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Vascularization is currently considered the biggest challenge in bone tissue engineering due to necrosis in the center of large scaffolds. We established a new expendable vascular bundle model to vascularize a three-dimensional printed channeled scaffold with and without bone morphogenetic protein-2 (BMP-2) for improved healing of large segmental bone defects. Bone formation and angiogenesis in an 8 mm critical-sized bone defect in the rat femur were significantly promoted by inserting a bundle consisting of the superficial epigastric artery and vein into the central channel of a large porous polycaprolactone scaffold. Vessels were observed sprouting from the vascular bundle inserted in the central tunnel. Although the regenerated bone volume in the group receiving the scaffold and vascular bundle was similar to that of the healthy femur, the rate of union of the group was not satisfactory (25% at 8 weeks). BMP-2 delivery was found to promote not only bone formation but also angiogenesis in the critical-sized bone defects. Both insertion of the vascular bundle alone and BMP-2 loading alone induced comparable levels of angiogenesis and when used in combination, significantly greater vascular volume was observed. These findings suggest a promising new modality of treatment in large bone defects. Level of Evidence: Therapeutic level I. IMPACT STATEMENT: Vascularization is currently the main challenge in bone tissue engineering. The combination of a vascular bundle and an osteoinductive three-dimensional printed graft significantly improved and accelerated bone regeneration and angiogenesis in critical-sized large bone defects, suggesting a promising new modality of treatment in large bone defects.

Background Postoperative arrhythmias are associated with increased morbidity and mortality in total joint arthroplasty (TJA) patients. HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) decrease atrial fibrillation rates after cardiac surgery, but it is unknown if this cardioprotective effect is maintained after joint reconstruction surgery. We aim to determine if perioperative statin use decreases the incidence of 90-day postoperative arrhythmias in patients undergoing primary TJA. Methods We performed a single-center retrospective cohort study in which 231 primary TJA patients (109 hips, 122 knees) received simvastatin 80 mg daily during their hospitalization as part of a single surgeon’s standard postoperative protocol. This cohort was matched to 966 primary TJA patients (387 hips and 579 knees) that did not receive simvastatin. New-onset arrhythmias (bradycardia, atrial fibrillation/tachycardia/flutter, paroxysmal supraventricular tachycardia, and ventricular tachycardia) and complications (readmissions, thromboembolism, infection, and dislocation) within 90 days of the procedure were documented. Categorical variables were analyzed using Fisher’s exact tests. Our study was powered to detect a 3% difference in arrhythmia rates. Results Within 90 days postoperatively, arrhythmias occurred in 1 patient (0.4%) who received a perioperative statin, 39 patients (4.0%) who did not receive statins (P = .003), and 24 patients (4.2%) who were on outpatient statins (P = .005). This is 10-fold reduction in the relative risk of developing a postoperative arrhythmia within 90 days of arthroplasty and an absolute risk reduction of 3.6%. Conclusion Treating as few as 28 patients with perioperative simvastatin prevents one new cardiac arrhythmia within 90 days in statin-naive patients undergoing TJA.

Cutaneous reactions to BRAF inhibitors are common, but severe reactions resembling or consistent with drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) are relatively rare. Several reports suggest that cutaneous reactions including DRESS/DIHS to BRAF inhibitors are more frequent and severe in the setting of previous immune checkpoint inhibition (ICI). To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of DIHS/DRESS to BRAF inhibitors. We identified 23 cases of DIHS to BRAF inhibitors following checkpoint inhibition and 14 cases without prior checkpoint inhibitor therapy. In both cohorts, DIHS occurred relatively early, with median time to onset from drug exposure of 8–10 days. Patients who received prior ICI were less likely to have peripheral eosinophilia (26% vs 71%), atypical lymphocytes (9% vs 50%), renal involvement (61% vs 79%), hepatic involvement (52% vs 86%), and lymphadenopathy (9% vs 43%) compared to patients who did not receive prior ICI. Thrombocytopenia was more common with prior ICI (17% vs 7%). Only patients who received prior ICI experienced hypotension (26%) during the course of their DIHS. All cases of BRAF-induced DIHS generally improved on systemic steroids/supportive care, and no cases of death were identified. Dermatologists should consider a diagnosis of DIHS following BRAF inhibitor initiation, particularly in the setting of past checkpoint inhibition, with atypical features including relatively rapid onset and steroid responsiveness, lack of peripheral eosinophilia, lymphocytosis, or lymphadenopathy, and increased risk of thrombocytopenia and hypotension.

Core decompression is the most common procedure for early-stage osteonecrosis of the femoral head (ONFH). This study investigated outcomes of core decompression with/without bone marrow aspirate concentrate (BMAC), based on the Kerboul combined necrotic angles using magnetic resonance imaging.We reviewed 66 patients (83 hips) with early ONFH, Association Research Circulation Osseous stages I-IIIa, who underwent core decompression alone (26 patients, 33 hips) or in combination with BMAC (40 patients, 50 hips). Survival rate and progressive collapse were analyzed using the Kaplan-Meier method, and conversion to total hip arthroplasty (THA) was evaluated. Subgroup analyses based on the modified Kerboul angle were performed: grade I (200°), grade II (200°-249°), grade III (250°-299°), and grade IV (≥300°).Mean follow-up was 36 ± 23 months. Femoral head collapse with BMAC (16 hips, 32%) was significantly lower than without BMAC (19 hips, 58%, P = .019). Conversion THA was significantly lower with BMAC (28%) than without (58%, P = .007). Survival rates among groups showed significant differences (P = .017). In grade I, 0/12 hips with BMAC collapsed while 3/9 (33%) without BMAC collapsed (P = .063); in grade II, 2/16 hips (12%) with BMAC collapsed while 7/13 (54%) without BMAC collapsed (P = .023). There was no significant difference in collapse with (64%) or without (82%) BMAC in grade III-IV hips (P = .256).Core decompression with/without BMAC had a high failure rate, by increasing disease progression and the necessity for THA, for combined necrotic angles250°. In our study, addition of BMAC had more reliable outcomes than isolated core decompression for precollapse ONFH if the combined necrotic angles were250°.

The management of large segmental bone defects caused by trauma or disease remains clinically challenging within orthopaedics. The major impediment to bone healing with current treatment options is insufficient vascularization and incorporation of graft material. Lack of rapid adequate vascularization leads to cellular necrosis within the inner regions of the implanted material and a failure of bone regeneration. Current treatment options for critical size bone defects include the continued "gold standard" autograft, allograft, synthetic bone graft substitutes, vascularized fibular graft, induced membrane technique, and distraction osteogenesis. Bone tissue engineering (BTE) remains an exciting prospect for the treatment of large segmental bone defects; however, current clinical integration of engineered scaffolds remains low. We believe that the barrier to clinical application of bone tissue engineering constructs lies in the lack of concomitant vascularization of these scaffolds. This mini-review outlines the progress made and the significant limitations remaining in successful clinical incorporation of engineered synthetic bone substitutes for segmental defects.

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

Background Secondary osteonecrosis of the knee (SOK) generally occurs in relatively young patients; at advanced stages of SOK, the only viable surgical option is total knee arthroplasty (TKA). We conducted a retrospective study to investigate implant survivorship, clinical and radiographic outcomes, and complications of contemporary cemented bicompartmental TKA with/without patellar resurfacing for SOK. Methods Thirty-eight cemented TKAs in 27 patients with atraumatic SOK, mean age 43 years (17 to 65), were retrospectively reviewed. Seventy-four percent had a history of corticosteroid use, and 18% had a history of alcohol abuse. Patellar osteonecrosis was coincidentally found in six knees (16%), and all were asymptomatic without joint collapse. The mean followup was 7 years (2 to 12). Knee Society Score (KSS) and radiographic outcomes were evaluated at 6 weeks, 1 year, then every 2 to 3 years. Results Ninety-two percent had implant survivorship free from revision with significant improvement in KSS. Causes of revision included aseptic tibial loosening (one), deep infection (one), and instability with patellofemoral issues (one). Four of six cases also with patellar osteonecrosis received resurfacing, including one with periprosthetic patellar fracture after minor trauma, with satisfactory clinical results after conservative treatment. None of the unrevised knees had progressive radiolucent lines or evidence of loosening. An unresurfaced patella, use of a stem extension or a varus-valgus constrained prosthesis constituted 18%, 8% and 3%, respectively. Conclusion Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation.

Introduction Tobacco use remains pervasive amongst veterans. Unfortunately, the negative impact on postoperative outcomes may preclude surgeons from offering operative intervention to veterans who smoke. As such, a major health event may provide added incentive to quit. We sought to describe the role of acute illness and interventional specialist involvement in Veterans Affairs Smoking Cessation Program referrals compared to primary care wellness initiatives. Methods We retrospectively reviewed consultations to the pharmacy-led Smoking Cessation Program (SCP) at the Middleton Memorial VA Hospital from 2017 to 2019. Consultations placed during the last three months were categorized based on the source of referral: primary care, acute care, and interventional specialties. Descriptive statistics were used to assess rates of veteran engagement based on referral source. Consultation completion was used as a proxy for veteran engagement. Results A total of 2993 new SCP consultations were placed during the study period. Overall, veteran engagement rose from 43% in 2017 to 53% in 2019. In recent months, there were 282 SCP referrals. While only 19 (7%) of these referrals were placed by interventional specialties - primarily cardiology and thoracic surgery - the rate of veteran engagement was 63%. The majority of referrals (65%) were placed by primary care providers with an engagement rate of 68%. In contrast, only 42% of consultations placed in the context of an acute illness were completed. Conclusions In our study, primary care directed smoking cessation referrals were most prevalent and resulted in the highest completion rates. The presence of an acute illness in isolation failed to impact program success. However, while surgeon-initiated referrals were meager in number, the engagement rate approached that of primary care. This finding suggests that surgeons play a powerful role in influencing patient behavior that may be harnessed to augment success of existing smoking cessation programs.

Background: Surgeons frequently add an Achilles tendon lengthening or gastrocnemius recession to increase dorsiflexion following total ankle replacement. Previous studies have looked at the effects of these procedures on total tibiopedal motion. However, tibiopedal motion includes motion of the midfoot and hindfoot as well as the ankle replacement. The current study examined the effects of Achilles tendon lengthening and gastrocnemius recession on radiographic tibiotalar motion at the level of the prosthesis only. Methods: Fifty-four patients with an average of 25 months follow-up after total ankle replacement were divided into 3 groups: (1) patients who underwent Achilles tendon lengthening, (2) patients who had a gastrocnemius recession, (3) patients with no lengthening procedure. Tibiotalar range of motion was measured on lateral dorsiflexion-plantarflexion radiographs using reference lines on the surface of the implants. Results: Both Achilles tendon lengthening and gastrocnemius recession significantly increased tibiotalar dorsiflexion when compared to the group without lengthening. However, the total tibiotalar range of motion among the 3 groups was the same. Interestingly, the Achilles tendon lengthening group lost 11.7 degrees of plantarflexion compared to the group without lengthening, which was significant. Conclusion: Both Achilles tendon lengthening and gastrocnemius recession increased radiographic tibiotalar dorsiflexion following arthroplasty. Achilles tendon lengthening had the unexpected effect of significantly decreasing plantarflexion. Gastrocnemius recession may be a better choice when faced with a tight ankle replacement because it increases dorsiflexion without a compensatory loss of plantarflexion. Level of Evidence: Level III, retrospective comparative study.

Jennifer M Hah,1 Heather Hilmoe,2 Peter Schmidt,2 Rebecca McCue,2 Jodie Trafton,3,4 Debra Clay,2 Yasamin Sharifzadeh,2 Gabriela Ruchelli,2 Tina Hernandez Boussard,5 Stuart Goodman,6 James Huddleston,7 William J Maloney,7 Frederick M Dirbas,8 Joseph Shrager,9 John G Costouros,7 Catherine Curtin,10 Sean C Mackey,1 Ian Carroll1 1Division of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, CA, USA; 2Stanford Systems Neuroscience and Pain Lab, Stanford University, Stanford, CA, USA; 3Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; 4VA Program Evaluation and Resource Center, VHA Office of Mental Health Operations, Palo Alto, CA, USA; 5Department of Medicine, Department of Biomedical Data Science, Stanford University, Stanford, CA, USA; 6Department of Orthopaedic Surgery and (by Courtesy) Bioengineering, Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; 7Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; 8Department of General Surgery, Stanford University, Stanford, CA, USA; 9Division of Thoracic Surgery, Stanford University, Stanford, CA, USA; 10Division of Hand and Plastic Surgery, Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USACorrespondence: Jennifer M HahDivision of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304, USATel +1 650-736-9415Fax +1 650-725-9642Email jhah@stanford.eduBackground: Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.Methods: In this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18– 75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively.Results: Overall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87– 1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68– 0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40– 0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39– 0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80– 0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89– 1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06– 1.77; P=0.016).Conclusion: Separate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.Keywords: persistent postsurgical pain, persistent postoperative opioid use, chronic opioid use after surgery, chronic pain after surgery

BACKGROUND Joint preservation is more effective in early-stage osteonecrosis of the femoral head (ONFH); thus, prompt diagnosis when the femoral head is still salvageable is important. We report a 20-year retrospective study that summarizes age at presentation, etiology, and Association Research Circulation Osseous stage at diagnosis. METHODS Our database was reviewed to identify patients younger than 65 years of age who were diagnosed with atraumatic ONFH between 1998 and 2018. Demographic characteristics of patients were evaluated and categorized into different subgroups. RESULTS Four hundred thirteen patients were identified. At initial presentation, 23% were diagnosed with early-stage ONFH, while 77% were diagnosed with late-stage ONFH. Forty-nine percent had a history of corticosteroid use, of which 13% were diagnosed with hematologic malignancy and 8% were diagnosed with lupus. Ethanol abuse, idiopathic, sickle cell disease, and human immunodeficiency virus were present in 11%, 30%, 3%, and 3%, respectively. The mean age of patients with corticosteroid use (40 ± 14 years) was significantly younger than ethanol use (46 ± 11 years, P = .014) and idiopathic causes (48 ± 11 years, P < .001), but significantly older than sickle cell disease (32 ± 11 years, P = .031). There was no difference in the age of presentation for early-stage and late-stage ONFH by etiology. CONCLUSION Nearly 80% of the patients presented with late-stage ONFH. Hence, we have a narrow window of opportunity for hip preservation surgery before femoral head collapse. A multidisciplinary approach to improve screening awareness for early detection by focusing on the etiologic identification and patient education might reduce the incidence of hip arthroplasty in young patients.

This article details efforts to characterize and develop a process control strategy for the manufacture of enone 2, a carfilzomib drug substance intermediate obtained through a Barbier-type Grignar...

Increasing utilization of unicompartmental knee arthroplasty (UKA) has driven a greater push for outpatient treatment and cost containment in the setting of bundled payments. The purpose of this study is to evaluate utilization trends of inpatient vs outpatient UKA, index episode and 90-day reimbursement, and any differences in medical or surgical complications.The PearlDiver database was employed to identify all inpatient and outpatient UKAs performed between 2007 and 2016 with 2-year follow-up. Patients were matched by age, gender, and Elixhauser Comorbidity Index. We tracked index procedure and global period reimbursement, 90-day medical and surgical complications, and 2-year surgical complications.The reimbursement and utilization cohort included 3181 outpatient and 5490 inpatient UKAs. Outpatient UKA and overall utilization of UKA increased over the study period. Mean index reimbursement of inpatient UKA was $2486.16 higher per procedure (P.001) while mean global period reimbursement was $2782.13 higher per inpatient procedure (P.001). Ninety-day medical complications including postoperative anemia (P.001), transfusion (P = .024), and arrhythmia (P = .004) were more common with inpatient UKAs, whereas surgical wound complications (P = .001) and operative debridement (P = .028) were more common among outpatient UKAs. Outpatient UKA was not associated with an increased risk of periprosthetic joint infection (P.05), aseptic loosening (P.05), or revision surgery (P.05) when compared to inpatient UKA.Outpatient UKA utilization is increasing and is associated with decreased reimbursement compared to inpatient UKA without increased risk of major medical complications, although it is associated with increased risk of wound complication and need for operative debridement at 90 days.

Aims To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). Methods A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). Results Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. Conclusion The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593–599.

Purpose: Anakinra (Kineret®) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions.Materials and methods: The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations.Results: Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions.Conclusion: Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.

Selective supplementation of acetabular component fixation with a screw during primary total hip arthroplasty (THA) assumes that the surgeon can detect when an acetabular component needs additional stability. In contrast, nonselective screw users do not alter their practice based on their interpretation of stability and either use screws all or none of the time. We aimed to determine the effect of selective screw use on aseptic acetabular component loosening. We retrospectively reviewed aseptic failures of acetabular components after primaty THA. We compared the survivorship of selective and nonselective supplementation of acetabular fixation with respect to time to revision, obesity, and screw use. Selective screw use (n = 16) was associated with earlier acetabular component aseptic loosening (median: 1.9 years; interquartile range [IQR]: 1.1-5.0) compared to nonselective screw use (n = 22; median: 5.6 years; IQR: 2.0-15.3; P = .010). Selective screw use was independently associated with earlier revision after adjusting for patient obesity. Obesity was associated with selective screw use in 50% of the cases vs 14% of nonselective cases (odds ratio: 6.3; confidence interval: 1.2-25.2; P = .028), possibly reflecting the increased difficulty in achieving acetabular component stability in this and other settings with compromised bone. Surgeons should carefully assess component stability at time of primary THA. If the acetabulum is not stable, the addition of screws alone may not be sufficient for acetabular component stability.

Background The purpose of this study is to determine the impact of total knee arthroplasty (TKA) on mental health. Methods A total of 205 patients who underwent primary TKA with baseline and 1-year postoperative Short Form-12 Mental Component Score (MCS) were included in this retrospective analysis. Eighty-five (41%) patients had a preoperative MCS less than 50 points, while 120 (59%) patients had a preoperative MCS over 50 points. Two groups were assigned to the patients based on their preoperative MCS: low MCS 50. Results A preoperative MCS less than 50 points was predictive of greater improvement in MCS at 1 year after TKA (P Conclusion Patients with lower baseline mental health had greater improvement in postoperative mental health following TKA than patients with higher baseline mental health. Low preoperative MCS was associated with less improvement in patient-reported outcome measures. Patients with lower baseline mental health scores before TKA benefit mentally and physically from the procedure.

Purpose: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. Materials and methods: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. Results: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. Conclusion: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.

Background: Driving to the basket in basketball involves acceleration, deceleration, and lateral movements, which may expose players to increased anterior cruciate ligament (ACL) injury risk. It is unknown whether players who heavily rely on driving have decreased performance on returning to play after ACL reconstruction (ACLR). Hypothesis: Players with a greater tendency to drive to the basket would be more likely to tear their ACL versus noninjured controls and would experience decreased performance when returning to play after ACLR. Study Design: Case-control study; Level of evidence, 3. Methods: Season-level performance statistics and ACL injuries were aggregated for National Basketball Association (NBA) seasons between 1980 and 2017 from publicly available sources. Players’ tendency to drive was calculated using 49 common season-level performance metrics. Each ACL-injured player was matched with 2 noninjured control players by age, league experience, and style of play metrics. Points, playing minutes, driving, and 3-point shooting tendencies were compared between players with ACL injuries and matched controls. Independent-samples t test was utilized for comparisons. Results: Of 86 players with a total of 96 ACL tears identified in the NBA, 50 players were included in the final analysis. Players who experienced an ACL tear had a higher career-average drive tendency than controls ( P = .047). Players with career-average drive tendency ≥1 standard deviation above the mean were more likely to tear their ACL than players with drive tendency Conclusion: NBA players with increased drive tendency were more likely to tear their ACL. However, players who were able to return after ACLR did not underperform compared with controls and did not alter their style of play compared with the normal changes seen with age. This information can be used to target players with certain playing styles for ACL injury prevention programs.

Merkel cell carcinoma (MCC) of the skin is most commonly treated with wide local excision (WLE) with or without adjuvant radiation therapy (RT). Mohs micrographic surgery (MMS) as monotherapy may offer an alternative treatment modality. The purpose of this study is to describe outcomes of patients with primary Stage I/II MCC treated with MMS alone and no RT.A retrospectively collected sample of 56 MCCs treated with MMS was studied over an 18-year period. Tumor and treatment characteristics were described, and follow-up was assessed.A total of 56 primary Stage I/II MCCs in 53 patients were treated with MMS as monotherapy from April 2001 through July 2019. Patients were followed for an average of 4.6 years (median 2.7 years, range 0.8 to 16.9 years), of which 19 (33.9%) had follow-up of 5 years or more. There were no local recurrences due to inadequate excision. The 5-year Kaplan-Meier MCC-specific survival for AJCC8 Stage I and AJCC8 Stage IIA were 91.2% and 68.6%, respectively.In comparison to historical controls, Mohs surgery offers a survival that is at least as good as WLE +/- RT, with the added benefits of no need for adjuvant RT or the need for further surgery for treatment of local recurrence.

In vivo bioreactors are a promising approach for engineering vascularized autologous bone grafts to repair large bone defects. In this pilot parametric study, we first developed a three-dimensional (3D) printed scaffold uniquely designed to accommodate inclusion of a vascular bundle and facilitate growth factor delivery for accelerated vascular invasion and ectopic bone formation. Second, we established a new sheep deep circumflex iliac artery (DCIA) model as an in vivo bioreactor for engineering a vascularized bone graft and evaluated the effect of implantation duration on ectopic bone formation. Third, after 8 weeks of implantation around the DCIA, we transplanted the prevascularized bone graft to a 5 cm segmental bone defect in the sheep tibia, using the custom 3D printed bone morphogenic protein 2 (BMP-2) loaded scaffold without prior in vivo bioreactor maturation as a control. Analysis by micro-computed tomography and histomorphometry found ectopic bone formation in BMP-2 loaded scaffolds implanted for 8 and 12 weeks in the iliac pouch, with greater bone formation occurring after 12 weeks. Grafts transplanted to the tibial defect supported bone growth, mainly on the periphery of the graft, but greater bone growth and less soft tissue invasion was observed in the avascular BMP-2 loaded scaffold implanted directly into the tibia without prior in vivo maturation. Histopathological evaluation noted considerably greater vascularity in the bone grafts that underwent in vivo maturation with an inserted vascular bundle compared with the avascular BMP-2 loaded graft. Our findings indicate that the use of an initial DCIA in vivo bioreactor maturation step is a promising approach to developing vascularized autologous bone grafts, although scaffolds with greater osteoinductivity should be further studied. IMPACT STATEMENT: This translational pilot study aims at combining a tissue engineering scaffold strategy, in vivo prevascularization, and a modified transplantation technique to accelerate large segmental bone defect repair. First, we three-dimensional (3D) printed a 5 cm scaffold with a unique design to facilitate vascular bundle inclusion and osteoinductive growth factor delivery. Second, we established a new sheep deep circumflex iliac artery model as an in vivo bioreactor for prevascularizing the novel 3D printed osteoinductive scaffold. Subsequently, we transplanted the prevascularized bone graft to a clinically relevant 5 cm segmental bone defect in the sheep tibia for bone regeneration.

Suboptimal implant rotation has consequences with respect to knee kinematics and clinical outcomes. We evaluated the functional outcomes of revision total knee arthroplasty (TKA) for poor axial implant rotation.We retrospectively reviewed 42 TKAs undergoing aseptic revision for poor axial implant rotation. We assessed improvements in Knee Society Score (KSS) and final range of motion (ROM). Subgroup analyses were performed for preoperative instability and stiffness, as well as the number of components revised and level of implant constraint used.Revision for poor axial rotation in isolation improved KSS from 52 ± 22 to 84 ± 25 (P.001), and flexion increased from 105 ± 21° to 115 ± 13° (P = .001). Revision in the setting of instability significantly improved the KSS (P.001) but did not affect ROM (P = .172). Revision in the setting of stiffness significantly improved both KSS (P.001) and ROM (P = .002). There was no statistically significant difference between the postoperative KSS (P = .889) and final knee flexion (P = .629) with single- or both-component revision TKA for isolated poor axial rotation or between the postoperative KSS (P = .956) and final knee flexion (P = .541) with or without the use of higher constraint during revision TKA for isolated poor axial rotation.Revision TKA for poor axial alignment improves clinical outcomes scores and functional ROM.

Introduction: Debate over the ideal agent for venous thromboembolism (VTE) prophylaxis after total hip arthroplasty (THA) has led to changes in prescribing trends of commonly used agents. We investigate variation in utilisation and the differences in VTE incidence and bleeding risk in primary THA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors. Methods: 8829 patients were age/sex matched from a large database of primary THAs performed between 2007 and 2016. Utilisation was calculated using compound annual growth rate. Incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications, postoperative anaemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days. Results: Aspirin use increased by 33%, enoxaparin by 7%, and factor Xa inhibitors by 31%. Warfarin use decreased by 1%. Factor Xa inhibitors (1.7%) and aspirin (1.7%) had the lowest incidence of DVT followed by enoxaparin (2.6%), and warfarin (3.7%) at 90 days. Factor Xa inhibitors (12%) and aspirin (12%) had the lowest incidence of blood transfusion followed by warfarin (15%) and enoxaparin (17%) at 90 days. There was no difference in incidence of blood transfusion or bleeding-related complications nor any detectable difference in symptomatic PE incidence. Conclusions: The utilisation of aspirin and factor Xa inhibitors increased over time. Aspirin and factor Xa inhibitors provided improved DVT prophylaxis with lower rates of postoperative anaemia compared to enoxaparin and warfarin.

PURPOSE: Apremilast is a phosphodiesterase-4 inhibitor FDA approved for psoriatic arthritis and moderate to severe plaque psoriasis. In recent years, multiple studies have suggested other potential uses for apremilast in dermatology. A summary of these various studies will be a valuable aid to dermatologists considering apremilast for an alternative indication. MATERIALS AND METHODS: The PubMed/MEDLINE and ClinicalTrials.gov databases were queried with the term ‘apremilast,’ with results manually screened to identify published data on off-label uses of apremilast. The article was structured by the quality of evidence available. RESULTS: Apremilast use in dermatology beyond plaque psoriasis and psoriatic arthritis is frequently described in the literature, with a mixture of positive and negative results. Randomized controlled data is available for Behçet’s disease, hidradenitis suppurativa, nail/scalp/palmoplantar psoriasis, alopecia areata, and atopic dermatitis. CONCLUSION: The relatively safe adverse effect profile of apremilast and its broad immunomodulatory characteristics may make it a promising option in the future for patients with difficult to treat diseases in dermatology, refractory to first line therapies, but further studies will be necessary to clarify its role.

Displaced talar neck fractures no longer constitute a surgical emergency; timing of definitive surgery has no bearing on the risk of osteonecrosis. Amount of initial fracture displacement is best predictor of osteonecrosis. Grossly displaced fractures or fracture-dislocations should be provisionally reduced, with or without temporary external fixation. Periosteal stripping should be limited to only that necessary to obtain anatomic reduction. Dissection within the sinus tarsi or tarsal canal should be avoided. Rigid internal fixation with solid cortical screws countersunk within the talar head and placed below the "equator" of the talar head is imperative for optimum stability.

Maloney, SJ, Richards, J, Jelly, L, and Fletcher, IM. Unilateral stiffness interventions augment vertical stiffness and change of direction speed. J Strength Cond Res 33(2): 372-379, 2019-It has previously been shown that preconditioning interventions can augment change of direction speed (CODS). However, the mechanistic nature of these augmentations has not been well considered. The current study sought to determine the effects of preconditioning interventions designed to augment vertical stiffness on CODS. Following familiarization, 10 healthy males (age: 22 ± 2 years; height: 1.78 ± 0.05 m; body mass: 75.1 ± 8.7 kg) performed 3 different stiffness interventions in a randomized and counterbalanced order. The interventions were: (a) bilateral-focused, (b) unilateral-focused, and (c) a control of CODS test practice. Vertical stiffness and joint stiffness were determined preintervention and postintervention using a single-leg drop jump task. Change of direction speed test performance was assessed postintervention using a double 90° cutting task. Performances following the unilateral intervention were significantly faster than control (1.7%; p = 0.011; d = -1.08), but not significantly faster than the bilateral intervention (1.0% faster; p = 0.14; d = -0.59). Versus control, vertical stiffness was 14% greater (p = 0.049; d = 0.39) following the unilateral intervention and 11% greater (p = 0.019; d = 0.31) following the bilateral intervention; there was no difference between unilateral and bilateral interventions (p = 0.94; d = -0.08). The findings of the current study suggest that unilateral preconditioning interventions designed to augment vertical stiffness improve CODS within this experimental cohort.

Systematic approaches for accurate repurposing of targeted therapies are needed. We developed and aimed to biologically validate our therapy predicting tool (TPT) for the repurposing of targeted therapies for specific tumor types by testing the role of Bromodomain and Extra-Terminal motif inhibitors (BETi) in inhibiting BRD4 function and downregulating Notch3 signaling in ovarian cancer. Utilizing established ovarian cancer preclinical models, we carried out in vitro and in vivo studies with clinically relevant BETis to determine their therapeutic effect and impact on Notch3 signaling. Treatment with BETis or siRNA-mediated BRD4 knockdown resulted in decreased cell viability, reduced cell proliferation, and increased cell apoptosis in vitro. In vivo studies with orthotopic mouse models demonstrated that treatment with BETi decreased tumor growth. In addition, knockdown of BRD4 with doxycycline-inducible shRNA increased survival up to 50% (P < 0.001). Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both in vitro and in vivo. BRD4 inhibition also decreased the expression of NOTCH3 targets, including HES1. Chromatin immunoprecipitation revealed that BRD4 was present at the NOTCH3 promoter. Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression. The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.

Introduction:While statins have been found to reduce postoperative atrial fibrillation after cardiac surgery, little is known about their use in total hip arthroplasty (THA). This study investigated if statins would similarly reduce postoperative arrhythmias in patients undergoing THA.Methods:We queried a large Medicare and private-payer database from 2005 to 2012 and identified 12,075 patients who were on a statin prior to THA. We then age and sex matched 34,446 non-statin users who underwent THA. Baseline comorbidities and postoperative complications were obtained and assessed via standard descriptive statistics.Results:The statin users had more preoperative comorbidities including congestive heart failure, valvular heart disease, pulmonary and renal disease, diabetes, hypertension, obesity, and anaemia (all p values < 0.001). Postoperatively, the statin users had a statistically higher 90-day incidence of transfusion, acute renal failure, heart failure, pneumonia, and sepsis/shock. All new-onset cardiac arrhythmia was significantly less frequent in the statin group at 2 weeks (3.88% vs. 4.72%, p < 0.001), 30 days (4.47% vs. 5.29%, p < 0.001), and 90 days (5.44% vs. 6.31%, p = 0.001) postoperative. There was no difference in the frequency of venous thromboembolism, myocardial infarction, postoperative anaemia, or bleeding at 90 days postoperative.Discussion:Despite being medically sicker at baseline with multiple risk factors for atrial fibrillation compared to the non-statin users, the statin users displayed a consistently lower occurrence of postoperative cardiac arrhythmia in this retrospective cohort study. Statins may therefore be beneficial in the preoperative optimisation of medically complex patients undergoing THA.

Proper patellofemoral alignment is an important goal in total knee arthroplasty (TKA). Acceptable patellar alignment is defined as patellar tilt less than or equal to 5° and patellar displacement less than or equal to 5 mm. Previous studies reported an incidence of post-operative patellar malalignment in TKA from 7 to 35%. However, correlation between patellar malalignment and clinical outcome after TKA remains unclear. The purpose of the present study was to evaluate the effect of patellar tilt and displacement on the clinical outcome of TKA. A retrospective review of 138 primary TKAs with a minimum of 2 year follow-up is reported. Pre-operative and post-operative mechanical axis, patellar tilting angle and patellar displacement were measured. Clinical outcomes were evaluated by the knee functional scores including the Knee Society Score (KSS), Knee injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario McMaster University Osteoarthritis Index (WOMAC) at final follow-up. Forty-two (30%) primary TKAs had suboptimal patellofemoral alignment with a patellar tilt angle greater than 5° or lateral patellar displacement of more than 5 mm. There was no statistical difference in pre-operative mechanical axis, pre-operative patellar tilt angle, or pre-operative lateral patellar displacement between the primary TKAs with proper patellofemoral alignment and those with suboptimal alignment. Patients with post-operative patellar tilt or displacement had clinically significant reductions in KSS, KOOS, and WOMAC when compared with patients without post-operative patellar tilt or displacement. The odds of having a fair or poor post-operative result, an odds ratio of 3.4 (95% CI 1.6–7.2) for KSS, 6.4 (95% CI 2.9–14.2) for KOOS, and 5.9 (95% CI 2.6–13.5) for WOMAC, were associated with suboptimal patellofemoral alignment. Establishing proper patellofemoral alignment remains an essential goal of primary TKA. There is a strong association between suboptimal post-operative patellofemoral alignment and poor clinical outcome scores after primary TKA.

Purpose Ruxolitinib (Jakafi) is a Janus kinase 1 and 2 small molecule inhibitor that the Food and Drug Administration approved for myelofibrosis and polycythemia vera. It has been expanded to off-label treatment for a variety of dermatologic conditions, with several clinical trials ongoing. A review of available studies and cases of off-label uses was performed to guide clinicians seeking evidence on the efficacy of this Janus kinase inhibitor for dermatologic disorders. Materials and methods PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term "ruxolitinib," and results were manually reviewed to identify published data on off-label uses of ruxolitinib. Studies included are structured by quality of evidence available. Results Ruxolitinib may have utility in the treatment of atopic dermatitis, psoriasis, and vitiligo, with data from open-label and randomized trials supporting efficacy of topical formulations. Evidence of utility for alopecia areata is mixed and differs depending on topical versus oral form. Evidence for numerous other conditions is available through case reports and case series. Conclusions There is growing evidence supporting potential off-label use of oral and topical ruxolitinib for a wide range of skin conditions. There are several ongoing investigations of ruxolitinib use in dermatology that will undoubtedly better define its efficacy and appropriate use in dermatology.

The manifestation of toxigenic fungi and their produced mycotoxins have proven to be a universal major agricultural calamity in maintaining secure safe nutritious food supply and a critical health issue in recent years. This is prevented by a spiked increment in the sullying of staple nourishments credited to different factors, for example, climate changes that favor mycotoxigenic fungal growth. Plant/crop development is governed by complex genetic regulatory networks/signaling pathways and it is through understanding these pathways, we can engineer crop assortments with improved yields, healthful properties, and better protection from fungal development/mycotoxin contamination. The understanding of the pathway of plant immunity from protection against pathogenic microorganisms is still in its infancy. The agriculture sector is currently experiencing an RNA interference (RNAi) and clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein-9 nuclease Cas9) revolution driven by genetically transforming and editing plants/crops for controlling mycotoxin contamination. The utilization of CRISPR/Cas9 and RNAi systems has an immense impact on understanding gene functioning and related properties. In this chapter, we discuss RNAi and CRISPR/Cas9 technologies that have been used to control mycotoxin contamination.

PURPOSE Over the past decade, many new biologic and small-molecule drugs have been approved for psoriasis. These specialty drugs tend to be expensive and place financial burden on the healthcare system as well as patients. This study aims to explore trends in Medicare Part D spending and prescription patterns for psoriasis drugs by dermatologists. METHODS The Centers for Medicare and Medicaid Services' (CMS) Medicare Part D Public Use Files from 2013 to 2017 were utilized to examine prescription rates and pricing FDA-approved psoriasis drugs. RESULTS From 2013 to 2017, psoriasis drugs accounted for 41% of total Medicare Part D spending by dermatologists in the database, of which biologics accounted for 86.5%. The proportion of psoriasis-related spending increased from 36% of total spending in 2013 to 53% in 2017. Prescriptions of etanercept decreased while prescribers of newly approved drugs increased significantly. The cost per day of biologics were significantly variable in 2013 but converged toward similar costs in 2017. CONCLUSION Psoriasis prescriptions comprise a large, increasing proportion of Medicare Part D spending related to dermatology. These increasing costs have significant implications for the healthcare system and affect out-of-pocket costs for patients who rely on such medications.

Category: Bunion; Basic Sciences/Biologics Introduction/Purpose: Minimally-invasive surgery (MIS) for hallux valgus correction has become increasingly common. This technique involves an osteotomy of the first metatarsal, followed by fixation with two cannulated screws. Since screws are typically not bicortical, they rely upon bone quality within the metatarsal head for fixation strength. However, bone mineral density (BMD) within different regions of the metatarsal head is unknown. Measuring the BMD in the target region may predict the strength of the bone-screw fixation. Similar to previous work which determined the optimal position for lag screw placement in the femoral head during hip fracture fixation, this study aimed to determine average BMD within four quadrants of the metatarsal head using CT and thus predict the optimal trajectories for cannulated screws during the MIS bunion procedure. Methods: All patients between 18-75 years of age scheduled to undergo MIS hallux valgus correction by one of two surgeons experienced in the MIS technique were eligible to participate. Patients were excluded if they had a prior first metatarsal surgery, pre-existing hardware, previous first metatarsal fracture, or a history of osteoporosis treatment. Patients were enrolled prospectively, and a weight-bearing CT scan of the affected foot was obtained pre-operatively. Demographic factors including age, sex, laterality, body mass index (BMI), comorbidities, and smoking status as well as standard three-view weight-bearing radiographs were collected for all patients.Using the coronal CT slice at maximal metatarsal head diameter, each head was divided into equal quadrants. Hounsfield units (HU) within each quadrant were measured independently by three study investigators using our hospital’s radiology viewing software (Merge PACS; IBM Corporation, Armonk, NY), and these density measurements were averaged. Statistical analysis was conducted using ANOVA and Student’s t-test. Results: Fifteen patients were included for preliminary analysis. All patients were female. The average age was 45.7 years. 9 of the 15 included feet were right feet. Average BMI was 28.0. One patient reported active smoking prior to surgery. Comorbidities included obesity in three patients; none were diabetic. One had a history of diplegic cerebral palsy. The average HVA on a weight- bearing AP foot x-ray was 28.2°, and the average IMA was 12.6°. The BMD within the metatarsal head varied by quadrant, with the two combined dorsal quadrants having higher average BMD than the two combined plantar quadrants (122 vs 85 HU; pConclusion: The density of the metatarsal head did vary by region within the head. The highest BMD was found in the dorsal lateral quadrant, and the lowest in the plantar lateral and plantar medial quadrants, which did not differ significantly from each other. Because strength of screw fixation is predicated upon screw design as well as bone density, these results suggest that surgeons may wish to direct screws toward the dorsolateral region of the metatarsal head in order to achieve optimal fixation. Further work is needed to determine whether this varies with patient age, gender, or hallux valgus angle. [Table: see text]

The IEC 61000-4-2 is a system level test, yet original equipment manufacturers (OEMs) continually ask the IC manufactures to test components with this waveform. The main problem to testing components to the IEC 61000-4-2 is that qualified generators (sometimes referenced as an IEC gun) produce different results for RF sensitive components. This work analyzes the frequency domain spectra to demonstrate why the IEC generators are not repeatable across equipment. In addition, it analyzes an IEC pulser's waveform to show the well-controlled spectrum and the repeatability from event to event which is something the generators lack. Using equipment that is repeatable is essential to get meaningful results across sites, especially for RF components.

Introduction Patient satisfaction has increasingly been used to assess physician performance and quality of care. Although there is evidence that patient satisfaction is associated with patient-reported health outcomes and communication-related measures, there is debate over the use of patient satisfaction in reimbursement policy. Patient characteristics that influence satisfaction have been studied, but the effects of personal and demographic characteristics of physicians on patient satisfaction have yet to be explored. Methods Outpatient satisfaction scores from 11,059 patients who rated 25 orthopaedic surgeons from a single institution were studied. In this study, we sought to explore the relationship between nonmodifiable physician characteristics, such as sex and race, and patient satisfaction with outpatient orthopaedic surgery care, as expressed in the Press Ganey Satisfaction Scores. Univariate logistic regression models were used to test the associations between each provider characteristic and patient satisfaction on the Press Ganey patient satisfaction questionnaire. Results Three nonmodifiable physician personal and demographic characteristics were markedly associated with lower patient satisfaction scores across overall satisfaction, communication, and empathy domains: (1) female gender, (2) Asian ethnicity, and (3) being unmarried. Asian ethnicity reduced the odds of receiving a 5-star rating for likelihood to recommend the provider by nearly 40%, but none of these nonmodifiable physician personal and demographic characteristics affected the likelihood to recommend the practice. Discussion Sex, ethnicity, and marital status are nonmodifiable provider characteristics, each associated with markedly lower odds of receiving a 5-star rating on Press Ganey patient satisfaction survey. These data reveal inherent patient biases that negatively affect physician-patient interactions and may exacerbate the lack of diversity in orthopaedic surgery. More research is necessary before using patient satisfaction ratings to evaluate surgeons or as quality measures that affect reimbursement policies.

Immune checkpoint inhibitors (ICI) improve the ability of the immune system to target cancer cells by blocking signaling through either the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD-1) receptor, or its ligand (PD-L1). They have been found to cause a variety of immune-related adverse events (irAEs) including a form of nonscarring alopecia that resembles alopecia areata (AA) in presentation and histology. Clinical features of ICI-induced AA are poorly described. We queried the Pubmed database for cases of AA secondary to ICI use reporting on extent of hair loss, treatments attempted, alopecia outcome, and time of follow-up with 13 cases identified. Although most patients had localized hair loss with subsequent regrowth, four of them experienced extensive and persistent AA, lasting up to a year. All but one patient continued ICI after the onset of hair loss. Many used topical corticosteroids with varying outcomes. Possible prognostic factors for severe and persistent disease may include young age and male sex. However, the low number of reported cases limits the generalizability of these findings. Tumor response was positive in every case of immune-induced AA where it was reported. Further investigation will be needed to better characterize clinical features of this irAE, risk factors for persistent disease, and determine its optimal management.

Introduction Young patients present a challenge for total hip arthroplasty (THA) survivorship. Highly cross-linked polyethylene (HXLPE) liners have decreased the prevalence of osteolysis; however, concerns exist regarding the biologic activity of wear particles. The purpose of this study was to determine the incidence and characteristics of osteolytic lesions in young HXLPE THA patients at an average 16-year follow up and determine the ability to detect osteolysis. Methods We performed a retrospective study involving 22 patients (26 THA) under age 50 at primary THA receiving HXLPE liners coupled with cobalt-chrome (CoCr) femoral heads. Computed tomography (CT) scans were reviewed for osteolysis. Chi-squared analysis was used for categorical variables and unpaired Kruskal-Wallis rank-sum test for continuous variables. Logistic regression was used to compare wear rates between those patients with and without osteolysis. Results The mean age at surgery was 38.5 years. The mean time from surgery to CT scan was sixteen years (range 14.25–19.5 years). Nine of the 26 THA showed osteolysis. The mean volume of the lesions was 2.8 cm3. Linear (mean 0.008 mm/y) and volumetric (mean 4.5 mm3/year) wear rates were negligible. One-third of osteolytic lesions were visible on radiographs. Logistic regression failed to demonstrate a correlation between wear rates or UCLA activity score and osteolysis. Conclusion We observed osteolysis in 35% of HXLPE THA in young patients at mean 16-year follow up despite zero revisions for wear-related problems and clinically insignificant wear rates. Level of Evidence IV.