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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

New models of survivorship care are needed that improve outcomes for the growing number of cancer survivors, address the increasing complexity of their health needs, and deal with the shortage of clinicians and rising costs of this care. Technology can aid the delivery of personalized, stratified survivorship care pathways where the intensity of care, the care setting, and the providers required for that care vary with survivors’ needs. Building a cancer data ecosystem of connected data streams that supports and learns from each patient can be used to streamline care, enhance efficiency, reduce costs, and facilitate research. This manuscript describes the input, analytics, and output components of the cancer data ecosystem that must be built and connected and also provides a real-world use case of how such a system could transform care in a large US comprehensive cancer center.

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.

Background Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies. Methods This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included. The exclusion criterion was lack of confirmatory standard of reference, either surgical pathology, intraoperative gross confirmation or imaging follow-up. SCI consisted of contrast-enhanced (CE) computed tomography (CT) of the chest/abdomen/pelvis, abdominal/pelvic CE-MR, and/or CE whole-body PET/CT with diagnostic quality (i.e. standard radiation dose) CT. Follow-up was evaluated until 3/2020. Results Thirty-one patients constituted the cohort, 16 (52%) male, median patient age was 53 years (interquartile range: 49-65 years). PET/MR and SCI results were divergent in 19% (95% CI 9-37%) of the cases, with PET/MR leading to management changes in all of them. The diagnostic accuracy of PET/MR was 90 ± 5%, versus 71 ± 8% for SCI. In a pairwise analysis, PET/MR outperformed SCI when compared to the reference standard (p = 0.0412). Conclusions These findings suggest the potential usefulness of PET/MR in the management of oligometastatic CRC.

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.

Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.

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 chimeric antigen receptor (CAR) T-cell therapy. METHODS A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021. RESULTS The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell–related toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell–associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell–associated neurotoxicity syndrome should be managed with corticosteroids and supportive care. Additional information is available at www.asco.org/supportive-care-guidelines .

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 .

Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that may cause severe symptoms and death in elderly or immunocompromised individuals. In light of an increasing resistance of B. microti to drugs, there is a lack of therapeutic alternatives. Species-specific proteases are essential for parasite survival and possible chemotherapeutic targets. However, the repertoire of proteases in B. microti remains poorly investigated. Herein, we employed several combined bioinformatics tools and strategies to organize and identify genes encoding for the full repertoire of proteases in the B. microti genome. We identified 64 active proteases and 25 nonactive protease homologs. These proteases can be classified into cysteine (n = 28), serine (n = 21), threonine (n = 14), asparagine (n = 7), and metallopeptidases (n = 19), which, in turn, are assigned to a total of 38 peptidase families. Comparative studies between the repertoire of B. bovis and B. microti proteases revealed differences among sensu stricto and sensu lato Babesia parasites that reflect their distinct evolutionary history. Overall, this data may help direct future research towards our understanding of the biology and pathogenicity of Babesia parasites and to explore proteases as targets for developing novel therapeutic interventions. Instituto de Patobiología Fil: Florin-Christensen, Monica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina Fil: Florin-Christensen, Monica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wieser, Sarah Nathaly. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Fil: Wieser, Sarah Nathaly. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Suarez, Carlos E. USDA-ARS. Animal Disease Research Unit; Estados Unidos Fil: Suarez, Carlos E. Washington State University. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina Fil: Schnittger, Leonhard. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan parasites of the order Piroplasmida, responsible for diseases in humans and animals. Members of the piroplasmid rhoptry-associated protein-1 (pRAP-1) family have a signature cysteine-rich domain and are important for parasite development. We propose that the closely linked B. microti genes annotated as BMR1_03g00947 and BMR1_03g00960 encode two paralogue pRAP-1-like proteins named BmIPA48 and Bm960. The two genes are tandemly arranged head to tail, highly expressed in blood stage parasites, syntenic to rap-1 genes of other piroplasmids, and share large portions of an almost identical ~225 bp sequence located in their 5′ putative regulatory regions. BmIPA48 and Bm960 proteins contain a N-terminal signal peptide, share very low sequence identity (&lt, 13%) with pRAP-1 from other species, and harbor one or more transmembrane domains. Diversification of the piroplasmid-confined prap-1 family is characterized by amplification of genes, protein domains, and a high sequence polymorphism. This suggests a functional involvement of pRAP-1 at the parasite-host interface, possibly in parasite adhesion, attachment, and/or evasion of the host immune defenses. Both BmIPA48 and Bm960 are recognized by antibodies in sera from humans infected with B. microti and might be promising candidates for developing novel serodiagnosis and vaccines.

Babesiosis is a tick-borne disease with global impact caused by parasites of the phylum Apicomplexa, genus Babesia. Typically, acute bovine babesiosis (BB) is characterized by fever, anemia, hemoglobinuria, and high mortality. Surviving animals remain persistently infected and become reservoirs for parasite transmission. Bovids in China can be infected by one or more Babesia species endemic to the country, including B. bovis, B. bigemina, B. orientalis, B. ovata, B. major, B. motasi, B. U sp. Kashi and B. venatorum. The latter may pose a zoonotic risk. Occurrence of this wide diversity of Babesia species in China may be due to a combination of favorable ecological factors, such as the presence of multiple tick vectors, including Rhipicephalus and Hyalomma, the coexistence of susceptible bovid species, such as domestic cattle, yaks, and water buffalo, and the lack of efficient measures of tick control. BB is currently widespread in several regions of the country and a limiting factor for cattle production. While some areas appear to have enzootic stability, others have considerable cattle mortality. Research is needed to devise solutions to the challenges posed by uncontrolled BB. Critical research gaps include risk assessment for cattle residing in endemic areas, understanding factors involved in endemic stability, evaluation of parasite diversity and pathogenicity of regional Babesia species, and estimation of whether and how BB should be controlled in China. Research should allow the design of comprehensive interventions to improve cattle production, diminish the risk of human infections, and increase the availability of affordable animal protein for human consumption in China and worldwide. In this review, we describe the current state of BB with reference to the diversity of hosts, vectors, and parasite species in China. We also discuss the unique risks and knowledge gaps that should be taken into consideration for future Babesia research and control strategies.

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.

Objective.The Outcome Measures in Rheumatology (OMERACT) Shared Decision Making (SDM) Working Group aims to determine the core outcome domain set for measuring the effectiveness of SDM interventions in rheumatology trials.Methods.A white paper was developed to clarify the draft core domain set. It was then used to prepare for interviews to investigate reasons for lack of consensus on it and to suggest further improvements.Results.OMERACT scientists/clinicians (n = 13) and patients (n = 10) suggested limiting the core domain set to outcome domains, removing process domains, and clarifying remaining domains.Conclusion.A revised core domain set will undergo further consensus-building.

The incidence and prevalence of babesiosis in animals and humans is increasing, yet prevention, control, or treatment measures remain limited and ineffective. Despite a growing body of new knowledge of the biology, pathogenicity, and virulence of Babesia parasites, there is still no well-defined, adequately effective and easily deployable vaccine. While numerous published studies suggest that the development of such anti-Babesia vaccines should be feasible, many others identify significant challenges that need to be overcome in order to succeed. Here, we review historic and recent attempts in babesiosis vaccine discovery to avoid past pitfalls, learn new lessons, and provide a roadmap to guide the development of next-generation babesiosis vaccines.

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.

New technologies can do more than just digitize health information; they can support multimedia platforms for patient education and health decision support. Technology can simplify the way health decisions are made by offering quick access to a vast amount of information that can be tailored to specific populations. Digital tools can increase knowledge and assist consumers in comparing health care alternatives. They are well received by patients because of the myriad features that render them visually appealing and entertaining, including audiovisual and interactive elements. To be effective, however, digital tools must be evidence based and developed following quality standards.

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.

Objective: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions.Methods: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating whiteboard videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set.Results: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1-Knowledge of options, their potential benefits and harms; 2-Chosen option aligned with each patient's values and preferences; 3-Confidence in the chosen option; 4-Satisfaction with the decision-making process; 5-Adherence to the chosen option and 6-Potential negative consequences of the SDM intervention.Conclusion: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set.Clinical significance: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.(c) 2021 Elsevier Inc. All rights reserved.

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

Theileria equi is a widely distributed apicomplexan parasite that causes severe hemolytic anemia in equid species. There is currently no effective vaccine for control of the parasite and understanding the mechanism that T. equi utilizes to invade host cells may be crucial for vaccine development. Unlike most apicomplexan species studied to date, the role of micronemes in T. equi invasion of host cells is unknown. We therefore assessed the role of the T. equi claudin-like apicomplexan microneme protein (CLAMP) in the invasion of equine erythrocytes as a first step towards understanding the role of this organelle in the parasite. Our findings show that CLAMP is expressed in the merozoite and intra-erythrocytic developmental stages of T. equi and in vitro neutralization experiments suggest that the protein is involved in erythrocyte invasion. Proteomic analyses indicate that CLAMP interacts with the equine erythrocyte α-and β- spectrin chains in the initial stages of T. equi invasion and maintains these interactions while also associating with the anion-exchange protein, tropomyosin 3, band 4.1 and cytoplasmic actin 1 after invasion. Additionally, serological analyses show that T. equi-infected horses mount robust antibody responses against CLAMP indicating that the protein is immunogenic and therefore represents a potential vaccine candidate.

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.

Background Babesia bovis reproduces sexually in the gut of its tick vector Rhipicephalus microplus, which involves expression of 6cys A and 6cys B proteins. Members of the widely conserved 6cys superfamily are candidates for transmission blocking vaccines (TBV), but intricacies in the immunogenicity of the 6cys proteins in the related Plasmodium parasites required the identification of transmission blocking domains in these molecules for vaccine design. Hereby, the immunogenic efficacy of recombinant (r) B. bovis 6cys A and B proteins as a TBV formulation was studied. Methods The immunogenicity of r6cys A and 6cys B proteins expressed in a eukaryotic system was evaluated in a cattle immunization trial (3 immunized and 3 control calves). A B. bovis sexual stage induction in vitro inhibition assay to assess the ability of antibodies to block the production of sexual forms by the parasite was developed. Results Immunized cattle generated antibodies against r6cys A and r6cys B that were unable to block sexual reproduction of the parasite in ticks. Additionally, these antibodies also failed in recognizing native 6cys A and 6cys B and peptides representing 6cys A and 6cys B functional domains and in inhibiting the development of sexual forms in an in vitro induction system. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of 6cys A and 6cys B recognized recombinant and native forms of both 6cys proteins as well as peptides representing 6cys A and 6cys B functional domains and were able to neutralize development of sexual forms of the parasite in vitro. Conclusions These data, combined with similar work performed on Plasmodium 6cys proteins, indicate that an effective 6cys protein-based TBV against B. bovis will require identifying and targeting selected regions of proteins containing epitopes able to reduce transmission. Graphical abstract

Bone health education publicly available through the Internet, if evidence-based and unbiased, could help patients deal with issues such as decision-making, maintaining healthy lifestyles, using medications correctly, and improving their communication with health professionals. We performed an environmental scan and quality assessment of the currently available osteoporosis and bone health patient education information on the World Wide Web. The sample websites were identified by using three separate search tools: Google Advanced, Bing, and Ask.com . Two independent investigators collected data and appraised the quality of selected websites. We identified 48 websites. Most websites were focused on risks factors of osteoporosis, preventive measures, screening recommendations, and topics to discuss with the physician. All websites provided adequate information describing treatment options; however, only 36% had information addressing duration of treatment, what happens when treatment stops, and the benefits and risks of various treatments. A total of 55% of the websites had their content updated to 2019 and 68% cited their sources of information to support their content. Reading levels ranged from 7.5 to 15.2 (higher than the recommended 6-grade level). Websites with information about bone health and osteoporosis commonly present information about initial treatment choices, but most fail to address risk-benefit issues, and common barriers than can occur throughout the course of the disease. In addition, many websites did not update their content, did not cite their sources of information, or were written at a 9-grade level or above (rendering them unsuitable for low-literacy populations).

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.

Bovine babesiosis, caused by Babesia bovis and B. bigemina, is a major tick-borne disease of cattle with global economic impact. The disease can be prevented using integrated control measures including attenuated Babesia vaccines, babesicidal drugs, and tick control approaches. Vaccination of cattle with the Rhipicephalus microplus Bm86-based recombinant vaccine reduces the fitness of R. microplus and R. annulatus, but several booster inoculations are required to maintain protection. Herein, we generated a stable transfected strain of B. bovis expressing an enhanced GFP (eGFP) and a chimeric version of Bm86 (B. bovis/Bm86/eGFP). The eGFP was expressed in the parasite cytoplasm, whereas Bm86 was displayed on the surface of merozoites. Three splenectomized calves experimentally infected with B. bovis/Bm86/eGFP showed mild signs of acute disease and developed long-lasting antibody responses to B. bovis and native Bm86. No evidence of sequestration of parasites in the cerebral capillaries was found upon postmortem analysis, confirming attenuation of the strain. This is the first report of transfected B. bovis expressing the tick antigen Bm86 on the merozoite surface that elicits an antibody response to native Bm86. These results represent a proof of concept for a novel live, attenuated, tagged dual-vaccine approach to attempt simultaneous control of babesiosis and tick infestation.

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.