Shared and unique risk factors for readmission exist following upper and lower extremity arthroplasty in the 30-day postoperative period.

PURPOSE: Joint arthroplasty has become increasingly more common in the United States, and it is important to examine the patient-based risk factors and surgical variables associated with hospital readmissions. The purpose of this study was to identify stratified rates and risk factors for readmission after upper extremity (shoulder, elbow, and wrist) and lower extremity (hip, knee, and ankle) arthroplasty. METHODS: All patients undergoing upper and lower extremity arthroplasty from 2008-2018 were identified using the National Surgical Quality Improvement Program dataset. Patient demographics, medical comorbidities and surgical characteristics were examined utilizing uni- and multi-variate analysis for significant predictors of 30-days hospital readmission. RESULTS: A total of 523,523 lower and 25,215 upper extremity arthroplasty patients were included in this study. A number of 22,183 (4.2%) lower and 1072 (4.4%) upper extremity arthroplasty patients were readmitted within 30 days of discharge. Significant risk factors for 30-days readmission after lower extremity arthroplasty included age, Body Mass Index (BMI), operative time, dependent functional status, American Society of Anesthesiologists (ASA) score ≥3, increased length of stay, and various medical comorbidities such as diabetes, tobacco dependency, and chronic obstructive pulmonary disease (COPD). An overweight BMI was associated with a lower odds of 30-days readmission when compared to a normal BMI for lower extremity arthroplasty. Analysis for upper extremity arthroplasty revealed similar findings of significant risk factors for 30-days hospital readmission, although diabetes mellitus was not found to be a significant risk factor. CONCLUSION: Nearly one in 25 patients undergoing upper and lower extremity arthroplasty experiences hospital readmission within 30-days of index surgery. There are several modifiable risk factors for 30-days hospital readmission shared by both lower and upper extremity arthroplasty, including tobacco smoking, COPD, and hypertension. Optimization of these medical comorbidities may mitigate the risk short-term readmission following joint arthroplasty procedures and improve overall cost effectiveness of perioperative surgical care.

Biceps Tenodesis Has Greater Expected Value Than Repair for Isolated Type II SLAP Tears: A Meta-analysis and Expected-Value Decision Analysis.

PURPOSE: To use an expected-value decision analysis to determine the optimal treatment decision between repair and biceps tenodesis (BT) for an isolated type II SLAP injury. METHODS: An expected-value decision analysis with sensitivity analysis was performed to systematically quantify the clinical decision. To determine outcome probabilities, a decision tree was constructed (repair vs BT) and a meta-analysis was conducted. To determine outcome utilities, we evaluated 70 patients with a chief complaint of shoulder pain regarding age, sex, Shoulder Activity Level, and visual analog scale score in terms of potential outcome preferences. Statistical fold-back analysis was performed to determine the optimal treatment. One-way sensitivity analysis determined the effect of changing the reinjury rate on the expected value of BT. RESULTS: The overall expected value was 8.66 for BT versus 7.19 for SLAP repair. One-way sensitivity analysis showed that BT was the superior choice if reinjury rates were expected to be lower than 28%. Meta-analysis of 23 studies and 908 patients revealed that the probability of a "well" outcome was significantly greater for BT (87.8%; 95% confidence interval [CI], 74.9%-94.6%; I2 = 0.0%) than for SLAP repair (62.9%; 95% CI, 55.9%-69.3%; I2 = 65.9%; P = .0023). The rate of reinjury was 1.5% for BT (95% CI, 0.05%-33.8%; I2 = 0.0%) and 6.4% for repair (95% CI, 4.2%-9.6%; I2 = 24%), which was not statistically significantly different (P = .411). A total of 50 participants (mean age, 25.4 years [standard deviation, 8.9 years]; 76% male patients; 50% overhead athletes) met the inclusion criteria. Forty-six percent of participants had a high Shoulder Activity Level score. CONCLUSIONS: Decision analysis showed that BT is preferred over repair for an isolated type II SLAP tear based on greater expected value of BT versus repair. Meta-analysis showed more frequent favorable outcomes with BT. Surgeons can use this information to tailor discussions with patients. LEVEL OF EVIDENCE: Level IV, meta-analysis of Level I-IV studies.

Reverse Total Shoulder Arthroplasty with Concurrent Latissimus Dorsi Tendon Transfer.

PURPOSE OF REVIEW: Reverse total shoulder arthroplasty (rTSA) has emerged as an effective treatment option for patients with rotator cuff arthropathy resulting from irreparable rotator cuff tears. However, patients with combined loss of abduction and external rotation may still experience functional deficits after rTSA. One option to address this has been the latissimus dorsi tendon transfer (LDTT), or modified L'Episcopo procedure. The purpose of this review is to describe the role of LDTT with rTSA and to critically evaluate the evidence on whether a supplemental LDTT ultimately improves patient function. RECENT FINDINGS: Patients with an intact rotator cuff demonstrated a significant increase in active external rotation following rTSA compared to those with a deficient rotator cuff following rTSA. Compared to their pre-operative baseline assessments, patients who undergo rTSA with LDTT report significant improvements in active external rotation. However, a randomized trial comparing rTSA patients with and without LDTT failed to demonstrate a significant difference in active external rotation or patient-reported outcomes between groups. Observational studies have shown that patients experience significant improvements in active range of motion and various patient-reported outcome measures following rTSA with latissimus dorsi tendon transfer. When directly comparing rTSA with LDTT to rTSA alone, the current literature fails to demonstrate a statistically significant difference in active external rotation or patient-reported outcomes at short-term follow-up. Further randomized controlled trials are required to fully understand the potential benefits of added tendon transfer in the rTSA patient population.

Implementation of a fracture liaison service and its effects on osteoporosis treatment adherence and secondary fracture at a tertiary care academic health system.

In this retrospective study, approximately 77% of patients who attended their osteoporosis clinic follow-up appointments following a fragility fracture were started on medical treatment. Approximately 82% of those patients were adherent with their treatment, and 1% of patients sustained a secondary fragility fracture while on treatment. PURPOSE: To assess the effects of implementation of a fracture liaison service at a tertiary care academic medical center on osteoporosis treatment adherence and secondary fracture rates. METHODS: We retrospectively reviewed over 6000 patients age 50 years or greater during a 5-year time period (2013-2018). Patients were identified as having a fragility fracture on presentation to the emergency department at the Wake Forest Baptist Medical Center and referred to our osteoporosis clinic using the electronic medical record. Data were collected regarding those patients who were recommended treatment, started treatment, maintained adherent to treatment, and those who sustained a secondary fracture. RESULTS: 6178 patients were identified as having a fragility fracture and referred to the osteoporosis clinic. 2631 of these patients successfully had a scheduled outpatient appointment at the osteoporosis clinic, of which 1937 attended their initial appointment and 1840 of these patients were prescribed treatment. Of the 1840 patients who were initially prescribed medication, 1416 (76.96%) initiated their treatment, and 1156 (81.64%) remained adherent to treatment. Fifteen patients (1.05%) on treatment sustained a secondary fracture after initiation of therapy. CONCLUSION: Implementation of a fracture liaison service at a tertiary care academic medical center is feasible and is associated with high rates of treatment implementation/adherence and low incidence of secondary fracture.

Editorial Commentary: Taking a "PEEK" at Suture Anchor Composition following Arthroscopic Rotator Cuff Repair: Is Bio Really Better?

The advent of modern suture anchor technology has not only revolutionized arthroscopic treatment options for management of complex shoulder pathology, but also engendered a materials science quest to identify the ultimate composition and design. What began as an open procedure with transosseous suture fixation has evolved dramatically with the widespread adoption of an arthroscopic, anchor-based technique for rotator cuff repair. Currently, a litany of commercially available "hard" and "soft" anchors are flooding the market, with limited qualitative comparisons to suggest superiority of one type. Ideally, suture anchor design should permit preservation of native glenohumeral bone stock with gradual osseointegration, limit disruption of local tissue homeostasis, and maintain time-zero mechanical strength until soft-tissue healing has occurred. At present, a vented, open-anchor architecture may facilitate better biologic incorporation with increased bony ingrowth through access to marrow elements, although these radiographic advantages have not conferred any clinically meaningful differences for our rotator cuff repair patients. For anchor composition, the jury is still out, and we need to continue to critically evaluate for perianchor cyst formation and longer term remodeling. In fact, the true merits of increased bony ingrowth and limited osteolysis may only be realized at the time of revision rotator cuff repair, during which prior implant position or secondary cystic change may further dictate suture anchor design, size, and placement.

Anoikis-resistant subpopulations of human osteosarcoma display significant chemoresistance and are sensitive to targeted epigenetic therapies predicted by expression profiling.

BACKGROUND: Osteosarcoma (OS) is the most common type of solid bone cancer, with latent metastasis being a typical mode of disease progression and a major contributor to poor prognosis. For this to occur, cells must resist anoikis and be able to recapitulate tumorigenesis in a foreign microenvironment. Finding novel approaches to treat osteosarcoma and target those cell subpopulations that possess the ability to resist anoikis and contribute to metastatic disease is imperative. Here we investigate anchorage-independent (AI) cell growth as a model to better characterize anoikis resistance in human osteosarcoma while using an expression profiling approach to identify and test targetable signaling pathways. METHODS: Established human OS cell lines and patient-derived human OS cell isolates were subjected to growth in either adherent or AI conditions using Ultra-Low Attachment plates in identical media conditions. Growth rate was assessed using cell doubling times and chemoresistance was assessed by determining cell viability in response to a serial dilution of either doxorubicin or cisplatin. Gene expression differences were examined using quantitative reverse-transcription PCR and microarray with principal component and pathway analysis. In-vivo OS xenografts were generated by either subcutaneous or intratibial injection of adherent or AI human OS cells into athymic nude mice. Statistical significance was determined using student's t-tests with significance set at α=0.05. RESULTS: We show that AI growth results in a global gene expression profile change accompanied by significant chemoresistance (up to 75 fold, p<0.05). AI cells demonstrate alteration of key mediators of mesenchymal differentiation (ß-catenin, Runx2), stemness (Sox2), proliferation (c-myc, Akt), and epigenetic regulation (HDAC class 1). AI cells were equally tumorigenic as their adherent counterparts, but showed a significantly decreased rate of growth in-vitro and in-vivo (p<0.05). Treatment with the pan-histone deacetylase inhibitor vorinostat and the DNA methyltransferase inhibitor 5-azacytidine mitigated AI growth, while 5-azacytidine sensitized anoikis-resistant cells to doxorubicin (p<0.05). CONCLUSIONS: These data demonstrate remarkable plasticity in anoikis-resistant human osteosarcoma subpopulations accompanied by a rapid development of chemoresistance and altered growth rates mirroring the early stages of latent metastasis. Targeting epigenetic regulation of this process may be a viable therapeutic strategy.

Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations.

Oculoectodermal syndrome (OES) is a rare disease characterized by a combination of congenital scalp lesions and ocular dermoids, with additional manifestations including non-ossifying fibromas and giant cell granulomas of the jaw occurring during the first decade of life. To identify the genetic etiology of OES, we conducted whole-genome sequencing of several tissues in an affected individual. Comparison of DNA from a non-ossifying fibroma to blood-derived DNA allowed identification of a somatic missense alteration in KRAS NM_033360.3(KRAS):c.38G>A, resulting in p.Gly13Asp. This alteration was also observed in the patient's other affected tissues including the skin and muscle. Targeted sequencing in a second, unrelated OES patient identified an NM_033360.3(KRAS):c.57G>C, p.Leu19Phe alteration. Allelic frequencies fell below 40% in all tissues examined in both patients, suggesting that OES is a mosaic RAS-related disorder, or RASopathy. The characteristic findings in OES, including scalp lesions, ocular dermoids, and benign tumors, are found in other mosaic and germline RASopathies. This discovery also broadens our understanding of the spectrum of phenotypes resulting from KRAS alterations. Future research into disease progression with regard to malignancy risk and investigation of RAS-targeted therapies in OES is warranted. KRAS sequencing is clinically available and may also now improve OES diagnostic criteria.

Old dogs and new tricks: length of stay for appendicitis improves with an acute care surgery program and transition from private surgical practice to multispecialty group practice.

Acute care surgery (ACS) programs have emerged mainly at academic medical centers to provide timely care for emergency general surgery and trauma patients. We hypothesized that the development of an ACS program in a multispecialty group practice would improve outcomes for patients with acute appendicitis. A retrospective analysis of patients with acute appendicitis was performed in two time periods: 18 months of private practice and the following 12 months with ACS coverage. Length of stay was the primary outcome measure. A total of 871 patients were studied (526 private practice, 345 ACS). The ACS group had a greater proportion of laparoscopic appendectomies (P < 0.001) and more transitions in care between surgeons (P < 0.001). Length of stay was shorter in the ACS group (1.6 ± 1.5 [mean ± standard deviation] vs 1.9 ± 2.4 days, P = 0.01) and a greater proportion of surgeries were performed during the daytime (44.9 vs 36.6%, P = 0.02). Multivariate analysis demonstrated length of stay was related to appendicitis grade (P < 0.001), American Society of Anesthesiologists class (P < 0.001), symptom duration (P = 0.001), and laparoscopic approach (P < 0.001). The initial transition from private practice to ACS resulted in decreased length of stay with no increase in morbidity related to transitions of surgical care in patients with appendicitis.

Genetic and functional studies of the intervertebral disc: a novel murine intervertebral disc model.

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration.

Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells.

Osteosarcoma (OS) is the most common type of solid bone cancer and remains the second leading cause of cancer-related death for children and young adults. Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF) class of transcription factors. Here we investigate hypoxia-induced changes in the Wnt/ß-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. Wnt/ß-catenin signaling is down-regulated by hypoxia in human OS cells, as demonstrated by decreased active ß-catenin protein levels and axin2 mRNA expression (p<0.05). This down-regulation appears to rely on both HIF-independent and HIF-dependent mechanisms, with HIF-1α standing out as an important regulator. Finally, we show that hypoxia results in resistance of human OS cells to doxorubicin-mediated toxicity (6-13 fold increase, p<0.01). These hypoxic OS cells can be sensitized to doxorubicin treatment by further inhibition of the Wnt/ß-catenin signaling pathway (p<0.05). These data support the conclusion that Wnt/ß-catenin signaling is down-regulated in human OS cells under hypoxia and that this signaling alteration may represent a viable target to combat chemoresistant OS subpopulations in a hypoxic niche.

Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response.

Aneurysmal bone cyst (ABC) is a benign tumor of bone presenting as a cystic, expansile lesion in both the axial and appendicular skeleton. Axial lesions demand special consideration, because treatment-related morbidity can be devastating. In similar lesions, such as giant cell tumor of bone (GCTB), the receptor-activator of nuclear kappaB ligand (RANKL)-receptor-activator of nuclear kappaB (RANK) signaling axis is essential to tumor progression. Although ABC and GCTB are distinct entities, they both contain abundant multinucleated giant cells and are osteolytic characteristically. We hypothesize that ABCs express both RANKL and RANK similarly in a cell-type specific manner, and that targeted RANKL therapy will mitigate ABC tumor progression. Cellular expression of RANKL and RANK was determined in freshly harvested ABC samples using laser confocal microscopy. A consistent cell-type-specific pattern was observed: fibroblastlike stromal cells expressed RANKL strongly whereas monocyte/macrophage precursor and multinucleated giant cells expressed RANK. Relative RANKL expression was determined by quantitative real-time polymerase chain reaction in ABC and GCTB tissue samples; no difference in relative expression was observed (P > 0.05). In addition, we review the case of a 5-year-old boy with a large, aggressive sacral ABC. After 3 months of targeted RANKL inhibition with denosumab, magnetic resonance imaging demonstrated tumor shrinkage, bone reconstitution, and healing of a pathologic fracture. Ambulation, and bowel and bladder function were restored at 6 months. Denosumab treatment was well tolerated. Post hoc analysis demonstrated strong RANKL expression in the pretreatment tumor sample. These findings demonstrate that RANKL-RANK signal activation is essential to ABC tumor progression. RANKL-targeted therapy may be an effective alternative to surgery in select ABC presentations.

A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery.

BACKGROUND: Deep venous thrombosis (DVT) is a significant risk in patients undergoing surgery for morbid obesity and may be associated with significant morbidity and mortality. In a consecutive group of patients in one bariatric surgery practice, the initial group of patients who received prophylaxis for DVT was given enoxaparin 30 mg q12h while the later group was given enoxaparin 40 mg q12h. METHODS: 481 patients who underwent primary and revisional bariatric surgery over 38 months (October 1997-December 2000) were evaluated. All patients received a multi-modality DVT prophylaxis protocol that included: early ambulation, graduated compression stockings, intermittent pneumatic compression, and enoxaparin (LMWH) in two dosage groups. The first 92 patients (19%) in the series (Group I) received LMWH 30 mg q12h while the subsequent 389 patients (81%) (Group II) received LMWH 40 mg q12h. RESULTS: Group I patients were not different from Group II patients in body mass index (BMI) (51.7 vs 50.3 kg/m2), age (43.7 vs 44.3 yrs), sex (men 20.2% vs 15.8%) or history of previous DVT (3.2% vs 3.9%). Group I patients did have significantly longer procedure times (213 vs 175 min, p < 0.05) and hospital stays (5.67 d vs 3.81 d, p < 0.05) than Group II. There were a total of 7 (1.4%) postoperative DVT complications. 5 DVT complications occurred in Group I (5.4%) compared with 2 DVT complications in Group II (0.6%) (p < 0.01 by Fisher Exact Test two-tailed). One patient in each group required treatment for hemorrhage. CONCLUSION: A multi-modality prophylaxis treatment protocol in patients undergoing bariatric surgery is feasible and achieves a low incidence of postoperative DVT complications. The use of a higher dose of enoxaparin, 40 mg q12h, may reduce the incidence of DVT complications in patients following bariatric surgery without an increase in bleeding complications.