There are limited data nationwide on the burden of systemic sclerosis (SSc)-related mortality. We aimed to determine recent trends in SSc and SSc-related pulmonary arterial hypertension (PAH) mortality overall and across population subgroups.Using death certificate data from the National Center for Health Statistics, we computed the age-adjusted mortality rates of SSc and SSc-SSc−PAH, a lethal prevailing complication, across demographic groups, geographic regions and comorbid cardiorespiratory conditions, and used Joinpoint regression analysis to calculate the average annual percentage change (APC) in mortality.From 2003 to 2016, 25 175 death records contained a code for SSc. Decedents were predominantly female (81%) and white (73%), with an average age of 66±14 years. The age-adjusted mortality rate decreased by 3% per year from 6.6 in 2003 to 4.3 per 1 000 000 population in 2016. Also, a decreasing trend was found when SSc was stratified by age, sex, race and geographic region. The prevalence of PAH was 23%. The odds of PAH were highest in female and black decedents, and in decedents with concomitant pulmonary embolism, cardiomyopathy and interstitial lung disease (ILD). SSc−PAH mortality remained stable from 2003 to 2008 then decreased by 3% per year from 2008 to 2016. In decedents with SSc−PAH, among all concomitant comorbidities, the mortality rate associated with ILD had the highest increase (average APC 6%, 95% CI 2%−10%).The mortality rate from SSc decreased from 2003 to 2016. Decreases in mortality rates were similar across demographic groups and geographic regions. SSc−PAH-related mortality remained stable. The death rate for SSc−ILD and concomitant PAH increased during this period.

A 58-year-old man presented to the rheumatology clinic for evaluation of skin induration of 6 months duration. History of present illnessOne month prior to rheumatology evaluation he was admitted to the hospital for progressive worsening of shortness of breath on exertion, epistaxis, and gingival bleeding. He had fatigue, poor appetite, and an unintentional weight loss of approximately 30 pounds over the preceding 2 years. He denied symptoms of chest pain, orthopnea, paroxysmal nocturnal dyspnea, or leg swelling. Laboratory tests during that admission showed profound leukopenia of 2.2 9 10 3 /mm 3 (normal range 3.8-9.8), macrocytic anemia with hemoglobin of 5.9 gm/dl (normal range 13.8-17.2), hematocrit of 17.3% (normal range 40.7-50.3), mean corpuscular volume (MCV) of 107.7 fl (normal range 80-100), and thrombocytopenia of 3 9 10 3 /mm 3 (normal range 140-440). He underwent bone marrow biopsy, which showed aplastic anemia. He received packed red blood cell and platelet transfusions with improvement of hemoglobin and hematocrit to 7.3 gm/dl and 21.6%, respectively, and platelet counts to 32 9 10 3 /mm 3 . He was discharged to followup with hematology.In the last 6 months, he had noticed induration of the skin over his chest, abdomen, low back, arms, and thighs, and stiffness in the upper and lower extremities because of the skin induration. These areas were not painful or itchy. He had difficulty raising his arms above the level of his shoulders due to the skin changes. Laboratory, histopathology, and radiologic evaluationAt the time of his rheumatologic evaluation, laboratory results were significant for a macrocytic anemia with

BackgroundPrior studies have demonstrated improved accuracy and efficacy when Intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. There is also growing evidence that many patients with knee osteoarthritis (OA) exhibit a pro-inflammatory catabolic synovial fluid (SF) profile. However, it is not known if temporary clinical improvement in pain and function after IA Hyaluronic acid (HA) injections is associated with changes in SF volumes.ObjectivesThe purpose of this study was to determine if IA HA injections delivered using US directed needle visualization with an external pneumatic compression device would result in improved clinical outcomes for knee OA at 3 and 6 months, and if this was associated with a reduction in the amount of knee synovial fluid (SF) measured on US.Methods49 eligible subjects with symptomatic Knee OA, BMI < 40 and KL radiographic rating of II or III OA were consented for this open label prospective IRB approved Investigator Initiated SF OA biomarker study (HS 3179, NCT 04093232). All standing radiographs were reviewed by a fellowship-trained MSK radiologist. 36 subjects had adequate aspirated SF volumes of > 500 mcl for biomarker analysis and therefore were eligible to receive two IA injections of HYADD4, 24 mg/3ml (Fidia Farmaceutici S.p.A. Italy) 7 days apart by a MSK US certified Rheumatologist. An external pneumatic compression device and US visualized needle insertion ensured injections were delivered into the intra-synovial space. Despite COVID-19 restrictions, 34 patients (17 women and 17 men) between 35 and 78 years of age returned for 3 month evaluations and 30 had evaluations at 6 months. The following clinical variables were measured: Western Ontario and McMaster Universities Index (WOMAC) total scores, Visual Analog Pain Scale (VAS, 0-10), PCS scores on the SF-36 health survey questionnaires (physical function/bodily pain and general health), 6-minute walking distance in meters (6 MWD), and measured SF depth before and after an external pneumatic compression device was inflated to 100 mmHg to facilitate aspiration by increasing available SF volumes under positive presure. The SF depth was measured on the recorded US image (GE logiq e) as the largest anechoic region selected for aspiration on either the lateral (n= 30) or medial (n=4) compartment. SF and simultaneous peripheral blood samples were centrifuged and cryopreserved at -80 o C within 45 minutes of aspiration for future analysis. Statistical differences between baseline values compared to those levels at 3 and 6 months were determined using a paired ANOVA test with p <0.05 significance.ResultsImprovements over baseline values were observed at 3 and 6 months respectively, after IA HA injections in WOMAC (40%, 40%), VAS (45%, 51%) and PCS (15%, 18%) all p< 0.0001. The 6 WWD improved by 7 % at 3 months (p< 0.007) but was not statistically improved at 6 months. US measured SF depth at baseline was 3.2 ± 2.2 mm before inflation and 6.4 + 3.7 mm after inflation of the pneumatic external compressioin device but statistical differences in SF depth were not observed at 3 and 6 months.ConclusionDespite improvements in WOMAC, VAS scores, and PCS scores on the SF 36 at 3 and 6 months after US guided knee injections with an HA product, a statistically significant reduction in the amount of US measured SF was not observed. The 6 MWD improved at 3 months but was not statistically different from the baseline distance by 6 months. IA injections using US needle visualization confirmed that the product was delivered into the synovial space with 100 % accuracy which might have resulted in improved efficacy results in this study compared to prior IA HA studies injected without US or using different HA products. In the future, we hope SF biomarkers may identify which individual OA patients will likely achieve the greatest benefit with IA HA injections and to determine if this is associated with a reduction in catabolic pro-inflammatory proteins.Disclosure of Interestsrichard Meehan Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. I was the PI., Mary Gill Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As the study coordinator she received salary support, Eric Hoffman Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As a biomedical engineer consultant he received some compensation for his work., Molly Wolf Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As the Immunology laboratory supervisor she received support from this grant for sample processing and analysis., Isabelle Amigues Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As a Rheumatologist who performed some of the aspirations and injections she did receive some very small salary support from this grant., Liudmila (Mila) Kastsianok Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As a Rheumatologist who performed some of the aspirations and injections she did receive some very small salary support from this grant., Elizabeth Regan Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As a orthopedic surgeon and immunologists she did receive some very small salary support from this grant., James Crooks Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As our biostatistician for this project he did receive some support from this grant for statistical analysis and consultation., Gregory Czuczman: None declared, claire Coeshott Consultant of: She was ben an employee for pharmaceutical companies in the past unrelated to this project and has no relationship in the past with Fidia who funded the study., Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As the director of the ADx immunology labs where this samples are processed her staff received some compensation for sample handling and biomarker analysis. She did not receive any salary support., Vijaya Knight Grant/research support from: This grant was funded by Fidia Pharmaceutici and Fidia Pharma USA as an Investigator Initiated grant for synovial fluid based biomarker research in osteoarthritis. As an Immunologists and prior director of the ADx immunology labs when the project started in 2019 her staff performed sample processing and testing and they received support from this grant by Dr Knight did not receive and salary support or direct compensation for her consultation expertise.