Total Joint Arthroplasty in Patients With an Implanted Left Ventricular Assist Device.

Left ventricular assist devices (LVADs) may be used as bridge therapy or destination therapy in heart failure patients. Total joint arthroplasty may improve the functional status of patients limited by arthritis. This retrospective case series evaluated patients with an implanted LVAD who underwent a total joint arthroplasty at 1 institution from 2012 to present. Five patients underwent 12 surgeries with 7 primary arthroplasties and 5 revisions. Their mortality, length of stay, coagulopathic events, incidence of infection or revision arthroplasty, and heart transplantation were evaluated, and is the largest study to date of this population. Two patients expired from thrombotic events while 3 progressed to heart transplantation. Joint arthroplasty is feasible in patients with an implanted LVAD with expected risk and perioperative multidisciplinary collaboration.

Pain associated with cemented and uncemented long-stemmed tibial components in revision total knee arthroplasty.

AIMS: Stemmed tibial components are frequently used in revision total knee arthroplasty (TKA). The purpose of this study was to evaluate patient satisfaction, overall pain, and diaphyseal tibial pain in patients who underwent revision TKA with cemented or uncemented stemmed tibial components. METHODS: This is a retrospective cohort study involving 110 patients with revision TKA with cemented versus uncemented stemmed tibial components. Patients who underwent revision TKA with stemmed tibial components over a 15-year period at a single institution with at least two-year follow-up were assessed. Pain was evaluated through postal surveys. There were 63 patients with cemented tibial stems and 47 with uncemented stems. Radiographs and Knee Society Scores were used to evaluate for objective findings associated with pain or patient dissatisfaction. Postal surveys were analyzed using Fisher's exact test and the independent-samples t-test. Logistic regression was used to adjust for age, sex, and preoperative bone loss. RESULTS: No statistically significant differences in stem length, operative side, or indications for revision were found between the two cohorts. Tibial pain at the end of the stem was present in 25.3% (16/63) of cemented stems and 25.5% (12/47) of uncemented stems (p = 1.000); 74.6% (47/63) of cemented patients and 78.7% (37/47) of uncemented patients were satisfied following revision TKA (p = 0.657). CONCLUSION: There were no differences in patient satisfaction, overall pain, and diaphyseal tibial pain in cemented and uncemented stemmed tibial components in revision TKA. Patient factors, rather than implant selection and surgical technique, likely play a large role in the presence of postoperative pain. Stemmed tibial components have been shown to be a possible source of pain in revision TKA. There is no difference in patient satisfaction or postoperative pain with cemented or uncemented stemmed tibial components in revision TKA. Cite this article: Bone Joint J 2021;103-B(6 Supple A):165-170.

Immunopathogenesis and biomarkers of recurrent atrial fibrillation following ablation therapy in patients with preexisting atrial fibrillation.

INTRODUCTION: Recurrent atrial fibrillation (RAF) following ablation therapy occurs in about 50% of patients. The pathogenesis of RAF is unknown, but is believed to be driven by atrial remodeling in the setting of background inflammation. Structural, electrophysiological and mechanical remodeling has been associated with atrial fibrillation (AF). Inflammation and fibrotic remodeling are the major factors perpetuating AF, as mediators released from the atrial tissues and cardiomyocytes due to mechanical and surgical injury could initiate the inflammatory process. In this article, we have critically reviewed the key mediators that may serve as potential biomarkers to predict RAF. Areas covered: Damage associated molecular patterns, heat shock proteins, inflammatory cytokines, non-inflammatory markers, markers of inflammatory cell activity, and markers of collagen deposition and metabolism are evaluated as potential biomarkers with molecular treatment options in RAF. Expert commentary: Establishing biomarkers to predict RAF could be useful in reducing morbidity and mortality. Investigations into the role of DAMPs participating in a sterile immune response may provide greater insight into the pathogenesis of RAF. Markers evaluating immune cell activity, collagen deposition, and levels of heat shock proteins show the greatest promise as potential biomarkers to predict RAF and develop novel therapies.

Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration.

Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive. Currently, techniques are being developed to directly transdifferentiate cardiac fibroblasts into induced cardiomyocytes. Viral vector-driven expression of a combination of transcription factors including Gata4, Mef2c, and Tbx5 induced cardiomyocyte development in mice. Subsequent combinational modifications have extended these results to human cell lines and increased efficacy. The miRNAs including combinations of miR-1, miR-133, miR-208, and miR-499 can improve or independently drive regeneration of cardiomyocytes. Similar results could be obtained by combinations of small molecules with or without transcription factor or miRNA expression. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-ß, enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.

Immunobiology of periprosthetic inflammation and pain following ultra-high-molecular-weight-polyethylene wear debris in the lumbar spine.

INTRODUCTION: Wear debris-induced osteolysis is a common cause of arthroplasty failure in several joints including the knee, hip and intervertebral disc. Debris from the prosthesis can trigger an inflammatory response that leads to aseptic loosening and prosthesis failure. In the spine, periprosthetic pain also occurs following accumulation of wear debris through neovascularization of the disc. The role of the immune system in the pathobiology of periprosthetic osteolysis of joint replacements is debatable. Areas covered: We discussed the stimulation of pro-inflammatory and pro-protective and pro-regenerative pathways due to debris from the prosthetics. The balance between the two pathways may determine the outcome results. Also, the role of cytokines and immune cells in periprosthetic inflammation in the etiology of osteolysis is critically reviewed. Expert commentary: Therapies targeting the inflammatory process associated with ultra-high-molecular-weight polyethylene wear debris could reduce implant failure. Additionally, therapies targeting neovascularization of discs following arthroplasty could mitigate periprosthetic pain.

Current Modalities and Mechanisms Underlying Cardioprotection by Ischemic Conditioning.

Ischemic preconditioning is a process which serves to mitigate reperfusion injury. Preconditioning of the heart can be achieved through natural, pharmacological, and mechanical means. Mechanical preconditioning appears to have the greatest chance of good outcomes while methods employing pharmacologic preconditioning have been largely unsuccessful. Remote ischemic preconditioning achieves a cardioprotective effect by applying cycles of ischemia and reperfusion in a distal limb, stimulating the release of a neurohumoral cardioprotective factor incited by stimulation of afferent neurons. The cardioprotective factor stimulates the reperfusion injury salvage kinase (RISK) and survivor activator factor enhancement (SAFE) signaling cascades in cardiomyocytes which promote cell survival by the expression of anti-apoptotic genes and inhibition of the opening of mitochondrial permeability transition pores. Clinical application of ischemic preconditioning involving targets in the RISK and SAFE signaling appears promising in the treatment of acute myocardial infarction; however, clinical trials have yet to demonstrate additional benefit to current therapy.

Increased expression of damage-associated molecular patterns (DAMPs) in osteoarthritis of human knee joint compared to hip joint.

Osteoarthritis (OA) is a degenerative disease characterized by the destruction of cartilage. The greatest risk factors for the development of OA include age and obesity. Recent studies suggest the role of inflammation in the pathogenesis of OA. The two most common locations for OA to occur are in the knee and hip joints. The knee joint experiences more mechanical stress, cartilage degeneration, and inflammation than the hip joint. This could contribute to the increased incidence of OA in the knee joint. Damage-associated molecular patterns (DAMPs), including high-mobility group box-1, receptor for advanced glycation end products, and alarmins (S100A8 and S100A9), are released in the joint in response to stress-mediated chondrocyte and cartilage damage. This facilitates increased cartilage degradation and inflammation in the joint. Studies have documented the role of DAMPs in the pathogenesis of OA; however, the comparison of DAMPs and its influence on OA has not been discussed. In this study, we compared the DAMPs between OA knee and hip joints and found a significant difference in the levels of DAMPs expressed in the knee joint compared to the hip joint. The increased levels of DAMPs suggest a difference in the underlying pathogenesis of OA in the knee and the hip and highlights DAMPs as potential therapeutic targets for OA in the future.

Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets.

Osteoarthritis (OA) is a chronic disease that degrades the joints and is often associated with increasing age and obesity. The two most common sites of OA in adults are the knee and hip joints. Increased mechanical stress on the joint from obesity can cause the articular cartilage to degrade and release damage-associated molecular patterns (DAMPs). These DAMPs are involved in various molecular pathways that interact with nuclear factor-kappa B and result in the transcription of inflammatory cytokines and activation of matrix metalloproteinases that progressively destroy cartilage. This review focuses on the interactions and contribution to the pathogenesis and progression of OA through the DAMPs: high-mobility group box 1 (HMGB-1), the receptor for advanced glycation end-products (RAGE), the alarmin proteins S100A8 and S100A9, and heparan sulfate. HMGB-1 is released from damaged or necrotic cells and interacts with toll-like receptors (TLRs) and RAGE to induce inflammatory signals, as well as behave as an inflammatory cytokine to activate innate immune cells. RAGE interacts with HMGB-1, advanced glycation end-products, and innate immune cells to increase local inflammation. The alarmin proteins are released following cell damage and interact through TLRs to increase local inflammation and cartilage degradation. Heparan sulfate has been shown to facilitate the binding of HMGB-1 to RAGE and could play a role in the progression of OA. Targeting these DAMPs may be the potential therapeutic strategies for the treatment of OA.