Search

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

Background: Augmentation of soft tissue repairs has been helpful in protecting surgically repaired tissues as they heal. FlexBand (Artelon, Marietta, Georgia) is a synthetic, degradable, polycaprolactone-based polyurethane urea (PUUR) matrix that has been investigated and used for soft tissue repair in a variety of settings. The purpose of this study was to evaluate the safety profile of a PUUR matrix in a large cohort of patients undergoing soft tissue repairs about the foot and ankle. Methods: A retrospective chart review of consecutive patients who underwent surgery using FlexBand to augment a soft tissue repair was performed to evaluate for major and minor complications related to the PUUR matrix. Results. A total of 105 patients with an average >6 months follow-up were included. The most common procedures were spring ligament repair, Achilles tendon repair, and Brostrom. There were 12 complications. Four major complications occurred with only 1 requiring PUUR matrix removal. Patients with wound complications had a higher body mass index (BMI) and rate of smoking. Conclusion: Complication rates involving PUUR matrix in soft tissue foot and ankle reconstruction procedures are low and comparable with historical complication rates. The PUUR matrix is safe for use in a variety of soft tissue procedures about the foot and ankle. Level of Evidence: Level 4, Retrospective case-series [ABSTRACT FROM AUTHOR]

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