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Risk assessment for early, severe right heart failure (RHF) after LVAD implantation remains imperfect. We sought to define the differences in RV adaptation and load after axillary Impella support between patients who experienced RHF and those who did not. Seventeen of 18 patients included were deemed intermediate or high risk for RHF by EUROMACS-RHF score. Before Impella insertion, RV adaptation parameters (RAP, RAP:PCWP, PAPi) were worse in the non-RHF group compared to the RHF group. In both groups, RV load parameters (effective pulmonary arterial elastance, pulmonary vascular resistance, and pulmonary vascular compliance) improved after Impella insertion. Lesser improvements in RV adaptation were seen in the RHF group. Moreover, load-to-adaptation relationships (EA/RAP and EA/RAP:PCWP) worsened to a greater degree. In patients at intermediate or high risk for RHF after LVAD, assessment of RV adaptation and load during axillary Impella support may improve risk stratification.

BACKGROUND There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning. METHODS A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors. RESULTS There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean. CONCLUSIONS In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion.

Background Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). Methods This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort (http://www.spinsclero.com/en/cohort) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. Discussion The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. Trial registration ClinicalTrials.govNCT04246528. Registered on 27 January 2020

Patient-reported outcomes play an essential role in improving care across the cancer continuum. This paper reports on the experience of a tertiary care center to standardize the use, collection, and reporting of patient-reported outcomes (PROs) in 10 disease-specific survivorship clinics. To minimize the burden of patients to complete surveys, an institutional committee with oversight on all patient surveys required an application be reviewed and approved before their distribution in a clinic. To begin collecting PROs, each clinic submitted an application tailored to its clinical operations, staffing, and scheduling characteristics. The dates for the submission of each application were staggered over a 2-year period, which contributed to a lack of uniformity in the project (ie, approval dates, start dates, collection and reporting of results). The delays were primarily due to the time and resources required to build the electronic version of the PRO survey into the institutional electronic medical record. To date, 6 of 10 survivorship clinics submitted applications, 5 were approved, and 4 launched the electronic MD Anderson Symptom Inventory (eMDASI) through the patient portal. Metrics collected between January 2019 and December 2020 for the thyroid, bone marrow transplant, genitourinary, and head and neck clinics indicated the numbers of eMDASIs sent to patients varied by clinic, with the lowest from the bone marrow transplant survivorship clinic (6) and the highest (746) in the thyroid Clinic. The total number of eMDASIs returned by the patients ranged from 2 (bone marrow transplant) to 429 (thyroid). Overall, patients’ return rates of the eMDASI ranged from 33.3% to 57.7%. Several strategies were implemented to increase the delivery, submission, and completion of eMDASIs. Our findings indicate the integration and implementation of PROs in survivorship clinics are achievable. Further work is needed to enhance the ePROs web-based process to adequately compare PROs across diverse cohorts of cancer survivors .

BACKGROUND Multicenter data on long term survival following LVAD implantation that make use of contemporary definitions of RV failure are limited. Furthermore, traditional survival analyses censor patients who receive a bridge to heart transplant. Here we compare the outcomes of LVAD patients who develop post-operative RV failure accounting for the transitional probability of receiving an interim heart transplantation. METHODS We use a retrospective cohort of LVAD patients sourced from multiple high-volume centers based in the United States. Five- and ten-year survival accounting for transition probabilities of receiving a heart transplant were calculated using a multi-state Aalen Johansen survival model. RESULTS Of the 897 patients included in the study, 238 (26.5%) developed post-operative RV failure at index hospitalization. At 10 years the probability of death with post-op RV failure was 79.28% vs 61.70% in patients without (HR 2.10; 95% CI 1.72 - 2.57; p = < .001). Though not significant, patients with RV failure were less likely to be bridged to a heart transplant (HR 0.87, p = .4). Once transplanted the risk of death between both patient groups remained equivalent; the probability of death after a heart transplant was 3.97% in those with post-operative RV failure shortly after index LVAD implant, as compared to 14.71% in those without. CONCLUSIONS AND RELEVANCE Long-term durable mechanical circulatory support is associated with significantly higher mortality in patients who develop post-operative RV failure. Improving outcomes may necessitate expeditious bridge to heart transplant wherever appropriate, along with critical reassessment of organ allocation policies.

We describe a 31-year-old woman with pulmonary homograft rupture and ventricular fibrillation arrest complicating a transcatheter pulmonary valve (TPV) procedure. She underwent extracorporeal membrane oxygenation (ECMO) with immediate surgical repair including bioprosthetic pulmonary valve replacement. She had difficulty weaning off ECMO due to hyperacute failure of the valve and ultimately underwent successful hybrid TPV with complete recovery. This case illustrates the importance of the heart team approach during catheter and surgical interventions in adult congenital heart disease.

OBJECTIVE: Prospective long-term observational studies (LOS) in rheumatoid arthritis (RA) lack a core set of universally collected outcome measures, particularly patient-centered outcomes, precluding accurate comparisons across studies. Our aim was to identify long-term outcome measures collected and reported in these studies.METHODS: We conducted a systematic review of registries and LOS of patients with RA, searching in ClinicalTrials.gov, the Agency for Healthcare Research and Quality Registry of Patient Registries, and Google Scholar. The names and acronyms of registries and LOS were further searched in the Medline and Embase databases to retrieve published articles. Two independent reviewers undertook data collection, quality appraisal, and data extraction.RESULTS: We identified 88 registries/LOS that met our eligibility criteria. These were divided into 2 groups: disease-based (52 [59%]) and therapy-based (36 [41%]). Methodologic and reporting standards varied across the eligible studies. For clinical outcomes, disease activity was recorded in 88 (100%) of all LOS/registries. The most commonly reported measure (86 [98%]) was the composite outcome Disease Activity Score using 28 joints. Of the patient-centered outcomes collected, physical functioning was most frequently reported (75 [85%]) with the Health Assessment Questionnaire (75 [85%]) as the most commonly used instrument within this domain. Other domains of patient-centered outcomes were comparatively infrequently recorded: mental (29 [33%]), social (20 [23%]), and health-related quality of life (37 [42%]).CONCLUSION: Most registries/LOS collect measures of disease activity and physical function. However, there is substantial heterogeneity in the collection of relevant patient-centered outcomes that measure symptom burden and mental and social ramifications of RA.

Aim: To evaluate adverse events in cancer patients with pre-existing sarcoidosis receiving immune checkpoint inhibitors (ICIs). Patients & methods: We retrospectively reviewed cancer patients with sarcoidosis who underwent treatment with ICI to determine frequency of sarcoidosis flares. Results: 32 patients with sarcoidosis received ICIs The median time to ICI initiation was 7 years (range: 1 month to 51 years). One patient (3%) with a 20-year remote history of sarcoidosis developed a clinically symptomatic exacerbation after three doses of atezolizumab, with hilar lymphadenopathy, subcutaneous nodules, arthritis and uveitis. Atezolizumab was discontinued and prednisone initiated. She had a fluctuating course with two additional flares. Conclusion: Frequency of flares in patients with a remote history of sarcoidosis who receive ICIs is low.

Objective The objective of this study was to assess the efficacy of self-administered patient educational tools in improving knowledge and behaviors for the management of knee osteoarthritis. Methods We conducted a randomized clinical trial in patients with knee osteoarthritis to assess the efficacy of providing a video for entertainment education, in combination with two booklets, compared with providing the booklets alone. We evaluated changes in scores on a patient knowledge questionnaire, the Decisional Conflict Scale, the Arthritis Self-Efficacy Scale, and the Effective Consumer Scale between baseline and same day, 3 months, and 6 months post intervention. We used linear regression models to explore associations between demographic characteristics and outcomes, testing for interactions. Results Two hundred nineteen participants were randomly assigned to receive the video + booklets (n = 109) or the booklets alone (n = 110). The mean age of participants was 64.6 (±8.3) years. At 6 months, statistically significant improvements were observed in knowledge and decisional conflict scores for both groups, and statistically significant improvements in the behavior to participate in their health care were observed in the video + booklets group. The video + booklets group was more knowledgeable immediately post intervention than the booklet group (mean difference 0.39 [95% confidence interval 0.02-0.76]). No other significant changes in outcomes were observed at 6 months between the two groups. The video + booklets combination was associated with decreased decisional conflict in Spanish speakers and increased self-efficacy in those with less than a high school education. Conclusion Although both education strategies were associated with improved knowledge and reduced decisional conflict at 6 months, receiving the video + booklets in combination, compared with receiving the booklets alone, proved to be more effective in changing behaviors and appeared to have some advantages for Spanish speakers and those who were less educated.

Women with estrogen receptor-positive breast cancer who receive an aromatase inhibitor (AI) are at risk for fractures. We aim to determine if dual-energy X-ray absorptiometry (DXA) scans made at the time of AI initiation are associated with decreased fractures. We retrospectively identified 25,158 women with local or regional breast cancer diagnosed between 2005 and 2013 who received AI therapy between 2007 and 2013 from the Medicare-linked Surveillance, Epidemiology, and End Results Program and Texas Cancer Registry databases. We defined baseline DXA screening using claims made between 1 year before and 6 months after each patient's first AI claim to examine determinants of baseline screening using a multivariable GENMOD model. We included a propensity score adjustment in Cox proportional hazard models to assess the association between time-varying DXA screening and the risk of fractures. Additionally, we compared the use of antiresorptive therapy drugs between the two groups. Of the study cohort, 14,738 (58.6%) received DXA screening. The screening rates increased annually from 52.1% in 2007 to 61.7% in 2013. Higher screening rates were observed in patients with younger age, married status, non-Hispanic white race, localized disease, fewer comorbidities, more than one type of aromatase inhibitor drug claim, no state buy-in (surrogate for low socioeconomic status), higher education level, and prior osteoporosis diagnosis. Baseline DXA screening was associated with decreased risk of subsequent fractures (hazard ratio = 0.91; 95% confidence interval, 0.86-0.97, p

Immune checkpoint inhibitors (ICIs) can cause profound immune-related adverse events (irAEs). The host genetic background is likely to play a role in irAE susceptibility because the presentation of toxicity varies among patients and many do not develop irAEs despite continued ICI use. We sought to identify potential genetic markers conferring risk for irAEs. We conducted a pilot exploratory study in 89 melanoma patients who received ICIs (44 with irAEs, and 45 without irAEs after at least 1 year from starting treatment). Genotyping was performed using the Infinium Multi-Ethnic Global-8 v1.0 Bead Chip. The genotype data were extracted using PLINK (v1.90b3.34) and processed for quality control. Population structure-based clustering was carried out using IBS matrix, pairwise population concordance test (p

There are limited data on the use of extracorporeal membrane oxygenation (ECMO) for pregnant and peripartum women with COVID-19 associated acute respiratory distress syndrome (ARDS). Pregnant women may exhibit more severe infections with COVID-19, requiring intensive care. We supported nine pregnant or peripartum women with COVID-19 ARDS with ECMO, all surviving and suffering no major complications from ECMO. Our case series demonstrates high-maternal survival rates with ECMO support in the management of COVID-19 associated severe ARDS, highlighting that these pregnant and postpartum patients should be supported with ECMO during this pandemic.

Objective To evaluate the association of preoperative psychosocial and demographic factors with total knee arthroplasty (TKA) outcomes and satisfaction in patients with osteoarthritis (OA) of the knee at 24 months after surgery. Methods A prospective cohort study of patients undergoing TKA was conducted. Outcome measures included: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form 36 (SF-36) scores at baseline and 24 months after surgery, and patient satisfaction with TKA at 24 months. Linear regression models were performed to evaluate the association of preoperative psychosocial determinants (ie, Medical Outcome Study Social Support Scale; Depression, Anxiety, and Stress Scale; Brief COPE inventory, The Life Orientation Test-Revised; Multidimensional Health Locus of Control; and Arthritis Self-Efficacy Scale) on outcomes. Results We included 178 patients. Increasing WOMAC pain scores at 24 months were associated with increasing age and body mass index (BMI); low tangible social support and low optimism were associated with higher levels of pain (R2 = 0.15). A decrease in WOMAC function scores was also associated with older age and higher BMI; low tangible support, increased stress, and low optimism were also associated with worse function (R2 = 0.22). When evaluating quality of life, lower SF-36 physical functioning scores at 24 months were associated with age, high BMI, and comorbidity (R2 = 0.34). Lower SF-36 mental functioning scores were associated with depression and low optimism (R2 = 0.38). Having a dysfunctional style of coping was associated with lower satisfaction with surgery after 24 months (adjusted R2 = 0.12). Conclusion Psychosocial factors, such as tangible support, depression, dysfunctional coping, and optimism, were associated with pain, function, and satisfaction 2 years after TKA. Perioperative programs identifying and addressing psychosocial problems may result in improvements in pain and function after TKA.

Immune-related adverse events (IrAEs) affecting the gastrointestinal (GI) tract and liver are among the most frequent and most severe inflammatory toxicities from contemporary immunotherapy. Inflammation of the colon and or small intestines (entero)colitis is the single most common GI IrAE and is an important cause of delay of discontinuation of immunotherapy. The severity of these GI IrAEs can range from manageable with symptomatic treatment alone to life-threatening complications, including perforation and liver failure. The frequency and severity of GI IrAEs is dependent on the specific immunotherapy given, with cytotoxic T lymphocyte antigen (CTLA)-4 blockade more likely to induce severe GI IrAEs than blockade of either programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1), and combination therapy showing the highest rate of GI IrAEs, particularly in the liver. To date, we have minimal prospective data on the appropriate diagnosis and management of GI IrAEs, and recommendations are based largely on retrospective data and expert opinion. Although clinical diagnoses of GI IrAEs are common, biopsy is the gold standard for diagnosis of both immunotherapy-induced enterocolitis and hepatitis and can play an important role in excluding competing, though less common, diagnoses and ensuring optimal management. GI IrAEs typically respond to high-dose corticosteroids, though a significant fraction of patients requires secondary immune suppression. For colitis, both TNF-α blockade with infliximab and integrin inhibition with vedolizumab have proved highly effective in corticosteroid-refractory cases. Detailed guidelines have been published for the management of low-grade GI IrAEs. In the setting of more severe toxicities, involvement of a GI specialist is generally recommended. The purpose of this review is to survey the available literature and provide management recommendations focused on the GI specialist.

Background Bisphosphonates and denosumab, as adjuvant therapy in breast cancer, have been associated in some studies with improved cancer outcomes. The potential benefits of these drugs used at the lower doses commonly given for osteoporosis have not been established. The objective of this study was to investigate the association between therapy with bone-modifying agents (BMAs) and survival in older women with early breast cancer. Methods The authors conducted a retrospective cohort study of women aged ≥66 years with breast cancer who were included in the Surveillance, Epidemiology, and End Results and Texas Cancer Registry Medicare-linked databases. Associations were examined between the receipt of BMAs at dosages indicated for osteoporosis within 2 years after diagnosis and overall and breast cancer-specific survival. Cox proportional hazards models and propensity score adjustment and matching were used for the analyses. Results Of the 37,724 women included, 7925 (21%) received at least 6 months of a BMA within the first 2 years of breast cancer diagnosis, including bisphosphonates only in 6898 women (80.7%), denosumab only in 1204 (15.2%), and both classes of BMAs in 323 (4.1%). The median follow-up was 64 months. The receipt of a bisphosphonate was associated with improved overall survival (hazard ratio [HR], 0.87; 95% CI, 0.82-0.93) and breast cancer-specific survival (HR, 0.77; 95% CI, 0.64-0.92) after multivariable adjustment. Benefits were primarily seen for patients who had stage II and III disease. No benefits were observed with denosumab (stage II: HR, 1.05 [95% CI, 0.90-1.22]; stage III: HR, 1.09 [95% CI, 0.66-1.82]). Conclusions Bisphosphonates at the doses recommended for osteoporosis are associated with improved survival in older postmenopausal women with early breast cancer.

While Doppler and cuff blood pressure techniques are prevalent methods of assessing blood pressure in patients with continuous flow left ventricular assist devices, the impact of pulsatility on measurement is not well established. Retrospective chart analysis of clinical variables including pulse perception, blood pressure (Doppler and standard cuff), and aortic valve opening on echo at clinic visit were abstracted. Stable outpatients on continuous flow left ventricular assist devices support with concomitant portable echo assessment were included. Mean average difference was calculated and Pearson’s correlation performed for all those patients who had both Doppler and cuff pressure obtained. In all, 74 Heartmate-II patients with a median time from implant of 380 days were analyzed. A pulse was perceived in 82% of patients with persistent aortic valve opening on portable echo and also in 30% of those who had a persistently closed aortic valve. The mean average difference between the Doppler and systolic cuff pressure was ~13 mmHg ( r = 0.5, p = 0.004) when a pulse was present and ~11 mmHg when aortic valve was open ( r = 0.68, p

Objectives This study presents the largest clinical experience of percutaneously placed axillary intra-aortic balloon pump (IABP) in patients with advanced heart failure. Background Transfemoral placement of IABP limits mobility and recuperation in patients who need prolonged support. We had previously reported a novel percutaneous method of IABP placement in the axillary artery and now present our expanded experience with this technique. Methods We performed a retrospective chart review of patients with advanced heart failure with percutaneous axillary IABP placement from November 2007 to June 2018 at Houston Methodist Hospital. We defined successful cardiac replacement therapy as heart transplant or left ventricular assist device implantation. We compared patients who had successful cardiac replacement with those who died and those who needed unplanned escalation of mechanical circulatory support. Results Of the 195 patients identified, 133 (68%) underwent successful cardiac replacement (120 transplants and 13 left ventricular assist device) as planned. End-organ function improved on IABP support in patients bridged to next therapy. There were 16 patients that died while on IABP support and 18 needed escalation of support. Higher right atrial/wedge ratio, higher right atrial pressure, smaller left ventricular end diastolic dimension, and ischemic cardiomyopathy were associated with death on the IABP in multivariate analysis. Post-transplant and post left ventricular assist device survival for those bridged successfully was 87% and 62%, respectively. Although bedside repositioning was frequent, 37% needed replacement for malfunction. Vascular complications occurred in a minority. Conclusions Percutaneous axillary approach for IABP placement is a feasible strategy for prolonged mechanical circulatory support in patients with advanced heart failure.

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitor (ICPi) therapy. METHODS A multidisciplinary panel of medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to update the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 through 2021. RESULTS A total of 175 studies met the eligibility criteria of the systematic review and were pertinent to the development of the recommendations. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS Recommendations for specific organ system–based toxicity diagnosis and management are presented. While management varies according to the organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert ≤ grade 1. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids. Corticosteroids should be tapered over the course of at least 4-6 weeks. Some refractory cases may require other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines .

Objective To evaluate consensus recommendations regarding management of rheumatoid arthritis (RA) in patients with cancer. Methods We searched electronic databases, guideline registries, and relevant web sites for cancer-specific recommendations on RA management. Reviewers independently selected and appraised the recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. We identified similarities and discrepancies among recommendations. Results Of 4,077 unique citations, 39 recommendations were identified, of which half described their consensus process. Average scores for the AGREE II domains ranged from 33% to 87%. Cancer risk in RA was addressed in 79% of recommendations, with acknowledgement of increased overall cancer risk. Recommendations did not agree on the safety of using disease-modifying antirheumatic drugs (DMARDs) in RA patients with cancer, except for the contraindication of tumor necrosis factor inhibitors in patients at risk for lymphoma. Most recommendations agreed that RA treatment should be stopped and re-evaluated with a new diagnosis of cancer. Recommendations for patients with a history of cancer differed depending on the drug, cancer type, and time since cancer diagnosis. Few recommendations addressed all issues. Conclusion Recommendations for the treatment of RA in patients with cancer often fail to meet expected methodologic criteria. There was agreement on the need for caution when prescribing DMARDs to these patients. However, several areas continue to lack consensus, and given the paucity of evidence, there is an urgent need for research and expert opinion to guide and standardize the management of RA in patients with cancer.

Biologic disease-modifying anti-rheumatic drugs (bDMARDs) interfere with the immune system and could theoretically increase risk of malignancies. However, recent evidence has not substantiated such concerns and physicians are less reluctant in treating patients with underlying cancer with such bDMARDs. We aimed to understand the current utilization patterns of bDMARDs for the treatment of rheumatoid arthritis (RA) in cancer patients.We performed a retrospective cohort study of patients with prevalent RA and cancer initially seen at MD Anderson Cancer Center between 2002 and 2014. A cohort of cancer patients was identified from the tumor registry, and patients with RA were identified through ICD-9 codes, followed by review of electronic medical records. We included patients 18 years and older, with a cancer diagnosis, and a diagnosis of RA by a rheumatologist. Patients were followed until 2016.We identified 431 patients with RA and cancer that met our inclusion criteria. Overall, 111 (26%) received bDMARDs after their cancer diagnosis; of these, 60 (54%) had received bDMARDs prior to their cancer diagnosis and continued to receive this therapy following their diagnosis. Thirteen (22%) switched to a different bDMARD, and the rest continued to receive the same agent after their cancer diagnosis. Of all patients on a bDMARD, 91 (82%) received tumor necrosis factor inhibitors (TNFi).The treatment landscape of patients with a history of cancer and RA is changing. Future studies evaluating the safety of bDMARDs in patients with a recent history of cancer or with active cancer are needed. Part of the data of this project was presented as a poster at the 2016 American College of Rheumatology annual meeting. Zamora NV, Siddhanamatha H, Barbo A, Tayar J, Lin H, Suarez-Almazor M. Utilization of Biologic Therapy in Patients with Rheumatoid Arthritis and Cancer [abstract].Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-biologic-therapy-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed September 30, 2019. Key Points • One in four patients with RA and concomitant cancer received bDMARDs, including TNFi, after their cancer diagnosis, at our institution. • Half of the patients with RA and cancer who received bDMARDs had initiated therapy prior to the cancer diagnosis, continuing thereafter.

Objective To assess methotrexate (MTX) adherence using the Medication Event Monitoring System (MEMS) and characterize associations with adherence in patients with rheumatoid arthritis (RA). Methods Eligible patients participated in Forward, the National Databank for Rheumatic Diseases, and recently (12 months or sooner) initiated oral MTX. MEMS was used to compile MTX weekly dosing over 24 weeks. The Beliefs about Medicines Questionnaire (BMQ) was completed, and baseline demographics and disease characteristics obtained. MTX adherence (percentage of weeks dose taken correctly), implementation (percentage of weeks dose taken correctly from initiation until last dose), and persistence (duration from initiation to last dose) were calculated. Analyses measured associations between patient characteristics and adherence, modeled using logistic generalized estimating equations and censored Poisson regression, and persistence modeled using Cox regression. Results Overall, 60 of 119 eligible patients were included in the analysis. MTX adherence, implementation, and persistence were 75%, 80%, and 83%, respectively, at 24 weeks. Demographics and disease characteristics were generally similar between patients with 1 week or less and 2 weeks or more of missed MTX. Unemployment, less disability, higher Patient Global scores, and no prior disease-modifying antirheumatic drug (DMARD) use were associated with correct dosing. No significant differences in adherence were observed between patients receiving concomitant MTX versus MTX monotherapy, and biologic DMARD-experienced versus biologic DMARD-naive patients. Higher scores in BMQ Specific Necessity (indicating a greater belief in the necessity of the medication) was associated with a decreased likelihood of dosing at an interval shorter than prescribed (odds ratio 0.89). Conclusion Even in a participatory group over a short period, MTX adherence was suboptimal and associated with certain demographics, medication experience, and beliefs about medicines. This suggests a need for screening and alternative treatment opportunities in nonadherent MTX patients with RA.

Background: Despite their efficacy, immune checkpoint inhibitors (ICIs) can cause significant immune-related adverse events (irAEs). Rheumatic and musculoskeletal irAEs can be serious and adversely affect the quality of life. The full spectrum of irAEs is still emerging, and to represent and better understand their scope, we evaluated the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: We used AERSMine, an open-access web application to mine FAERS data across 11,919,342 patients from 2011 (first quarter) to 2018 (fourth quarter). Measures of disproportionality were calculated using well-established pharmacovigilance metrics, proportional reporting ratios, and safety signals (information component), in patients receiving ICI. Results: We analyzed 63,979 cancer patients for reports of ICI-associated AEs. Eighty-two percent of these reports were in relation with anti-PD-1 inhibitors. Rates of rheumatic and musculoskeletal AEs were higher in men and in patients >65 years of age. Several statistically significant AEs were identified, most in relation with PD-1 inhibitors. AEs with the highest number of reports included arthralgia (n = 1062), followed by myalgia (n = 532), myositis (n = 438), arthritis (n = 403), and rhabdomyolysis (n = 230). Novel AEs affecting the skeleton included compression fractures, fractures at various skeletal sites (rib, thoracic vertebral, and humerus), osteonecrosis of the jaw, osteitis, and osteomyelitis. Conclusion: A wide spectrum of rheumatic and musculoskeletal AE signals were detected within the FAERS data which may signify the emerging trends of irAEs post approval of ICI. Additional research to explore mechanisms and identify optimal management strategies of these AEs is warranted.

Background Postoperative bleeding complications are associated with less favorable outcomes in cardiac surgery and contribute to excessive overall healthcare costs. HEMOBLAST (Biom'up, Lyon, France) (HB) is a novel ready-to-use hemostatic powder that consists of porcine collagen, bovine chondroitin sulfate, and human pooled plasma thrombin that may help reduce surgical bleeding. Aims The aim of this study was to describe the techniques of application for this new combination powder-based hemostat, HB, and demonstrate its use employing photographs of application methods during cardiac procedures. Materials and methods The initial 24 procedures in which HB was used at our institution included: left ventricular assist device (LVAD) insertions, lung transplants, heart transplants, aortic valve replacements, coronary artery bypass grafting, and mitral valve repair. Results Hemostasis was achieved in all cases and there were no instances of mediastinitis, sternal infections, allergic reactions, or 30-day mortality. Discussion This report describes the best methods of application of HB including use for treatment of mediastinal bleeding in a re-operative procedure in a patient on antiplatelet agents and sternal bleeding during an LVAD insertion. Proper application can facilitate excellent hemostasis using this powder. Conclusion HB is a novel powder-based multiple component hemostatic agent that promotes focal or large area hemostasis. We have presented the techniques of use that are important to the successful application of HB to facilitate hemostasis.

Patients with cancer and systemic lupus erythematosus (SLE) may have worse outcomes than those without SLE, given their comorbidities. We examined survival in elderly women with breast cancer (BC) and SLE and hypothesized that survival would be decreased compared with women with BC but without SLE.We identified patients with BC and SLE and patients with BC without SLE in the Texas Cancer Registry and Surveillance, Epidemiology, and End Results, linked to Medicare claims. Overall survival (OS) was estimated after matching (age and cancer stage) and in multivariable Cox proportional hazards models adjusting for other cancer characteristics, treatment, and comorbidities. Two additional cohorts of women without cancer with and without SLE were also studied.We identified 494 BC SLE cases and 145,517 BC non-SLE cases, of whom we matched 9,708. Women with SLE were less likely to receive radiation, breast conserving surgery, or endocrine therapy. The 8-year OS estimate for women with early BC (stages 0-II) with and without SLE was 52% (95% confidence interval [95% CI] 45%-59%) and 74% (95% CI 73%-75%), respectively. In the Cox multivariable model, BC and SLE had increased risk of death (hazard ratio [HR] 1.65, 95% CI 1.38-1.98). Women with BC and SLE also had increased risk of death compared with women with SLE but without cancer (HR 1.42, 95% CI 1.05-1.92) after adjusting for SLE severity. Women with SLE and BC received less glucocorticoids, antimalarials, and immunosuppressants after cancer diagnosis than those without cancer.Systemic lupus is a risk factor for increased mortality in women with early BC.

PURPOSE: Readmissions for the medical treatment of cancer have traditionally been excluded from readmission measures under the Hospital Readmissions Reduction Program. Patients with cancer often have higher readmission rates and may need heightened support to ensure effective care transitions after hospitalization. Estimating readmission risk before discharge may assist in discharge planning efforts and help promote care coordination at time of discharge. PATIENTS AND METHODS: We developed and validated a readmission risk scoring system among a cohort of adult cancer patients with solid tumor admitted at a comprehensive cancer center. Multivariate logistic regression analysis was used to develop the model. The model's discriminative capacity was evaluated through a receiver operating characteristic curve analysis. We further compared the performance of the developed score with existing risk scores for 30-day readmission. RESULTS: The 30-day unplanned readmission rate in the total cohort was 16.0% (n = 1,078 of 6,720). After multivariate analysis, Cancer site, Recent emergency room visit within 30 days, non-English primary language, Anemia defined as hemoglobin < 10 g/dL, > 4 Days length of stay during the index admission, unmarried Marital status, Increased white blood cell count > 11 × 109/L, and distant Tumor spread were significantly associated with risk of unplanned 30-day readmission. The derived score, which we call the Cancer READMIT score, had modest discriminatory performance in predicting readmissions (area under the curve for the model receiver operating characteristic curve = 0.647). CONCLUSION: The Cancer READMIT score was able to predict 30-day unplanned readmissions to our institution with fairly modest performance. External validation of our derived risk scoring system is recommended.

Purpose The risks and benefits of remote corticosteroid weaning in heart transplant recipients more than 2 years post-transplant are unknown. We compared outcomes in patients undergoing early and remote steroid weaning after heart transplantation. Methods We performed a retrospective study (range 09, 1991-04, 2017). Primary outcomes included short-term and long-term mortality, allograft dysfunction, and burden of rejection. Secondary outcomes included impact on hemoglobin A1c, lipid panel, bone scan T-score, and body mass index. Results 63 patients underwent corticosteroid weaning between 2012 and 2017. Outcomes of patients weaned early (n = 34; median time from transplant = 1.1 years) were compared with those weaned late (n = 29; median time from transplant = 4.4 years). 52 (82.5%) patients were successfully weaned off corticosteroids. No statistically significant difference in outcomes was found between the early and late weaning groups (p = .20). There were no differences in allograft function (p-value = .16), incidence of rejection (p = .46), or mortality (p = .15). Improvement in metabolic profile was seen in both groups but was not statistically significant. Conclusions In heart transplant recipients, remote vs early weaning of corticosteroids is not associated with significant differences in graft function or the incidence of rejection after 1-year follow-up. Moreover, there were no significant differences in survival up to 3 years between the two groups.

This study aimed to develop a definition of vasoplegia that reliably predicts clinical outcomes. Vasoplegia was evaluated using data from the electronic health record for each 15-minute interval for 72 hours following cardiopulmonary bypass. Standardized definitions considered clinical features (systemic vascular resistance [SVR], mean arterial pressure [MAP], cardiac index [CI], norepinephrine equivalents [NEE]), threshold strategy (criteria occurring in any versus all measurements in an interval), and duration (criteria occurring over multiple consecutive versus separated intervals). Minor vasoplegia was MAP 60 mm Hg or SVR 800 dynes⋅sec⋅cm-5 with CI 2.2 L/min/m2 and NEE ≥ 0.1 µg/kg/min. Major vasoplegia was MAP 60 mm Hg or SVR 700 dynes⋅sec⋅cm-5 with CI 2.5 L/min/m2 and NEE ≥ 0.2 µg/kg/min. The primary outcome was incidence of vasoplegia for eight definitions developed utilizing combinations of these criteria. Secondary outcomes were associations between vasoplegia definitions and three clinical outcomes: time to extubation, time to intensive care unit discharge, and nonfavorable discharge. Minor vasoplegia detected anytime within a 15-minute period (MINOR_ANY_15) predicted the highest incidence of vasoplegia (61%) and was associated with two of three clinical outcomes: 1 day delay to first extubation (95% CI: 0.2 to 2) and 7 day delay to first intensive care unit discharge (95% CI: 1 to 13). The MINOR_ANY_15 definition should be externally validated as an optimal definition of vasoplegia.

Rationale: Growing literature on the coronavirus disease 2019 (COVID-19) suggests that obesity (BMI > 30 kg/m2) is a strong risk factor for increasing disease severity, hospitalization and admission to the intensive care unit (ICU). In such critically ill patients with acute respiratory distress syndrome (ARDS), the use of extracorporeal membrane oxygenation (ECMO) can serve as salvage therapy. The Extracorporeal Life Support Organization (ELSO) COVID-19 ECMO registry reports that 49% of its patients were classified as obese as of 12/01/2020. However, the morbidity and mortality outcomes of this subgroup remains unclear. As such, this high-risk population merits further examination. Methods: We identified adult COVID-19 ARDS patients who were candidates for either veno-venous ECMO or veno-arterial ECMO between March 13, 2020 and August 31, 2020. The eligibility for ECMO was selected based on our institutional algorithm and the EOLIA Trial criteria (except for high BMI cutoff). Patients were divided into two groups, obese (BMI > 30 kg/m2) and non-obese (BMI < 29.9 kg/m2). We compared the pre-cannulation characteristics including time elapsed between admission to ECMO, intubation to ECMO and respiratory indices. We then examined length on ECMO, ICU or hospital length of stay and disposition. Fisher's exact and Mann-Whitney U tests were used to analyze categorical and continuous data. Results: We identified a total of 41 patients, 33 (80.5%) were obese and 8 (19.5%) were non-obese [Table 1]. The average age of the obese and non-obese groups was 47.8 years and 55.5 years respectively. The median BMI was 39.85 kg/m2 (IQR: 35.63, 43.00) in the obese group and 29.05 kg/m2 (IQR: 25.35, 29.39) in the non-obese group (p

Objectives To identify patient-centered core domains for prospective longitudinal observational studies (LOS) in rheumatoid arthritis. Methods Our working group held a virtual meeting in November 2020 to review data from a literature review and patient qualitative interviews, and to discuss strategies to move forward on domain identification and selection using the OMERACT 2.1 domain selection process. Results Important candidate domains and subdomains were identified including in the areas of life impact. Consensus was reached on moving forward with a Delphi process. Conclusions The meeting provided future directions to identify and select a core set of domains for use in LOS.

Aims Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant remains a challenge. The EUROMACS right-sided heart failure (EUROMACS-RHF) risk score was proposed as a prediction tool for post-LVAD RHF but lacks from large external validation. The aim of our study was to externally validate the score. Methods and results From January 2007 to December 2017, 878 continuous-flow LVADs were implanted at three tertiary centres. We calculated the EUROMACS-RHF score in 662 patients with complete data. We evaluated its predictive performance for early RHF defined as either (i) need for short- or long-term right-sided circulatory support, (ii) continuous inotropic support for ≥14 days, or (iii) nitric oxide for ≥48 h post-operatively. Right heart failure occurred in 211 patients (32%). When compared with non-RHF patients, pre-operatively they had higher creatinine, bilirubin, right atrial pressure, and lower INTERMACS class (P Conclusion In an external cohort, the EUROMACS-RHF had limited discrimination predicting RHF. The clinical utility of this score remains to be determined.

As the use of cancer immunotherapy expands, a personalized benefit-risk profile of these agents needs to be considered in special populations at higher risk of experiencing adverse events with these agents. Cancer patients with preexisting autoimmune conditions or those who experience rheumatic adverse events with immunotherapy are faced with difficult decisions regarding their treatment. Often, therapeutic gains in survival need to be balanced with a deleterious impact on quality of life. Risk consideration should include types of potential benefits and harms, magnitude of effects, alternative therapeutic options, and, most importantly, patient values and preferences. Future research should aim to quantify risks in these special populations to ensure evidence-based decision-making that considers patient trade-offs between quality of life and survival.

Summary Background Pain is an important and detrimental feature of systemic sclerosis but is often overlooked or deprioritised in research and clinical care. Raynaud's phenomenon, arthritis, and cutaneous ulcers are among the commonly reported disease manifestations of systemic sclerosis that could be associated with pain. We aimed to assess levels of pain intensity and interference and to evaluate disease factors associated with pain intensity and interference. Methods In this multicentre cross-sectional study, participants from the Scleroderma Patient-centered Intervention Network cohort who completed pain intensity and interference measures (Patient Reported Outcomes Information System-29 profile, version 2·0) as part of baseline assessments were included. Patients were recruited from 46 centres in Australia, Canada, France, Mexico, Spain, the UK, and the USA between April 15, 2014, and Jan 7, 2020. Eligible patients included those aged 18 years or older who met the criteria for systemic sclerosis devised by the American College of Rheumatology and the European League Against Rheumatism. Associations of pain intensity and pain interference with systemic sclerosis-related variables and overlap syndromes, controlling for sociodemographic variables, were assessed with multiple linear regression. Continuous independent variables were standardised. Findings Among 2157 participants with systemic sclerosis (268 [12%] males and 1889 [88%] females), 1870 (87%) reported mild, moderate, or severe pain (defined as ≥1 on a 0 to 10 scale), and 815 (38%) reported moderate or severe pain (defined as ≥5). Moreover, 757 (35%) participants reported moderate or severe pain interference. Greater pain intensity was independently associated with female sex (0·58 points [95% CI 0·26–0·90]), non-White race or ethnicity (0·50 points [0·21–0·79]), fewer years in formal education (0·30 points per SD [0·19–0·41]), country (reference: USA; Canada: 0·29 points [0·01–0·57] and UK: 0·58 points [0·21–0·95]), greater body-mass index (0·35 points per SD [0·24–0·45]); joint contractures (0·67 points [0·39–0·94]), digital ulcers (0·33 points [0·10–0·55]), gastrointestinal involvement (0·66 points [0·33–0·98]), skin involvement (measured using modified Rodnan skin score; 0·22 points per SD [0·10–0·35]), rheumatoid arthritis (0·96 points [0·50–1·43]), and Sjogren's syndrome (0·42 points [0·01–0·83]). Pain interference results were similar. Interpretation Pain is common among people with systemic sclerosis. Controlling for sociodemographic variables, greater pain was associated with multiple systemic sclerosis-related manifestations, including joint contractures, digital ulcers, gastrointestinal involvement, skin involvement, and the presence of overlap syndromes. Health-care providers should work with patients to address pain, including identifying and addressing systemic sclerosis manifestations associated with their pain, and supporting behavioural approaches to minimise impact on function and quality of life. Funding Canadian Institutes of Health Research, Arthritis Society, The Lady Davis Institute for Medical Research of the Jewish General Hospital, Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclerodermie Quebec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland.

Background Patients' information needs may differ from what their care providers may perceive to be the patients' needs. This discordance needs to be recognized and addressed. Objective We conducted a qualitative study to explore the perceptions of patients with selected musculoskeletal disorders and those of rheumatologists, on their preferred strategies for delivery of disease management information. Methods Fifty-two patients diagnosed with either rheumatoid arthritis, knee osteoarthritis, or osteoporosis took part in 6 focus groups and 18 individual semistructured interviews. In addition, 11 rheumatologists participated in 2 focus groups and 4 semistructured individual interviews. Data were explored by thematic content analysis. Perceived preferences were identified and compared between patients and rheumatologists regarding (a) media, (b) setting, (c) messengers, and (d) key message content. Results Patients' preferred media for disease management information were electronic (television and videos delivered as digital optical discs or the Internet), group instruction, and printed material. Patients preferred the information to be delivered in the setting of their homes, doctor's offices, or clinic waiting areas by the rheumatologists and patients with disease experience, addressing healthy lifestyle changes, medication adherence, and consequences of noncompliance. For rheumatologists, the perceived preference for information delivery was through printed material (brochures, booklets, and pamphlets) delivered in waiting areas by nurses and physicians, addressing nature of the disease, complications, and treatment adverse effects. Conclusions Provider perspectives on strategies for education may differ from those of patients. Our findings highlight the need for considering different stakeholder perspectives in designing educational tools and decision support materials for patients with chronic diseases. Take-home message Rheumatologists' preferences on strategies for education (mode of delivery, delivery setting, messengers, and topics) differ from those of patients. For example, patients want to learn about lifestyle changes and consequences of compliance versus noncompliance, whereas rheumatologists considered more important for patients to understand their disease, treatment adverse effects, and consequences of noncompliance.

Introduction: Post-operative right ventricular failure (RV failure) is the single largest contributor to short-term mortality in patients with left ventricular assist devices (LVAD); yet predicting which patient is at risk of developing this complication in the pre-operative setting has remained beyond the abilities of experts in the field. We hypothesized that deep artificial intelligence (AI) driven characterization of subtle pre-operative myocardial motion features, could predict post-operative RV failure in LVAD patients. Methods: We developed a novel echocardiography AI system using an improved dense trajectory algorithm that tracks motion vectors in an unsupervised fashion, and a 3-dimensional convolutional neural network that tracks spatiotemporal features from videos. We used pre-operative ECHO videos from a 536 patient multicenter echocardiographic and clinical dataset, and via a standard 10-fold cross validation, trained and validated the AI system to predict severe or higher grades of post-operative RV failure at the time of index hospitalization. Finally, we independently benchmarked our AI system against clinicians equipped with contemporary clinical risk scores to predict post-operative RV failure (Penn and CRITT score) and manually derived echocardiographic metrics of RV function. Results: 173 (32%) patients were adjudicated to have severe post-operative RV failure. The area under the receiver operator characteristic curve (AUC ROC) for the AI system was 0.86 (95% CI 0.824-0.896). The performance of our AI system exceeded that of both the best performing clinical risk score and manually derived echocardiographic metric by a significant margin (ΔAUC +0.30, 95% CI 0.27 - 0.33 and ΔAUC +0.24, 95% CI 0.21 - 0.27; both p &lt 0.0001). Conclusions: A novel ECHO AI system trained and validated on a multicenter dataset outperformed clinical experts equipped with both contemporary risk scores and manually calculated echocardiographic metrics.

Background Immune checkpoint inhibitors (ICIs) have resulted in unprecedented advances in the treatment of cancer. By disinhibiting the immune system, they enhance anti-tumor immunity, but provoke off-target inflammatory and immune-related adverse events (irAEs) which can seriously impact morbidity and mortality. The exact immunobiology of irAEs is not completely understood, but may involve specific immune pathways. To date, there is no validated biomarker test to predict the development of irAEs in patients treated with ICIs. Methods To identify possible biomarkers of irAEs, we performed in-depth proteomic profiling of blood samples obtained from cancer patients receiving ICIs. The plasmas were processed with Hu-14 immuno-depletion column (Agilent Technologies) and the samples were labeled with TMT (Thermo Scientific). The proteins were next pre-fractionated with HPLC, trypsin digested and analyzed by nanoAQUITY LC coupled Synapt G2-Si ion-mobility mass spectrometry (WATERS). Results A total of 12 patients were enrolled in the study; all were receiving anti-programmed cell death-1 (PD-1) agents. Cancer types included melanoma (n=9), renal cell carcinoma (n=2), and non-small cell lung cancer (n=1). Eight patients had irAEs with active toxicity symptoms at blood draw (4 with pneumonitis-irAE and 4 with arthritis-irAE); 6 of those patients were receiving corticosteroids (ranging from 5 to 60 mg/d), and 1 was receiving tocilizumab (an anti-IL-6 receptor antibody). Four patients who completed a minimum of one year of anti-PD1 treatments without irAEs were enrolled as control group. Median time from ICI initiation until blood draw was 16 months (range, 4–31) among patients with irAEs and 23 months (range, 17–28) among controls.We identified 925 protein gene products from 2.5 million mass spectra that can cover 107 dynamic range of plasma proteins. Among them, 19 proteins showed statistically significant differences between patients with and without irAEs (P Conclusions In-depth plasma proteome analysis identified possible biomarkers of adverse events modulated by ICI treatment. We plan a prospective validation cohort study of melanoma patients initiating treatment with ICIs to further evaluate the potential clinical utility of the identified biomarkers and their association with immune toxicity, and tumor response to ICI therapy. Ethics Approval The study was approved by The Institutional Review Board at The University of Texas MD Anderson Cancer Center, approval number PA16-0928 Consent Written informed consent was obtained from all patients who agreed to participate in the study

Background Autoimmunity is associated with increased risk of malignancy. However, patients with pre-existing autoimmune diseases (AIDs) were excluded from immune checkpoint inhibitor (ICI) trials as these agents can cause immune-related adverse events (irAEs). Data are limited on the safety and efficacy of combination immunotherapy in this at-risk population. Methods We conducted a multi-center retrospective study to evaluate the safety and efficacy of ICI therapy in patients with pre-existing AID treated at NYU and at MD Anderson Cancer Center. Primary endpoints were occurrence of irAEs and AID flares. Secondary endpoints were time to treatment failure (TTF) and overall survival (OS). Results Of 121 patients identified from our institutional databases, 53% received single-agent anti-PD-1 therapy, and 47% received ICI combination. Over half of malignancies were lung cancer (34%) and melanoma (20%). Preexisting AIDs included: rheumatologic (58%), gastrointestinal (12%), endocrine (16%) and neurologic (4%). Overall, 94% had asymptomatic AID, and 21% were receiving systemic immunomodulatory drugs at ICI initiation. Median duration of follow up after ICI initiation was 9 (0.4–41.9) months in patients receiving ICI combination and 8 (0.2–47.3) months in patients receiving anti-PD-1 monotherapy. Combination therapy was associated with higher rates of irAEs compared with anti-PD-1 monotherapy (56% versus 28%). Grade 3/4 irAEs were equivalent in both groups: combination (38%) and anti-PD-1 group (39%). Treatment related deaths were not observed in any group. AID flares occurred in 36% of the anti-PD-1 group versus 29% of combination group. Adverse events (irAEs and/or flares) required systemic immunomodulatory therapies more frequently in the combination group (84%) versus the anti-PD-1 group (59%), and permanent ICI discontinuation was reported in 19% of patients in the combination group versus 11% in the anti-PD-1 group. Tumor progression was observed in 49% of patients on combination ICI and TTF was 14.5 months (95% CI 0.000–31.5), while progression was observed in 64% of patients on anti-PD-1 monotherapy and TTF was 6.4 months (95% CI 4.01–8.9) (p=0.019). Median OS in the combination therapy group was not reached whereas it was 27.3 months in the anti-PD-1 monotherapy group. Conclusions Our novel findings suggest that high rates of adverse events were observed in patients with pre-existing AIDs treated with ICI combination therapy. However, they were manageable and rarely required permanent ICI discontinuation. Taken together, these data show that ICIs should be offered, albeit with caution in patients with AIDs, to achieve durable cancer remission. Prospective clinical data are needed to guide these complex decisions. Ethics Approval The study was approved by NYU Langone’s Ethics Board, approval number i18-01657 and MD Anderson’s Ethics Board, approval number PA19-0089

Introduction Microinvasive diseases of the cervix are conventionally treated with radical hysterectomy after confirmation of invasion depth and lymphovascular invasion in excisional biopsy. In some cases conization could be the definitive treatment in patients who wish to preserve fertility, it is essential to know the state of the section margins. The objective of this presentation is to demonstrate the risk of residual disease with cone positive margins. Methods Retrospective review of patients with microinvasive cervical cancer between December 2014 and February 2020. The contact of the lesion directly with the edge of the cone was taken as positive margin, we compared results of cone biopsies and hysterectomies. Results The study included 47 patients (median age 42.9). Diagnoses of microinvasive cervical cancer: insitu adenocarcinoma, (FIGO IA1 and IA2), histological: adenocarcinoma and squamous. 42 patients met the inclusion criteria (cone biopsy and hysterectomy). 30 (71%) with squamous cancer and 12 (29%) with adenocarcinoma. In 30 patients with squamous types, 14 cones had a positive margins, from which 10 (71%) surgical specimens resulted with residual disease, and 16 cones with negative margins, from which 1 (6.25%) specimen resulted with residual disease. In 12 patients with adenocarcinoma, there were 8 cones with positive margins, 6 (75%) surgical pieces were found with residual disease; 4 cones with negative margins, 3 (75%) surgical pieces were found with residual disease. Conclusions Patients with positive margins regardless of histologic type are at increased risk for residual disease and is clearly more risky in adenocarcinomas due to multifocality.

Introduction The objective of this presentation is to evaluate the reason for referral of patients with a diagnosis of cervical adenocarcinoma treated in the Cervical Pathology Unit of the Hospital San Borja Arriaran. Material and Method Retrospective analysis of records of patients treated for cervical adenocarcinoma, between the years 2008 to January 2019. Results Of 5353 positive cytologies studied between January 2008 and January 2019, a total of 105 adenocarcinoma were found, with a median age of 47 years (between 20 to 85 years). Out of these 105 patients: 15% were referred due to clinical suspicion, of which 5 patients (30%) had a visible tumor; and 89 patients (85%) were referred due to altered cytology, corresponding to 2% of the total. Analyzing the cytology that originated the referral of these 89 patients with abnormal results, 41.5% (37) had a PAP suggestive of adenocarcinoma, 6.7% (6) were suggestive of squamous carcinoma, 28% (25) had a PAP NIE II-III, and 23.5% (21) had an atypical in one of its three varieties [double non-specific atypical: 9.5% (2), glandular atypical: 47.6% (10) and atypical that does not exclude high-grade injury 42.8% (9)]. Conclusions Cervical adenocarcinoma is an emerging entity and it is difficult to diagnose. Screening programs do not necessarily decrease its incidence, on the contrary, they have become the main source of referral for cervical adenocarcinoma. In our review, it corresponded to 85% of the cases. Despite the difficulty of investigating an adenocarcinoma through PAP, this was the main cause of referral. The referral for clinical suspicion corresponded to 15%.

Background Management of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients. Methods We searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed. Results Median age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%). Conclusions Our data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs. Ethics Approval The study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

Hospital San Borja Arriaran, Chile Upon the publication of the LACC study, increasing evidence has emerged regarding the superiority of open versus minimally invasive surgery (MIS) in the treatment of cervical cancer. Introduction to report and compare the surgical results among woman undergoing surgery for cervical cancer with open versus MIS in San Borja Arriaran Hospital. Methods retrospective analysis, involving patients with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer undergoing open or MIS between 2015 to 2019. Data obtained from oncology committee registry. Analysis of demographic, histological and surgical variables. Data analyzed using the Chi2, Student’s t, and Fischer test with a 95% confidence interval and a P value of Results 42 patients analyzed, 20 in the open surgery and 22 MIS group. The mean age (46.2 ± 2.9 v/s 46.9 ± 2.37; P = 0.49). Surgical result, the number of nodes obtained in open surgery was significantly higher than in the MIS technique (27.4 ± 2.6 v/s 20.3 ± 2.04; P = 0.038), with no differences in the number of positive nodes, compromise of surgical margins, parametrial compromise, tumor size or in lymphovascular invasion. There was no significant difference in adjuvance treatment. Due to the short follow-up period in the open surgery group, no recurrence or survival analysis was performed. Conclusion Despite the small sample size, a significant difference in known variables of the oncological result, such as the number of lymph nodes obtained. This provides a first approach regarding oncological outcome. Survival analysis will be evaluated in future analysis.

Assess the association between digoxin use and gastrointestinal bleeding (GIB) in a multicenter continuous flow left ventricular assist device (LVAD) cohort.Patients implanted with continuous flow LVADs with data on GIB and digoxin use from two centers were included in the analysis (n = 649). GIB events were captured up to 2 years of follow-up. Digoxin use was defined as digoxin prescribed at discharge or within the first 3 months after LVAD implantation. A negative binomial regression model was performed to determine the association between digoxin use and number of GIB events over the follow-up period.Mean age of the cohort was 57 years (±14) and 45% (293/649) were bridge to transplant (BTT). Digoxin was prescribed in 33% of patients. Digoxin use was associated with an unadjusted 32% reduction in the incidence of rate of all cause GIB (IRR 0.68, 95% CI 0.46-0.99, p = 0.049). After adjusting for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, renal function, and implanting center there was still a 34% reduction in the incidence rate (IRR 0.67, 95% CI 0.45-0.99, p = 0.048). When limiting the analysis to those with likely arteriovenous malformation associated GIB, the association strengthened (unadjusted: IRR 0.48, 95 % CI 0.26-0.89, p = 0.02, adjusted: IRR 0.47, 95 % CI 0.25-0.9, p = 0.022).In this multicenter study, inclusive of contemporary devices, digoxin use was associated with reduced GIB events. Prospective data will be required to confirm this association.

Introduction No studies have examined factors associated with fear in any group of people vulnerable during COVID-19 due to pre-existing medical conditions. Objective To investigate factors associated with fear of consequences of COVID-19 among people living with a pre-existing medical condition, the autoimmune disease systemic sclerosis (SSc; scleroderma), including country. Methods Pre-COVID-19 data from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort were linked to COVID-19 data collected in April 2020. Multivariable linear regression was used to assess factors associated with continuous scores of the 10-item COVID-19 Fears Questionnaire for Chronic Medical Conditions, controlling for pre-COVID-19 anxiety symptoms. Results Compared to France (N = 156), COVID-19 Fear scores among participants from the United Kingdom (N = 50) were 0.12 SD (95% CI 0.03 to 0.21) higher; scores for Canada (N = 97) and the United States (N = 128) were higher, but not statistically significant. Greater interference of breathing problems was associated with higher fears due to COVID-19 (Standardized regression coefficient = 0.12, 95% CI 0.01 to 0.23). Participants with higher financial resources adequacy scores had lower COVID-19 Fear scores (Standardized coefficient = −0.18, 95% CI −0.28 to −0.09). Conclusions Fears due to COVID-19 were associated with clinical and functional vulnerabilities in this chronically ill population. This suggests that interventions may benefit from addressing specific clinical issues that apply to specific populations. Financial resources, health policies and political influences may also be important. The needs of people living with chronic illness during a pandemic may differ depending on the social and political context in which they live., Highlights • People with chronic diseases may experience high levels of fear due to COVID-19. • We examined factors associated with fears due to COVID-19 in an at-risk population. • We used the validated COVID-19 Fears Questionnaire for Chronic Medical Conditions. • Fears due to COVID-19 among people with SSc differed substantially by country. • Interference of breathing problems and financial adequacy were related to fears.

Background Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. Methods We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. Results The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. Conclusions Our results support the need for a standardized framework for patients’ reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients’ and investigators’ perspectives. Registration PROSPERO: CRD42018108393

Management of rheumatoid arthritis (RA) in patients with cancer is complex and requires a multidisciplinary approach. A few studies have examined the risk for recurrence in patients with RA receiving disease-modifying antirheumatic drugs, primarily tumor necrosis factor-α inhibitors. Although these agents seem to be safe in patients with a history of cancer and no evidence of disease, additional information is needed to determine their potential effects in patients with RA and active cancer. Patients with RA undergoing cancer therapy, including surgery, radiation, chemotherapy, and immunotherapy, need to be carefully monitored because they are at increased risk for adverse events.

The effects of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs.We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate.We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1 years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively.No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer. Key Points •We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not. •Most patients who received bDMARDs had been diagnosed with early stage cancer •As few patients with advanced cancer received bDMARDs safety for this group cannot be established •No significant differences were observed between TNFi and nonTNFi, but the sample size was small.

OBJECTIVE To determine rates of cervical cancer screening and associated abnormal results in women with systemic lupus erythematosus (SLE). METHODS We identified women with an initial diagnosis of SLE in the MarketScan Commercial Claims and Encounters Database from 2001 to 2014. Cervical cancer screening rates and associated diagnostic claims within 3 years of the initial claim were determined. Multivariable logistic regression was performed to evaluate the association of screening with lupus treatment. A matched logistic regression analysis was conducted to compare screening rates to those in age-matched women without connective tissue disease. RESULTS We included 4,316 women with SLE. Screening rates were higher in women with SLE than in general controls (73.4% versus 58.5%; P < 0.001). Factors associated with decreased screening included recent time (odds ratio [OR] 0.70 [95% confidence interval (95% CI)] 0.55-0.89) (2012-2014 compared to 2001-2005), age ≥61 years (OR 0.27 [95% CI 0.18-0.39]), comorbidity score ≥2 (OR 0.71 [95% CI 0.6-0.83]), corticosteroid use (OR 0.77 [95% CI 0.61-0.97]), and use of immunosuppressants (OR 0.80 [95% CI 0.69-0.94]). Abnormal pathology result claims were more common in women with SLE than in general controls (12.3% versus 9.8%; P < 0.001). CONCLUSION Though with higher rates than the general cohort, over 25% of the patients with SLE were not screened, and screening rates seem to be decreasing over time. Patients with SLE are at higher risk of abnormal cervical screening test results than controls, supporting the need for regular screening.

Background To date, there have not been any epidemiologic studies that have evaluated the association between swimming over a lifetime and knee health. Objective The study aimed to evaluate the relationship of a history of swimming with knee pain, radiographic knee OA (ROA), and symptomatic knee OA (SOA). Design Cross-sectional retrospective study. Setting Four academic centers in the United States. Participants Respondents to the historical physical activity survey within the Osteoarthritis Initiative with knee radiographs and symptom assessments. Methods In this retrospective study nested within the Osteoarthritis Initiative, researchers performed logistic regression with the predictor being swimming over a lifetime and over particular age ranges. Main outcome measurements Person-based definitions of frequent knee pain, ROA, and SOA. Results A total of 2637 participants were included, with a mean age of 64.3 years (SD 8.9), body mass index of 28.4 kg/m2 (SD 4.9), and 44.2% male. Over a lifetime, the adjusted prevalence measures for frequent knee pain, ROA, and SOA for any versus no history of swimming were 36.4% (33.4% - 39.5%) v. 39.9% (37.4% - 42.5%), 54.3% (51.0% - 57.6%) v. 61.1% (58.4% - 63.7%), and 21.9% (19.4% - 24.7%) v. 27.0% (24.7% - 29.4%) respectively. Conclusions This is the first epidemiologic study to indicate that swimming is potentially beneficial toward knee health, particularly when performed earlier in life (before age 35). Future prospective studies are needed to confirm these findings and to better scrutinize the associations in older age groups.

Background Identifying changes in pain score associated with clinically meaningful outcomes is necessary when using self-report measures to assess pain in children. We aimed to determine the changes in pain score associated with a minimum clinically significant difference (MCSD), ideal clinically significant difference (ICSD), and patient-perceived adequate analgesia (PPAA) and to evaluate for differences based on initial pain intensity and patient characteristics. Methods This was a cross-sectional study of children 6 to 17 and 4 to 17 years old who were assessed using the Verbal Numerical Rating Scale (VNRS) and Faces Pain Scale-Revised (FPS-R), respectively. Children qualitatively described any endorsed change in pain score; those who received an analgesic were asked if they wanted additional analgesics to decrease their pain intensity. We used a receiver operating characteristic curve-based methodology to identify changes in pain score associated with "a little less" and "much less" pain (MCSD and ICSD, respectively) and patients declining additional analgesics because of adequate analgesia (PPAA). Results We enrolled 431 children with painful conditions. For the VNRS, raw change and percent reductions in pain scores associated with MCSD, ICSD, and PPAA were 2/10 and 20%, 3/10 and 44%, and 2/10 and 29%, respectively, and for the FPS-R, 2/10 and 33%, 4/10 and 60%, and 4/10 and 40%, respectively. Raw change in pain scores increased with increasing initial pain intensity, but percent reductions remained stable. There were no significant differences based on patient characteristics such as age, sex, and race/ethnicity. Conclusion Our findings provide patient-centered outcomes in children that are suitable for designing trials and are generalizable across patient characteristics.

Objectives Immune checkpoint inhibitors (ICIs) can successfully treat cancer, but their use can be hindered by serious immune-related adverse events. We report six patients receiving ICIs who presented with de novo myositis. Methods We identified patients with myositis who were receiving ICIs between January 2004 and September 2016 at The University of Texas MD Anderson Cancer Center. Results Six patients developed de novo myositis. The mean age was 64.3 years and five patients were male. Cancer types included melanoma, urothelial carcinoma, renal cell carcinoma, and prostate cancer. ICI regimens included single-agent ipilimumab (n = 1), pembrolizumab (n = 1), or atezolizumab (n = 1); nivolumab and ipilimumab (n = 3). The median time to development of de novo myositis from first infusion was 5.4 weeks (range: 2.1–17.1 weeks). All patients with myositis had elevated levels of creatinine kinase, ranging from 514 to 13,710 U/L. Two of them developed rhabdomyolysis, one with concurrent myocarditis. Five patients were treated with 1–2 mg/kg corticosteroids, with variable response rates; one patient received nonsteroidal anti-inflammatory drugs. Two patients with myositis died as a result of cancer progression. Conclusion We found several occurrences of de novo myositis following ICI therapy. These preliminary data suggest that myositis can occur early after onset of ICI therapy with serious adverse outcomes.