Matthew F. Dilisio

Arthroscopic Tissue Culture for the Evaluation of Periprosthetic Shoulder Infection

BACKGROUND Periprosthetic shoulder infections can be difficult to diagnose. The purpose of this study was to investigate the utility of arthroscopic tissue culture for the diagnosis of infection following shoulder arthroplasty. Our hypothesis was that culture of arthroscopic biopsy tissue is a more reliable method than fluoroscopically guided shoulder aspiration for diagnosing such infection. METHODS A retrospective review identified patients who had undergone culture of arthroscopic biopsy tissue during the evaluation of a possible chronic periprosthetic shoulder infection. The culture results of the arthroscopic biopsies were compared with those of fluoroscopically guided glenohumeral aspiration and open tissue biopsy samples obtained at the time of revision surgery. RESULTS Nineteen patients had undergone arthroscopic biopsy to evaluate a painful shoulder arthroplasty for infection. All subsequently underwent revision surgery, and 41% of those with culture results at that time had a positive result, which included Propionibacterium acnes in each case. All arthroscopic biopsy culture results were consistent with the culture results obtained during the revision surgery, yielding 100% sensitivity, specificity, positive predictive value, and negative predictive value. In contrast, fluoroscopically guided glenohumeral aspiration yielded a sensitivity of 16.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 58.3%. CONCLUSIONS Arthroscopic tissue biopsy is a reliable method for diagnosing periprosthetic shoulder infection and identifying the causative organism. LEVEL OF EVIDENCE Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

ECM production of primary human and bovine chondrocytes in hybrid PEG hydrogels containing type i collagen and hyaluronic acid

The development of advanced materials that facilitate hyaline cartilage formation and regeneration in aging populations is imperative. Critical to the success of this endeavor is the optimization of ECM production from clinically relevant cells. However, much of the current literature focuses on the investigation of primary bovine chondrocytes from young calves, which differ significantly than osteoarthritic cells from human sources. This study examines the levels of extracellular matrix (ECM) production using various levels of type I collagen and hyaluronic acid in poly(ethylene glycol) dimethacrylate (PEGDM) hydrogels in total knee arthroplasties, compared with the results from bovine chondrocytes. The addition of type 1 collagen in both the presence and absence of low levels of hyaluronic acid increased ECM production and/or retention in scaffolds containing either bovine or human chondrocytes. These findings are supported consistently with colorimetric quantification, whole mount extracellular matrix staining for both cell types, and histological staining for glycoaminoglycans and collagen of human chondrocyte containing samples. While exhibiting similar trends, the relative ECM productions levels for the primary human chondrocytes are significantly less than the bovine chondrocytes which reinforces the need for additional optimization.

Recent strategies in cartilage repair: A systemic review of the scaffold development and tissue engineering

Osteoarthritis results in irreparable loss of articular cartilage. Due to its avascular nature and low mitotic activity, cartilage has little intrinsic capacity for repair. Cartilage loss leads to pain, physical disability, movement restriction, and morbidity. Various treatment strategies have been proposed for cartilage regeneration, but the optimum treatment is yet to be defined. Tissue engineering with engineered constructs aimed towards developing a suitable substrate may help in cartilage regeneration by providing the mechanical, biological and chemical support to the cells. The use of scaffold as a substrate to support the progenitor cells or autologous chondrocytes has given promising results. Leakage of cells, poor cell survival, poor cell differentiation, inadequate integration into the host tissue, incorrect distribution of cells, and dedifferentiation of the normal cartilage are the common problems in tissue engineering. Current research is focused on improving mechanical and biochemical properties of scaffold to make it more efficient. The aim of this review is to provide a critical discussion on existing challenges, scaffold type and properties, and an update on ongoing recent developments in the architecture and composition of scaffold to enhance the proliferation and viability of mesenchymal stem cells.

Risk Factors for Manipulation After Total Knee Arthroplasty: A Pooled Electronic Health Record Database Study

A commercially available software platform, Explorys (Explorys, Inc., Cleveland, OH), was used to mine a pooled electronic healthcare database consisting of the medical records of more than 27 million patients. A total of 229,420 patients had undergone a total knee arthroplasty; 3470 (1.51%) patients were identified to have undergone manipulation under anesthesia. Individual risk factors of being female, African American race, age less than 60, BMI >30 and nicotine dependence were determined to have relative risk of 1.25, 2.20, 3.46, 1.33 and 1.32 respectively. Depressive disorder, diabetes mellitus, opioid abuse/dependence and rheumatoid arthritis were not significant risk factors. African Americans under the age of 60 at time of TKA had the greatest incidence of MUA (5.17%) and relative risk of 3.73 (CI: 3.36, 4.13).

Intramedullary nailing of the proximal humerus: evolution, technique, and results

Proximal humerus fractures are the third most common fracture in the elderly. Although most fractures can be treated conservatively with acceptable outcomes, certain fracture patterns are at high risk for progression to humeral malunions, nonunions, stiffness, and post-traumatic arthrosis. The goal of antegrade humeral nailing of proximal humerus fractures is to provide stability to a reduced fracture that allows early motion to optimize patient outcomes. Certain technical pearls are pivotal in managing these difficult fractures with nails; these include rotator cuff management, respect of the soft tissues, anatomic tuberosity position, blood supply maintenance, knowledge of the deforming forces on the proximal humerus, fracture reduction, and rehabilitation strategies. Modern proximal humeral nail designs and techniques assist the surgeon in adhering to these principles and have demonstrated promising outcomes. Humeral nail designs have undergone significant innovation during the past 40 years and now can provide stable fixation in the humeral shaft distally as well as improved stability in the head and tuberosity fragments, which were the common site of fixation failure with earlier generation implants. Compared with other fixation strategies, such as locking plate fixation, no compelling evidence exists to suggest one technique over another. The purpose of this review is to describe the history, results, new designs, and techniques that make modern intramedullary nailing of proximal humerus fractures a viable treatment option.

TREM-1, HMGB1 and RAGE in the Shoulder Tendon: Dual Mechanisms for Inflammation Based on the Coincidence of Glenohumeral Arthritis

Rotator cuff injury (RCI) is a major musculoskeletal disorder in the adult population where inflammation and pain are major contributing factors. Coincidence of other clinical conditions like glenohumeral arthritis aggravates inflammation and delays the healing response. The mechanism and signaling factors underlying the sustenance of inflammation in the rotator cuff joint are largely unknown. The present article aims to elucidate the involvement of inflammatory molecule, TREM-1 (Triggering Receptors Expressed on Myeloid cells-1), and danger-associated molecular patterns (DAMPs), including high mobility group protein 1 (HMGB-1) and RAGE (receptor for advanced glycation end products), in the setting of RCI with respect to the severity of glenohumeral arthritis. Biceps tendons (15 specimens) from the shoulder and blood (11 samples) from patients with glenohumeral arthritis (Group-1, n = 4) and without glenohumeral arthritis (Group-2, n = 11) after RCI surgery were obtained for the study. Molecular and morphological alterations between the groups were compared using histology, immunofluorescence, RT-PCR and flow cytometry. MRI and histomorphology assessment revealed severe inflammation in Group-1 patients while in Group-2 ECM disorganization was prominent without any hallmarks of inflammation. A significant increase in TREM-1 expression in circulating neutrophils and monocytes was observed. Elevated levels of TREM-1, HMGB-1 and RAGE in Group-1 patients along with CD68+ and CD16+ cells confirmed DAMP-mediated inflammation. Expression of TREM-1 in the tendon of Group-2 patients even in the absence of immune cells presented a new population of TREM-expressing cells that were confirmed by real-time PCR analysis and immunofluorescence. Expression of HMGB-1 and RAGE in the biceps tendon from the shoulder of patients without glenohumeral arthritis implied TREM-1-mediated inflammation without involving immune cells, whereas in patients with glenohumeral arthritis, infiltration and the activation of the immune cells, primarily macrophages, release mediators to induce inflammation. This could be the reason for ECM disorganization without the classical signs of inflammation in patients without glenohumeral arthritis.

Osteonecrosis Following Short-term, Low-dose Oral Corticosteroids: A Population-based Study of 24 Million Patients

Although the association between chronic, high-dose corticosteroid use and osteonecrosis is well known, the incidence of osteonecrosis following short-term, low-dose steroid taper packs has never been reported across a large population. The goal of this study was to report the incidence and risk of osteonecrosis after methylprednisolone taper pack (MTP) prescriptions in a multicenter electronic medical records database. A commercially available software platform was used to evaluate the records of 24,533,880 patients to determine the incidence of osteonecrosis in patients who had received single or multiple MTP over a 12-year period. This was compared with the incidence of osteonecrosis in patients who had never been prescribed an MTP. Patients with a history of osteonecrosis or prior corticosteroid use were excluded from the study. A total of 98,390 patients were identified who had received a single MTP. One hundred thirty (0.132%; 95% confidence interval [CI], 0.176%-0.283%) of these patients were subsequently diagnosed with osteonecrosis. The incidence of osteonecrosis in patients who had been prescribed 2 or more MTPs was 0.230% (95% CI, 0.176%-0.283%). Compared with the 0.083% incidence of osteonecrosis in the control group that had never been prescribed an MTP, the relative risk of osteonecrosis after the prescription of a single MTP or multiple MTPs was 1.591 and 2.763, respectively, with a statistically significant difference between cohorts (P<.001). Short-term, low-dose oral corticosteroid administration may be associated with a low but statistically significant increased incidence of osteonecrosis when compared with patients who have never been prescribed a steroid product.

Conversion to Reverse Shoulder Arthroplasty: Humeral Stem Retention Versus Revision.

As the volume of shoulder arthroplasty procedures performed in the United States continues to increase, the predicted number of revision shoulder arthroplasties grows even higher. Conversion of failed shoulder arthroplasty to reverse total shoulder arthroplasty has become common. Many commercially available shoulder arthroplasty systems now offer a platform humeral stem that is used for both anatomic shoulder arthroplasty and reverse total shoulder arthroplasty. This study investigated whether retaining the humeral stem offers advantages over revising the humeral stem in conversion of failed shoulder arthroplasty to reverse total shoulder arthroplasty. The study included 26 patients (mean age, 68.46 years) with failed shoulder arthroplasty who underwent conversion to reverse total shoulder arthroplasty with a minimum 2-year follow-up (mean, 34.38 months). Patients who had retention of the humeral stem were compared with those who had stem revision. Humeral stem retention was associated with a significantly shorter operative time (178.92 vs 237 minutes, P=.02). Decreases in blood loss, complications, and length of hospitalization were observed, but the differences were not statistically significant. Minimal differences were observed for patient-reported outcomes. Of patients undergoing humeral stem removal, 21.4% had an intraoperative humeral shaft or tuberosity fracture compared with none in the stem retention group. Humeral stem retention was associated with decreased operative time compared with humeral stem revision in the conversion of failed shoulder arthroplasty to reverse total shoulder arthroplasty. The use of a platform shoulder arthroplasty system may benefit patients with failed shoulder arthroplasty undergoing conversion to reverse total shoulder arthroplasty by avoiding humeral stem revision.

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.

Immunobiological factors aggravating the fatty infiltration on tendons and muscles in rotator cuff lesions

Rotator cuff lesions (RCLs) are a common cause of shoulder pain and dysfunction. The rotator cuff tendons can degenerate and/or tear from the greater tuberosity of the humerus, which is associated with several anatomical, physiological, biochemical, and molecular changes in tendon and muscle. In this article, these pathways are critically reviewed and discussed with various management strategies of RCLs. The article also highlights the immunobiological responses following the RCL and the inherent repair mechanisms elicited by the body. The greatest difficulty in treating this pathology is that the muscle can undergo irreversible fatty infiltration in the setting of chronic tears that is associated with poor surgical outcomes. The article also investigates the key molecular pathways of the muscle homeostasis (mTOR, Rho kinase, AMPK, and Ca2+) with the energy metabolism to propose a possible mechanism for fatty infiltration. Future research is warranted to target the key players of these pathways in the management of fatty infiltration and thus RCL.