Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

BACKGROUND: We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). METHODS: Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. RESULTS: This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200-2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678-1.455), after adjusting for other baseline characteristics. CONCLUSIONS: The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

A comprehensive review of advanced trends: from artificial synapses to neuromorphic systems with consideration of non-ideal effects.

A neuromorphic system is composed of hardware-based artificial neurons and synaptic devices, designed to improve the efficiency of neural computations inspired by energy-efficient and parallel operations of the biological nervous system. A synaptic device-based array can compute vector-matrix multiplication (VMM) with given input voltage signals, as a non-volatile memory device stores the weight information of the neural network in the form of conductance or capacitance. However, unlike software-based neural networks, the neuromorphic system unavoidably exhibits non-ideal characteristics that can have an adverse impact on overall system performance. In this study, the characteristics required for synaptic devices and their importance are discussed, depending on the targeted application. We categorize synaptic devices into two types: conductance-based and capacitance-based, and thoroughly explore the operations and characteristics of each device. The array structure according to the device structure and the VMM operation mechanism of each structure are analyzed, including recent advances in array-level implementation of synaptic devices. Furthermore, we reviewed studies to minimize the effect of hardware non-idealities, which degrades the performance of hardware neural networks. These studies introduce techniques in hardware and signal engineering, as well as software-hardware co-optimization, to address these non-idealities through compensation approaches.

Clinical Utility of a CT-based AI Prognostic Model for Segmentectomy in Non-Small Cell Lung Cancer.

Background Currently, no tool exists for risk stratification in patients undergoing segmentectomy for non-small cell lung cancer (NSCLC). Purpose To develop and validate a deep learning (DL) prognostic model using preoperative CT scans and clinical and radiologic information for risk stratification in patients with clinical stage IA NSCLC undergoing segmentectomy. Materials and Methods In this single-center retrospective study, transfer learning of a pretrained model was performed for survival prediction in patients with clinical stage IA NSCLC who underwent lobectomy from January 2008 to March 2017. The internal set was divided into training, validation, and testing sets based on the assignments from the pretraining set. The model was tested on an independent test set of patients with clinical stage IA NSCLC who underwent segmentectomy from January 2010 to December 2017. Its prognostic performance was analyzed using the time-dependent area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for freedom from recurrence (FFR) at 2 and 4 years and lung cancer-specific survival and overall survival at 4 and 6 years. The model sensitivity and specificity were compared with those of the Japan Clinical Oncology Group (JCOG) eligibility criteria for sublobar resection. Results The pretraining set included 1756 patients. Transfer learning was performed in an internal set of 730 patients (median age, 63 years [IQR, 56-70 years]; 366 male), and the segmentectomy test set included 222 patients (median age, 65 years [IQR, 58-71 years]; 114 male). The model performance for 2-year FFR was as follows: AUC, 0.86 (95% CI: 0.76, 0.96); sensitivity, 87.4% (7.17 of 8.21 patients; 95% CI: 59.4, 100); and specificity, 66.7% (136 of 204 patients; 95% CI: 60.2, 72.8). The model showed higher sensitivity for FFR than the JCOG criteria (87.4% vs 37.6% [3.08 of 8.21 patients], P = .02), with similar specificity. Conclusion The CT-based DL model identified patients at high risk among those with clinical stage IA NSCLC who underwent segmentectomy, outperforming the JCOG criteria. © RSNA, 2024 Supplemental material is available for this article.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Rheumatoid Arthritis and Risk of Depression in South Korea.

Importance: Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. Objective: To investigate the risk of depression following RA diagnosis among patients in South Korea. Design, Setting, and Participants: This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Exposures: Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Main Outcomes and Measures: Newly diagnosed depression (ICD-10 codes F32 or F33). Results: The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). Conclusions and Relevance: This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Correction: Soung et al. Therapeutic Potential of Chemically Modified MiR-489 in Triple-Negative Breast Cancers. Cancers 2020, 12, 2209.

In the original publication [...].

Partner Plan Choices and Medicare Advantage Enrollment Decisions Among Older Adults.

This study examines the association of partner Medicare Advantage plan status over 1 year with beneficiary and plan characteristics.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

Programmable Threshold Logic Implementations in a Memristor Crossbar Array.

In this study, we demonstrate the implementation of programmable threshold logics using a 32 × 32 memristor crossbar array. Thanks to forming-free characteristics obtained by the annealing process, its accurate programming characteristics are presented by a 256-level grayscale image. By simultaneous subtraction between weighted sum and threshold values with a differential pair in an opposite way, 3-input and 4-input Boolean logics are implemented in the crossbar without additional reference bias. Also, we verify a full-adder circuit and analyze its fidelity, depending on the device programming accuracy. Lastly, we successfully implement a 4-bit ripple carry adder in the crossbar and achieve reliable operations by read-based logic operations. Compared to stateful logic driven by device switching, a 4-bit ripple carry adder on a memristor crossbar array can perform more reliably in fewer steps thanks to its read-based parallel logic operation.

The Importance of Autonomy and Performance Goals in Perceived Workload Among Behavioral Health Providers.

OBJECTIVE: The authors sought to assess workplace characteristics associated with perceived reasonable workload among behavioral health care providers in the Veterans Health Administration. METHODS: The authors evaluated perceived reasonable workload and workplace characteristics from the 2019 All Employee Survey (AES; N=14,824) and 2019 Mental Health Provider Survey (MHPS; N=10,490) and facility-level staffing ratios from Mental Health Onboard Clinical Dashboard data. Nine AES and 15 MHPS workplace predictors of perceived reasonable workload, 11 AES and six MHPS demographic predictors, and facility-level staffing ratios were included in mixed-effects logistic regression models. RESULTS: In total, 8,874 (59.9%) AES respondents and 5,915 (56.4%) MHPS respondents reported having a reasonable workload. The characteristics most strongly associated with perceived reasonable workload were having attainable performance goals (average marginal effect [AME]=0.10) in the AES and ability to schedule patients as frequently as indicated (AME=0.09) in the MHPS. Other AES characteristics significantly associated with reasonable workload included having appropriate resources, support for personal life, skill building, performance recognition, concerns being addressed, and no supervisor favoritism. MHPS characteristics included not having collateral duties that reduce care time, staffing levels not affecting care, support staff taking over some responsibilities, having spirit of teamwork, primary care-mental health integration, participation in performance discussions, well-coordinated mental health care, effective veteran programs, working at the top of licensure, and feeling involved in improving access. Facility-level staffing ratios were not significantly associated with perceived reasonable workload. CONCLUSIONS: Leadership may consider focusing resources on initiatives that support behavioral health providers' autonomy to schedule patients as clinically indicated and develop attainable performance goals.

Telehealth and delivery of alcohol use disorder treatment in the Veterans Health Administration.

BACKGROUND: The use of telehealth treatment of alcohol use disorder (AUD) has increased since the start of the COVID-19 pandemic. However, it is unclear which patients are using telehealth and how telehealth visits are associated with treatment duration. This study examined characteristics associated with telehealth use among Veterans Health Administration patients receiving AUD treatment. METHODS: Using a national retrospective cohort study, we examined data from March 01, 2020 to February 28, 2021 to: First, identify patient characteristics associated with (a) any telehealth versus only in-person care for AUD treatment, and (b) video (≥1 video visit) versus only telephone visits for AUD treatment (≥1 telephone visit, no video) among any telehealth users. This analysis used mixed-effects logistic regression models to adjust for potential correlation across patients treated at the same facility. Second, we assessed whether visit modality was associated with the amount of AUD treatment received (number of AUD psychotherapy visits or medication coverage days). This analysis used mixed-effects negative binomial regression models. RESULTS: Among 138,619 patients who received AUD treatment, 52.8% had ≥1 video visit, 38.1% had ≥1 telephone but no video visits, and 9.1% had only in-person visits. In the regression analyses, patients who were male or had an opioid or stimulant use disorder (compared to having no non-AUD substance use disorder) were less likely to receive any telehealth-delivered AUD treatment compared to only in-person AUD treatment. Among patients who received any telehealth-delivered AUD treatment, those who were ≥45 years old (compared to 18-29 years old), Black (compared to White), diagnosed with a cannabis or stimulant use disorder, or diagnosed with a serious mental illness were less likely to receive a video visit than only telephone visits. Receiving any AUD telehealth was associated with receiving more psychotherapy visits and medication coverage days than only in-person care. CONCLUSIONS: Telehealth, a common modality for AUD treatment, supported a greater number of psychotherapy visits and a longer duration of medication treatment for AUD. However, some groups were less likely to receive any video telehealth than telephone visits, suggesting that multiple treatment modalities should remain available to ensure treatment access.

Inflammatory Bowel Disease Hospitalizations Are Similar for Patients Receiving Televisit-Delivered Outpatient Care and Those Receiving Traditional In-Person Care.

INTRODUCTION: The coronavirus disease 2019 pandemic resulted in widespread expansion of telehealth. However, there are concerns that telehealth-delivered outpatient care may limit opportunities for managing complications and preventing hospitalizations for patients with inflammatory bowel disease (IBD). We aimed to assess the association between outpatient IBD care delivered through televisit (video or phone) and IBD-related hospitalizations. METHODS: We conducted a case-control study of patients with IBD who had an IBD-related index hospitalization between April 2021 and July 2022 and received their care in the Veterans Health Administration. We matched these hospitalized patients to controls who were not hospitalized based on age, sex, race, Charlson comorbidity index, IBD type, IBD-related emergency department use, IBD-related hospitalizations, and outpatient gastroenterology visits in the preceding year. The variable of interest was the percentage of total clinic visits delivered through televisit in the year before the index hospitalization. We compared the risk of IBD-related hospitalization by exposure to televisit-delivered care using conditional logistic regression. RESULTS: We identified 534 patients with an IBD-related hospitalization and 534 matched controls without an IBD-related hospitalization during the study period. Patients with IBD with a higher percentage of televisit-delivered (vs in-person) outpatient care were less likely to be hospitalized during the study period (for every 10% increase in televisit use, odds ratio 0.97, 95% confidence interval 0.94-1.00; P = 0.03). DISCUSSION: Televisit-delivered outpatient IBD care is not associated with higher risk of IBD-related hospitalization. These findings may reassure clinicians that televisit-delivered outpatient care is appropriate for patients with complex chronic diseases such as IBD.

Poly(ADP-ribosyl)ation of TIMELESS limits DNA replication stress and promotes stalled fork protection.

Poly(ADP-ribosyl)ation (PARylation), catalyzed mainly by poly(ADP-ribose) polymerase (PARP)1, is a key posttranslational modification involved in DNA replication and repair. Here, we report that TIMELESS (TIM), an essential scaffold of the replisome, is PARylated, which is linked to its proteolysis. TIM PARylation requires recognition of auto-modified PARP1 via two poly(ADP-ribose)-binding motifs, which primes TIM for proteasome-dependent degradation. Cells expressing the PARylation-refractory TIM mutant or under PARP inhibition accumulate TIM at DNA replication forks, causing replication stress and hyper-resection of stalled forks. Mechanistically, aberrant engagement of TIM with the replicative helicase impedes RAD51 loading and protection of reversed forks. Accordingly, defective TIM degradation hypersensitizes BRCA2-deficient cells to replication damage. Our study defines TIM as a substrate of PARP1 and elucidates how the control of replisome remodeling by PARylation is linked to stalled fork protection. Therefore, we propose a mechanism of PARP inhibition that impinges on the DNA replication fork instability caused by defective TIM turnover.

Rheumatoid Arthritis Increases the Risk of COPD: A Nationwide Retrospective Cohort Study.

BACKGROUND: Most reports of pulmonary manifestations in rheumatoid arthritis (RA) have been related to interstitial lung diseases. RA and COPD are both chronic inflammatory systemic diseases. RESEARCH QUESTION: Does RA increase the risk of developing COPD? Is there a difference between seropositive and seronegative RA in the risk of COPD? STUDY DESIGN AND METHODS: Using the Korean National Health Insurance Database, we screened individuals diagnosed with RA between 2010 and 2017. We identified 46,030 patients with RA (32,608 with seropositive RA and 13,422 with seronegative RA) and 276,180 matched control individuals; we monitored them until December 2019. We used multivariate Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) of risk factors for the development of COPD. RESULTS: The incidence of COPD among patients with RA was 5.04 per 1,000 person-years; it was 2.23 per 1,000 person-years in the control group. Patients with RA showed a higher risk of developing COPD (aHR, 2.11; 95% CI, 1.96-2.28) compared with the control group. Although both seropositive RA and seronegative RA were associated with an increased risk of COPD, patients with seropositive RA had a higher risk for the development of COPD (aHR, 1.26; 95% CI, 1.09-1.46) than patients with seronegative RA. In the subgroup analyses, smoking history did not demonstrate significant interactions between RA and COPD development. INTERPRETATION: RA is associated with an increased risk of COPD development, augmented by seropositivity. Physicians should monitor respiratory symptoms and pulmonary function carefully in patients with RA.

Burnout and Perceived Workload Among Behavioral Health Providers During the COVID-19 Pandemic: Importance of Supervisory, Leadership, and Organizational Support.

PURPOSE: To assess the relationship between behavioral health provider (BHP) perceptions of support during COVID-19 and burnout and self-reported workload. DESIGN: We conducted a cross-sectional analysis of provider-level data collected from the 2020 and 2021 All Employee Survey (AES). SETTING: The Veterans Health Administration. SUBJECTS: 36,541 (10,332 [28.28%] with missing data) respondents in 2020 and 2021 combined. MEASURES: Main outcomes were self-reported burnout and self-reported workload. Main predictors were 6 COVID-19-related provider-perceived support domains. Covariates were 11 AES demographic predictors. ANALYSIS: We conducted mixed-effects logistic regression modeling for each domain and outcome pairing. We summarized our results using average marginal effects (AMEs) and odds ratios (ORs). RESULTS: All 6 domains of feeling prepared, heard, protected, cared for, honored, and having flexible policies were significantly negatively associated with burnout (AMEs -.20 to -.10, ORs .38-.63, P < .001) and positively associated with reasonable workload (AMEs .11-.20, ORs 1.63-2.59, P < .001). Feeling prepared had the largest associations with burnout (OR .38) and reasonable workload (OR 2.59). CONCLUSION: Creating a work environment with flexible policies and where staff feel prepared, heard, protected, cared for, and honored could support BHPs in feeling less burned out and that their workload is reasonable.

Relationship between facility number of clinicians and prescribing intensity of psychotropic medications, opioids, and antibiotics in ambulatory practice.

BACKGROUND: Promoting appropriate pharmacotherapy requires understanding the factors that influence how clinicians prescribe medications. While prior work has focused on patient and clinician factors, features of the organizational setting have received less attention, though identifying sources of variation in prescribing may help identify opportunities to improve patient safety and outcomes. OBJECTIVE: To evaluate the relationship between the number of clinicians who prescribe medications in a facility and facility prescribing intensity of six individual medication classes by clinician specialty: benzodiazepines, antipsychotics, antiepileptics, and antidepressants by psychiatrists and antibiotics, opioids, antiepileptics, and antidepressants by primary care clinicians (PCPs). DESIGN: We used 2017 Veterans Health Administration (VHA) administrative data. SUBJECTS: We included patient-clinician dyads of older patients (> 55 years) with an outpatient encounter with a clinician in 2017. Patient-clinician data from 140 VHA facilities were included (n = 13,347,658). Analysis was repeated for years 2014 to 2016. MAIN MEASURES: For each medication, facility prescribing intensity measures were calculated as clinician prescribing intensity averaged over all clinicians at each facility. Clinician prescribing intensity measures included percentage of each clinician's patients prescribed the medication and mean number of days supply per patient among all patients of each clinician. KEY RESULTS: As the number of prescribing clinicians in a facility increased, the intensity of prescribing decreased. Every increase of 10 facility clinicians was associated with a significant decline in prescribing intensity for both specialties for different medication classes: for psychiatrists, declines ranged from 6 to 11%, and for PCPs, from 2 to 3%. The pattern of more clinicians less prescribing was significant across all years. CONCLUSION: Future work should explore the mechanisms that link the number of facility clinicians with prescribing intensity for benzodiazepines, antipsychotics, antiepileptics, antidepressants, antibiotics, and opioids. Facilities with fewer clinicians may need additional resources to avoid unwanted prescribing of potentially harmful or unnecessary medications.

Impact of Rheumatoid Arthritis and Seropositivity on the Risk of Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: Despite the coexistence of bronchiectasis and rheumatoid arthritis (RA) and the poor prognosis associated with the combination of conditions, to our knowledge, no longitudinal studies that comprehensively evaluated whether patients with RA have a higher risk of bronchiectasis compared with those without RA have been published. Whether seropositivity is associated with an increased risk of bronchiectasis in RA is the subject of ongoing controversy. RESEARCH QUESTION: Does RA influence the development of bronchiectasis? Is seropositivity associated with an increased risk of bronchiectasis in RA? STUDY DESIGN AND METHODS: The incidence of bronchiectasis was compared between individuals with RA (n = 50,651; seropositive rheumatoid arthritis [SPRA]: n = 35,879 and seronegative rheumatoid arthritis [SNRA]: n = 14,772) and 1:5 age- and sex-matched control patients (n = 253,255) enrolled between 2010 and 2017 in the Korean National Health Insurance Service database. The participants were followed from 1 year after RA diagnosis or the corresponding index date to the date of bronchiectasis incidence, censored date, or December 2019. RESULTS: The cumulative incidence of bronchiectasis at 9 years of follow-up was approximately 7% in participants with RA. During a median follow-up of 4.3 years (interquartile range, 2.6-6.3 years), participants with RA showed a 2.12-fold higher risk of developing bronchiectasis than matched control participants, even after adjusting for potential confounders related to bronchiectasis development (95% CI, 2.00-2.25). In an analysis of RA serologic status using a fully adjusted model, participants with SPRA and those with SNRA showed 2.34-fold (95% CI, 2.20-2.49) and 1.56-fold (95% CI, 1.40-1.73) increased risks, respectively, compared with matched control participants. INTERPRETATION: Individuals with RA had approximately twice the risk of developing bronchiectasis than matched control individuals, even after adjusting for potential confounders. The increased risk was more evident in individuals with SPRA than in those with SNRA, implying that rheumatic inflammation plays a major role in the development of RA-bronchiectasis overlap.

Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.