An experimental paradigm for triggering a depressive syndrome.

Research investigating whether depression is an adaptation or a disorder has been hindered by the lack of an experimental paradigm that can test causal relationships. Moreover, studies attempting to induce the syndrome often fail to capture the suite of feelings, thoughts, and behaviors that characterize depression. An experimental paradigm for triggering depressive symptoms can improve our etiological understanding of the syndrome. The present study attempts to induce core symptoms of depression, particularly those related to rumination, in a healthy, nonclinical sample through a controlled social experiment. These symptoms are sad or depressed mood, anhedonia, feelings of worthlessness or guilt, and difficulty concentrating. One hundred and thirty-four undergraduate students were randomly assigned to either an exclusion (E) or control (C) group. Participants in the exclusion group were exposed to a modified Cyberball paradigm, designed to make them feel socially excluded, followed by a dual-interference task to assess whether their exclusion interfered with their working memory. Excluded participants: (a) self-reported a significant increase in sadness and decrease in happiness, but not anxiety or calmness; (b) scored significantly higher in four of five variables related to depressive rumination; and (c) performed significantly worse on a dual-interference task, suggesting an impaired ability to concentrate. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Systematic review and meta-analysis evaluating clinical outcomes in adult acute myeloid leukemia patients with central nervous system involvement.

Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication.

Psychosocial interventions to improve sexual functioning in women with cancer: a systematic review of randomized controlled trials.

INTRODUCTION: Many women with cancer struggle with sexual side effects during and after treatment. Although preliminary evidence indicates that psychosocial interventions may be efficacious in improving sexual functioning for women with cancer, no systematic review has summarized the state of the science in this area. OBJECTIVES: The primary goal of this review was to narratively synthesize the results of randomized controlled trials (RCTs) testing the efficacy of psychosocial interventions to address sexual dysfunction in women with cancer. A secondary goal was to describe the diversity of the included samples (ie, racial/ethnic and sexual minority). METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted examining RCTs of psychosocial interventions to improve sexual functioning for women with cancer. Articles were identified using MEDLINE, Embase, PsycINFO, and Cochrane CENTRAL. Two reviewers independently assessed each article for inclusion, with a third to resolve discrepancies. RESULTS: Seventeen studies were included in the review, 12 of which provided sufficient information to calculate effect sizes. Ten of the 12 studies primarily aimed to improve sexual functioning, all of which demonstrated positive effects on at least 1 outcome of sexual functioning. In the 2 RCTs of psychosocial interventions in which sexual function was a secondary aim, effects were negligible (ds = -0.04 and -0.15). Commonalities among the studies with large effect sizes were that they included education, mindfulness/acceptance, and communication/relationship skills as intervention components. Of note, there was an overall lack of sample diversity across studies, and most studies failed to report the race/ethnicity or sexual orientation of the participants. CONCLUSION: Results support interventions targeting sexual functioning outcomes for women with cancer and suggest that multimodal interventions including education, mindfulness/acceptance, and communication/relationship skills may be most effective. Future research should also focus on examining the efficacy and potential adaptations of extant sexual functioning interventions for underrepresented groups.

Systematic review: Scores used to predict outcomes in acute severe ulcerative colitis.

Predictive scores for ASUC outcomes according to time of application.

Impact of exercise on continence in prostate cancer patients post robotic assisted radical prostatectomy: a systematic review.

INTRODUCTION: Urinary incontinence is one of the most common long term side effects after robotic prostatectomy (RALP), and significantly impacts patient quality of life. Pelvic floor muscle training (PFMT) has been a standard part of the urologist's armamentarium for maximizing continence outcomes post-op. Recently, aerobic and resistance exercises have been described as improving functional outcomes post RALP. We performed a systematic review to determine the influence of exercise, in the form of PFMT, aerobic exercise, and resistance training, on incontinence post-RALP. MATERIALS AND METHODS: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with database searches performed on January 14, 2022 and again on August 10, 2022 to account for any new publications. The search identified 1675 papers. Of the 1675 papers, 1007 were found to be duplicates, leaving 668 total studies for screening. Of the 668 papers, nine met all inclusion criteria. Of the nine, four studies presented data from patients who had undergone RALP and were included in the final descriptive systematic review. RESULTS: Sayilan et al. and Milios et al. showed postoperative PFMT and physical activity resulted in significantly improved continence outcomes at 1 and 6 months and 2, 6, and 12 weeks postoperatively, respectively. Heydenreich et al. combined PFMT with an oscillating rod therapy, which was found to significantly improve both postoperative urinary continence and health related quality of life compared to PFMT and relaxation techniques alone. On the contrary, Goode et al. examined delivery of exercise information and demonstrated no difference in continence outcomes between focused telehealth PFMT program and generic prostate cancer education. CONCLUSION: Pelvic floor muscle training, with or without adjunct therapies, results in improved continence outcomes post RALP. Supervised training programs may or may not accelerate this finding. There is no recent literature to support or refute the benefit of aerobic exercise or resistance training on reducing post-prostatectomy incontinence after RALP.

Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD. METHODS: MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger's test. RESULTS: Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4-52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05). CONCLUSIONS: There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings.

An overlooked mimic? Autoimmune myelofibrosis-A scoping review of the literature.

BACKGROUND AND OBJECTIVES: Autoimmune myelofibrosis (AIMF) is a rare cause of bone marrow fibrosis (BMF) occurring in the presence or absence of a defined autoimmune disease (secondary or primary AIMF, sAIMF/pAIMF, respectively). Unlike primary myelofibrosis (PMF), AIMF responds well to immunosuppressive therapy with a benign clinical course. Diagnostic criteria for AIMF in opposition to PMF have been lacking, though recent work has helped better characterise molecular and pathological features of AIMF, improving diagnostic precision. METHODS: Using a modern clinical and pathophysiological understanding of AIMF, we apply scoping review methodology and rigorous case-criteria to retrospectively analyse the case literature. We examine its patient-population, describing patient-associated factors, presentation, bone marrow pathology, genetics, treatment and outcomes. RESULTS: Fifty-five studies were identified, describing 139 AIMF patients. Patients were mostly young females (~4:1 ratio female:male, median age 40.8 years) and typically presented with cytopenias. Splenomegaly was rare. sAIMF was more common than pAIMF (~3:1 ratio), and most cases responded well to immunosuppressive therapy. CONCLUSIONS: Our results strengthen the emerging picture of AIMF's patient population, natural history and response to treatment. Further work should continue to use reproducible diagnostic criteria, and explore AIMF's pathophysiology, response to different therapies, and sequelae over larger timescales, as well as differences between pAIMF, sAIMF and PMF.

Relating movement markers of schizophrenia to self-experience-a mixed-methods study.

Introduction: Basic self-disorders on the one hand and motor symptoms on the other hand are discussed as endophenotypes of schizophrenia psychopathology. However, the systematic interaction between motor symptoms and the self-experience of patients is rarely studied. Methods: In a previous study we defined motor markers of schizophrenia via a data-driven analysis of patients' gait patterns. In this study, we related the movement markers to measures of basic self-disorder obtained with EASE interviews. We substantiated the correlations with a qualitative content analysis of the interviews of a subset of four patients. We related qualitative and quantitative data on an intra- and interpersonal level. Results: Our results suggest an association between the previously defined, theory-independent movement markers and basic self-disorders, specifically in the domain of cognition, self-experience and bodily experiences. While movement marker manifestation was not precisely reflected in the individuals' descriptions of anomalous self- and body experience, we found clear trends of more and more intense descriptions with increasing movement marker scores, when looking at specific experiences, such as hyper reflexivity. Discussion: These results foster an integrated view of the patient and could stimulate therapeutic approaches aiming at an improvement of self- and body-experience of patients with schizophrenia.

Psychoeducation for individuals at clinical high risk for psychosis: A scoping review.

Psychoeducation is recommended in the treatment of patients with schizophrenia and has been shown to improve satisfaction with mental health service and treatment adherence, reduce relapse and hospital readmission rates, and enhance functioning and quality of life. Youth at clinical high risk for psychosis (CHR) may also benefit from receiving psychoeducation as part of their treatment. The goal of this study was to conduct a scoping review to map out the existing literature on psychoeducation for CHR individuals, including content, utilization, and benefits, in order to identify areas for future research and clinical care. Following PRISMA guidelines, we conducted a systematic search of electronic databases (MEDLINE, Embase, PsycINFO, Scopus, and Web of Science Core Collection) to identify literature through 02/25/2022 that provided data or significant commentary about the provision of psychoeducation to CHR individuals. After screening titles and abstracts, four co-authors assessed full-text articles for eligibility. Thirty-three studies were included in the review. Psychoeducation is recommended in the treatment of CHR individuals, is a preferred treatment option among CHR individuals, and many CHR programs report offering psychoeducation. However, details about the psychoeducational content and method of delivery are notably absent from recommendations and reports on the provision of CHR psychoeducation in real-world settings. We identified two brief and structured CHR psychoeducation interventions and one longer-term psychoeducational multifamily group model for CHR that show feasibility and promise, though they have not yet undergone randomized trials to evaluate effectiveness of the psychoeducation. We also identified several comprehensive CHR interventions that included an explicit psychoeducation module, though the unique role of the psychoeducational component is unknown. Despite being recommended as a critical component of treatment for CHR individuals and preferred by CHR individuals, the ways in which psychoeducation are being delivered to CHR individuals in real-world practice is still largely ambiguous. Rigorous evaluations of psychoeducation treatment models are needed, as well as investment from clinical programs to facilitate the implementation and dissemination of standardized psychoeducation for CHR individuals.

Assessing the Severity of COVID-19 Lung Injury in Rheumatic Diseases Versus the General Population Using Deep Learning-Derived Chest Radiograph Scores.

OBJECTIVE: COVID-19 patients with rheumatic disease have a higher risk of mechanical ventilation than the general population. The present study was undertaken to assess lung involvement using a validated deep learning algorithm that extracts a quantitative measure of radiographic lung disease severity. METHODS: We performed a comparative cohort study of rheumatic disease patients with COVID-19 and ≥1 chest radiograph within ±2 weeks of COVID-19 diagnosis and matched comparators. We used unadjusted and adjusted (for age, Charlson comorbidity index, and interstitial lung disease) quantile regression to compare the maximum pulmonary x-ray severity (PXS) score at the 10th to 90th percentiles between groups. We evaluated the association of severe PXS score (>9) with mechanical ventilation and death using Cox regression. RESULTS: We identified 70 patients with rheumatic disease and 463 general population comparators. Maximum PXS scores were similar in the rheumatic disease patients and comparators at the 10th to 60th percentiles but significantly higher among rheumatic disease patients at the 70th to 90th percentiles (90th percentile score of 10.2 versus 9.2; adjusted P = 0.03). Rheumatic disease patients were more likely to have a PXS score of >9 (20% versus 11%; P = 0.02), indicating severe pulmonary disease. Rheumatic disease patients with PXS scores >9 versus ≤9 had higher risk of mechanical ventilation (hazard ratio [HR] 24.1 [95% confidence interval (95% CI) 6.7, 86.9]) and death (HR 8.2 [95% CI 0.7, 90.4]). CONCLUSION: Rheumatic disease patients with COVID-19 had more severe radiographic lung involvement than comparators. Higher PXS scores were associated with mechanical ventilation and will be important for future studies leveraging big data to assess COVID-19 outcomes in rheumatic disease patients.

Propofol misuse in medical professions: a scoping review.

PURPOSE: We aimed to describe the current literature concerning propofol misuse in medical professionals, specifically relating to the individual demographics of those misusing propofol and the outcomes of propofol misuse. METHODS: We conducted a retrospective scoping review of the literature using a modified PRISMA approach. We used MEDLINE, EMBASE, and PsycINFO databases to identify relevant studies based on search terms. Studies describing individual medical professionals misusing propofol were included. RESULTS: Twenty-four articles describing 88 individual cases of propofol misuse were included for data charting and analysis. Anesthesiologists and certified registered nurse anesthetists were most commonly identified. Death was a common method of identification of misuse, while rehabilitation and death were common final outcomes associated with propofol misuse. CONCLUSIONS: Despite knowledge of the pharmacokinetic and pharmacodynamic properties of propofol by those misusing this medication, death was a common outcome reported in the literature. Data related to long-term outcomes including re-entry to clinical practice or success of rehabilitation were limited.

RéSUMé: OBJECTIF: Nous avons cherché à décrire la littérature actuelle concernant l'abus de propofol chez les professionnels de la santé, en particulier en ce qui concerne les données démographiques individuelles de ceux qui abusent du propofol et les issues d'un tel abus. MéTHODE: Nous avons réalisé une étude de portée rétrospective de la littérature à l'aide d'une approche PRISMA modifiée. Nous avons utilisé les bases de données MEDLINE, EMBASE et PsycINFO pour identifier les études pertinentes en fonction des termes de recherche. Les études décrivant des professionnels de la santé abusant du propofol ont été incluses. RéSULTATS: Vingt-quatre articles décrivant 88 cas individuels d'abus de propofol ont été inclus pour la cartographie et l'analyse des données. Les anesthésiologistes et les infirmières anesthésistes autorisées certifiées ont été le plus souvent identifiés. La mort était une méthode courante d'identification de l'abus, tandis que la réhabilitation et la mort étaient des issues finales fréquemment associées à l'abus de propofol. CONCLUSION: Malgré la connaissance des propriétés pharmacocinétiques et pharmacodynamiques du propofol par ceux qui abusent de ce médicament, le décès était une issue fréquente rapportée dans la littérature. Les données relatives aux issues à long terme, y compris le retour à la pratique clinique ou le succès de la réhabilitation, étaient limitées.

DMARD disruption, rheumatic disease flare, and prolonged COVID-19 symptom duration after acute COVID-19 among patients with rheumatic disease: A prospective study.

OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). METHODS: We surveyed people with pre-existing SARDs who had confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. RESULTS: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 25 days (IQR 11, 160). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. CONCLUSION: DMARD disruption, SARD flare, and prolonged COVID-19 symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

Movement markers of schizophrenia: a detailed analysis of patients' gait patterns.

Motor abnormalities occur in the majority of persons with schizophrenia but are generally neglected in clinical care. Psychiatric diagnostics fail to include quantifiable motor variables and few assessment tools examine full-body movement. We assessed full-body movement during gait of 20 patients and 20 controls with motion capture technology, symptom load (PANSS, BPRS) and Neurological Soft Signs (NSS). In a data-driven analysis, participants' motion patterns were quantified and compared between groups. Resulting movement markers (MM) were correlated with the clinical assessment. We identified 16 quantifiable MM of schizophrenia. While walking, patients and controls display significant differences in movement patterns related to posture, velocity, regularity of gait as well as sway, flexibility and integration of body parts. Specifically, the adjustment of body sides, limbs and movement direction were affected. The MM remain significant when controlling for medication load. They are systematically related to NSS. Results add assessment tools, analysis methods as well as theory-independent MM to the growing body of research on motor abnormalities in schizophrenia.

Outcomes of rotational atherectomy followed by cutting balloon versus plain balloon before drug-eluting stent implantation for calcified coronary lesions: A meta-analysis.

OBJECTIVE: The aim of this study is to compare outcomes of rotational atherectomy and cutting balloon (RACB) versus rotational atherectomy and plain balloon (RAPB) before drug-eluting stent (DES) implantation in calcified coronary lesions. METHODS: Randomized controlled trials (RCT) and observational studies comparing RACB with RAPB were identified through a systematic search of published literature across multiple databases. Random effect meta-analysis was performed to compare the outcome between the two groups. RESULTS: Four studies were included in the meta-analysis (three observational and one RCT) involving a total of 315 patients. 166 patients had RACB, and 149 patients had RAPB before DES placement with a median follow-up of 11.5 months. Compared with patients who had RAPB there was no difference in MACE (composite of death, myocardial infarction, and target vessel revascularization) (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.25-2.18], slow flow/no reflow (OR: 0.71; 95% CI: 0.23-2.16), all-cause mortality (OR: 2.02; 95% CI: 0.28-14.60), and device success rate (OR: 1.79; 95% CI: 0.28-11.18) in the RACB approach. There was a benefit towards less target lesion revascularization in the RACB group; however, this outcome was reported in two studies (OR: 0.29; 95% CI: 0.08-0.99). On meta-regression there was no association between age, sex, diabetes, or lesion location with MACE and all-cause mortality. The studies were homogenous across all outcomes. CONCLUSION: RACB, as compared with RAPB, had a similar risk of MACE, all-cause mortality, device success, and complication, but a lower risk of target lesion revascularization.

Associations of the MUC5B promoter variant with timing of interstitial lung disease and rheumatoid arthritis onset.

OBJECTIVES: To investigate the associations of the common MUC5B promoter variant with timing of RA-associated interstitial lung disease (RA-ILD) and RA onset. METHODS: We identified patients with RA meeting 2010 ACR/EULAR criteria and available genotype information in the Mass General Brigham Biobank, a multihospital biospecimen and clinical data collection research study. We determined RA-ILD presence by reviewing all RA patients who had CT imaging, lung biopsy or autopsy results. We determined the dates of RA and RA-ILD diagnoses by manual records review. We examined the associations of the MUC5B promoter variant (G>T at rs35705950) with RA-ILD, RA-ILD occurring before or within 2 years of RA diagnosis and RA diagnosis at age >55 years. We used multivariable logistic regression to estimate odds ratios (ORs) for each outcome by MUC5B promoter variant status, adjusting for potential confounders including genetic ancestry and smoking. RESULTS: We identified 1005 RA patients with available genotype data for rs35705950 (mean age 45 years, 79% female, 81% European ancestry). The MUC5B promoter variant was present in 155 (15.4%) and was associated with RA-ILD [multivariable OR 3.34 (95% CI 1.97, 5.60)], RA-ILD before or within 2 years of RA diagnosis [OR 4.01 (95% CI 1.78, 8.80)] and RA onset after age 55 years [OR 1.52 (95% CI 1.08, 2.12)]. CONCLUSIONS: The common MUC5B promoter variant was associated with RA-ILD onset earlier in the RA disease course and older age of RA onset. These findings suggest that the MUC5B promoter variant may impact RA-ILD risk early in the RA disease course, particularly in patients with older-onset RA.

Demographic, Lifestyle, and Serologic Risk Factors for Rheumatoid Arthritis (RA)-associated Bronchiectasis: Role of RA-related Autoantibodies.

OBJECTIVE: To investigate demographic, lifestyle, and serologic risk factors for isolated rheumatoid arthritis (RA)-associated bronchiectasis (RA-BR) that is not a result of interstitial lung disease (ILD). METHODS: We performed a case-control study using patients with RA from the Mass General Brigham Biobank. We reviewed the records of all patients with RA meeting the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria with computed tomography (CT) chest imaging to identify RA-BR cases and controls with RA and RA-related lung disease. For each patient, the CT chest imaging that was performed closest to enrollment was independently reviewed by 2 radiologists for the presence of RA-related lung diseases. Cases had clinical and radiologic evidence of RA-BR without interstitial lung abnormalities on imaging. Controls had RA and no evidence of bronchiectasis or ILD. We examined the associations between demographic, lifestyle, and serologic factors with RA-BR using multivariable logistic regression. RESULTS: We identified 57 cases of isolated RA-BR and 360 RA controls without RA-related lung disease. In multivariable models, RA-BR was associated with older age at RA onset (OR 1.37 per 10 years, 95% CI 1.02-1.82), lower BMI at RA diagnosis (OR 0.94 per kg/m2, 95% CI 0.89-0.99), seropositive RA (OR 3.96, 95% CI 1.84-8.53), positive rheumatoid factor (OR 4.40, 95% CI 2.14-9.07), and positive anticyclic citrullinated peptide (OR 3.47, 95% CI 1.65-7.31). Higher titers of RA-related autoantibodies were associated with higher odds of RA-BR. CONCLUSION: Seropositivity, older age at RA diagnosis, and lower BMI at RA onset were associated with isolated bronchiectasis in RA that was not a result of ILD. These findings expand the list of potential risk factors for RA-BR and suggest a pathogenic link between airway inflammation and RA-related autoantibodies.

DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study.

OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). METHODS: We surveyed patients with SARDs after confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. RESULTS: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 14 days (IQR 9,29). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. CONCLUSION: DMARD disruption, SARD flare, and prolonged symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

Predictors of Rheumatic Immune-Related Adverse Events and De Novo Inflammatory Arthritis After Immune Checkpoint Inhibitor Treatment for Cancer.

OBJECTIVE: To identify predictors of rheumatic immune-related adverse events (irAEs) following immune checkpoint inhibitor (ICI) treatment for cancer. METHODS: We performed a case-control study to predict the occurrence of rheumatic irAEs in cancer patients who initiated ICI treatment at Mass General Brigham and the Dana-Farber Cancer Institute between 2011 and 2020. We screened for the presence of rheumatic irAEs by reviewing the medical records of patients evaluated by rheumatologists or those prescribed nonglucocorticoid immunomodulatory drugs after the time of ICI initiation (baseline). Review of medical records confirmed the presence of rheumatic irAEs and the indications necessitating immunomodulatory drug treatment. Controls were defined as patients who did not experience rheumatic irAEs, did not have preexisting rheumatic disease, did not have a clinical evaluation by a rheumatologist after ICI treatment, did not receive an immunomodulatory drug after ICI, did not receive systemic glucocorticoids after ICI, and survived at least 6 months after the initial ICI treatment. We used logistic regression to estimate the odds ratios (ORs) (with 95% confidence intervals [95% CIs]) for the risk of a rheumatic irAE in the presence of various baseline predictors. RESULTS: A total of 8,028 ICI recipients were identified (mean age 65.5 years, 43.1% female, 31.8% with lung cancer). After ICI initiation, 404 patients (5.0%) were evaluated by rheumatologists, and 475 patients (5.9%) received an immunomodulatory drug to treat any irAEs. There were 226 confirmed rheumatic irAE cases (2.8%) and 118 de novo inflammatory arthritis cases (1.5%). Rheumatic diseases (either preexisting rheumatic diseases or rheumatic irAEs) were a common indication for immunomodulatory drug use (27.9%). Baseline predictors of rheumatic irAEs included melanoma (multivariable OR 4.06 [95% CI 2.54-6.51]) and genitourinary (GU) cancer (OR 2.22 [95% CI 1.39-3.54]), both relative to patients with lung cancer; combination ICI treatment (OR 2.35 [95% CI 1.48-3.74]), relative to patients receiving programmed death 1 inhibitor monotherapy; autoimmune disease (OR 2.04 [95% CI 1.45-2.85]) and recent glucocorticoid use (OR 2.13 [95% CI 1.51-2.98]), relative to patients not receiving a glucocorticoid, compared to the 2,312 controls without rheumatic irAEs. Predictors of de novo inflammatory arthritis were similar to those of rheumatic irAEs. CONCLUSION: We identified novel predictors of rheumatic irAE development in cancer patients, including baseline presence of melanoma, baseline presence of GU tract cancer, preexisting autoimmune disease, receiving or having received combination ICI treatment, and receiving or having received glucocorticoids. The proportion of cancer patients experiencing rheumatic irAEs may be even higher than was reported in the present study, since we used stringent criteria to identify cases of rheumatic irAEs. Our findings could be used to identify cancer patients at risk of developing rheumatic irAEs and de novo inflammatory arthritis and may help further elucidate the pathogenesis of rheumatic irAEs in patients with cancer who are receiving ICI treatment.