Diren Arsoy

Outcomes and complications following total hip arthroplasty in the super-obese patient, BMI > 50.

The results of total hip arthroplasty in 42 primary total hip arthroplasties in super-obese patients (BMI ≥ 50) were reviewed. The mean body mass index for the study group was 53.2 kg/m(2) (range 50-64). The mean preoperative Harris hip score improved from 35 to 74.8 postoperatively (P<0.001). Twenty-four of the THAs had at least one complication. At least one major complication occurred in 11 of the THAs and at least one minor complication in 14 THAs When compared to matched 2:1 control group the super-obese patient had a significantly increased risk to experience a complication (HR 5.6 , CI = 2.8-11.0). Caution should be used when proceeding with primary total hip arthroplasty with a BMI greater than 50.

Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis

Aims Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. DOI: 10.1302/2046-3758.51.2000593

RNA sequencing reveals a depletion of collagen targeting microRNAs in Dupuytren’s disease

BackgroundDupuytren’s disease is an inherited disorder in which patients develop fibrotic contractures of the hand. Current treatment strategies include surgical excision or enzymatic digestion of fibrotic tissue. MicroRNAs, which are key posttranscriptional regulators of genes expression, have been shown to play an important regulatory role in disorders of fibrosis. Therefore in this investigation, we apply high throughput next generation RNA sequencing strategies to characterize microRNA expression in diseased and healthy palmar fascia to elucidate molecular mechanisms responsible for pathogenic fibrosis.MethodsWe applied high throughput RNA sequencing techniques to quantify the expression of all known human microRNAs in Dupuytren’s and control palmar fascia. MicroRNAs that were differentially expressed between diseased and healthy tissue samples were used for computational target prediction using the bioinformatics tool ComiR. Molecular pathways that were predicted to be differentially expressed based on computational analysis were validated by performing RT-qPCR on RNA extracted from diseased and non-diseased palmar fascia biopsies.ResultsA comparison of microRNAs expressed in Dupuytren’s fascia and control fascia identified 74 microRNAs with a 2-fold enrichment in Dupuytren’s tissue, and 32 microRNAs with enrichment in control fascia. Computational target prediction for differentially expressed microRNAs indicated preferential targeting of collagens and extracellular matrix related proteins in control palmar fascia. RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues.DiscussionControl palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia. Thus alterations in microRNA regulatory networks may play an important role in driving the pathogenic fibrosis seen in Dupuytren’s disease via direct regulatory effects on extracellular matrix protein synthesis.ConclusionDupuytren’s fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins.Dupuytren’s disease is an inherited disorder in which patients develop fibrotic contractures of the hand. Current treatment strategies include surgical excision or enzymatic digestion of fibrotic tissue. MicroRNAs, which are key posttranscriptional regulators of genes expression, have been shown to play an important regulatory role in disorders of fibrosis. Therefore in this investigation, we apply high throughput next generation RNA sequencing strategies to characterize microRNA expression in diseased and healthy palmar fascia to elucidate molecular mechanisms responsible for pathogenic fibrosis. We applied high throughput RNA sequencing techniques to quantify the expression of all known human microRNAs in Dupuytren’s and control palmar fascia. MicroRNAs that were differentially expressed between diseased and healthy tissue samples were used for computational target prediction using the bioinformatics tool ComiR. Molecular pathways that were predicted to be differentially expressed based on computational analysis were validated by performing RT-qPCR on RNA extracted from diseased and non-diseased palmar fascia biopsies. A comparison of microRNAs expressed in Dupuytren’s fascia and control fascia identified 74 microRNAs with a 2-fold enrichment in Dupuytren’s tissue, and 32 microRNAs with enrichment in control fascia. Computational target prediction for differentially expressed microRNAs indicated preferential targeting of collagens and extracellular matrix related proteins in control palmar fascia. RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues. Control palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia. Thus alterations in microRNA regulatory networks may play an important role in driving the pathogenic fibrosis seen in Dupuytren’s disease via direct regulatory effects on extracellular matrix protein synthesis. Dupuytren’s fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins.

Joint contracture is reduced by intra-articular implantation of rosiglitazone-loaded hydrogels in a rabbit model of arthrofibrosis: ROSIGLITAZONE-LOADED HYDROGELS IN A RABBIT MODEL OF ARTHROFIBROSIS

Trauma, surgery, and other inflammatory conditions can lead to debilitating joint contractures. Adjunct pharmacologic modalities may permit clinical prevention and treatment of recalcitrant joint contractures. We investigated the therapeutic potential of rosiglitazone by intra‐articular delivery via oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. OPF hydrogels loaded with rosiglitazone were characterized for drug elution properties upon soaking in minimum essential media (MEM) with 10% fetal bovine serum and measurements of drug concentrations via High Performance Liquid Chromatography (HPLC). Drug‐loaded scaffolds were surgically implanted into 24 skeletally mature female New Zealand White rabbits that were divided into equal groups receiving OPF hydrogels loaded with rosiglitazone (1.67 mg), or vehicle control (10 µl DMSO). After 8 weeks of joint immobilization, rabbits were allowed unrestricted cage activity for 16 weeks. Contracture angles of rabbit limbs treated with rosiglitazone showed statistically significant improvements in flexion compared to control animals (mean angles, respectively, 64.4° vs. 53.3°, p < 0.03). At time of sacrifice (week 24), animals in the rosiglitazone group continued to exhibit less joint contracture than controls (119.0° vs. 99.5°, p = 0.014). The intra‐articular delivery of rosiglitazone using implanted OPF hydrogels decreases flexion contractures in a rabbit model of arthrofibrosis without causing adverse effects (e.g., gross inflammation or arthritis). Statement of Clinical Significance: Post‐traumatic joint contractures are common and debilitating, with limited available treatment options. Pharmacologic interventions can potentially prevent and treat such contractures. This study is translational in that a commercially approved medication has been repurposed through a novel delivery device.

Mobile Compression Reduces Bleeding-related Readmissions and Wound Complications After THA and TKA

Background The use of chemoprophylaxis to prevent thromboembolic disease after primary THA and TKA can be associated with postoperative bleeding complications. Mechanical prophylaxis has been studied as an alternative to chemoprophylaxis with greater safety in patients undergoing THA, but no data have been published comparing the safety of chemoprophylaxis versus mechanical methods for patients undergoing TKA. The risk of readmission resulting from bleeding and venous thromboembolism (VTE) has also not been determined for patients undergoing THA or TKA when treated with low-molecular-weight heparin (LMWH) alone compared with mechanical prophylaxis plus aspirin (ASA). Question/purposes We sought to answer four questions: For the THA and TKA cohorts, respectively, (1) was the incidence of readmission resulting from VTE and bleeding complications higher with LMWH than mobile compression plus ASA; and (2) was the incidence of wound bleeding complications higher with LMWH than mechanical compression plus ASA? For the TKA cohort specifically, (3) was the frequency of systemic bleeding events and complications related to chemical prophylaxis higher with LMWH compared with mechanical compression plus ASA? (4) Was there a difference in symptomatic VTEs between LMWH and mechanical compression plus ASA? Methods Between November 2008 and April 2011, 632 patients underwent primary THA and TKA. Seventy-two patients (11%) were identified before surgery as being at high risk for VTE (31 patients) or bleeding (41 patients) and were excluded from the study. Five hundred sixty patients (89%) were considered to be at standard risk for VTE and bleeding and comprise the study cohort. Between November 2008 and November 2009, 252 patients (76 THAs, 176 TKAs) underwent THA and TKA and were treated with LMWH (5 mg dalteparin given subcutaneously daily for 14 days) and in-hospital nonmobile mechanical compression. Between November 2009 and April 2011, a total of 308 patients undergoing THA and TKA (108 THAs, 200 TKAs) were treated using a mobile compression device plus oral aspirin once daily for 2 weeks after surgery. All complications and readmissions that occurred within 6 weeks of surgery were noted. There were no differences between the VTE treatment groups with regard to age, sex, or body mass index. Results For the THA cohort, there was no difference in the frequency of readmission for a bleeding complication (wound or systemic) between the two groups (2.6% for LMWH versus 0.9% for mobile compression; p = 0.57; odds ratio [OR], 2.9). Patients undergoing TKA treated with LMWH had higher readmission rates within 6 weeks of surgery because of a bleeding complication, a wound infection, or the development of a VTE (6.8% for LMWH versus 1.5% for mobile compression; p = 0.015; OR, 4.8). For the THA cohort, there was higher wound bleeding complication frequency with LMWH (9.2% for LMWH versus 0.9% for mechanical compression; p = 0.009; OR, 10.9). Patients undergoing TKA treated with LMWH had a higher frequency of wound bleeding complications or infection (3.9% for LMWH versus 0.5% for mobile compression; p = 0.028; OR, 8.2). Patients undergoing TKA treated with LMWH had higher rates of systemic bleeding or a complication secondary to LMWH administration (2.8% for LMWH versus 0% for mobile compression; p = 0.022; OR, 12.8). No difference was noted in the rate of symptomatic VTEs between either group (for THA: 2.6% for the LMWH group versus 1.9% for the mechanical compression group; p = 1; for TKA: 1.1% versus 0%, respectively; p = 0.22). Conclusions Based on these results, we advocate for routine use of mobile mechanical compression devices in the prevention of VTEs and complications associated with more potent chemical anticoagulants. However, more focused randomized clinical trials are needed to validate these findings. Level of Evidence: Level III, therapeutic study.

Continuous Femoral Nerve Catheters Decrease Opioid-related Side Effects and Increase Home Disposition Rates Among Geriatric Hip Fracture Patients

Objective: To evaluate the effect of continuous femoral nerve catheter (CFNC) for postoperative pain control in geriatric proximal femur fractures compared with standard analgesia (SA) treatment. Design: Retrospective comparative study. Setting: Academic Level 1 trauma center. Patients/Participants: We retrospectively identified 265 consecutive geriatric hip fracture patients who underwent surgical treatment. Intervention: One hundred forty-nine patients were treated with standard analgesia without nerve catheter whereas 116 patients received an indwelling CFNC. Main Outcome Measurement: Daily average preoperative and postoperative pain scores, daily morphine equivalent consumption, opioid-related side effects and discharge disposition. Results: Patients with CFNC patients reported lower average pain scores preoperatively (1.9 ± 1.7 for CFNC vs. 4.7 ± 2 for SA; P < 0.0001), on postoperative day 1 (1.5 ± 1.6 for CFNC vs. 3 ± 1.7 for SA; P < 0.0001) and postoperative day 2 (1.2 ± 1.5 for CFNC vs. 2.6 ± 2.1 for SA; P < 0.0001). CFNC group consumed 39% less morphine equivalents on postoperative day 1 (4.4 ± 5.8 mg for CFNC vs. 7.2 ± 10.8 mg for SA; P = 0.005) and 50% less morphine equivalent on postoperative day 2 (3.4 ± 4.4 mg for CFNC vs. 6.8 ± 13 mg for SA; P = 0.105). Patients with CFNC had a lower rate of opioid-related side effects compared with patients with SA (27.5% for CFNC vs. 47% for SA; P = 0.001). More patients with CFNC were discharged to home with or without health services than patients with SA (15% for CFNC vs. 6% for SA; P = 0.023). Conclusion: Continuous femoral nerve catheter decreased daily average patient-reported pain scores, narcotic consumption while decreasing the rate of opioid-related side effects. Patients with CFNC were discharged to home more frequently. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.