relevant therapeutic targets.

Collectin-11 (CL-11) Is a Major Sentinel at Epithelial Surfaces and Key Pattern Recognition Molecule in Complement-Mediated Ischaemic Injury.

The complement system is a dynamic subset of the innate immune system, playing roles in host defense, clearance of immune complexes and cell debris, and priming the adaptive immune response. Over the last 40 years our understanding of the complement system has evolved from identifying its presence and recognizing its role in the blood to now focusing on understanding the role of local complement synthesis in health and disease. In particular, the local synthesis of complement was found to have an involvement in mediating ischaemic injury, including following transplantation. Recent work on elucidating the triggers of local complement synthesis and activation in renal tissue have led to the finding that Collectin-11 (CL-11) engages with L-fucose at the site of ischaemic stress, namely at the surface of the proximal tubular epithelial cells. What remains unknown is the precise structure of the damage-associated ligand that participates in CL-11 binding and subsequent complement activation. In this article, we will discuss our hypothesis regarding the role of CL-11 as an integral tissue-based pattern recognition molecule which we postulate has a significant contributory role in complement-mediated ischaemic injury.