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BACKGROUND Pulmonary thromboendarterectomy (PTE) is a curative procedure for chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricular free wall strain (RV FWS) and right atrial strain (RAS) are not well studied in a CTEPH population. We sought to determine temporal trends in RAS and RV FWS in patients post-PTE. METHODS 28 patients undergoing PTE for CTEPH were prospectively enrolled in a surgical database. Comprehensive echocardiographic assessment of the right heart was performed including RV FWS, right atrial volume, and the three components of RAS: reservoir, conduit, and booster strain. RESULTS Patients undergoing PTE demonstrated improvement in NYHA functional class (P

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

Objective To report the 2‐year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular‐course juvenile idiopathic arthritis (JIA). Methods Patients ages 2–17 years with active polyarticular‐course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open‐label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] 1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open‐label TCZ. At week 104 of the study, efficacy was assessed using JIA‐ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS‐71). Safety was assessed in the all‐exposure population per 100 patient‐years of exposure. Results Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent‐to‐treat group who received TCZ, JIA‐ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS‐71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient‐years and 11.1 per 100 patient‐years, respectively. The infection rate was 151.4 per 100 patient‐years, and the serious infection rate was 5.2 per 100 patient‐years. Conclusion Patients treated with TCZ for polyarticular‐course JIA showed high‐level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.

Made available in DSpace on 2022-04-28T17:22:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Janssen Research & Development, LLC Objectives. To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods. Children aged 2 to = 2months received 80 mg/m(2) golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUC(ss)) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results. In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUC(ss) were 0.40 mu g/ml and 399 mu g. day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUC(ss) were consistent across age categories and comparable to i.v. golimumab dosed 2mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion. Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. IRCCS Ist Giannina Gaslini Clin Pediat & Reumatol, PRINTO, Genoa, Italy Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA Univ Autonoma Chihuahua, Fac Med, Circuito Univ Campus 2, Chihuahua, Mexico Panorama Med Ctr, Cape Town, South Africa Hosp Mexico Americano, Ctr Reumatol & Autoinmunidad CREA, Guadalajara, Jalisco, Mexico Ctr Med Privado Reumatol, Rheumatol Sect, San Miguel De Tucuman, Tucuman, Argentina Randall Childrens Hosp Legacy Emanuel, Portland, OR USA Univ Calgary, Alberta Childrens Hosp, Cumming Sch Med, Dept Pediat, Calgary, AB, Canada Pontificia Univ Catolica Chile, Sch Med, Dept Pediat Infect Dis & Immunol, Santiago, Chile Hosp Pedro de Elizalde, Rheumatol Sect, Buenos Aires, DF, Argentina Univ Utah, Pediat Rheumatol, Salt Lake City, UT USA Bashkir State Med Univ Minist Healthcare Russian, Fed State Budget Educ Inst Higher Educ, Ufa, Russia Univ Cape Town, Red Cross War Mem Childrens Hosp, Cape Town, South Africa Univ Cape Town, Groote Schuur Hosp, Paediat Rheumatol, Cape Town, South Africa Clin Hosp 5, Pediat Dept, Tolyatti, Russia Univ Fed Sao Paulo, Escola Paulista Med, Pediat, Sao Paulo, Brazil Inst CAICI, Rheumatol, Rosario, Argentina Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil UNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, Brazil Hosp Infantil Mexico Dr Federico Gomez, Med Interna & Reumatol, Mexico City, DF, Mexico Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA Janssen Res & Dev LLC, Spring House, PA USA Janssen Res & Dev LLC, Raritan, NJ USA Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, Genoa, Italy UNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, Brazil

Ibrutinib ist ein bekannter Inhibitor der Bruton-Tyrosinkinase (BTK) und der Interleukin-2-induzierbaren T-Zell-Kinase (ITK), der zur Behandlung von B-Zell-Erkrankungen (chronische lymphatische Leukämie [CLL] und verschiedene andere Lymphome) und der chronischen Graft-versus-Host-Erkrankung nach allogener Transplantation von hämatopoetischen Zellen eingesetzt wird. Da es als immunsuppressiv gilt, stellt sich bei Patienten mit einer aktiven Infektion häufig die Frage nach einer Fortführung der Ibrutinib-Therapie, und im Zusammenhang mit der Coronavirus-Erkrankung 2019 (COVID-19) ist diese Entscheidung besonders schwierig. In der vorliegenden Arbeit beschreiben wir einen Patienten mit CLL, der mit Ibrutinib behandelt wurde und im weiteren Verlauf eine schwere COVID-19-Infektion entwickelte, die eine mechanische Beatmung erforderlich machte. Wir beschlossen, die Gabe von Ibrutinib noch am Tag der Intubation fortzusetzen, mit der Argumentation, dass die BTK-Inhibition in myeloischen Immunzellen nachgewiesenermaßen die influenza-vermittelte akute Lungenschädigung verringert oder sogar umkehrt und dass die ITK-Inhibition in T-Zellen mit einer Reduzierung der Virusreplikation korreliert und daher in diesem Setting von Nutzen sein könnte. Darüber hinaus hat sich gezeigt, dass Ibrutinib auch Kinasen der Src-Familie blockiert, was möglicherweise ein verringertes Eindringen der Viren zur Folge hat und zu einer verminderten inflammatorischen Zytokinreaktion in der Lunge führt. Der Patient wurde nach 9 Tagen und einem komplizierten stationären Verlauf extubiert und schließlich unter Raumluftatmung entlassen. Die einzige Möglichkeit, solche Entscheidungen rational zu untermauern und ähnliche potenziell vielversprechende Hinweise in dieser Pandemie zu untersuchen, sind sorgfältig durchgeführte klinische Studien.

Objectives To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). Methods In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or Results Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. Conclusion s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

OBJECTIVE: To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood-onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant improvement (CRIc SLE ). METHODS: Pediatric nephrology and rheumatology subspecialists (n = 213) experienced in cSLE management were invited to define CRIc SLE and rate a total of 433 unique patient profiles for the presence/absence of CRIc SLE . Patient profiles included the following cSLE core response variables (CRVs): global assessment of patient well-being (patient-global), physician assessment of cSLE activity (MD-global), disease activity index score (here, we used the Systemic Lupus Erythematosus Disease Activity Index), urine protein-to-creatinine ratio, and Child Health Questionnaire physical summary score. Percentage and absolute changes in these cSLE- CRVs (baseline versus follow-up) were considered in order to develop candidate algorithms and validate their performance (sensitivity, specificity, area under the receiver operating characteristic curve [AUC] ; range 0-1). RESULTS: During an international consensus conference, unanimous agreement on a definition of CRIc SLE was achieved ; cSLE experts (n = 13) concurred (100%) that the preferred CHILI algorithm considers absolute changes in the cSLE- CRVs. After transformation to a range of 0-100, a CHILI score of ≥54 had outstanding accuracy for identifying CRIc SLE (AUC 0.93, sensitivity 81.1%, and specificity 84.2%). CHILI scores also reflect minor, moderate, and major improvement for values exceeding 15, 68, and 92, respectively (all AUC ≥0.92, sensitivity ≥93.1%, and specificity ≥73.4%). CONCLUSION: The CHILI is a new, seemingly highly accurate index for measuring CRI in cSLE over time. This index is useful to categorize the degree of response to therapy in children and adolescents with cSLE.

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.

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– Conclusions Patients aged 2–5 years with pJIA who received 2–24 months of weekly subcutaneous abatacept, with or without concomitant methotrexate and/or low-dose corticosteroids, maintained effective diphtheria and tetanus vaccination protection without new safety signals. Trial registration ClinicalTrials.gov (NCT01844518); registered May 1, 2013; https://clinicaltrials.gov/ct2/show/NCT01844518?term=NCT01844518&rank=1

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.

Objective: To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods: In this phase III, open-label, international, multicenter, single-arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease-modifying antirheumatic drug was unsuccessful received weight-tiered SC abatacept weekly: 10 to

The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.

Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes. Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study. Methods: Epicardial (myocardium and chamber) RV volume (RV(EV)), distal pulmonary arterial blood vessel volume (arterial BV5: vessels

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.

Rationale: D-dimer is primarily used in the diagnosis of venous thromboembolic (VTE) disease. Recently the Ddimer test has been used as a marker of inflammation in COVID-19 pneumonia and has been shown to correlate with worse outcomes. An understanding of trajectories and relation to clot burden and outcomes of this novel use of serial measurements of D-dimer in COVID-19 ICU patients remains to be explored. Methods: We reviewed patients who were admitted to the Northwestern Hospital COVID ICUs from 3/1/20 to 7/31/20. We obtained demographics, d-dimer lab values, venous duplex studies from upper and lower extremities (UE/LE dopplers), CT-angiogram (CTA) reports, and mortality outcomes from our electronic medical record database. Reports were processed using string analysis with manual physician validation. Analysis was done in R with nonparametric numeric variables being compared by two-tailed Mann Whitney tests. Results: We had 370 patients in our cohort, with median (interquartile range (IQR)) age being 60 (49-69), 229/370 (62%) male, 128 (35%) of Hispanic ethnicity, 117 (32%) of African-American ethnicity, and 135 (36%) of Caucasian descent. 70 patients died (19%). The total number of VTE imaging tests included: 87 CTAs, 102 UE dopplers, and 232 LE dopplers. Clot was discovered in 43/102 (42%) UE dopplers, 62/232 (27%) of LE dopplers, and 25/87 (29%) of CTAs. Patients underwent a median of 2 (1-3) imaging studies, and 10 (4-20) d-dimer measurements. 79 unique patients (21%) had VTE detected. There was no statistically significant difference in age between the clot vs noclot groups: 57(45-68) vs 61(49-59) years, p=0.34, or BMI: 30.5(25.6-34.8) in clot vs 29(25.4-34.5) kg/m2 in no-clot group (p=0.55). Mortality was significantly higher at 36% in the clot group vs 15% in the group without clot (p

Introduction: As the management of COVID-19 has continued to evolve, the question as to whether delaying intubation is beneficial or harmful for patients with COVID-19 induced hypoxic respiratory failure has yet to be answered. Early reports suggested that patients may benefit from early intubation during a period of severe hypoxia;later management shifted towards delaying intubation as much as possible using non-invasive ventilation. Additionally, the pathophysiologic implications of timing of intubation are poorly understood, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis. This study examines the differences in outcomes and respiratory mechanics between subjects who are intubated earlier versus later in their COVID-19 disease course. Study Design and Methods: Retrospective single-center cohort study of subjects intubated for COVID-19 ARDS between March and June 2020. 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. Data regarding baseline characteristics, hospitalization, ventilator mechanics and outcomes were extracted and analyzed. 10 clinically available CT scans for these patients were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. 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 days vs 11.8 days;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 ventilator mechanics at the time of intubation. However, 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 segments with dilated and tortuous peripheral vessels on imaging (2 segments vs 5 segments). Interpretation: As our approaches to treatment of COVID-19 continue to evolve, the decision of timing of intubation remains paramount. While non-invasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered.

Rationale: The frequency of superinfection with Aspergillus among patients with severe COVID-19-related respiratory failure is unknown. The association of bronchoalveolar lavage (BAL) fluid markers, such as galactomannan, with the presence of Aspergillus infections is also unclear. Methods: Our cohort included all patients with COVID-19 admitted to the Northwestern Memorial Hospital ICU from March to November 2020 who were intubated and underwent a BAL;patients were identified as having COVID-19 by the presence of a flag in the electronic medical record. We evaluated BAL fluid data for fungal organisms and markers. Data analysis was performed in Excel and Prism, with non-parametric values compared by two-tailed Mann Whitney tests. Results: We identified 274 patients meeting study entry criteria. The median (interquartile range) age was 62 years (47-69), and 93 (34%) were female. 714 BALs were performed on these patients, and 457 galactomannan tests were sent from these BALs. Only six (2.2%) patients grew Aspergillus on BAL fluid culture;one patient never grew Aspergillus but given his significantly elevated BAL galactomannan of 7.81, was empirically treated. The median (IQR) optical density index of galactomannan for the BAL samples that grew Aspergillus was 6.69 (3.37-8.87) compared with 0.08 (0.06-0.13) for those that did not, p 0.5 as positive, with patients who grew Aspergillus on culture as gold standard, the test sensitivity was 91.7% and specificity was 94.6%;using the ATS recommended cutoff of >1.0 as positive, the sensitivity was 75.0% and specificity was 97.5%. The median (IQR) age of patients who grew Aspergillus was 71.5 years (64-80.5) (p=0.02 compared with the overall cohort). Only two were immunocompromised (diffuse large B-cell lymphoma and another was status post liver transplant). Of note, two patients who grew Aspergillus had visible mold or plaque seen during bronchoscopy;three had cavitary findings on imaging;three died. Conclusions: Aspergillus superinfection is uncommon among ventilated patients with COVID-19 but can occur in patients without typical immunocompromising risk factors. BAL fluid galactomannan levels are lower in patients without Aspergillus, and had reasonable specificity especially if cutoff of >1.0 was used. Future analysis should focus on additional factors that differentiate between these two groups.

BackgroundSARS-CoV-2 can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2 at our tertiary-care, urban teaching hospital.MethodsWe reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and ICU and hospital lengths-of-stay (LOS) in SARS-CoV-2 patients who received tracheostomies. Early tracheostomy was considered ResultsFrom March 2020 to January 2021, our center had 370 patients intubated for SARS-CoV-2, and 59 (16%) had percutaneous bedside tracheostomy. Median time from intubation to tracheostomy was 19 (IQR 17 – 24) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter ICU LOS and a trend towards shorter ventilation. To date, 34 (58%) of patients have been decannulated, 17 (29%) before hospital discharge; median time to decannulation was 24 (IQR 19-38) days. Decannulated patients were younger (56 vs 69 years), and in regression analysis, pneumothorax was associated was associated with lower decannulation rates (OR 0.05, 95CI 0.01 – 0.37). No providers developed symptoms or tested positive for SARS-CoV-2.ConclusionsTracheostomy is a safe and reasonable procedure for patients with prolonged SARS-CoV-2 respiratory failure. We feel that tracheostomy enhances care for SARS-CoV-2 since early tracheostomy appears associated with shorter duration of critical care, and decannulation rates appear high for survivors.

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.

BackgroundSevere community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations.MethodsWe obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care.ResultsThe 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days.ConclusionsWith use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

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, P P 65 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 (

Background: Jones fractures of the proximal fifth metatarsal are predisposed to delayed union and nonunion due to a tenuous blood supply. Solid intramedullary (IM) screw fixation is recommended to improve healing, traditionally followed by delayed weightbearing (DWB). However, early weightbearing (EWB) postoperatively may facilitate functional recovery. The purpose of this study was to compare union rates and time to union after solid IM screw fixation of Jones fractures in patients treated with an EWB protocol to those treated with a DWB protocol, as well as to identify any factors that may be predictive of delayed or nonunion. Methods: True Jones (zone 2 fifth metatarsal base) fractures treated from April 2012 through January 2018 with IM screw fixation and 6 months follow-up were identified (41 fractures in 40 patients; mean ± SD age, 45.3 ± 17.9 years). Patients were divided into EWB and DWB cohorts (within or beyond 2 weeks, respectively). Delayed union (12.5 weeks) was statistically derived from established literature. Union times were compared between cohorts. Regression analyses were conducted to investigate possible confounders contributing to delayed union. There were 20 fractures in the EWB cohort and 21 fractures in the DWB cohort. Results: There was no significant difference in healing times (EWB: 25% by 6th week, 55% by the 12th week, 20% delayed; DWB: 33% by 6th week, 43% by 12th week, 24% delayed; P = .819) or delayed unions (EWB, 20% vs DWB, 24%; P > .999). There were no nonunions. No significant confounding risk factors were identified. Conclusion: Postoperative protocols using early weightbearing following solid IM screw fixation of Jones fractures appear to be safe and do not delay fracture healing or increase the risk of delayed union. Older age may be a risk for delayed union, but larger studies are needed to evaluate this with appropriate power in light of possible confounders. EWB protocols may allow better functional recovery without compromising outcomes by increasing the risk of delayed union. Level of Evidence: Therapeutic level III, retrospective comparative study.

Background: Wound complications after total ankle arthroplasty (TAA) are a common postoperative complication occurring in 14% to 66% of all surgeries. Soft tissue breakdown along the anterior incision can cause exposure of anterior tendons and implant, and adhesions of the extensor tendons of the foot. Recent publications have advocated for the implantation of dehydrated human amniotic membrane (DHAM) allograft during closure of anterior ankle incisions during TAA. The goal of this study was to determine whether implantation of DHAM allograft in TAAs decreased overall postoperative wound complications. Methods: One hundred seventy patients with end-stage ankle arthritis refractory to conservative management underwent TAA with a standard anterior approach by 1 of 3 board-certified foot and ankle orthopedic surgeons. Ninety-one patients underwent closure of the anterior incision with addition of DHAM, whereas 79 patients served as the control (no addition of DHAM). The primary endpoints considered were postoperative complications and reoperation. Included in the postoperative complications was return to the operating room, postoperative plastic surgery intervention, wound communication with the implant, removal of the implant, neurolysis, tendon debridement, and extensor hallucis longus contracture/adhesions. Results: In the analysis of our demographically homogenous cohorts, there was no statistically significant difference in any postoperative complications between patients closed with DHAM and controls. Return to the operating room occurred in 8.9% of controls and 15.4% of the DHAM group ( P = .291). Similarly, there was no statistically significant difference in postoperative plastic surgery, wound communication with the implant, implant removal, neurolysis, and tendon debridement between the control and DHAM groups. Conclusion: The application of DHAM theoretically acts to decrease overall wound complications in TAA. The use of DHAM preceding wound closure in TAA did not show a statistically significant reduction in overall wound complications in our retrospective analysis. Further study, including prospective randomized studies, is needed to further investigate the effectiveness of DHAM in reducing wound complications in TAAs. Level of Evidence: Level III, retrospective cohort study.

The association between lung disease and cardiovascular disease later in life has been well described. Both obstructive and restrictive lung physiology as measured with spirometry have been associated with cardiovascular disease and poor health outcomes.

Background Disease-specific patient-reported outcome (PRO) instruments are important in assessing the impact of disease and treatment. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is the first instrument for quantifying pulmonary arterial hypertension (PAH) symptoms and impacts developed according to the 2009 US Food and Drug Administration PRO guidance; previous qualitative research in patients with PAH supported its initial content validity. Methods Content finalization and psychometric validation were conducted by using data from A Study of Macitentan in Pulmonary Arterial Hypertension to Validate the PAH-SYMPACT (SYMPHONY), a single-arm, 16-week trial with macitentan 10 mg in US patients with PAH. Item performance, Rasch analysis, and factor analyses were used to select the final item content of the PRO and to define its domain structure. Internal consistency, test-retest reliability, known-group and construct validity, sensitivity to change, and influence of oxygen on item performance were evaluated. Results Data from 278 patients (79% female; mean age: 60 years) were analyzed. Following removal of redundant/misfitting items, the final questionnaire has 11 symptom items across two domains (cardiopulmonary and cardiovascular symptoms) and 11 impact items across two domains (physical and cognitive/emotional impacts). Differential item function analysis confirmed that PRO scoring is unaffected by oxygen use. For all four domains, internal consistency reliability was high (Cronbach's alpha > 0.80), and scores were highly reproducible in stable patients (intraclass correlation coefficient: 0.84-0.94). Correlations with the Cambridge Pulmonary Hypertension Outcome Review questionnaire and the 36-item Medical Outcomes Study Short Form Survey were moderate to high ([r] = 0.34-0.80). The questionnaire differentiated well between patients with varying disease severity levels and was sensitive to improvements in clinician- and patient-reported disease severity. Conclusions The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is a brief, disease-specific PRO instrument possessing good psychometric properties that can be administered in clinical practice and clinical studies. Trial Registry ClinicalTrials.gov; No.: NCT01841762; URL: www.clinicaltrials.gov.

Pulmonary hypertension (PH) is a progressive disease with high associated morbidity and mortality despite the development of novel therapies. Palliative care is a multidisciplinary field focused on optimization of quality of life and overall supportive care for patients and their families in the setting of life-limiting illness. Although the benefits of palliative care in oncology are well described, there are few studies regarding the timing and involvement of palliative care in PH patients. In this paper, we describe the importance of longitudinal advance care planning, including suggestions for addressing difficult topics such as end-of-life care, and the role of palliative care providers in helping guide these discussions throughout the course of the illness.

Rationale: There are limited data on factors in young adulthood that predict future lung disease.Objectives: To determine the relationship between respiratory symptoms, loss of lung health, and inc...

Background:The calcium-binding proteins S100A8/A9 (calprotectin) and S100A12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) are involved in multiple signalling pathways to mediate inflammation, can be secreted by activated monocytes/macrophages and exhibit cytokine-like extracellular functions. Circulating levels of these proteins have been associated with disease and clinical responses in systemic juvenile idiopathic arthritis (sJIA), including treatment response.1 Studies suggest that serum S100A8/A9 and S100A12, which are released at inflammation sites, are more specific biomarkers of local inflammation (e.g. in the synovium) than systemic biomarkers such as CRP and ESR.2,3Objectives:To investigate if baseline S100A8/A9 and S100A12 predict clinical response to abatacept treatment in polyarticular JIA (pJIA), and to assess whether changes from baseline in S100A8/A9 or S100A12 can be better prognostic markers for response to abatacept treatment than CRP in pJIA.Methods:Data are from a phase III trial of SC abatacept for the treatment of pJIA (NCT01844518).4 This 24-month, single-arm, open-label, international, multicentre, two-part study included male and female patients with pJIA aged 2–17 years. This analysis examined the correlation between biomarkers (S100A8/A9, S100A12 and high-sensitivity CRP [hsCRP]) and disease activity (measured using Juvenile Arthritis Disease Activity Score [JADAS]) at baseline, baseline biomarker values as predictors of future treatment response (ACR and JADAS endpoints), and the correlation between change from baseline in biomarker values and treatment response at Day 113.Results:Of 219 total patients, 158 (72%) had S100A8/A9 values and 155 (71%) had S100A12 values at baseline. Median S100A8/A9 and S100A12 values were 3295 ng/mL (normal range, 716–3004 ng/mL) and 176 ng/mL (normal range, 32–385 ng/mL), respectively. S100A8/A9, S100A12 and hsCRP (median 0.20 mg/dL; normal ≤0.6 mg/dL) had a low-to-moderate but significant association with disease activity at baseline; coefficients for associations between JADAS71-CRP low disease activity (LDA) and the biomarkers S100A8/A9, S100A12 and hsCRP were 0.23 (p=0.0038), 0.16 (p=0.0448) and 0.26 (p=0.0001), respectively. Baseline S100A8/A9 level above the median was associated with lower odds of ACR100 at Day 113 (p=0.0052). Figure 1 shows the associations of baseline biomarker values with Day 113 ACR and JADAS scores in the overall population. Baseline S100A8/A9 or S100A12 did not significantly influence ACR50 or ACR70 responses at Day 113, but high baseline values were associated with reduced odds of ACR90 (p=0.01), ACR100 (p=0.005), ACR-inactive disease (ID) (p=0.0001), and JADAS71-CRP (LDA) (p=0.02). By Day 477, elevated baseline S100A12 was still significantly associated with lower odds of ACR100 overall (0.467; p=0.0248) but baseline S100A8/A9 was not; at Day 645, neither was significantly associated with ACR100 response. At Day 113, changes from baseline in S100A8/A9 and S100A12 were correlated with ACR100 (coefficients of 0.22 [p=0.0082] and 0.26 [p=0.0015], respectively) and with ACR-ID (0.22 [p=0.0067] and 0.26 [p=0.0014], respectively); change in hsCRP was not significantly correlated with disease response.Conclusion:S100A8/A9 and S100A12 may serve as prognostic biomarkers to predict response to abatacept treatment at Day 113. Changes from baseline S100A8/A9 and S100A12 levels were more highly correlated with efficacy outcomes including ACR100 and ACR-ID at Day 113 compared with hsCRP.References:[1]Aljaberi N, et al. Pediatr Rheumatol Online J 2020;18:7.[2]Hammer H, et al. Arthritis Res Ther 2011;13:R178.[3]Nordal HH, et al. BMC Musculoskelet Disord 2014;15:335.[4]Brunner H, et al. Arthritis Rheumatol 2018;70:1144–1154.Acknowledgements:Professional medical writing and editorial assistance was provided by Rob Coover, MPH, at Caudex and was funded by Bristol Myers Squibb.Disclosure of Interests:Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Consultant of: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions (>10.000 USD each) from the following industries in the last 3 years: Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Grant Schulert Speakers bureau: Novartis, Consultant of: SOBI, Alyssa Sproles: None declared, Sherry Thornton: None declared, Gabriel Vega Cornejo Speakers bureau: AbbVie, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Janssen, Parexel, Sanofi, Jordi Anton Speakers bureau: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Consultant of: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Grant/research support from: AbbVie, Amgen, Gebro, GlaxoSmithKline, Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, Ruben Cuttica Speakers bureau: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Paid instructor for: AbbVie, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Michael Henrickson: None declared, Ivan Foeldvari Consultant of: Bristol Myers Squibb, Gilead, Hexal, MEDAC, Novartis, Pfizer, Sanofi, Daniel Kingsbury Consultant of: Pfizer, Margarita Askelson Consultant of: Currently working for Syneos Health providing services to Bristol Myers Squibb, Jinqi Liu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sumanta Mukherjee Shareholder of: Bristol Myers Squibb, GlaxoSmithKline, Employee of: Bristol Myers Squibb, GlaxoSmithKline, Robert Wong Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Daniel J Lovell Speakers bureau: Genentech, Wyeth Pharm, Consultant of: Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Regeneron, Takeda, UBC, Wyeth Pharma, Xoma, Alberto Martini Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, Pfizer, Alexei Grom Consultant of: AB2Bio, Novartis, Sobi (NovImmune), Grant/research support from: AB2Bio, Novartis, Sobi (NovImmune), Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, Pfizer, Roche, Paid instructor for: Novartis, Pfizer (funds go to CCHMC/employer), Consultant of: Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, UCB (funds go to CCHMC/employer), Grant/research support from: Bristol Myers Squibb, Pfizer (funds go to CCHMC/employer).

Objectives This study sought to investigate how right ventricular (RV) contractile function and its coupling with pulmonary circulation (PC) stratify clinical phenotypes and outcome in heart failure preserved ejection fraction (HFpEF) patients. Background Pulmonary hypertension and RV dysfunction are key hemodynamic abnormalities in HFpEF. Methods Three hundred eighty seven HFpEF patients (mean age 64 ± 12 years, 59% females, left ventricular ejection fraction 59 ± 7%) underwent RV and pulmonary hemodynamic evaluation by echocardiography (entire population) and right heart catheterization (219 patients). Patients were investigated by tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and stratified according to TAPSE/PASP ratio tertiles (1: 0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to PC coupling based on the correlation with invasively evaluated RV systolic elastance/arterial elastance (r = 0.35; p Results Groups had similar prevalence of comorbidities except for a higher prevalence of atrial fibrillation and kidney dysfunction in tertile 1. Progressively increasing levels of natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal exercise aerobic capacity and ventilatory inefficiency were observed from the highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery compliance (r = 0.69; p Conclusions A thorough assessment of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at different level of risk. These observations shift the interest toward therapeutic strategies that may benefit the right heart as primary unmet need in the complex pathophysiology of the HFpEF syndrome.

Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM.Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data.Results: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference.Conclusion: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.

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

Beyond the risks of smoking, there are limited data on factors associated with change in lung function over time.To determine whether cardiorespiratory fitness was longitudinally associated with preservation of lung health.Prospective data were collected from 3,332 participants in the Coronary Artery Risk Development in Young Adults study aged 18-30 in 1985 who underwent treadmill exercise testing at baseline visit, and 2,735 participants with a second treadmill test 20 years later. The association between cardiorespiratory fitness and covariate adjusted decline in lung function was evaluated.Higher baseline fitness was associated with less decline in lung function. When adjusted for age, height, race-sex group, peak lung function, and years from peak lung function, each additional minute of treadmill duration was associated with 1.00 ml/yr less decline in FEVGreater cardiopulmonary fitness in young adulthood, less decline in fitness from young adulthood to middle age, and achieving increased fitness from young adulthood to middle age are associated with less decline in lung health over time. Clinical trial registered with www.clinicaltrials.gov (NCT 00005130).

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.

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

Background: Tocilizumab (TCZ) administered intravenously (IV) was effective for the treatment of polyarticular (p)JIA and systemic (s)JIA.1,2 Objectives: To evaluate the long-term safety and efficacy of subcutaneous (SC) TCZ in patients (pts) with pJIA or sJIA enrolled in a long-term extension (LTE) phase of two 52-week, open-label studies. Methods: Pts aged 1-17 years received body weight (BW)–based TCZ SC: pJIA pts who failed/could not tolerate MTX received TCZ 162 mg every 3 weeks for BW Results: Most pJIA (n=44) and sJIA (n=38) pts were female (72.7% and 55.3%) and white (88.6% and 84.2%); median (range) age was 9.0 (2-18) years. AE rates (Table) were similar regardless of BW. Most AEs were grade 1 or 2; grade ≥3 AEs were reported by 10/44 (20.8%) pJIA pts and 4/38 (10.5%) sJIA pts, most commonly nasopharyngitis (pJIA, 17/44 [38.6%]; sJIA, 11/38 [28.9%]). Other AEs reported in ≥15% of pts included arthralgia, gastroenteritis, cough, vomiting, diarrhea, pyrexia, headache, and oropharyngeal pain (pJIA) and upper respiratory tract infection, cough, pyrexia, arthralgia, and rash (sJIA). No opportunistic infections developed. Neutropenia AEs were reported by 6/44 (13.6%) pJIA pts and 7/38 (18.4%) sJIA pts. SAEs occurred in 5/44 (11.4%) pJIA pts (furuncle, appendicitis, pneumonia, eye pain/headache, infectious mononucleosis) and 2/38 (5.3%) sJIA pts (pneumonia, craniocerebral injury from a fall); only pneumonia (pJIA) was considered treatment related. Neutralizing anti-TCZ antibodies developed in 2 (4.7%) pJIA pts and no sJIA patients. No deaths were reported in the LTE study. Conclusion: In this LTE study in children with pJIA or sJIA, SC TCZ continues to have an acceptable tolerability profile with no new safety concerns. References: [1] Brunner HI et al. Ann Rheum Dis. 2015;74:1110-1117. [2] 2. De Benedetti F et al. N Engl J Med. 2012;367:2385-2395. Disclosure of Interests: Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background Efficacy of SC abatacept (ABA) in patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA) was shown in a 2-year, open-label, Phase III international study (NCT01844518).1 Restricted growth and delayed puberty are associated with pJIA;2 however, the effect of ABA on growth and development is unknown. Objectives To investigate the effect of ABA on height, BMI and Tanner staging, and to assess the impact of BMI on ABA efficacy in pts with pJIA. Methods Patients with pJIA were grouped into two age cohorts (2–5 and 6–17 years [yrs]) and received weight-tiered SC ABA (10 to −2 to ≤1), overweight (>1 to ≤2) and obese (>2) (intent-to-treat, non-responder imputation for missing efficacy data). In the 6–17-yr cohort, Tanner staging was recorded at BL and at discontinuation or completion of study. Results Data for standardised height and BMI are presented. In 6–17-yr-old pts with BL Tanner stage ≤3 (n=100), BL mean (SD) height was −0.53 (1.53); at D645, mean (95% CI) change was 0.20 (0.06, 0.34; Figure 1). In 6–17-yr-old pts with a BL height ≤−1 (n=42), BL mean (SD) height was −2.10 (1.01) and mean (95% CI) change at D645 was 0.49 (0.23, 0.76). In 2–5-yr-old pts, BL mean (SD) height was 0.07 (1.37); at D645, mean (95% CI) change was 0.13 (−0.09, 0.36). In 13 pts aged 6–17 yrs of the lowest height (Tanner stage ≤3 and BL height ≤−2), mean (SD) height increased from −3.28 (1.10) at BL to −2.59 (1.31) by D645. At BL, mean (SD) BMI was 0.20 (1.33) in the 6–17-yr cohort (n=173) and 0.25 (1.57) in the 2–5-yr cohort (n=46); at D645, mean (95% CI) change in BMI was 0.02 (−0.13, 0.16; Figure 2) and 0.17 (−0.08, 0.42), respectively. Overall, no relationship was seen between change from BL in Juvenile Arthritis Disease Activity Score 71 (JADAS71) and BL BMI in either age cohort. The proportions (odds ratio [OR]; 95% CI of OR) of obese pts aged 6–17 yrs achieving JIA-ACR30 (0.15; 0.04, 0.55), JIA-ACR50 (0.18; 0.05, 0.63), JIA-ACR70 (0.17; 0.04, 0.67) and JADAS71 minimal disease activity (0.27; 0.07, 1.03) at Day 645 were significantly lower compared with pts with a normal BMI, but the sample size in the obese category was low (n=12); this effect was not seen in overweight pts (n=37). In female pts (n=92), shifts in Tanner stages from BL to D645 were as expected; male sexual maturation was difficult to assess due to the small sample size (n=20). Conclusion Abatacept improves growth and development in pts with pJIA. Early therapeutic intervention with abatacept may help reduce growth restrictions in pts with pJIA. BMI may impact the efficacy response, resulting in lower efficacy in obese, but not in overweight, pts with pJIA versus pts with normal BMI. References [1] Brunner HI, et al. Arthritis Rheumatol2018;70:1144–54. [2] Umlawska W, et al. Arch Med Sci2010;6:19–23. Acknowledgement Professional medical writing: Lola Parfitt, MRes, Caudex; funding: Bristol-Myers Squibb Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus ( I perform consultancy activities on behalf of the Gaslini Institute for the companies listed below: AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, R-Pharm. The money received for these activities are directly transferred to the Gaslini Institute’s bank account. Before March 2016, I was the head of the Pediatric Rheumatology Department at the G. Gaslini Hospital, where the PRINTO Coordinating Centre is located. For the coordination activity of the PRINTO network, the Gaslini Hospital received contributions from the industries listed in this section. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Daniel J Lovell Consultant for: Consulting fees and/or honoraria from Astra Zeneca, Wyeth Pharma, Amgen, Abbott, Pfizer, F. Hoffmann-La Roche, Novartis, UBC, Takeda, GSK, Boehringer, and Celgene

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. 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. 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

Objective.To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases.Methods.The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria.Results.In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor–positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody–positive JIA. The other forms were gathered under the term “others.” These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities.Conclusion.An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical termJIA. These preliminary criteria will be formally validated with a dedicated project.

Osteochondral lesions of the talus are a frequently encountered treatment challenge for the foot and ankle surgeon. Treatment options for these lesions can vary. Nonoperative treatment has a low success rate, while operative intervention has better outcomes. Multiple operative treatment modalities exist. These include excision with debridement and drilling or microfracture, as well as osteochondral grafting, using autograft or allograft. Knowledge of the proper exposures and treatment modalities is essential for the foot and ankle surgeon.

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: NCT 00005130.

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA).MethodsPatients (2–19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population.Results144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed.ConclusionResponse to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab.Trial registration numbersNCT00886769, NCT00889863, NCT00426218 and NCT00891046.