2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

Oral Health Status and Factors Related to Oral Health in Patients with Schizophrenia: A Matched Case-Control Observational Study.

Background: Schizophrenia (SCZ) patients have disproportionately poor oral health outcomes owing to a multidimensional set of factors, such as pathophysiology of the disease, drug-related adverse effects and lower utilization rate of dental healthcare services. The aim of the present observational study was to compare the indicators of dental and periodontal health in patients with SCZ to those of nonaffected healthy controls; furthermore, the influence of various anamnestic factors and lifestyle habits on oral health status were also assessed. Methods: A total of 50 SCZ patients-in remission-receiving treatment at the Department of Psychiatry, University of Szeged, were compared with 50 age- and gender-matched healthy controls attending the Faculty of Dentistry, University of Szeged. Participants' dental (decayed, missing and filled surfaces [DMF-S] and decayed, missing and filled teeth [DMF-T]) and periodontal (plaque index [%], bleeding on probing [BOP%], pocket depth [PD] and attachment loss [AL]) status was measured according to the World Health Organization (WHO) criteria. Results: In total, 74.0%, 80.0% and 78.0% of SCZ patients received second-generation antipsychotics, benzodiazepines and mood stabilizers, respectively. Patients with SCZ had significantly higher DMFs (81.30 ± 40.16 vs. 61.64 ± 40.56; p = 0.010), D (8.18 ± 7.73 vs. 4.18 ± 4.22; p < 0.001) and DMF-T (18.20 ± 8.36 vs. 14.42 ± 8.21; p = 0.024) scores but significantly lower F (1.84 ± 0.29 vs. 4.62 ± 3.98; p < 0.001) scores compared to the controls; male subjects had significantly lower DMFs (74.52 ± 39.72 vs. 90.67 ± 39.1; p = 0.020) and DMF-T (16.52 ± 8.12 vs. 20.52 ± 8.32; p = 0.031) scores. Additionally, SCZ patients had significantly higher plaque indices (56.96 ± 23.19 vs. 27.44 ± 17.53; p < 0.001), BOP% (58.96 ± 22.89 vs. 23.56 ± 17.53; p < 0.001), PD (2.84 ± 0.67 vs. 2.19 ± 0.49; p = 0.024) and AL (3.39 ± 1.72 vs. 2.49 ± 0.76; p < 0.001) values compared to controls. Smoking > 10 cigarettes/day was associated with worse dental and periodontal indices, while consuming ≥ 4 units/week of alcohol was associated with worse periodontal indices, respectively (p < 0.05 in all cases). In contrast, coffee consumption rates and vitamin supplementation status had no significant effect on oral health status indicators. Conclusions: Our study highlights the overall poor oral health status of individuals affected by SCZ and the need for targeted preventive interventions.

Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis.

PURPOSE: To determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate response. METHODS: This is a secondary analysis of the Rheumatoid Arthritis Comparison of Active Treatments (RACAT) trial and the (TEAR) trial. Both studies compared treatment strategies starting with conventional disease-modifying anti-rheumatic drugs (DMARDs) (triple therapy) versus etanercept plus methotrexate. We compared response rates between TNFi and triple therapy among patients with different BMI. Adipokines were measured at enrolment and associations with treatment response were examined using regression, adjusting for age, sex, BMI and baseline disease activity. RESULTS: In RACAT (n=306), participants who were normal/underweight were more likely to benefit from TNFi versus triple therapy, with greater change in Disease Activity Score in 28 and greater ACR20 response (ACR 20: 64% vs 23%, p=0.001). In contrast, overweight/obese participants had similar response to TNFi versus triple therapy (p-for-interaction=0.001). Similarly, but modest patterns were observed in TEAR (n=601; ACR20: 67% vs 52%, p=0.05). In RACAT, adipokine scores consistent with lower adiposity also predicted greater response to TNFi (ACR20: 58% vs 37%, p=0.01) with better model fit compared with BMI alone. CONCLUSIONS: Lower BMI and evidence of lower adiposity based on adipokine profiles were associated with a superior response to TNFi compared with triple therapy. There was no difference between treatments among overweight/obese participants. The results support TNFi being a particularly important therapeutic among normal/underweight patients, with implications for clinical decisions and trial design.

Changes in Characteristics of Patients Initiating and Discontinuing Advanced Therapies for Rheumatoid Arthritis Following the Release of Safety Data.

OBJECTIVE: The objective of this study was to determine the impact of emerging safety data on practice patterns by describing the characteristics of patients initiating and discontinuing advanced therapies for rheumatoid arthritis (RA) before and after January 2021. METHODS: This cohort study evaluated US veterans with RA between April 2019 and September 2022. This period was divided into two 664-day periods before and after January 2021. Eligible patients had ≥1 diagnosis code for RA and initiated a tumor necrosis factor inhibitor (TNFi), non-TNFi biologic, or JAK inhibitor (JAKi). We tested for interaction within regression models to determine whether changes in patient characteristics for tofacitinib recipients were different from changes observed for other therapies. We also evaluated factors associated with therapy discontinuation in Cox models adjusted for age, sex, and duration on therapy, including assessment for effect modification. RESULTS: When comparing patients with RA initiating tofacitinib before (n = 2,111) with those initiating tofacitinib after (n = 1,664) January 2021, there was a decrease in mean age (64.1 vs 63.0 years) and in the proportion with cardiovascular comorbidities (all P < 0.01). These changes were significantly different from those observed for patients initiating TNFi or non-TNFi biologics. Among active advanced therapy recipients, the likelihood of discontinuation was higher for tofacitinib than TNFi (hazard ratio 1.18, 95% confidence interval 1.10-1.26, P < 0.001). The higher rate of tofacitinib discontinuation was more pronounced in the presence of cardiovascular comorbidities (P < 0.05). CONCLUSION: Recent safety data significantly affected prescribing practices for advanced therapies, with a reduction in JAKi initiation and an increase in JAKi discontinuation among older patients and those at high cardiovascular risk.

Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs. METHODS: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class. RESULTS: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]). CONCLUSION: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.

A high-throughput electrophysiology assay to study the response of PIEZO1 to mechanical stimulation.

PIEZO1 channels are mechanically activated cation channels that play a pivotal role in sensing mechanical forces in various cell types. Their dysfunction has been associated with numerous pathophysiological states, including generalized lymphatic dysplasia, varicose vein disease, and hereditary xerocytosis. Given their physiological relevance, investigating PIEZO1 is crucial for the pharmaceutical industry, which requires scalable techniques to allow for drug discovery. In this regard, several studies have used high-throughput automated patch clamp (APC) combined with Yoda1, a specific gating modifier of PIEZO1 channels, to explore the function and properties of PIEZO1 in heterologous expression systems, as well as in primary cells. However, a combination of solely mechanical stimulation (M-Stim) and high-throughput APC has not yet been available for the study of PIEZO1 channels. Here, we show that optimization of pipetting parameters of the SyncroPatch 384 coupled with multihole NPC-384 chips enables M-Stim of PIEZO1 channels in high-throughput electrophysiology. We used this approach to explore differences between the response of mouse and human PIEZO1 channels to mechanical and/or chemical stimuli. Our results suggest that applying solutions on top of the cells at elevated pipetting flows is crucial for activating PIEZO1 channels by M-Stim on the SyncroPatch 384. The possibility of comparing and combining mechanical and chemical stimulation in a high-throughput patch clamp assay facilitates investigations on PIEZO1 channels and thereby provides an important experimental tool for drug development.

Racial and Ethnic Distribution of Rheumatic Diseases in Health Systems of the National Patient-Centered Clinical Research Network.

OBJECTIVE: To evaluate the relative prevalence of 8 rheumatic and musculoskeletal diseases (RMDs) across racial and ethnic groups within the National Patient-Centered Clinical Research Network (PCORnet). METHODS: Electronic health records from participating PCORnet institutions and systems from January 1, 2013, to December 31, 2018, were used to identify adult patients with ≥ 2 diagnosis codes for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoporosis (OP), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), giant cell arteritis (GCA), and Takayasu arteritis (TAK). Among those with race and ethnicity data available, we compared prevalence of RMDs by race and ethnicity. RESULTS: Data from 28,059,546 patients were available for analysis. RA was more common in patients who were American Indian or Alaska Native vs White, with a prevalence of 11.57 vs 10.11/1000 (odds ratio [OR] 1.15, 95% CI 1.09-1.22). SLE was more common in patients who were Black or African American (6.73/1000), American Indian or Alaska Native (3.82/1000), and Asian (3.39/1000) vs White (2.80/1000; OR 2.43, 95% CI 2.39-2.46; OR 1.39, 95% CI 1.25-1.53; OR 1.26, 95% CI 1.21-1.31, respectively). SLE was more common in patients who were Hispanic vs non-Hispanic (prevalence 3.93 vs 3.45/1000, OR 1.14, 95% CI 1.12-1.16). TAK was more common in patients who were Asian vs White (prevalence 0.05 vs 0.04/1000, OR 1.43, 95% CI 1.00-2.03). OP, RA, and the vasculitides were all more common in patients who were White vs Black or African American. CONCLUSION: These data provide important information on the prevalence of RMDs by race and ethnicity in the United States. PCORnet can be used as a reliable data source to study RMDs within a large representative population.

Changes in Patterns of Use of Advanced Therapies Following Emerging Data About Adverse Events in Patients With Rheumatoid Arthritis From the Veterans Affairs Health System.

OBJECTIVE: To determine whether prescribing practices for Janus kinase inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic agents changed after the results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance trial were released in January 2021. METHODS: This is a retrospective study in adult patients with rheumatoid arthritis (RA) receiving advanced therapies within the Veterans Affairs Health System from January 2012 through September 2022. Eligible patients were required to have at least one diagnosis code for RA and to have received a biologic disease-modifying antirheumatic drug or JAKi. Treatment courses were defined from pharmacy dispensing data and the number of new courses of each advanced therapy was quantified over time. We assessed changes in the use of each therapy before and after the release of safety data (January 2021). RESULTS: A total of 88,253 individual drug courses (in 34,656 unique patients) were included in the study. There was a consistent increase in the number and proportion of new courses of JAKi leading up to January 2021, which was followed by a significant net decrease in JAKi use through September 2022. There was significantly less tofacitinib use after the release of safety data, with a significant difference in the slope of change in use with time. In contrast, whereas TNFi use declined leading up to 2021, its use significantly increased after January 2021. CONCLUSION: Changes in prescribing in response to new evidence emphasize the impact that safety trials have on prescribing practices. Ongoing study in this area, with attention to specific patient characteristics and risk profiles, will help characterize these changes in practice.

Measuring the Efficacy of Thymectomy for Pediatric Myasthenia Gravis Across Tertiary Children's Hospitals.

BACKGROUND: Thymectomy is a treatment for pediatric myasthenia gravis, but the efficacy over time is unknown. Multi-institutional data are also lacking. Therefore, the objective of this study was to determine the efficacy of thymectomy for pediatric myasthenia gravis using medication burden and health care utilization as proxies for disease severity. METHODS: This was a cross-sectional study of the Pediatric Health Information System database among children who underwent thymectomy at one of 49 children's hospitals from 2004 to 2022. Differences in annual median number of doses of myasthenia-related medications, admissions, and health care costs in the year before thymectomy to three years after were compared. A comparison cohort that did not undergo thymectomy was utilized. Medians were compared using the Wilcoxon signed-rank test. Generalized linear regression estimated the effect of surgical approach on outcomes. RESULTS: A total of451 patients (238 patients who underwent thymectomy and 213 nonthymectomy patients) were identified. Following thymectomy, the decrease in annual median total number of myasthenia-related doses was 12.0 (interquartile range: 6 to 31) (P < 0.001). The decrease in number of annual admissions was 2.0 (1 to 4) (P < 0.001), which represented a cost difference of $5292 ($3533 to $8681) (P < 0.001). No differences were observed in the control cohort. In a generalized linear regression model, surgical approach was not associated with the efficacy of thymectomy (P = 0.55). CONCLUSIONS: Thymectomy is an effective treatment for pediatric myasthenia gravis, evidenced by the decreased medication burden and health care utilization after surgery. Surgical approach did not influence the success of surgery. Thymectomy should be considered earlier in the treatment algorithm.

Engaging Multistakeholder Perspectives to Identify Patient-Centered Research Priorities Regarding Vaccine Uptake Among Adults With Autoimmune Conditions.

OBJECTIVE: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. METHODS: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. RESULTS: Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were "How well a vaccine works for adults with autoimmune conditions" and "How beliefs about vaccine safety affect vaccine uptake." CONCLUSION: A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Prognostic Serum Biomarkers of Inflammaging in Patients Undergoing Emergency Laparotomy.

Surgeons are increasingly faced with an ageing and frail patient population. There is a significant absence of biomarkers capable of risk stratifying patients undergoing emergency laparotomy. Inflammaging describes a state of chronic inflammation associated with ageing and frailty that may predict worse outcomes after surgery. This retrospective observational study evaluated pre-morbid inflammatory markers in the prognostication of older adult patients undergoing emergency laparotomy. Patients aged ≥65 years undergoing surgery between 1 April 2017 and 1 April 2022 were identified. Pre-admission and acute C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total white cell count (WCC), neutrophil count (NC) and lymphocyte count (LC) datapoints were captured. Pre-operative risk stratification scores and post-operative outcomes were recorded using the National Emergency Laparotomy Audit (NELA) database. A cohort of 196 patients was included: 57.7% were female, median age 74.5 years. High risk (NELA risk of mortality ≥ 5%) and frail (clinical frailty scale ≥ 4) patients experienced a significantly longer hospital and critical care stay (p < 0.05). Pre-admission ESR ≥ 16 and LC ≥ 4.1 were significantly associated with a longer critical care stay (p < 0.05); no statistical significance was observed with CRP, WCC and NC in predicting adverse outcomes. We found that an elevated pre-morbid ESR and LC identifies a potential inflammaging cohort that demonstrates worse outcomes following emergency laparotomy. The prognostication of older adult surgical patients remains a challenge and represents an area of research deserving of future attention.

Vitamin D and lactoferrin attenuate stress-induced colitis in Wistar rats via enhancing AMPK expression with inhibiting mTOR-STAT3 signaling and modulating autophagy.

Irritable bowel syndrome (IBS) is a global gastrointestinal disorder closely related to psychological stress exposure and local colonic inflammation. Herein, we investigated the effect of wrap-restraint stress (WRS) on rat behavior, on adenosine monophosphate-activated protein kinase-mammalian/mechanistic target of rapamycin-signal transducer and activator of transcription 3 (AMPK-mTOR-STAT3) signaling, and autophagy in colonic mucosa. The impact of chronic administration of vitamin D3 and lactoferrin was compared. Twenty-four male Wistar rats were randomly divided into four groups. Chronic WRS protocol was applied as a rodent model of IBS. Group I: naïve animals, Group II: WRS animals, Group III: WRS-exposed and treated with vitamin D3 (500 IU/kg/day), and Group IV: WRS-exposed and treated with lactoferrin (300 mg/kg/day). In this study, we found that chronic administration of each of vitamin D3 and lactoferrin resulted in a significant increase in social interaction test, interleukin-10, AMPK, optical density of LC3B, goblet cell count and marked decrease in serum cortisol level, STAT3, inflammatory cell count, and optical density of mTOR in comparison to the WRS rats. Our findings suggest that both vitamin D3 and Lactoferrin could augment colonic autophagy through enhanced AMPK expression and inhibition of mTOR-STAT3 signaling, which offers practical insights into their clinical use in the prevention and therapy of IBS. However, lactoferrin intake as a nutritional supplement could be more helpful for stress-induced colitis treatment than vitamin D3.

Specialization in Acute Type A Aortic Dissection Repair: The Outcomes and Challenges.

With increasing specialization within the field of cardiac surgery and a positive relationship between case volume and surgical outcomes in many areas, the concept of dedicated aortic surgeons performing acute type A aortic dissection (ATAAD) repair was investigated. From 1996 to 2014, 436 patients underwent open surgical repair of an ATAAD and were subsequently divided based on surgeon subspecialization, aortic-surgeon (AS, n = 401) vs non-aortic-surgeon (NAS, n = 35). Each aortic surgeon performed an average of 13 ATAAD repair operations per year. Preoperative comorbidities were similar between groups. Intraoperatively, the AS group had 36% aortic root replacement vs 23% in the NAS group, P = 0.12, and 36% zone 1/2/3 arch replacement vs 26% in the NAS group, P = 0.20). Postoperatively, the AS group had significantly better outcomes, including intraoperative mortality (1.2% vs 5.7%), 30-day mortality (6.5% vs 17%), and composite outcomes (23% vs 46%). Multivariable logistic regression showed NAS was a risk factor for 30-day mortality with an odds ratio (OR) of 4.4 (P = 0.03), as were COPD (OR = 4.0, P = 0.046) and cardiogenic shock (OR = 13.4, P < 0.0001). The 10-year survival was 66% in the AS group vs 46% in the NAS group, P = 0.02. NAS (HR = 2.2), Age (hazard ratio (HR) = 1.05), COPD (HR = 1.96), acute stroke (HR = 3.0), and New York Heart Association class III or IV (HR = 1.75) were significant risk factors for long-term mortality. Managing ATAAD by subspecialized aortic surgeons resulted in improved short- and long-term outcomes. Our specialty could consider ATAAD repair by high-volume aortic surgeons for better patient outcomes.

Evolution and Applications of Artificial Intelligence to Cataract Surgery.

Topic: Despite significant recent advances in artificial intelligence (AI) technology within several ophthalmic subspecialties, AI seems to be underutilized in the diagnosis and management of cataracts. In this article, we review AI technology that may soon become central to the cataract surgical pathway, from diagnosis to completion of surgery. Clinical Relevance: This review describes recent advances in AI in the preoperative, intraoperative, and postoperative phase of cataract surgery, demonstrating its impact on the pathway and the surgical team. Methods: A systematic search of PubMed was conducted to identify relevant publications on the topic of AI for cataract surgery. Articles of high quality and relevance to the topic were selected. Results: Before surgery, diagnosis and grading of cataracts through AI-based image analysis has been demonstrated in several research settings. Optimal intraocular lens (IOL) power to achieve the desired postoperative refraction can be calculated with a higher degree of accuracy using AI-based modeling compared with traditional IOL formulae. During surgery, innovative AI-based video analysis tools are in development, promoting a paradigm shift for documentation, storage, and cataloging libraries of surgical videos with applications for teaching and training, complication review, and surgical research. Situation-aware computer-assisted devices can be connected to surgical microscopes for automated video capture and cloud storage upload. Artificial intelligence-based software can provide workflow analysis, tool detection, and video segmentation for skill evaluation by the surgeon and the trainee. Mixed reality features, such as real-time intraoperative warnings, may have a role in improving surgical decision-making with the key aim of reducing complications by recognizing surgical risks in advance and alerting the operator to them. For the management of patient flow through the pathway, AI-based mathematical models generating patient referral patterns are in development, as are simulations to optimize operating room use. In the postoperative phase, AI has been shown to predict the posterior capsule status with reasonable accuracy, and can therefore improve the triage pathway in the treatment of posterior capsular opacification. Discussion: Artificial intelligence for cataract surgery will be as relevant as in other subspecialties of ophthalmology and will eventually constitute a future cornerstone for an enhanced cataract surgery pathway.

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

Elevations in adipocytokines and mortality in rheumatoid arthritis.

OBJECTIVES: This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with RA. METHODS: Participants were adults from the Veterans Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrolment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality. RESULTS: A total of 2583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower BMI, autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrolment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs lowest quartile) was associated with higher all-cause mortality [hazard ratio (HR): 1.46 (95% CI: 1.11, 1.93), P = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75), P = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality. CONCLUSIONS: Elevations in adipokines are associated with age, BMI, comorbidity and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes.

Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer.

BACKGROUND: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers. METHODS: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis. RESULTS: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10-7-2.8 × 10-2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80). CONCLUSIONS: Urinary VOC analysis could aid the diagnosis and surveillance of UBC.

Association between depression, anxiety, chronic pain, or opioid use and tumor necrosis factor inhibitor persistence in inflammatory arthritis.

INTRODUCTION: Depression, anxiety, and chronic pain are common comorbidities in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and may substantially impact patient outcomes. We aimed to determine whether these comorbidities were associated with earlier TNF-inhibitor (TNFi) discontinuation. METHODS: This retrospective cohort study using Optum's de-identified Clinformatics® Data Mart Database 2000-2014 identified patients with RA, PsA, and AS initiating a first TNFi. Depression/anxiety, chronic pain, and opioid use were identified using diagnosis codes and prescription fill data. Cox proportional hazards models were used to compare time to medication discontinuation in patients with or without each of these risk factors and to assess the additive effect of having multiple risk factors. RESULTS: Among 33,744 patients initiating a TNFi (23,888 RA, 6443 PsA, 3413 AS), depression/anxiety, chronic pain, and opioid use were common, with ≥ 1 risk factor in 48.1%, 42.5%, and 55.4% of patients with RA, PsA, and AS respectively. Each risk factor individually was associated with a 5-7-month lower median treatment persistence in each disease (all p < 0.001). Presence of multiple risk factors had an additive effect on time to discontinuation with HR (95% CI) 1.19 (1.14-1.24), 1.41 (1.33-1.49), and 1.47 (1.43-1.73) for 1, 2, or 3 risk factors respectively in RA. Findings were similar in PsA and AS. CONCLUSIONS: Depression, anxiety, chronic pain, and opioid use are common in inflammatory arthritis and associated with earlier TNFi discontinuation. Recognizing and managing these risk factors may improve treatment persistence, patient outcomes, and cost of care. Key Points • Depression, anxiety, chronic pain, and opioid use are common in patients with inflammatory arthritis. • In patients initiating treatment with a TNF-inhibitor, depression, anxiety, chronic pain, or recent opioid use are associated with sooner discontinuation of TNFi therapy. • Patients with multiple of these risk factors are even more likely to discontinue therapy sooner.