Research Group Registry Research Articles

Tofacitinib versus thalidomide for mucocutaneous lesions of systemic lupus erythematosus: A real-world CSTAR cohort study XXVII.

Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. At 3 and 6months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

The additional role of anti-nucleosome antibodies in the prediction of renal damage in systemic lupus erythematosus based on CSTAR (XXV).

The predominant determinant of an unfavorable prognosis among Systemic Lupus Erythematosus (SLE) patients resides in the irreversible organ damage. This prospective cohort study aimed to identify the additional value of anti-nucleosome antibodies on organ damage accumulation in SLE patients. Based on the Chinese SLE Treatment and Research group (CSTAR) registry, demographic characteristics, autoantibodies profiles, and clinical manifestations were collected at baseline. Follow-up data were collected by reviewing clinical records. Of 2481 SLE patients with full follow-up data, 663 (26.7%) were anti-nucleosome antibodies positive and 1668 (68.0%) were anti-dsDNA antibodies positive. 764 (30.8%) patients developed new organ damage during a mean follow-up of 4.31 ± 2.60 years. At baseline, patients with positive anti-nucleosome antibodies have a higher rate of lupus nephritis (50.7% vs 36.2%, p < .001). According to the multivariable Cox regression analysis, both anti-nucleosome (HR = 1.30, 95% CI, 1.09-1.54, p < .001) and anti-dsDNA antibodies (HR=1.68, 95% CI, 1.38-2.05, p < .001) were associated with organ damage accumulation. Anti-nucleosome (HR = 2.51, 95% CI, 1.81-3.46, p < .001) and anti-dsDNA antibodies (HR = 1.69, 95% CI, 1.39-2.06, p < .001) were independent predictors for renal damage. Furthermore, the combination of the two antibodies can provide more accurate information about renal damage in overall SLE patients (HR = 3.19, 95% CI, 2.49-4.10, p < .001) and patients with lupus nephritis at baseline (HR = 2.86, 95% CI, 2.29-3.57, p < .001). Besides anti-dsDNA antibodies, anti-nucleosome antibodies can also provide information about organ damage accrual during follow-up. The ability of co-positivity of anti-nucleosome and anti-dsDNA antibodies in predicting renal damage may lead to additional benefits in the follow-up of these patients.

Perioperative Outcomes and Management in Patients with Myeloproliferative Neoplasms: A Multicentric Retrospective Analysis of 354 Surgical Interventions

Background: Classic myeloproliferative neoplasms (MPN) polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are characterized by concurrent risk of thrombotic and hemorrhagic complications. These risks are reported to be further compounded perioperatively ( Blood, 2008), though scarce contemporary data exist. Further, the lack of evidence-based guidelines leads to heterogeneous management. The objective of this study was to comparatively assess perioperative complication rates (thrombotic, hemorrhagic, and survival) and management practices in a large MPN population. Methods: Consecutive surgical interventions in patients with WHO-defined PV, ET and MF recruited from the Quebec MPN Research Group Registry (6 centers; between 1986-2023) were analyzed. Endpoints (90 days post-surgery) and surgical definitions were per convention. Standard statistics were used (JMP® Pro 14.1.0 software; SAS Institute, Cary, NC, USA). Results: A total of 354 procedures were captured in 184 patients: PV, n=87 (47%); ET, n=66 (36%); MF, n=31 (17%). Cardiovascular risks were balanced; previous venous thrombosis was enriched in PV (p=0.04; Table 1A). Major surgeries were performed in 45 cases (30%), primarily PV (p=0.004); most being general (69%) (Table 1B). Interventions were urgent in 41 cases (28%); 49 (42%) of 195 evaluable were under general anesthesia. The majority of PV/ET subjects continued antiplatelet and cytoreductive agents peri-intervention, though cytoreduction was stopped in 12-22%. Thromboprophylaxis was administered in n=42 (23%). Surgical bleeding occurred in n=8 (2%). At 90-day follow-up, arterial/venous thrombosis occurred each in n=3 (1%), hemorrhage in n=25 (8%), and death in n=4 (1%). Overall complication rate was 12% (n=40). PV patients displayed significantly higher rates of surgical bleeding (6%; p=0.0006) and perioperative hemorrhage (13%; p=0.04). Factors impacting 90-day surgical outcomes: Hemorrhage-free survival (HFS): PV: General anaesthesia (p=0.04) and antithrombotic prophylaxis (p=0.05) negatively impacted HFS on multivariate testing (Table 2). ET: Driver mutation status CALR vs JAK2 (HR 24.6; 95% CI 1.2-504; p=0.05) and urgent interventions (HR 11.5; 95% CI 0.93-144; p=0.03) emerged as independent predictors for HFS. MF: Discontinuation of antiplatelet agents perioperatively was the sole factor impacting HFS (p=0.01). Perioperative complication-free survival (CFS; composite endpoint): PV: While several factors were significant on univariate testing (procedure, leukocytosis, ruxolitinib exposure, cytoreduction modification, thromboprophylaxis), multivariate testing disclosed only lower hematocrit (&amp;lt; 35%; p=0.05) to impact complication rates. ET: Urgent (p&amp;lt;0.0001) and major procedures (p=0.009), thromboprophylaxis use (p=0.001), platelet count &amp;gt; 450 x 10 9/L (p=0.02), and absence of antiplatelet (p=0.02) were significant independent predictors of CFS. MF: Antiplatelet discontinuation (HR 6.5; 95% CI 0.8-50.4; p=0.02), nature of cytoreduction (ruxolitinib vs hydrea; p=0.04) and cytoreduction discontinuation pre-operatively (p=0.006) negatively impacted CFS on multivariate analysis. Limited informative events for thrombosis/survival precluded analyses. Conclusions: This is, to our knowledge, the largest and most contemporary analysis of surgical procedures in patients with MPN. Firstly, it confirms prevalent bleeding perioperatively, though balanced by fewer thrombotic events, calling for further study of thromboprophylaxis/antiplatelet practices in this setting. Second, it discloses key management patterns, notably routine discontinuation of cytoreduction, which had a detrimental impact on outcomes. Third, correlation of uncontrolled platelets and overzealous hematocrit control with higher complication rates in ET and PV, respectively, underscores importance of judicious target control. Further, CALR driver mutation status associated with bleeding risk in ET, independent of platelet count, suggesting additional contributing mechanisms. Finally, ruxolitinib use was an independent predictor of perioperative complications in MF, though this may reflect skewing towards higher-risk populations. Further studies will be required to validate findings, with this data serving as a preliminary signal for awareness of risk and reappraisal of management strategies.

Prospective Symptom Burden Analysis in 784 Patients with Myeloproliferative Neoplasms: High Burden Correlates with Inflammatory/Genetic Biomarkers and Reduced Survival

Background: Myeloproliferative neoplasms (MPN) are associated with significant symptom burden, influencing patient quality of life and management. Thorough assessment of this burden is crucial; however, data from large populational registries are limited. Our objective was to characterize symptom burden in a large MPN cohort, determining: i) age-associated differences; ii) treatment effect; iii) biologic correlatives, and iv) impact on overall survival (OS) in a large, real-world population based setting. Methods: This is a multicenter prospective study analyzing patient-reported outcomes per MPN-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), a validated questionnaire grading (0-10) ten MPN symptoms ( JCO, 2012). Recruitment: Quebec CML-MPN Research Group registry (&amp;gt;20 community/academic centers). Eligibility: i) diagnosis of polycythemia vera (PV), essential thrombocytosis (ET), or myelofibrosis (MF) per WHO criteria; ii) completion of 1+ MPN-SAF TSS between 2013-2022. Conventional statistics were used (JMP® Pro 14.1.0 software; SAS Institute, NC, USA). Results: 4105 MPN-SAF TSS were completed by 784 patients (n= 285 PV, n=422 ET, n=77 MF). Median age at diagnosis was 63 years (range 19-96); female preponderance (56%). A median of 5 questionnaires were completed/patient (range 1-16). Mean symptom score was 16.7 (+/-12.3). A clinically significant total score, defined as &amp;gt;20, was reported by 33% of patients (n=261); most frequently women (p&amp;lt;0.0001) and MF cases (p=0.03). Symptom burden in the young: N=74 (9%) were age &amp;lt;40 years at diagnosis. At recruitment, mean aggregate and maximum MPN-SAF TSS scores were comparable across younger and older subsets (p=0.3-0.9) (Table 1), despite lower risk scores in the former (p&amp;lt;0.05). When scores were deconstructed, younger patients - vs older, had significantly higher levels of fatigue (p=0.03) and abdominal pain (0.007). Impact of therapy: Of those with high MPN-SAF scores, a considerable proportion were not treated (n=69/179, 39%). Higher mean scores were also reported in those having initiated therapy &amp;gt;36 months from diagnosis (p=0.0009). Of those with available MPN-SAF pre/post treatment, 37% showed deteriorating scores following cytoreduction, regardless of agent (p=0.4). Notably, those not on antiplatelet therapy had significantly higher mean (p=0.0006) and sub-item scores (excluding fever/night sweats). Over time, all interventions confounded, n=338 (43%) experienced worsening of MPN-SAF scores. Clinical biomarkers: Patients with anemia (hemoglobin &amp;lt;100 g/L) had significantly higher mean MPN-SAF scores and worse fatigue, inactivity, concentration, bone pain, and weight loss (all p&amp;lt;0.05). Increased C reactive protein (CRP) associated significantly with higher MPN-SAF scores (p=0.03), as well as fatigue, inactivity, early satiety, and bone pain (all p&amp;lt;0.05). Notably, patients with JAK2V617F variant allele frequency &amp;gt;50% (VAF) had higher average (p=0.03) and maximum (p=0.001) MPN-SAF, higher inactivity scores (p=0.02), and more frequent worsening scores over time (p=0.05). Survival impact: Higher mean MPN-SAF score had a significantly detrimental impact on OS (p=0.05) (Figure 1). Multivariate analysis revealed absence of antiplatelet therapy, age at diagnosis &amp;gt;65 years, male sex, and high-level inactivity to be independent predictors of inferior OS (HR 29, 6, 3 and 3 respectively). Conclusions: This is a large-scale study comprehensively appraising symptom burden in MPN patients, disclosing several novel findings. First, it unexpectedly exposes disproportionately severe symptoms (fatigue/abdominal pain) in younger patients. Second, it reveals deterioration of symptoms in the face of therapy in a significant number of patients, underscoring inadequacy of current therapies in symptom control. Third, it discloses anemia, elevated CRP, and JAK2 VAF&amp;gt;50% as putative biomarkers of symptom burden; potential adjuncts in identifying highly symptomatic subsets, particularly in situations where symptom assessment is challenging. Finally, it confirms negative survival impact of high symptom burden in a real-world setting. Overall this data exposes a critical unmet need for new therapeutic avenues aimed at alleviating symptom burden in patients with MPN. Further delineation of the inflammation-symptom relationship and future studies using novel prevention strategies are warranted.

Do the features of juvenile psoriatic arthritis change according to age? A comprehensive evaluation of the PeRA Research Group Registry.

To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and compare the distinct patterns of the disease between early-onset and late-onset age groups. Patients with JPsA followed regularly for at least 6 months between 2010 and 2020 in seven paediatric rheumatology centres in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies and outcomes of the patients were evaluated retrospectively. A total of 87 (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 years (s.d. 4.5). Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis and arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints and 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by MRI. ANA was positive in 35 (40.2%) patients. Twelve children (13.8%) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at month 6 and at the last control compared with baseline. About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with PsA seem to display two different phenotypes. Younger children have a female predominance, ANA positivity and uveitis, while older children have more axial involvement.

Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII

BackgroundAvascular necrosis is a common organ damage in SLE patients, which can influence patients’ life quality. Conflicting results exist in risk factors of AVN in SLE patients. The aim of this study was to illustrate risk factors predicting the occurrence of avascular necrosis (AVN), also known as osteonecrosis, in systemic lupus erythematosus (SLE) patients in Chinese SLE Treatment and Research Group (CSTAR), a multi-center cohort of Chinese SLE patients.MethodsSLE patients in CSTAR without existing AVN at registration were included. At least two follow-ups and an observation period of no less than 2 years for AVN event were required. Univariate and multivariate Cox regression analyses were used to evaluate risk factors for AVN in SLE patients. Coefficient B was transformed to risk score for the development of a risk stratification model.ResultsOne hundred six (2.59%) of 4091 SLE patients were diagnosed AVN during follow-ups of no less than 2 years. Multi-variate Cox regression analysis suggested that SLE onset age ≤ 30 (HR 1.616, p 0.023), arthritis (HR 1.642, p 0.018), existing organ damage (SDI ≥ 1) at registration (HR 2.610, p < 0.001), positive anti-RNP (HR 1.709, p 0.006), and high glucocorticoid maximum daily dose at registration (HR 1.747, p 0.02) were independent risk factors. A risk stratification system was developed according to the risk factors, and patients were divided into high risk (3–6) and low risk (0–2). The AUC of 0.692 indicated moderate discrimination. The calibration curve in internal validation was drawn.ConclusionPatients with SLE onset age ≤ 30, arthritis, existing organ damage (SDI ≥ 1) at registration, positive anti-RNP, and high glucocorticoid maximum daily dose at registration are at high risk for AVN and require attention.

Organic solvent exposure and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group registry

Organic solvent exposure and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group registry

Occupation as a gendered-role and outcome in systemic sclerosis.

Sex and gender are of growing scientific interest in disease onset and course. While sex differences have been shown to exist in systemic sclerosis, there is a paucity of data on gender. Our objective was to examine the association between occupation, a gender-related role and outcomes in systemic sclerosis. An occupation score ranging from 0 to 100, with lower scores representing occupations traditionally held by men and higher scores traditionally held by women, was constructed using the National Occupational Classification 2016 and data from Statistics Canada. Subjects in the Canadian Scleroderma Research Group registry were assigned an occupation score based on self-reported occupation. Multivariate models, adjusted for sex, age, smoking and education were used to estimate the independent effect of occupation score on systemic sclerosis outcomes. We included 1104 subjects, of which 961 were females (87%) and 143 (13%) males. There were differences between females versus males: disease duration (9.9 vs 7.6 years, p = 0.002), diffuse disease (35% vs 54%, p < 0.001), interstitial lung disease (28% vs 37%, p = 0.021) and pulmonary hypertension (10% vs 4%, p = 0.033), but not pain, response to treatment and mortality. The median occupation scores differed between females and males (84.3 (interquartile range 56.8, 89.4) vs 24.9 (4.3, 54.1), p < 0.001). The Spearman correlation between sex and occupation score was 0.44, indicating a weak correlation. In adjusted analyses, occupation score was not an independent predictor of disease subset (diffuse vs limited), interstitial lung disease, pulmonary hypertension, pain, response to treatment or mortality. We did not find independent associations between an occupation score, a gender-related role and outcomes in systemic sclerosis. These results should be interpreted with caution as occupation may be a poor measure of gender. Future research using a validated measure of gender will be needed to generate robust data on the effect of gender in systemic sclerosis.

Chinese SLE Treatment and Research Group Registry (CSTAR) XIV: the subjective well-being of patients with systemic lupus erythematosus.

BackgroundSystemic lupus erythematosus (SLE) can significantly influence patients’ quality of life and subjective well-being (SWB), but the relationships between clinical characteristics, SWB, and related psychological factors have been little studied.ObjectiveTo measure SWB in patients with SLE and examine how major clinical determinants, emotional variables, and related positive factors affect SWB.MethodsOverall, 1,110 patients with SLE from the Chinese SLE Treatment and Research Group (CSTAR) and 198 age and gender-matched individuals from the general population without self-reported SLE were invited to complete questionnaires of SWB evaluated by the satisfaction with life scale (SWLS), emotional variables assessed by the patient health questionnaire-9 (PHQ-9), and general anxiety disorder-7 (GAD-7) and related positive factors assessed by the self-esteem scale (SES), general self-efficacy scale (GESE), and Connor-Davidson resilience scale (CD-RISC). The multivariate linear regression was used to examine the relationship between clinical manifestations and SWB.ResultsLife satisfaction was significantly lower (p < 0.001) in patients with SLE than in the general population. Active skin involvement (OR = 0.923, 95% CI = 0.868–0.981, p < 0.05) was negatively associated with life satisfaction scores, and age at enrollment (OR = 1.160, 95% CI = 1.092–1.230, p < 0.001) were positively associated with life satisfaction scores in the multivariate regression model. The cumulative organ damage was significantly associated with depression (OR = 1.085, 95% CI = 1.022–1.153, p < 0.01) and the loss of self-esteem (OR = 1.067, 95% CI = 1.004–1.133, p < 0.05).ConclusionSWB provides useful insight into the impact of SLE on psychological health and opportunities to improve quality of life and clinical care.

Sex differences in systemic lupus erythematosus (SLE): an inception cohort of the Chinese SLE Treatment and Research Group (CSTAR) registry XVII.

The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower. Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.

Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model.

To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Effect of pregnancy on scleroderma progression.

To explore the trajectory of scleroderma disease activity in women who experienced a pregnancy after systemic sclerosis diagnosis compared to nulliparous women. We analyzed data from the Canadian Scleroderma Research Group registry by identifying nulliparous women and women with ⩾1 pregnancy after systemic sclerosis diagnosis. Patient characteristics were compared between groups at registry entry. Controlling for age, smoking, and time since systemic sclerosis diagnosis, generalized estimating equations tested the effect of pregnancy on force vital capacity, diffusing capacity of the lungs for carbon monoxide, right ventricular systolic pressure, glomerular filtration rate, antibody status, active digital ulcers, physician global assessment of activity, and severity over 9 years. At registry entry, numbers of women in the nulliparous and pregnancy after systemic sclerosis diagnosis groups were 153 and 45, respectively. Corresponding numbers at 6 and 9 years were 48 and 21, and 18 and 9, respectively. The prevalence of anti-topoisomerase positivity was 18.3% in nulliparous and 12.5% in pregnancy after systemic sclerosis diagnosis. Baseline differences included mean (Standard deviation) age of diagnosis (nulliparous: 38.8 (14.0), pregnancy after systemic sclerosis diagnosis: 22.6 (6.8) years, p < 0.001), disease duration (nulliparous: 9.6 (8.9), pregnancy after systemic sclerosis diagnosis: 21.9 (9.6) years; p < 0.001), and inflammatory arthritis (nulliparous: 41 (28%), pregnancy after systemic sclerosis diagnosis: 22 (49%), p = 0.009). There were no significant differences between groups in the change of any outcomes over time. Results demonstrated that having ⩾1 pregnancy after systemic sclerosis diagnosis did not appear to significantly impact long-term renal, respiratory, or global function outcomes. While this offers a hopeful message to systemic sclerosis patients planning a pregnancy, physicians and patients should remain vigilant for potential post-partum complications.

Association of stone surgery with patient-reported complications after spinal cord injury.

To determine if a history of urinary stone surgery in individuals with spinal cord injury (SCI) is associated with an increased incidence of SCI-related complications and lower quality of life (QOL). The Neurogenic Bladder Research Group (NBRG) registry is a multicenter, prospective, observational study which measures QOL after acquired SCI. Over 1.5 years, 1479 participants were enrolled and grouped according to history of stone surgery. We evaluated SCI-related complications, QOL, and associations between patient factors and prior stone surgery using multivariable regression. Participants were a median of 11 years post-SCI and 189 (12.8%) reported prior bladder or kidney stone surgery; 95.8% of these occurred after the SCI. Median time between SCI and first stone was 5.6 years (IQR: 1.8-12.8). Hospitalizations were higher for those with prior stone surgery, with common reasons including UTIs, blood clots, pressure ulcers, and pneumonia (p < 0.001). During the year of observation, the incidence of stone surgery was 17% in those with a prior history of stone surgery and 2% per year in those without prior stone surgery (p < 0.001). Controlling for covariates, bladder management strategy, age, BMI, and years since SCI were associated with history of stone surgery. People with SCI and a history of surgical stone disease are at high risk for episodes of recurrent stones and increased hospitalizations, particularly those with kidney stones and indwelling catheter use. Identification of high-risk patients may guide tailored surveillance for complications and stone prevention strategies.

Very Elderly Patients with Myeloproliferative Neoplasms: Phenotypic Distinctions and Prognostic Determinants of Complications and Mortality

▪Background and methods:Increasing life expectancy has had the impact of increasing the proportion of patients with myeloproliferative neoplasms (MPN) aged ≥75 years (very elderly patients; VEP). However, few studies have evaluated the phenotype and prognostic factors specific to this population.This is a retrospective multicenter chart review (11 Quebec centers) of VEP with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) diagnosed between 1978 and 2019, enrolled in the CML-MPN Quebec Research Group registry. All diagnoses were made according to World Health Organization 2016 criteria (Blood. 2016;127:2391), with exemption of bone marrow biopsies in select patients. Standard statistical methods were used for all analyses.Results:Of the 753 patients studied in the registry, 114 patients (15%) were ≥75 years old (VEP) (Table 1). These subjects had a median age of 79 years (range 75-95) with incidence of PV, ET and MF of 38%, 51% and 11% respectively. Compared to patients <75 years old, VEP were less likely to be male (35% vs 45%, p = 0.05), had more frequent and higher levels of leukocytosis (11.4 vs 9.7 x 10 9 / L, p <0.0001), were more frequently “triple negative” and less commonly CALR-mutated (p = 0.0005), and presented significantly higher allelic burdens (45% vs 36%, p = 0.03). VEP also had more cardiovascular comorbidities (p <0.0001) and were more often classified as “high risk” (86% vs. 43%, <0.0001). A history of arterial thrombosis prior to/at diagnosis was more common in VEP vs younger patients (14% vs 7.2%, p = 0.02), as was a global history of arterial and/or venous thrombosis at any time during the follow up (25% vs 18%, p = 0.05). Sites of venous events were specifically skewed towards lower extremity deep vein thrombosis in VEP (75%) vs variously distributed in younger patients (p = 0.05). Bleeding rates were similar among the two groups (16% VEP and 17% non-VEP, p = 0.7) while fewer fibrotic (3% vs 8%, p = 0.03) and leukemic transformations (0 vs 2%, p = 0.04) were recorded in VEP. Significantly fewer bone marrow biopsies were performed in VEP (41% versus 54%, p = 0.01). This cohort was, however, more likely to receive cytoreductive therapy (76% vs 67%, p = 0.05), predominantly hydroxyurea (70% vs 59%, p = 0.02).Multivariate analysis revealed the presence of splenomegaly (HR 4.5; 1.2-17.1, p = 0.03) and smoking status (active/former vs never smokers) (HR 5.2; 1.1-24.9, p = 0.03) as predictors of shortened overall survival for the VEP population (Table 2). It also disclosed higher leukocyte count (p = 0.005) and the presence of diabetes mellitus (p = 0.05) as significant risk factors for shortened hemorrhage-free survival. Platelet count (p = 0.03) and smoking status (p = 0.02) were found to be significant determinants of thrombosis-free survival in univariate analysis but did not maintain their significance in multivariate testing.Kaplan-Meier survival data examining age-stratified outcomes in VEP vs younger patients revealed significantly shorter overall survival in VEP (14.2 years vs not reached, p < 0.0001) (Figure 1). The VEP cohort also displayed significantly reduced arterial thrombosis-free survival (incidence of 6.1% vs 3.9%, p = 0.01). There was no significant difference in event data for venous thrombosis-free (4% in both, p = 0.2) and myelofibrosis-free (2.6% versus 7.8%, p = 0.6) survival.Conclusion:This data addressing VEP with MPN exposes, for the first time: i) a characteristic phenotype (predominantly female, higher leukocyte counts, higher allele burden), ii) distinct adverse outcome patterns, particularly with regard to arterial thrombosis, and iii) unique and independent prognostic factors for survival, suggesting that VEP with MPN constitute a biologically, phenotypically, and prognostically distinct population. [Display omitted] DisclosuresBusque: Novartis: Consultancy. Szuber: Novartis: Honoraria.

Association between autoantibodies in systemic sclerosis and cancer in a national registry.

A close temporal relationship between SSc onset and cancer has been reported in anti-RNA polymerase III-positive patients. We investigated the association between cancer and other SSc autoantibodies in a national SSc registry. SSc patients enrolled in the Canadian Scleroderma Research Group registry from 2004 to 2019 were characterized according to autoantibodies to centromere, topoisomerase I/Scl70, RNA polymerase III, fibrillarin, Th/To (hPOP1), PM/Scl, Ku, NOR90, Ro52/TRIM21 and U1RNP. Logistic regression was used to examine the association between a close cancer-SSc interval and autoantibody status, adjusted for age, sex, race and smoking history. Of 1698 SSc patients, 1481 (87%) had available autoantibody data. Cancer was diagnosed within 2, 3 and 5 years of the first non-Raynaud manifestation in 1.3%, 2.1% and 3.5% of patients. The most frequent cancers diagnosed within 2 years were breast (33%), gynaecological (19%) and haematological (14%) cancers. The risk of cancer within 2 years was increased among anti-topoisomerase I [odds ratio (OR) 3.43, 95% CI: 1.04, 10.05] and anti-U1-RNP-positive patients (OR 5.54, 95% CI: 1.16, 20.40), but not with anti-RNA polymerase III. None of the anti-fibrillarin, Th/To, PM/Scl, Ku and NOR90-positive patients had cancer within 2 years. Patients with anti-centromere or none of the tested autoantibodies had numerically lower risks of developing cancer within two years. Synchronous cancer was rare in this large cohort of predominantly female and White SSc patients. The risk of cancer within 2 years was increased among anti-topoisomerase I and anti-U1-RNP-positive patients. Screening strategies guided by autoantibodies require further careful consideration.

NT-proBNP, hs-cTnT, and CRP predict the risk of cardiopulmonary outcomes in systemic sclerosis: Findings from the Canadian Scleroderma Research Group.

The aim of this study was to determine the independent value of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein to predict onset of cardiopulmonary disease in a large, multi-center systemic sclerosis cohort followed prospectively. Subjects from the Canadian Scleroderma Research Group registry with data on N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were identified. Outcomes of interest were death, systolic dysfunction (left ventricular ejection fraction < 50% or medications for heart failure), pulmonary arterial hypertension by right heart catheterization, pulmonary hypertension by cardiac echocardiography (systolic pulmonary artery pressures ⩾ 45 mmHg), arrhythmias (pacemaker/implantable cardiac defibrillator or anti-arrhythmic medications), and interstitial lung disease. Multivariate Cox proportional hazard models were generated for each outcome. A total of 675 subjects were included with a mean follow-up of 3.0 ± 1.8 years. Subjects were predominantly women (88.4%) with mean age of 58.2 ± 11.3 years and mean disease duration of 13.7 ± 9.1 years. One hundred and one (101, 15%) subjects died during follow-up, 37 (6.4 %) developed systolic dysfunction, 18 (2.9%) arrhythmias, 34 (5.1%) pulmonary arterial hypertension, 43 (7.3%) pulmonary hypertension, and 48 (12.3%) interstitial lung disease. In multivariate analyses, elevated levels of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were associated with increased risk of death, while elevated levels of N-terminal pro b-type natriuretic peptide and C-reactive protein were associated with increased risk of developing pulmonary hypertension. In systemic sclerosis, N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein have independent predictive value for death and pulmonary hypertension. A larger study would be required to determine the predictive value of these biomarkers for less common systemic sclerosis outcomes.

Long-term Outcomes of Patients with Systemic Lupus Erythematosus: A Multicenter Cohort Study from CSTAR Registry.

To study the long-term outcomes, in the context of both mortality and organ damage in patients with systemic lupus erythematosus (SLE) in the Chinese SLE Treatment and Research group (CSTAR) registry cohort. Patients were enrolled from April 2009 to February 2010 and they were followed up. The demographic data, clinical manifestations, labs test results and imaging examinations, disease activity (SLEDAI-2K), damage scores (SLLIC/Damage Index [SDI]), and medications were collected. Data were censored at either the last clinic visit or telephonic interview. Survival rate was analyzed by Kaplan-Meier (KM) method. COX proportional hazard model was adopted to perform the analysis of predicting factors for mortality and organ damage. Logistic regression analysis was employed to discuss the relationship among mortality, organ damage, and flare. A total of 2104 patients were recruited at baseline and 1494 patients were followed up. The cumulative 1-year, 3-year, and 5-year survival rates were 98.3%, 96.9%, and 95.7%, respectively. Seventy-eight patients died during follow-up, and the main causes of death were infection (34.6%), active disease (26.9%), cardiovascular and cerebrovascular events (5.13%), and malignancy (5.13%). At entry, 247 patients presented with irreversible organ damage and it increased to 398 patients at the endpoint. The major accumulated organ damages were kidney (25.9%), musculoskeletal disease (20.2%), neuropsychiatric disease (12.2%), and pulmonary damage (10.9%). Cox regression analysis further showed that male, late disease onset, delayed diagnosis (diagnosis from disease onset >1 year), baseline organ damage, and specific organ involvements predicted for higher mortality. In addition, early disease onset was a protecting factor for organ damage, and anti-SSA was an independent predicting factor for new organ damage. Logistic regression analysis showed that flare predicted for more organ damage. The 5-year survival rate of Chinese SLE patients has improved and is comparable to Caucasians SLE patients. Disease flare impact on prognosis is the increasing risk of damage development. Early diagnosis, prevention for flare and damage to maintain remission, may improve outcome.

MP54-16 ASSOCIATION OF URINARY STONES WITH PATIENT-REPORTED COMPLICATIONS IN SPINAL CORD INJURY

You have accessJournal of UrologyStone Disease: Epidemiology & Evaluation II (MP54)1 Sep 2021MP54-16 ASSOCIATION OF URINARY STONES WITH PATIENT-REPORTED COMPLICATIONS IN SPINAL CORD INJURY Khushabu Kasabwala, Michael Borofsky, John T. Stoffel, Blayne Welk, Jeremy B. Myers, Sara M. Lenherr, and Sean P. Elliott Khushabu KasabwalaKhushabu Kasabwala More articles by this author , Michael BorofskyMichael Borofsky More articles by this author , John T. StoffelJohn T. Stoffel More articles by this author , Blayne WelkBlayne Welk More articles by this author , Jeremy B. MyersJeremy B. Myers More articles by this author , Sara M. LenherrSara M. Lenherr More articles by this author , and Sean P. ElliottSean P. Elliott More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002084.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: People with spinal cord injury (SCI) have an increased risk of urinary stone formation and morbidity from the surgeries to remove them. The highest risk of stones has been postulated to be in the first year after SCI, yet the natural history and health-related impact of stone disease among this patient population remains poorly defined. We hypothesized that a history of urinary stones would be associated with an increased incidence of SCI-related complications and lower quality of life (QOL). METHODS: 1479 participants with SCI in the Neurogenic Bladder Research Group registry were asked about urinary stone history (pre-dating or since SCI), SCI-related complications and neurogenic bladder-related QOL. Eligibility: age ≥ 18 years with acquired SCI and followed for 12 months. Neurogenic Bladder Symptom Score (NBSS) was used for QOL assessment. Continuous variables were compared by the t-test and categorical variables were compared by the chi-square test (R version 3.5.2). Because the presence of stones was assessed by participant recall, we limited to those with a history of stone surgery to capture clinically significant urinary calcifications. RESULTS: At study entry, participants were a median of 11 years post-SCI and 189 (12.8%) reported a history of bladder or kidney stone surgery; 99.5% of these occurred after the SCI. Median time between SCI and first stone was 5.6 years (IQR: 1.8 - 12.8). During the year of observation, the incidence of stone surgery was 8%-9% in those with a history of stone surgery and 2% per year in those without prior stone surgery (p=0.001). The rate of patient-reported UTI did not differ between cohorts, but those with prior stone surgery had an increased rate of UTI-related hospitalizations (p=0.013). There was a higher rate of hospitalizations for those with prior stone surgery, commonly for blood clots, UTI, pressure ulcers, and pneumonia (p=0.001). There was no clinically significant difference in NBSS QOL scores across the three cohorts. CONCLUSIONS: Urinary stones in people with SCI are associated with patient-reported complications though they do not appear to affect QOL. Those with a history of urinary stones warrant careful surveillance both for additional stone episodes and for other negative health outcomes. Source of Funding: PCORI/CER-1409-21,348 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e955-e956 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Khushabu Kasabwala More articles by this author Michael Borofsky More articles by this author John T. Stoffel More articles by this author Blayne Welk More articles by this author Jeremy B. Myers More articles by this author Sara M. Lenherr More articles by this author Sean P. Elliott More articles by this author Expand All Advertisement Loading ...

Trends in risk classification at diagnosis and choice of primary therapy for prostate cancer: An analysis of 10839 patients from the Nara Urological Research and Treatment Group registry between 2004 and 2015.

To evaluate trends in risk classification at diagnosis and choice of primary therapy in patients diagnosed with prostate cancer. This retrospective study included 10839 patients who were newly diagnosed with prostate cancer between 2004 and 2015 at 23 Japanese institutions. Risk classification and primary therapies between 2004 and 2015 were evaluated. The trends in risk classification and primary therapy were evaluated using chi-squared tests for trend during four periods (2004-2006; 2007-2009; 2010-2012; and 2013-2015). Binary logistic analysis was used to evaluate the extent to which factors such as age, risk classification, and institution influenced primary therapy choice in the 2013-2015 cohort. The number of patients with very-low or low-risk classification (P<0.001) and metastasis (P=0.04) decreased and the number with intermediate-risk classification (P<0.001) increased during the four periods. A tendency to choose radical prostatectomy as primary therapy for prostate cancer was not observed during the four periods (P=0.90). The number of patients who chose radiation therapy (P<0.001) and active surveillance/watchful waiting (P<0.001) as primary therapies increased during the four periods and the number of patients who chose androgen deprivation therapy (P<0.001) decreased. Age, institution, and risk classification significantly influenced primary therapy choice. We have shown the trends in risk classification of prostate cancer and primary therapy choices between 2004 and 2015 in Japan. Age, institution, and risk classification significantly influenced the decision on primary therapy for prostate cancer.

Factors impacting bowel symptoms in a contemporary spinal cord injury cohort: results from the Neurogenic Bladder Research Group Registry.

Cross sectional. To identify variables associated with severe bowel symptoms in spinal cord injured people. National cohort. Adult spinal cord injured (SCI) people were recruited for an online registry and 1373 were included for analysis. Univariate analysis and logistic regression was used to evaluate associations between severity of bowel symptoms and variables. Bowel symptoms were assessed by the Neurogenic Bowel Dysfunction (NBD) score and patients scoring ≥14 were categorized as having severe bowel symptoms. Autonomic dysreflexia (AD) severity was measured using a six item questionnaire and reported as total AD score (0-24). Bladder management was categorized as: voiding, clean intermittent catheterization (CIC), surgery (augmentation/diversion) or indwelling catheter. Severe bowel symptoms were reported in 570 (42%) On multivariable logistic regression, every point increase of AD total score was associated with 5% increased odds of having more severe bowel symptoms [OR 1.05 95% CI 1.03-1.10]. Type of bladder management was also associated with more severe symptoms (p = 0.0001). SCI people with indwelling catheters (OR = 2.16, 95% CI 1.40-3.32) or reconstructive surgery (OR = 1.79, 95% CI 1.08-3.32) were almost twice as likely to report more severe bowel symptoms than those performing CIC.