Citations

Abstract Background Inflammatory bowel disease (IBD)–associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. Methods A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. Results A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. Conclusions This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

Introduction: The incidence and risk factors for sudden cardiac death (SCD) in patients with systemic right ventricle (sRV) and D-TGA palliated with atrial switch procedures is not well understood. Methods: This cohort was examined retrospectively for the composite end point of SCD, sustained ventricular tachycardia (VT) >30 s or appropriate ICD therapy for VT. Clinical characteristics of those with and without the end point were compared using the Kruskal-Wallis or Chi-square test as appropriate. Results: The composite end point occurred in 15 of 148 (10%) patients (63.5% male) at a mean age of 36.4 (SD 10.3) years. SCD occurred in 6 patients (n=2 successfully resuscitated), sustained VT in 6 patients and ICD therapy for VT in 3 patients who had previously received a primary prevention ICD. Patients with SCD/VT had lower sRV ejection fraction (EF) compared to patients without SCD/VT [28±11 vs 40±10%, P<0.001]. The odds ratio of SCD/VT in patients with sRVEF≤35% compared to sRVEF>35% was 13.3 (95% CI 2.8 - 64.4). Kaplan Meier analysis of time to SCD/VT stratified by sRV EF is presented in figure. QRS duration, QRS fragmentation, QTc and history of systemic AV valve surgery were not significantly associated with SCD/VT. Non-sustained ventricular tachycardia (NSVT) on Holter monitoring occurred more frequently in SCD/VT patients (80 vs 39%, p=0.003). All 11 survivors of SCD/VT received an ICD; appropriate ICD therapy occurred in 27% of these patients during follow-up. Conclusion: SCD or VT occurred in one-tenth of D-TGA patients palliated with atrial switch, predominantly in 3 rd and 4 th decade of life. Reduced sRV EF was the most important association and ICD implantation for primary prevention of SCD is a reasonable consideration in those with reduced sRV EF.

Background: Patients with ccTGA have a high incidence of atrial arrhythmias and premature failure of the systemic right ventricle. We sought to better define this risk. Methods: A retrospective review of all clinical data for patients with ccTGA followed at a large tertiary care institution was performed. The primary outcome was a composite of death and cardiac transplantation. Results: A cohort of 165 patients (age 41±16 years, 53% male) were followed for 11±8 years; 41 patients died, 7 underwent cardiac transplantation, and 4 underwent VAD placement. Male sex (HR 2.7, p=0.002), older age (HR 1.04, p<0.001), clinical heart failure symptoms (HR 7, p<0.001), heart failure hospitalization (HR 4.9, p<0.001), syncope (HR 1.8, p=0.04) and pulmonary hypertension (HR 2.77, p<0.001) were significant predictors of the primary outcome. Atrial fibrillation (HR 3.5, p=0.002), atrial flutter (HR 3.05, p=0.04), and prolonged QRS duration (HR 1.01, p=0.004) on the first ECG, as well as right and left atrial enlargement (HR 4, p<0.001 and 3.7, p<0.003) and severe systemic AV valve regurgitation (HR 3.8, p=0.03) on the first echocardiogram were associated with poor outcomes. Atrial arrhythmias occurred in 110(67%) patients: atrial fibrillation in 75(45%), atrial flutter in 50(30%), and supraventricular tachycardia in 16(9.7%) patients. Arrhythmias were largely asymptomatic in 109(66%) patients, while 25(14.5%) experienced palpitations, dizziness or presyncope, and 10(6%) presented with decompensated heart failure. Cardioversion and antiarrhythmic therapy were utilized in 53(32%) patients. Surgical pulmonary vein isolation or atrial MAZE were performed in 15(9%) patients, cryoablation of the CTI in 3 patients, and surgical ablation of an accessory pathway in 2 patients. One or more catheter ablation procedures were also performed in 18(11%) patients. Conclusions: Atrial fibrillation and flutter, heart failure, prolonged QRS duration, systemic AV valve regurgitation and pulmonary hypertension predict worse outcomes in ccTGA. Although asymptomatic in a majority of patients, atrial arrhythmias are associated with significant morbidity and mortality. Whether a rhythm control strategy even in asymptomatic patients may improve outcomes remains unknown.

e14591 Background: Combined immune checkpoint inhibitors (ICPI) have revolutionized treatment of solid tumors. Their use can lead to treatment-related adverse events (TRAEs) resulting in hospital admissions, treatment discontinuation and increased morbidity. We aim to evaluate gastrointestinal (GI) TRAEs of different combination ICPI. Methods: A comprehensive search of multiple databases from inception to October 2021 was performed. Phase 2 and 3 trials assessing safety and efficacy of combined ICPI in solid tumors were included. Trials reporting concurrent use of chemotherapy, immunosuppressants, targeted therapy, or sequential ICPI therapy were excluded. Primary outcome was pooled luminal, hepatic and pancreatic TRAEs. A meta-analysis of proportions was done for outcomes using a random-effects model. I2 % was used to assess heterogeneity. Results: Out of 3696 citations screened, 53 trials reporting TRAEs in 6186 patients were included. Data from 41 study arms of 35 trials in nivolumab plus ipilimumab (N+I), 15 study arms of 15 trials in durvalumab plus tremelimumab (D+T), 4 study arms of 3 trials in pembrolizumab plus ipilimumab (P+I). The most common indications for combined ICPI were melanoma (26.4%) and lung cancer (24.5%). Pooled GI TRAE rates from the D+T, P+I and two different dosing combinations of N+I are shown in the table. Conclusions: Our study provides pooled data of TRAEs from different combination ICPI use in solid tumors and demonstrates high incidence of all grades and ≥ 3 GI TRAEs. Combined ICPI related TRAEs should be recognized early, as it may require treatment discontinuation. Further studies are required to assess overall impact of TRAEs on treatment course and outcomes.[Table: see text]