Cytokine responses in nonlesional psoriatic skin as clinical predictor to anti-TNF agents.

BACKGROUND: A major issue with the current management of psoriasis is our inability to predict treatment response. OBJECTIVE: Our aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for patients with psoriasis. METHODS: We conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles were assessed in more than 200 RNA-seq samples. RESULTS: We demonstrated correlation between clinical response and molecular changes during the course of the treatment, particularly for genes responding to IL-17A/TNF in keratinocytes. Intriguingly, baseline gene expressions in nonlesional, but not lesional, skin were the best marker of treatment response at week 12. We identified USP18, a known regulator of IFN responses, as positively correlated with Psoriasis Area and Severity Index (PASI) improvement (P = 9.8 × 10-4) and demonstrate its role in regulating IFN/TNF responses in keratinocytes. Consistently, cytokine gene signatures enriched in baseline nonlesional skin expression profiles had strong correlations with PASI improvement. Using this information, we developed a statistical model for predicting PASI75 (ie, 75% of PASI improvement) at week 12, achieving area under the receiver-operating characteristic curve value of 0.75 and up to 80% accurate PASI75 prediction among the top predicted responders. CONCLUSIONS: Our results illustrate feasibility of assessing drug response in psoriasis using nonlesional skin and implicate involvement of IFN regulators in anti-TNF responses.

Anatomic Total Shoulder Arthroplasty: Component Size Prediction with 3-Dimensional Pre-Operative Digital Planning.

Background: The rate, complexity, and cost of total shoulder arthroplasty (TSA) continues to grow. Technology has advanced pre-operative templating. Reducing cost of TSA has positive impact for the patient, manufacturer, and hospital. The aim of this study was to evaluate the accuracy of implant size selection based on 3-D templating. Our hypothesis was that pre-operative templating would enable accurate implant prediction within one size. Methods: Multicenter retrospective study of anatomic TSAs templated utilizing 3-D virtual planning technology. This program uses computed tomography (CT) scans allowing the surgeon to predict component sizes of the glenoid and humeral head and stem. Pre-operative templated implant size were compared to actual implant size at the time of surgery. Primary data analysis utilized unweighted Cohen's Kappa test. Results: 111 TSAs were analyzed from five surgeons. Pre-operative templated glenoid sizes were within one size of actual implant in 99% and exactly matched in 89%. For patients requiring a posterior glenoid augment (n = 14), 100% of implants were within one size of the template and 93% matched exactly. For stemless humeral components (n = 87) implanted, 98% matched the pre-operative template within one size with 79% exactly matched. For stemmed components (n = 24), 88% of cases were within one size of the preoperative plan and exactly matching in 83%. Humeral head diameter matched within one size of the pre-operative template in 84% of cases and exactly matched in 72%. Conclusion: Pre-operative 3-D templating for TSAs can accurately predict glenoid and humeral component size. This study sets the groundwork for utilization of pre-operative 3-D templating as a potential method to reduce overall TSA costs by managing cost of implants, reducing inventory needs, and improving surgical efficiency.

Michigan Initiative for Anterior Cruciate Ligament Rehabilitation (MiACLR): A Protocol for a Randomized Clinical Trial.

OBJECTIVE: Restoring quadriceps muscle strength following anterior cruciate ligament reconstruction (ACLR) may prevent the posttraumatic osteoarthritis that affects over 50% of knees with ACLR. However, a fundamental gap exists in our understanding of how to maximize muscle strength through rehabilitation. Neurological deficits and muscle atrophy are 2 of the leading mechanisms of muscle weakness after ACLR. High-intensity neuromuscular electrical stimulation (NMES) and eccentric exercise (ECC) have been shown to independently target these mechanisms. If delivered in succession, NMES and then ECC may be able to significantly improve strength recovery. The objectives of this study were to evaluate the ability of NMES combined with ECC to restore quadriceps strength and biomechanical symmetry and maintain cartilage health at 9 and 18 months after ACLR. METHODS: This study is a randomized, double-blind, placebo-controlled, single-center clinical trial conducted at the University of Michigan. A total of 112 participants between the ages of 14 and 45 years and with an anterior cruciate ligament rupture will be included. Participants will be randomly assigned 1:1 to NMES combined with ECC or NMES placebo combined with ECC placebo. NMES or NMES placebo will be delivered 2 times per week for 8 weeks beginning 10 to 14 days postoperatively and will be directly followed by 8 weeks of ECC or ECC placebo delivered 2 times per week. The co-primary endpoints are change from baseline to 9 months and change from baseline to 18 months after ACLR in isokinetic quadriceps strength symmetry. Secondary outcome measures include isometric quadriceps strength, quadriceps activation, quadriceps muscle morphology (cross-sectional area), knee biomechanics (sagittal plane knee angles and moments), indexes of patient-reported function, and cartilage health (T1ρ and T2 relaxation time mapping on magnetic resonance imaging). IMPACT: The findings from this study might identify an intervention capable of targeting the lingering quadriceps weakness after ACLR and in turn prevent deterioration in cartilage health after ACLR, thereby potentially improving function in this patient population.