Presentation, Management, and Outcomes of Pathologic Scars Within a Pediatric Otolaryngology Practice.

OBJECTIVES: This study aims to review the spectrum of scarring that may present to an urban, pediatric otolaryngology practice and determine if associations exist between race, scar location, treatment modality, and outcomes following interventions for scarring. METHODS: Retrospective cohort study among 115 pediatric patients with 138 unique keloids or hypertrophic scars (HTS), and 141 children presenting for tonsillectomy at Tufts Medical Center. Age at presentation and sex assigned at birth were collected for both populations. For those presenting for pathologic scars, income quintile, self-identified race/ethnicity, anatomical location, treatment number and type, and clinical outcome were also analyzed. Multivariate analyses calculated adjusted odds ratios (aORs) and 95% confidence intervals to assess associations between scar subsite, intervention type, and persistence after treatment. RESULTS: Compared to individuals presenting for tonsillectomy, a disproportionate percentage of patients presenting for scarring identified as Black (26.6% vs. 13.5%) or Asian (17.4% vs. 7.1%, p = 0.016) or were male (61.7% vs. 49.7%, p = 0.053). Individuals identifying as Black or Asian were more likely to present with ear lobe and neck scars, respectively (50.0% vs. 45.5%, p = <0.001). Ear scars were significantly more likely to receive excision at initial treatment (aOR = 5.86 [1.43-23.96]) compared to other subsites, and were more likely to require >1 treatment (aOR = 5.91 [1.53-22.75]). CONCLUSION: Among pediatric patients presenting with keloids or HTS, children who identified as Black or Asian were more likely to present with ear and neck scars, respectively. Ear scars were frequently treated with excision and appear more likely to require adjuvant treatments and multiple interventions. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3127-3135, 2024.

External Validation of the Breast Cancer Surgery Risk Calculator (BCSRc): A Predictive Model for Postoperative Complications.

BACKGROUND: The breast cancer surgical risk calculator (BCSRc) is a prognostic tool that determines a breast cancer patient's unique risk of acute complications following each possible surgical intervention. When used in the preoperative setting, it can help to stratify patients with an increased complication risk and enhance the patient-physician informed decision-making process. The objective of this study was to externally validate the four models used in the BCSRc on a large cohort of patients who underwent breast cancer surgery. METHODS: The BCSRc was developed by using a retrospective cohort from the National Surgical Quality Improvement Program database from 2005 to 2018. Four models were built by using logistic regression methods to predict the following composite outcomes: overall, infectious, hematologic, and internal organ complications. This study obtained a new cohort of patients from the National Surgical Quality Improvement Program by utilizing participant user files from 2019 to 2020. The area under the curve, brier score, and Hosmer-Lemeshow goodness of fit test measured model performance, accuracy, and calibration, respectively. RESULTS: A total of 192,095 patients met inclusion criteria in the development of the BCSRc, and the validation cohort included 60,144 women. The area under the curve during external validation for each model was approximately 0.70. Accuracy, or Brier scores, were all between 0.04 and 0.003. Model calibration using the Hosmer-Lemeshow statistic found all p-values > 0.05. All of these model coefficients will be updated on the web-based BCSRc platform: www.breastcalc.org . CONCLUSIONS: The BCSRc continues to show excellent external-validation measures. Collectively, this prognostic tool can enhance the decision-making process, help stratify patients with an increased complication risk, and improve expectant management.

Acute and postacute COVID-19 outcomes for patients with rheumatoid arthritis: lessons learned and emerging directions 3 years into the pandemic.

PURPOSE OF REVIEW: To summarize the findings of studies investigating patients with rheumatoid arthritis (RA) and risk of acute and postacute COVID-19 outcomes 3 years into the pandemic. RECENT FINDINGS: Most studies early in the pandemic included all patients with systemic autoimmune rheumatic diseases (SARDs), not only those with RA, due to limited sample size. Many of these studies found that patients with SARDs were at higher risk of COVID-19 infection and severe outcomes, including hospitalization, hyperinflammation, mechanical ventilation, and death. Studies performed later were able to focus on RA and found similar associations, while also identifying RA-specific factors such as immunosuppressive medications, disease activity/severity, and interstitial lung disease as risk factors for severe COVID-19. After COVID-19 vaccination, the risks for COVID-19 infection and severity were reduced for patients with RA, but a gap between the general population persisted, and some patients with RA are susceptible to breakthrough infection after vaccination. Preexposure prophylaxis, effective treatments, and changes in viral variants have also contributed to improved COVID-19 outcomes throughout the pandemic. Emerging data suggest that patients with RA may be at risk for postacute sequelae of COVID-19 (PASC). SUMMARY: Although COVID-19 outcomes have improved over the pandemic for patients with RA, some experience poor acute and postacute outcomes after COVID-19. Clinicians and patients should remain vigilant about risk mitigation for infection and consider early treatment for RA patients with COVID-19. Future studies are needed to investigate clinical outcomes and mechanisms of PASC among patients with RA.

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.

Comparing oncoplastic breast reduction with immediate symmetry surgery to standard breast reduction surgery: Are postoperative complications worse?

INTRODUCTION: Oncoplastic breast reduction mammoplasty (ORM) is an excellent treatment option for women with breast cancer and macromastia undergoing breast conservation therapy. Here, we aim to better understand the risks associated with ORM compared to standard reduction mammoplasty (SRM). METHODS: A retrospective chart review was performed of patients undergoing ORM or SRM from 2015 to 2021. Primary outcomes included the occurrence of major or minor postoperative complications in the two groups and delays to adjuvant therapy (>90 days) among the women undergoing ORM. RESULTS: Women in the ORM group (n = 198) were significantly older (p < 0.001) with a higher prevalence of smoking (p < 0.001), diabetes mellitus (p < 0.01), and a Charlson comorbidity index ≥ 3 (p < 0.001) compared to women undergoing SRM (n = 177). After controlling for potential confounders, there were no significant between-group differences in the odds of developing postoperative complications (odds ratio = 0.80, 95% confidence interval: 0.36-1.69). Only 3% (n = 4) of the 150 women undergoing adjuvant radiation or chemotherapy experienced delays related to postoperative complications. CONCLUSION: ORM has a similar safety profile as SRM, despite the older age and higher number of comorbidities often seen in patients undergoing ORM, and is a safe option for achieving contralateral symmetry at the time of partial mastectomy without delays to adjuvant therapy.

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.

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.

Association of Sinusitis and Upper Respiratory Tract Diseases With Incident Rheumatoid Arthritis: A Case-control Study.

OBJECTIVE: We aimed to determine whether specific respiratory tract diseases are associated with increased rheumatoid arthritis (RA) risk. METHODS: This case-control study within the Mass General Brigham Biobank matched newly diagnosed RA cases to 3 controls on age, sex, and electronic health record history. We identified RA using a validated algorithm and confirmed by medical record review. Respiratory tract disease exposure required 1 inpatient or 2 outpatient codes at least 2 years before the index date of RA clinical diagnosis or matched date. Logistic regression models calculated ORs for RA with 95% CIs, adjusting for confounders. We then stratified by serostatus ("seropositive" was positive rheumatoid factor and/or anticitrullinated protein antibodies) and smoking. RESULTS: We identified 741 RA cases and 2223 controls (both median age 55, 76% female). Acute sinusitis (OR 1.61, 95% CI 1.05-2.45), chronic sinusitis (OR 2.16, 95% CI 1.39-3.35), and asthma (OR 1.39, 95% CI 1.03-1.87) were associated with increased risk of RA. Acute respiratory tract disease burden during the preindex exposure period was also associated with increased RA risk (OR 1.30 per 10 codes, 95% CI 1.08-1.55). Acute pharyngitis was associated with seronegative (OR 1.68, 95% CI 1.02-2.74) but not seropositive RA; chronic rhinitis/pharyngitis was associated with seropositive (OR 2.46, 95% CI 1.01-5.99) but not seronegative RA. Respiratory tract diseases tended towards higher associations in smokers, especially > 10 pack-years (OR 1.52, 95% CI 1.02-2.27, P = 0.10 for interaction). CONCLUSION: Acute and chronic sinusitis, pharyngitis, and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract.

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.

Coronavirus Disease 2019 Outcomes Among Recipients of Anti-CD20 Monoclonal Antibodies for Immune-Mediated Diseases: A Comparative Cohort Study.

OBJECTIVE: Patients with immune-mediated diseases treated with anti-CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID-19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown. METHODS: We identified patients with immune-mediated diseases who received anti-CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction-confirmed COVID-19 between January 31, 2020, and January 31, 2021. General population comparators with COVID-19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti-CD20 monoclonal antibodies versus comparators were estimated by using Cox regression. RESULTS: We identified 114 cases patients COVID-19 who had received anti-CD20 monoclonal antibodies for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). Patients treated with anti-CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03-4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62-1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36-1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti-CD20 monoclonal antibody use (<1 or ≥1 year) and after patients with interstitial lung disease, those with cancer, and those on glucocorticoids prior to COVID-19 diagnosis were excluded. CONCLUSION: Patients who received anti-CD20 monoclonal antibodies for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in recipients of anti-CD20 monoclonal antibodies during the ongoing pandemic.

Screening for preclinical parenchymal lung disease in rheumatoid arthritis.

OBJECTIVES: Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD). METHODS: RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities. RESULTS: Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures. CONCLUSION: We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.

COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study.

OBJECTIVE: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown. METHODS: We identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression. RESULTS: We identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. CONCLUSIONS: Patients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic. KEY MESSAGES: What is already known about this subject?: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes than those treated with other immunomodulatory medications, but differences compared to the general population are unknown.What does this study add?: CD20 inhibitor-treated cases had over two-fold higher risk of mortality than matched general population comparators, although risks of hospitalization and mechanical ventilation were similar.How might this impact on clinical practice or future developments?: There is an urgent need for risk mitigation strategies, such as SARS-CoV-2 monoclonal antibodies or booster vaccinations, for patients with immune-mediated diseases treated with CD20 inhibitors during the ongoing COVID-19 pandemic.

Challenges and Opportunities of Targeted Behavioral Interventions for Groups at Risk for Developing Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a serious autoimmune disease which causes painful, swollen joints and can impact quality of life and increase morbidity and mortality. There are several preclinical stages of RA that correspond to at-risk groups that include: genetic risk, risk from behaviors, elevation of RA-related autoantibodies, and early clinical disease manifestations such as undifferentiated arthritis. Early interventions are crucial to slowing progression to and potentially preventing RA onset. Modification of behaviors among at-risk individuals may decrease RA risk. There are several challenges and opportunities in implementing preventative behavioral interventions, which may vary within different at-risk groups. Methods: We performed a narrative review of the literature, including meta-analyses focused on RA risk-related behaviors as well as publications investigating the potential efficacy of behavioral modifications on RA risk. Results: There are multiple behavioral risk factors associated with RA, including smoking, obesity, low physical activity, low quality diet, and poor dental hygiene, which may contribute to progression to clinical RA. Meta-analyses have been performed for smoking, excess body weight, and physical activity. Likelihood of adopting behavioral modifications may increase as RA risk increases. Conclusions: Clinicians may be able to tailor preventative approaches to various RA at-risk groups to help reduce RA risk, but further research is needed. A better understanding of the relationship of behaviors with RA risk and optimized approaches to implementing behavioral changes may allow for clinicians to tailor their preventative approaches for at-risk individuals.

Laboratory trends, hyperinflammation, and clinical outcomes for patients with a systemic rheumatic disease admitted to hospital for COVID-19: a retrospective, comparative cohort study.

BACKGROUND: COVID-19 can induce a hyperinflammatory state, which might lead to poor clinical outcomes. We aimed to assess whether patients with a systemic rheumatic disease might be at increased risk for hyperinflammation and respiratory failure from COVID-19. METHODS: We did a retrospective, comparative cohort study of patients aged 18 years or older admitted to hospital with PCR-confirmed COVID-19 at Mass General Brigham (Boston, USA). We identified patients by a search of electronic health records and matched patients with a systemic rheumatic disease 1:5 to comparators. We compared individual laboratory results by case status and extracted laboratory results and COVID-19 outcomes for each participant. We calculated the COVID-19-associated hyperinflammation score (cHIS), a composite of six domains (a score of ≥2 indicating hyperinflammation) and used logistic regression to estimate odds ratios (ORs) for COVID-19 outcomes by hyperinflammation and case status. FINDINGS: We identified 57 patients with a systemic rheumatic disease and 232 matched comparators who were admitted to hospital with COVID-19 between Jan 30 and July 7, 2020; 38 (67%) patients with a rheumatic disease were female compared with 158 (68%) matched comparators. Patients with a systemic rheumatic disease had higher peak median neutrophil-to-lymphocyte ratio (9·6 [IQR 6·4-22·2] vs 7·8 [4·5-16·5]; p=0·021), lactate dehydrogenase concentration (421 U/L [297-528] vs 345 U/L [254-479]; p=0·044), creatinine concentration (1·2 mg/dL [0·9-2·0] vs 1·0 mg/dL [0·8-1·4], p=0·014), and blood urea nitrogen concentration (31 mg/dL [15-61] vs 23 mg/dL [13-37]; p=0·033) than comparators, but median C-reactive protein concentration (149·4 mg/L [76·4-275·3] vs 116·3 mg/L [58·8-225·9]; p=0·11) was not significantly different. Patients with a systemic rheumatic disease had higher peak median cHIS than comparators (3 [1-5] vs 2 [1-4]; p=0·013). All patients with a peak cHIS of 2 or more had higher odds of admission to intensive care (OR 3·45 [95% CI 1·98-5·99]), mechanical ventilation (66·20 [8·98-487·80]), and in-hospital mortality (16·37 [4·75-56·38]) than patients with a peak cHIS of less than 2. In adjusted analyses, patients with a rheumatic disease had higher odds of admission to intensive care (2·08 [1·09-3·96]) and mechanical ventilation (2·60 [1·32-5·12]) than comparators, but not in-hospital mortality (1.78 [0·79-4·02]). Among patients who were discharged from hospital, risk of rehospitalisation (1·08 [0·37-3·16]) and mortality within 60 days (1·20 [0·58-2·47]) was similar in patients and comparators. INTERPRETATION: Patients with a systemic rheumatic disease who were admitted to hospital for COVID-19 had increased risk for hyperinflammation, kidney injury, admission to intensive care, and mechanical ventilation compared with matched comparators. However, among patients who survived, post-discharge outcomes were not significantly different. The cHIS identified patients with hyperinflammation, which was strongly associated with poor COVID-19 outcomes in both patients with a rheumatic disease and comparators. Clinicians should be aware that patients with systemic rheumatic diseases and COVID-19 could be susceptible to hyperinflammation and poor hospital outcomes. FUNDING: None.

Elevated Anti-Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and Risks for Chronic Obstructive Pulmonary Disease or Asthma.

OBJECTIVE: To investigate elevation of anti-citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma. METHODS: We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre-RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls. RESULTS: We analyzed 283 women who were pre-RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04 [95% confidence interval (95% CI) 1.33-7.00]) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72-4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65 [95% CI 1.11-2.46]). CONCLUSION: Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre-RA ACPA status.

Correction to: Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry.

The publisher regrets that the two sections under the Results omitted inadvertently on the original published version of the above article.