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Abstract Background Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Methods Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. Results At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25–5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48–9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03–8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02–5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23–5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46–9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76–7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07–3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10–4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15–8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Conclusion Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity.

We present unusual coronary-pulmonary collaterals in a 65-year-old CTEPH patient. Perfusion mapping of a dual-energy computed tomography (DECT) study revealed areas of right lung that were minimally perfused despite unilateral occlusion of the right pulmonary artery, leading to the discovery of coronary-pulmonary collaterals via invasive coronary angiography. Pulmonary thromboendarterectomy removed the clot en-bloc. Post-surgery DECT and catheterization confirmed restoration of pulmonary arterial circulation and excellent hemodynamic response. Here, suggestion of perfusion to a proximally obstructed lung with DECT helped to document the presence of rarely documented coronary-pulmonary artery collaterals.

Category: Midfoot/Forefoot; Lesser Toes; Other Introduction/Purpose: Bunionette Deformity is defined as a painful lateral prominence of the fifth metatarsal head. Conservative treatment entails footwear and activity modification. Symptoms can be exacerbated in the athletic population and activities with specific footwear such as cycling, winter sports and water sports. In refractory cases, patients may pursue operative intervention. Historically, open surgical correction carried risks of wound complications, prolonged recovery time, and nonunion risk. Minimally invasive techniques have gained popularity due to the decreased risk of wound complications, preservation of blood supply and healing potential, and faster operative and recovery times. The purpose of the current study is to examine radiographic and clinical outcomes of minimally invasive bunionette correction with a sliding distal 5th metatarsal osteotomy and lateral closing wedge proximal phalanx (Akinette) osteotomy. Methods: A retrospective review examined 36 feet in 28 patients who underwent minimally invasive bunionette correction from 01/2021 to 12/2021. The study patients were treated at a single center by 3 participating providers trained in minimally invasive techniques. All patients underwent a distal 5th metatarsal osteotomy and Akinette osteotomy of the proximal phalanx. Length of follow up ranged from 3 to 12 months. Radigraphic measurements including 4,5 intermetatarsal angle (IMA), 5th metatarsophalangeal angle, and osteotomy displacement (mm) were compared pre and postoperatively. Patients were asked to complete postoperative satisfaction survey and lesser toe American Orthopaedic Foot & Ankle Society (AOFAS) score. Results: Preliminary analysis shows a radiographic 4,5 IMA correction of 4.9 degrees to 3.4 degrees. Fifth metatarsophalangeal angle was corrected from 20.3 degrees preoperatively to 5.3 degrees postoperatively. Average medial displacement of the metatarsal osteotomy was 2.64 mm. There was one nonunion of the 5th metatarsal in a revision case that had previously been treated at an outside facility with open techniques, which was treated with bone grafting. Two other patients underwent revision surgery for complications from concomitant procedures that were performed (1 lapidus nonunion and 1 lapidus wound dehiscence). There were no wound or neurovascular complications involving the 5th ray. Conclusion: Our data shows that minimally invasive bunionette correction with sliding 5th metatarsal and Akinette osteotomy leads to reliable radiographic correction and clinical improvement. This operation has favorable safety profile with low incidence of complications and a high union rate.

ObjectiveInadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH.MethodsTwenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA).ResultsIn patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (ZC =2.31±0.38 vs 1.33±0.15 WU×m2 at rest; p=0.003) and PA compliance was decreased (CPA=0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p

Imaging plays a central role in the diagnosis and management of all forms of pulmonary hypertension (PH). Although Doppler echocardiography is essential for the evaluation of PH, its ability to optimally evaluate the right ventricle and pulmonary vasculature is limited by its 2-dimensional planar capabilities. Magnetic resonance and computed tomography are capable of determining the etiology and pathophysiology of PH, and can be very useful in the management of these patients. Exciting new techniques such as right ventricle tissue characterization with T1 mapping, 4-dimensional flow of the right ventricle and pulmonary arteries, and computed tomography lung perfusion imaging are paving the way for a new era of imaging in PH. These imaging modalities complement echocardiography and invasive hemodynamic testing and may be useful as surrogate endpoints for early phase PH clinical trials. Here we discuss the role of magnetic resonance imaging and computed tomography in the diagnosis and management of PH, including current uses and novel research applications, and we discuss the role of value-based imaging in PH.

Abstract Ibrutinib, a known Burton's tyrosine kinase (BTK) and interleukin‐2 inducible T‐cell kinase (ITK) inhibitor, is used for the treatment of B‐cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation. Because it is considered an immunosuppressant, continuation of ibrutinib is often debated when patients have an active infection, and this becomes an especially difficult decision in the setting of coronavirus disease 2019 (COVID‐19). Here, we describe a patient with CLL who was on ibrutinib then developed severe COVID‐19 infection requiring mechanical ventilation. We elected to continue ibrutinib the same day he was intubated, reasoning that BTK inhibition in myeloid immune cells has been shown to reduce or even reverse influenza‐mediated acute lung injury and that ITK inhibition in T cells has correlated with reduction in viral replication, and therefore may have an advantage in this setting. Ibrutinib also has been shown to block Src family kinases, which potentially could result in reduction of viral entry and the inflammatory cytokine response in the lungs. The patient was extubated after 9 days with a complex hospital course and eventually discharged on room air. The only way to rationally inform these decisions and explore similar potentially promising leads in this pandemic is to conduct carefully done clinical trials.

Abstract Background Patients with polyarticular-course juvenile idiopathic arthritis (pJIA), receiving disease-modifying anti-rheumatic drugs with immunosuppressive effects, may be at increased risk of vaccine-preventable infections. This substudy assessed protective antibody responses to diphtheria and tetanus vaccination given prior to study enrolment in patients with pJIA. Findings This was a substudy of a 24-month, single-arm, open-label, multicenter, Phase III trial (NCT01844518) of subcutaneous abatacept in children with active pJIA (N = 219). Patients aged 2–5 years, with ≥2 continuous months of weekly weight-tiered (10– 0.1 IU/mL), and safety, were assessed. Overall, 29 patients were analyzed: 19 (65.5%), 1 (3.4%) and 9 (31.0%) patients had > 12, 6–12 and 2–

Category: Hindfoot; Sports; Trauma Introduction/Purpose: Surgical treatments for Achilles tendon ruptures (ATR) or insertional Achilles tendinitis (IAT) traditionally have prolonged postoperative recoveries. Patients are typically kept non-weight bearing or protected weight bearing on the operative extremity for weeks after surgery to protect the repairs. The purpose of this study is to show that augmentation of typical Achilles tendon repairs with a synthetic scaffold is safe, allows for early weight bearing while preserving functional outcome and has a high patient satisfaction. Methods: A retrospective chart review was performed on all patients surgically treated for ATR or IAT from 2018 - 2020. The surgeries were performed by two fellowship trained Foot and Ankle Orthopaedic surgeons. All repairs were augmented with a synthetic scaffold made of polycaprolactone-based polyurethane urea (PUUR). Achilles tendon ruptures were direct end-to-end repairs and IAT repairs were performed with double row biocomposite anchors in the calcaneus after a calcaneus exostectomy. Exclusion criteria included flexor hallucis longus transfer, non-insertional achilles tendinosis, patients undergoing additional surgical procedures, and ATR or IAT repairs not treated with PUUR. Patients were evaluated as a cohort as well as acute ruptures, chronic ruptures (defined as more than 6 weeks old), and IAT subgroups. Primary outcomes were date of weight bearing and patient satisfaction. Secondary outcomes were final strength and ankle dorsiflexion. The Wilcoxon signed-rank test (WSR) was used to compare baseline and final follow-up NRS scores. Results: A total of 33 patients met the inclusion criteria with 12 ATR (9 acute and 3 chronic) and 21 IAT. Mean follow-up length was 150 days (43 - 314). Mean weight bearing began on postoperative day (POD) 7.33 (6-13) for acute ruptures, 14.33 (6-19) for chronic ruptures, and 9.9 (5-42) for IAT. Patient satisfaction, based on a binary yes/no response at final followup, was obtained on 27 of 33 patients with 92.6% positive indicating satisfaction with surgical outcome. Final strength averaged 5/5 for 83.9% and 4/5 for 16.1% of all patients. Final active dorsiflexion of at least 10 degrees was obtained in 93.5%. Mean numerical rating scale (NRS) for pain significantly decreased from 5.2 to 0.6 for all patients (WSR p

Objectives:. Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course. Design:. Retrospective cohort study. Setting:. Northwestern Memorial Hospital ICUs. Patients:. All patients intubated for coronavirus disease 2019 between March 2020 and June 2020. Interventions:. Patients were stratified by time to intubation: 30 subjects were intubated 4–24 hours after presentation and 24 subjects were intubated 5–10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Measurements and Main Results:. Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments). Conclusions:. The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation.

Abstract Background The anti–interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years. Methods Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2–17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing

Abstract Background Prednisone (PDN) in juvenile dermatomyositis (JDM), alone or in association with other immunosuppressive drugs, namely methotrexate (MTX) and cyclosporine (CSA), represents the first-line treatment option for new onset JDM patients. No clear evidence based guidelines are actually available to standardize the tapering and discontinuation of glucocorticoids (GC) in JDM. Aim of our study was to provide an evidence-based proposal for GC tapering/discontinuation in new onset juvenile dermatomyositis (JDM), and to identify predictors of clinical remission and GC discontinuation. Methods New onset JDM children were randomized to receive either PDN alone or in combination with methotrexate (MTX) or cyclosporine (CSA). In order to derive steroid tapering indications, PRINTO/ACR/EULAR JDM core set measures (CSM) and their median absolute and relative percent changes over time were compared in 3 groups. Group 1 included those in clinical remission who discontinued PDN, with no major therapeutic changes (MTC) (reference group) and was compared with those who did not achieve clinical remission, without or with MTC (Group 2 and 3, respectively). A logistic regression model identified predictors of clinical remission with PDN discontinuation. Results Based on the median change in the CSM of 30/139 children in Group 1, after 3 pulses of methyl-prednisolone, GC could be tapered from 2 to 1 mg/kg/day in the first two months from onset if any of the CSM decreased by 50–94%, and from 1 to 0.2 mg/kg/day in the following 4 months if any CSM further decreased by 8–68%, followed by discontinuation in the ensuing 18 months. The achievement of PRINTO JDM 50–70-90 response after 2 months of treatment (ORs range 4.5–6.9), an age at onset > 9 years (OR 4.6) and the combination therapy PDN + MTX (OR 3.6) increase the probability of achieving clinical remission (p

Immunologic risk factors contribute to endothelial dysfunction and development of pulmonary vascular disease. Immune checkpoint inhibitors, used as immunotherapies for malignancies, have a wide range of reported immune-related adverse events. We retrospectively describe the impact of immune checkpoint inhibitors on the development of pulmonary vascular injury and right ventricular dysfunction as compared across both computed tomography and transthoracic echocardiography. Twenty-four of 389 patients treated with immune checkpoint inhibitors at a single academic center between 2015 and 2019 were evaluated. Thirteen (54%) patients were treated with anti-programmed cell death receptor 1 (PD-1), 8 (33%) with anti-programmed death receptor ligand 1 (PD-L1) therapy, and 3 (13%) with combination anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. At a median of 85 days of immune checkpoint inhibitor therapy, RVfwLS significantly increased from –20.6% to –16.7% ( p = 0.002). After a median of 59 days of immune checkpoint inhibitor therapy, median pulmonary artery to aorta ratio worsened from 0.83 to 0.89 ( p = 0.03). There was an correlation of duration of immune checkpoint inhibitor therapy (β = –0.574, p = 0.003) with percent change in RVfwLS. Patients who received anti-PD-1 therapy (β = –0.796, p = 0.001) showed the greatest correlation of duration of immune checkpoint inhibitor therapy with percent change in RVfwLS. Exposure to immune checkpoint inhibitors are associated with RV dysfunction and vascular changes as measured by strain and computed tomography, respectively.

Through bound apolipoprotein A-I (apoA-I), high-density lipoprotein cholesterol (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation. Because patients with sickle cell disease (SCD) have low apoA-I and endothelial dysfunction, we conducted a randomized, double-blinded, placebo-controlled trial to test whether extended-release niacin (niacin-ER) increases apoA-I-containing HDL-C and improves vascular function in SCD. Twenty-seven patients with SCD with levels of HDL-C

Category: Lesser Toes; Midfoot/Forefoot Introduction/Purpose: The Jones fracture of the proximal fifth metatarsal metadiaphysis is predisposed to delayed union and nonunion due to a tenuous blood supply. Surgical fixation followed by delayed weightbearing is commonly recommended, though the optimal period of nonweightbearing after surgery is not well defined. In response to more recent literature and in an effort to facilitate functional recovery, the trend in our practice has begun to shift toward earlier weightbearing for all patients after Jones fracture fixation. The purpose of this study is to investigate the effect of earlier weightbearing after surgical fixation of Jones fractures. Methods: All Jones fractures treated with an intramedullary (IM) screw in a large, urban practice from 2012-2018 were identified. We excluded fractures that were chronic in nature and patients with underlying metabolic disease. We defined a delayed union as longer than 12.5 weeks based on published data. Time to weightbearing and early weightbearing (within 1 week of surgery) were investigated as risk factors for delayed union using logistic regression and Fisher exact tests, respectively. The relationship between time to weightbearing and time to union was assessed with Spearman correlation. Additional variables were explored in bivariate analysis: time to surgery from initial presentation; age, sex, chronicity, tobacco use, weight, BMI, screw size; preoperative NSAID use, and postoperative VTE prophylaxis. Multivariate regression analyses were then performed to identify variables independently predictive of delayed union. Results: Forty-one cases were included (17 males, 24 females), all treated with IM fixation. Median age in the sample was 45 years ( IQR, 32-62 years). Overall mean time to union was 10.9 +- 7.0 weeks (range, 4.9-41.4 weeks). There were nine (22.0%) delayed unions. Earlier weightbearing was not significantly predictive of delayed union (OR 1.02; 95% CI, 0.99-1.05; P = 0.211), and the incidence of nonunion was not significantly different between early and delayed weightbearing groups (OR, 1.20; 95% CI, 0.02- 17.54; P > .999). In bivariate analysis, increasing age was associated with increasing risk of delayed union (OR, 1.06; 95% CI, 1.01- 1.12; P = 0.031), and was correlated with time to union (ρ = 0.327, P = 0.037). Mutivariate analaysis demonstarted no significant variables. Conclusion: Our results suggest that earlier weightbearing after internal fixation of Jones fractures is not a risk factor for delayed union and does not significantly alter healing time. These findings are consistent with previously published data, but go further by assessing the effects of time to weightbearing in continuous regression models.

Category: Basic Sciences/Biologics; Ankle; Hindfoot; Midfoot/Forefoot; Sports Introduction/Purpose: Artelon is a synthetic degradable polyurethaneurea graft which has been investigated and utilized for soft tissue reconstruction in a variety of orthopaedic settings. However, in the field of foot and ankle surgery, there is very limited reported clinical data on outcomes of surgery utilizing Artelon. The goal of this study was look at outcomes of foot and ankle surgery in which Artelon is used, including post-op VAS scores and complications including adverse foreign body reaction, infection, repeat surgery, and implant failure. Our hypothesis was that soft tissue reconstruction procedures utilizing artelon will have a low complication rate, similar to established complication rates for other soft tissue reconstruction procedures such as those utilizing allograft, autograft, or other synthetic tissue. Methods: The treating surgeon’s first 55 consecutive patients 18 years and older who were treated with artelon graft as part of a foot and ankle surgery are being included in this IRB-approved study. Through retrospective chart review, outcome measures including the procedure for which artelon was utilized, pre and post-op Visual Analogue Scale (VAS) scores, and complications including repeat surgery for graft failure, foreign body reaction, wound healing issues, infection, and osteolysis were assessed. Statistical analysis was done utilizing Student’s t-test for continuous variables and chi square test for categorical variables. Results: Average follow-up time was 246.5 days. The majority of patients had artelon placed for spring ligament reconstruction, brostrom procedures, or achilles tendon reconstruction. VAS scores dropped significantly from before surgery to 3 weeks post- operatively (5.6 to 3.2, p

Pulmonary embolism is associated with high rates of mortality and morbidity. It is important to understand direct comparisons of current interventions to differentiate favorable outcomes and complications. The objective of this study was to compare ultrasound-accelerated thrombolysis versus systemic thrombolysis versus anticoagulation alone and their effect on left ventricular outflow tract velocity time integral. This was a retrospective cohort study of subjects ≥18 years of age with a diagnosis of submassive or massive pulmonary embolism. The primary outcome was the percent change in left ventricular outflow tract velocity time integral between pre- and post-treatment echocardiograms. Ultrasound-accelerated thrombolysis compared to anticoagulation had a greater improvement in left ventricular outflow tract velocity time integral, measured by percent change. No significant change was noted between the ultrasound-accelerated thrombolysis and systemic thrombolysis nor systemic thrombolysis and anticoagulation groups. Pulmonary artery systolic pressure only showed a significant reduction in the ultrasound-accelerated thrombolysis versus anticoagulation group. The percent change of right ventricular to left ventricular ratios was improved when systemic thrombolysis was compared to both ultrasound-accelerated thrombolysis and anticoagulation. In this retrospective study of submassive or massive pulmonary embolisms, left ventricular outflow tract velocity time integral demonstrated greater improvement in patients treated with ultrasound-accelerated thrombolysis as compared to anticoagulation alone, a finding not seen with systemic thrombolysis. While this improvement in left ventricular outflow tract velocity time integral parallels the trend seen in mortality outcomes across the three groups, it only correlates with changes seen in pulmonary artery systolic pressure, not in other markers of echocardiographic right ventricular dysfunction (tricuspid annular plane systolic excursion and right ventricular to left ventricular ratios). Changes in left ventricular outflow tract velocity time integral, rather than echocardiographic markers of right ventricular dysfunction, may be considered a more useful prognostic marker of both dysfunction and improvement after reperfusion therapy.

Background Although historical trends before 1998 demonstrated improvements in mortality caused by pulmonary embolism (PE), contemporary estimates of mortality trends are unknown. Therefore, our objective is to describe trends in death rates caused by PE in the United States, overall and by sex‐race, regional, and age subgroups. Methods and Results We used nationwide death certificate data from Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research to calculate age‐adjusted mortality rates for PE as underlying cause of death from 1999 to 2018. We used the Joinpoint regression program to examine statistical trends and average annual percent change. Trends in PE mortality rates reversed after an inflection point in 2008, with an average annual percent change before 2008 of −4.4% (−5.7, −3.0, P65 years). Conclusions Our study findings demonstrate that PE mortality has increased over the past decade and racial and geographic disparities persist. Identifying the underlying drivers of these changing mortality trends and persistently observed disparities is necessary to mitigate the burden of PE‐related mortality, particularly premature preventable PE deaths among younger adults (

Michael J Cuttica,1 Surya P Bhatt,2 Sharon R Rosenberg,1 Lauren Beussink,3 Sanjiv J Shah,3 Lewis J Smith,1 Mark T Dransfield,2 Ravi Kalhan1 1Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 2Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama-Birmingham, Birmingham, AL, 3Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Background: The ratio of the diameter of the pulmonary artery (PA) to the diameter of the aorta (PA:A) on computed tomography (CT) imaging is associated with both COPD exacerbation and pulmonary hypertension. The mechanisms of PA enlargement in COPD are poorly understood. Methods: In this retrospective, single center study we evaluated pulmonary function, CT scans, right heart catheterizations, and echocardiography in 88 subjects with mild-to-moderately severe COPD. A sensitivity analysis was performed in 43 subjects in whom CT scan and echocardiogram were performed within 50 days of each other. To evaluate the association between PA:A ratio and echocardiographic parameters and hemodynamics, we performed simple correlations and multivariable linear regression analysis adjusting for lung function, age, sex, race, and diastolic function. Results: All subjects had preserved left ventricular (LV) systolic function (LV ejection fraction 62.7%±5.5%). Among them, 56.8% had evidence of diastolic dysfunction. There was no association between PA:A ratio and the presence of diastolic dysfunction. In a multivariable model, PA:A ratio was associated with right ventricular (RV) chamber size (β=0.015; P

Category: Ankle Arthritis Introduction/Purpose: Wound complications after total ankle replacement (TAR) lead to increased postoperative morbidity with lasting consequences. Previous studies demonstrate delayed wound healing in 6.6% to 28% of all TARs. Soft tissue breakdown along the anterior incision can cause exposure of anterior tendons and the implants. In addition, adhesions of the extensor tendons can develop causing significant morbidity. Recent publications advocate for the use of dehydrated human amnion/chorion membrane allograft (dHACM) during closure of anterior ankle incisions during TAR. dHACM is shown to promote increased epithelial cell proliferation, recruitment, and differentiation and reduce the likelihood of tendon adhesions. The goal of this study was to review the use of dHACMs in TARs and to investigate the number and type of postoperative wound complications including extensor tendon adhesions. Methods: We retrospectively reviewed 92 TARs performed between April, 2016 through August, 2018 by two board certified, fellowship trained foot and ankle orthopaedic surgeons. A standard anterior approach was done in all cases. All TARs had dHACM graft placed deep to the tibialis anterior and extensor longus tendon and along the extensor retinaculum prior to final closure of the wound. Upon data review, we identified the subset of patients who had anterior wound dehiscence postoperatively requiring an additional procedure(s) for wound coverage. We compared the demographics, medical comorbidities, and operative characteristics of those with and without perioperative wound complications. Results: 12 patients who underwent TARs sustained wound dehiscence below the subcutaneous tissue and required operative intervention (13%). Of these 12 cases, 5 required bipedical or rotational fasciocutaneous flap coverage (5.4%), 6 required less extensive soft tissue surgery (6.5%) and one case involved a deep periprosthetic infection that resulted in explant and antibiotic spacer placement (1.1%). 6 of the 12 cases required a split thickness skin graft application (6.5%) and 2 cases required tenolysis of extensor tendon adhesions (2.2%). Normal excursion of extensor tendons was seen in 90 patients (97.8%). Except for the one infected ankle, there were no cases with wound dehiscence that communicated with the joint. There were no statistically significant differences in medical comorbidities/operative characteristics between patients with wound complications and those without. Conclusion: Wound complications after total ankle replacements often lead to poor long-term outcomes for patients. Our data suggests that the application of the amniotic membrane allograft and its inherent healing potential decreases postoperative tendon adhesions and significant wound dehiscence. This may lead to less deep wound infections that communicate with the joint and may be protective against total ankle replacement failures due to these complications.

Category: Bunion Introduction/Purpose: Proximal metatarsal osteotomies are commonly employed to treat moderate to severe hallux valgus deformities. An understudied area with respect to these procedures is the effect on articular contact properties following the surgeries. Potential long-term risks include altered joint mechanics and possible arthritic progression. A biomechanical comparison of articular characteristics of the proximal opening wedge and Ludloff osteotomies was performed in this study. It is hypothesized that the proximal opening wedge osteotomy (POWO) would lead to greater alterations in articular contact properties along the first ray. Methods: Seven paired fresh-frozen below-knee cadaveric limbs with hallux valgus deformity were selected. The first ray inclusive of the navicular-medial cuneiform articulation was dissected and potted in resin. Specimens in each pair were tested in the intact state and then randomized to receive either a Ludloff or POWO. A 4 mm opening wedge osteotomy was used in all cases. The FHL was dissected and isolated. Testing was conducted in a customized apparatus with the cuneiform pinned to the apparatus and positioned at 10 degrees of declination. Loading of the FHL was conducted to 100 N utilizing an instrumented tensioner. A 28 N load was added at the distal phalanx to simulate the ground reaction force(Fig.1). First MTP and TMT articular properties were recorded simultaneously using two pressure sensors. For each state, a pressure map was generated and contact area, peak pressure and center of pressure were calculated. Results: Average peak pressure was noted to be elevated at the MTP (4.6 mPa vs 6.9 mPa, P = 0.08) and TMT (3.3 mPa vs 5.1 mPa, P = 0.16) joints when comparing the Ludloff and the POWO respectively, but was not significant. Contact area was also noted to be lower in the POWO vs Ludloff states for the MTP (86. 6mm2 vs 69.1mm2, P = 0.15) but not the TMT joints (89.1 mm2 vs 88.5mm2, P = 0.96). A trend towards decreased contact force within the TMT joint was noted following opening wedge osteotomy relative to the intact state (103.8 N vs 113.9 N, P = 0.31), while forces were elevated at the MTP joint (104.3 N vs. 96.0 N, P = 0.63), although not statistically significant. Conclusion: POWO can potentially change articular contact characteristics along the TMT and MTP articulations of the first ray. This could possibly lead to altered loading patterns and possible long-term arthritic progression versus other osteotomies. However, it is unlikely that the changes observed with the sizes of the osteotomy commonly used would lead to long term significant consequences.

Background: An understudied area of proximal first metatarsal osteotomies is the effect on articular contact properties following the surgeries. Potential long-term risks include altered joint mechanics and possible arthritic progression. A biomechanical comparison of articular characteristics of the proximal opening wedge and Ludloff osteotomies was performed in this study. It was hypothesized that the proximal opening wedge osteotomy (POWO) would lead to greater alterations in articular contact properties along the first ray. Methods: Seven paired fresh-frozen below-knee cadaveric limbs with hallux valgus were selected. Specimens in each pair were tested in the intact state and then randomized to receive either a Ludloff or POWO. A 4-mm opening wedge osteotomy was used in all cases. Loading of the flexor hallucis longus was to 100 N using an instrumented tensioner. A 28-N load was added at the distal phalanx to simulate the ground reaction force. First metatarsophalangeal (MTP) and tarsometatarsal (TMT) articular properties were recorded simultaneously using 2 pressure sensors. For each state, a pressure map was generated and contact area, peak pressure, and center of pressure were calculated. Wilcoxon signed-rank test was used to assess statistical significance. Results: Average peak pressure was noted to be elevated at the MTP (4.6 vs 6.9 mPa, P = .04) and TMT (3.3 mPa vs 5.1 mPa, P = .30) joints when comparing the Ludloff and the POWO, respectively. Contact area was also noted to be lower in the POWO relative to the Ludloff for the MTP (86.6 vs 69.1 mm 2 , P = .30) but not the TMT joints (89.1 vs 88.5 mm 2 , P = .97). There was a slight plantar-lateral and dorsomedial shift in pressure at the MTP and TMT articulations, respectively, of the POWO relative to the Ludloff. A trend toward decreased contact force within the TMT joint was noted following opening wedge osteotomy relative to the intact state (103.8 vs 113.9 N, P = .31), while forces were elevated at the MTP joint (104.3 vs 96.0 N, P = .63), although not statistically significant. Smaller increases in TMT and MTP joint forces were noted following the Ludloff when compared to the intact state (95.6 vs 93.3 N at TMT and 109.2 vs 103.2 N at MTP). Conclusion: POWO can potentially change articular contact characteristics along the TMT and MTP articulations of the first ray. This could possibly lead to altered loading patterns and possible long-term damage vs other osteotomies. Clinical Relevance: While it is unlikely that the changes observed with the sizes of the osteotomy commonly used would lead to long-term significant clinical consequences, further study with larger group sizes would be beneficial.

Pseudohypoparathyroidism type 1A (PHP1A) is usually diagnosed in childhood or early adulthood. We describe the case of a 64-year-old woman admitted to the Neurological Unit for recurrent episodes of loss of consciousness and seizures. Glycemia and ECG were normal, while hypocalcemia was noted. Clinical history revealed carpo-pedal spasm since the age of 30 years, cognitive impairment, hypothyroidism since early adulthood, and menopause at 30 years. She was taking oral calcium and cholecalciferol for chronic hypocalcemia. Physical features suggested Albright’s osteodystrophy. Blood calcium was confirmed low, with increased parathyroid hormone, moderate 25OH-vitamin D deficiency, and normal creatinine. Brain CT scan revealed calcifications of the basal ganglia, cortical and subcortical white matter, and cerebellum. Therapy was switched to oral calcitriol, with normalization of calcium levels; levetiracetam was started and no further seizures occurred. The clinical diagnosis of PHP1A was confirmed by molecular analysis, which demonstrated the heterozygous c.568_571del mutation of the GNAS gene. Our report illustrates the natural history of a patient with PHP1A, which went undiagnosed until the age of 64 years, with multi-hormonal resistance and clinical sequelae evolving throughout life, and underlines the importance of diagnosing this rare disease, which has a great impact on patients and their family life.

Background Diminished peak lung function in young adulthood is a risk factor for future chronic obstructive pulmonary disease. The association between lung disease and cardiovascular disease later in life is well documented. Whether peak lung function measured in young adulthood is associated with risk of future cardiovascular events is unknown. Methods and Results CARDIA (The Coronary Artery Risk Development in Young Adults) study is a prospective, multicenter, community‐based, longitudinal cohort study including 4761 participants aged 18 to 30 years with lung function testing we investigated the association between lung health in young adulthood and risk of subsequent cardiovascular events. We performed Cox proportional hazards regression to test the association between baseline and years 10 and 20 pulmonary function with incident cardiovascular events. Linear and logistic regression was performed to explore the associations of lung function with development of risk factors for cardiovascular disease as well as carotid intima‐media thickness and coronary artery calcified plaque. At baseline, mean age (±SD) was 24.9±3.6 years. Baseline forced expiratory volume in 1 second (hazard ratio) per −10‐unit decrement in percent predicted forced expiratory volume in 1 second (hazard ratio, 1.18; 95% CI, 1.06–1.31 [P=0.002]) and FVC per −10‐unit decrement in percent predicted FVC (hazard ratio, 1.19; 95% CI, 1.06–1.33 [P=0.003]) were associated with future cardiovascular events independent of traditional cardiovascular risk factors. Baseline lung function was associated with heart failure and cerebrovascular events but not coronary artery disease events. Conclusions Lung function in young adulthood is independently associated with cardiovascular events into middle age. This association appears to be driven by heart failure and cerebrovascular events rather than coronary heart disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005130.

Category: Sports Introduction/Purpose: Ruptures of the anterior tibial tendon are rare injuries usually occurring in patients over the age of 40. Delayed diagnosis is common and reconstruction often involves the use of autograft or allografts. This paper reports on the use of a polycaprolactone-based polyurethane urea (PUUR) hyperelastic polymer (Artelon) in the repair or reconstruction of anterior tibial tendon ruptures. Methods: Artelon® is a knitted textile matrix that is manufactured from fibers of polycaprolactone-based polyurethane urea (PUUR), a hyperelastic and creep-resistant polymer. Previous studies have demonstrated that Artelon integrates without immune reaction, has mechanical properties that resemble healing tendons and ligaments, and degrades benignly through hydrolysis over a 5-6 year span. This is a retrospective examination of the first 6 cases of anterior tibial tendon reconstruction using the Artelon PUUR graft. Patient outcomes are measured with AOFAS scores. In addition, range of motion and strength of the injured side is compared to the native, uninjured side. Results: There were no complications using the Artelon graft to augment anterior tibial tendon reconstruction and repair. Patient outcomes at 6 months were significantly improved compared to preoperative. Range of motion and strength were similar to the contralateral, uninjured side. Conclusion: Artelon is a safe, effective soft tissue augmentation device that can be used in the setting of anterior tibial tendon repaair or reconstruction.