Brain implantation of tissue-level-soft bioelectronics via embryonic development.

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3-9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry.

OBJECTIVES: An estimated 5-20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered "difficult-to-treat" (D2T), posing a substantial clinical challenge for rheumatologists. A European Alliance of Associations for Rheumatology (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR's D2T definition in a cohort of patients with established RA to assess prevalence and we compared clinical characteristics of participants with D2T-RA with matched comparisons. METHODS: Data from the longitudinal Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry was used. Participants were classified as D2T if they met EULAR's definition. A comparison group of non-D2T RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. RESULTS: We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8-16.3 per 100 persons) among 1,581 participants with RA, and 22.3 (95% CI: 19.9-25.0 per 100 persons) among 1,021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities, and RA disease activity between D2T-RA and non-D2T RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6-17.5 per 100 persons. CONCLUSION: EULAR's proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.

Interprofessional Collaboration amongst Healthcare Workers of a Tertiary Hospital in North-Eastern Nigeria.

BACKGROUND: Interprofessional collaboration in healthcare is important to optimise healthcare delivery. However, relatively few studies have been conducted on the topic in Nigeria, especially in the North. OBJECTIVE: The objective of this study was to determine the levels of interprofessional collaboration, enablers and barriers amongst healthcare workers. MATERIALS AND METHODS: Data were collected using a five-domain modified Assessment of Interprofessional Team Collaboration Scale questionnaire, with a Likert scale of 1-5. The ideal mean score was ≤2 for the barriers domain and ≥4 for the other domains. Data were analysed using the Statistical Package for the Social Sciences (SPSS) version 23. RESULTS: Two hundred and sixty-six participants responded to the questionnaire. Male and female respondents were 131 (49.2%) each. Half of the respondents were 31 to 40 years old. One hundred and thirty-six (51.1%) of the respondents were nurses, and 48 (18.0%) were doctors. The modal working experience was 6-11 years (41.4%), and 117 (44.0%) respondents had at least a bachelor's degree. The mean scores for the domains were 4.1032 for partnership, 3.2383 for cooperation, 3.6309 for coordination, 4.2844 for enablers and 3.7902 for barriers. CONCLUSION: There was adequate level of partnership and enablers amongst the healthcare workers but insufficient cooperation and coordination and high level of barriers. Staff training on cooperation, coordination and identified barriers is necessary to improve interprofessional collaboration in the hospital.

Switching Human Immunodeficiency Virus Therapy: Basic Principles and Options.

The number of options for effective antiretroviral therapy (ART) is steadily increasing. Although older regimens may achieve the goal of virologic suppression, newer options can offer advantages in safety, tolerability, and convenience. In this article, we offer guiding principles for switching ART, highlighting reasons to pursue a switch and key factors to consider when selecting a new regimen.

Herpes Simplex Virus Encephalitis in Patients With Autoimmune Conditions or Exposure to Immunomodulatory Medications.

BACKGROUND AND OBJECTIVES: Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is most common, accounting for ∼15%-40% of adult encephalitis diagnoses. We aim to investigate the association between immune status and HSV encephalitis (HSVE). Using a US Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. METHODS: We used the US Medicaid Analytic eXtract data between 2007 and 2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age and sex-matched adult cases of HSVE with a sufficient enrollment period (12 months before HSVE diagnosis) to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson Comorbidity Index, and non-autoimmune comorbidities. RESULTS: Incidence of HSVE was ∼3.01 per 105 person-years among adults. A total of 951 HSVE cases and 95,100 age and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong (adjusted odds ratio (OR) 2.6; 95% CI 2.2-3.2). The association of HSVE and immunomodulating medications had an OR of 2.2 (CI 1.9-2.6), also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: OR 2.3 (CI 1.9-2.7) for autoimmune disease and 2.0 (CI 1.7-2.3) for immunosuppressive and immunomodulatory medications. DISCUSSION: In a large, national population, HSVE is strongly associated with preexisting autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date.

Identifying the association between serum urate levels and gout flares in patients taking urate-lowering therapy: a post hoc cohort analysis of the CARES trial with consideration of dropout.

OBJECTIVE: To investigate gout flare rates based on repeated serum urate (SU) measurements in a randomised controlled trial of urate-lowering therapy (ULT), accounting for dropout and death. METHODS: We performed a secondary analysis using data from Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout, which randomised participants to febuxostat or allopurinol, titrated to target SU <6 mg/dL with flare prophylaxis for 6 months. SU was categorised as ≤3.9, 4.0-5.9, 6.0-7.9, 8.0-9.9 or ≥ 10 mg/dL at each 3-6 month follow-up. The primary outcome was gout flare. Poisson regression models, adjusted for covariates and factors related to participant retention versus dropout, estimated gout flare incidence rate ratios by time-varying SU category. RESULTS: Among 6183 participants, the median age was 65 years and 84% were male. Peak gout flare rates for all SU categories were observed in months 0-6, coinciding with the initiation of ULT and months 6-12 after stopping prophylaxis. Flare rates were similar across SU groups in the initial year of ULT. During months 36-72, a dose-response relationship was observed between the SU category and flare rate. Lower flare rates were observed when SU ≤3.9 mg/dL and greater rates when SU ≥10 mg/dL, compared with SU 4.0-5.9 mg/dL (p for trend <0.01). CONCLUSION: Gout flare rates were persistently higher when SU ≥6 mg/dL after the first year of ULT after accounting for censoring. The spike in flares in all categories after stopping prophylaxis suggests a longer duration of prophylaxis may be warranted.

Gout risk in adults with pre-diabetes initiating metformin.

OBJECTIVE: Despite the strong association between gout and pre-diabetes, the role of metformin in gout among individuals with pre-diabetes remains uncertain. We compared the incidence rates of gout in adults with pre-diabetes starting metformin with those not using antidiabetic treatments. METHODS: We conducted a new-user, propensity score-matched cohort study using electronic health records from an academic health system (2007-2022). Pre-diabetes was defined based on haemoglobin A1c levels. Metformin users were identified and followed from the first metformin prescription date. Non-users of antidiabetic medications were matched to metformin users based on propensity score and the start of follow-up. The primary outcome was incident gout. Cox proportional hazards models estimated the HR for metformin. Linear regression analyses assessed the association between metformin use and changes in serum urate (SU) or C-reactive protein (CRP). RESULTS: We identified 25 064 individuals with pre-diabetes and propensity score-matched 1154 metformin initiators to 13 877 non-users. Baseline characteristics were well balanced (all standardised mean differences <0.1). The median follow-up was 3.9 years. The incidence rate of gout per 1000 person-years was lower in metformin users 7.1 (95% CI 5.1 to 10) compared with non-users 9.5 (95% CI 8.8 to 10.2). Metformin initiation was associated with a reduced relative risk of gout (HR 0.68, 95% CI 0.48 to 0.96). No relationship was found between metformin and changes in SU or CRP. CONCLUSIONS: Metformin use was associated with a reduced risk of gout among adults with pre-diabetes, suggesting that metformin may be important in lowering gout risk in individuals with pre-diabetes.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. METHODS: In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. FINDINGS: Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). INTERPRETATION: Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. FUNDING: Research Council of Norway and South-Eastern Norway Regional Health Authority.

Interplay Between Systemic Inflammation, Myocardial Injury, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis: Results From the LiiRA Study.

BACKGROUND: Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. METHODS AND RESULTS: Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. CONCLUSIONS: In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.

Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife.

Importance: Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. Objective: To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. Design, Setting, and Participants: The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Exposures: Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Main Outcomes and Measures: Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Results: Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Conclusions and Relevance: Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.

Longitudinal Follow-Up of Fibrosis-4 in Patients at Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease Receiving Low-Dose Methotrexate Treatment.

Several noninvasive liver fibrosis tests have been developed and appear to predict the severity of fibrosis, possibly replacing invasive liver biopsy as a monitoring tool.1 The fibrosis-4 (FIB-4) score originally was proposed to help assess liver fibrosis in patients with human immunodeficiency virus and hepatitis C virus co-infection.1 FIB-4 has been used widely to monitor the severity of liver fibrosis, especially in patients with nonalcoholic fatty liver disease,2 now termed metabolic dysfunction-associated steatotic liver disease (MASLD).3.

Thoracic Duct Visualization in Esophageal Resection: A Pilot Trial.

INTRODUCTION: Inadvertent thoracic duct injury is common during esophagectomy and may result in postoperative chylothorax. This study's objective was to investigate utility of patent blue injection as a modality for intraoperative thoracic duct visualization. METHODS: A prospective, single-arm, interventional study of patients undergoing minimally invasive esophagectomy was performed. Patients were injected with patent blue dye into both groins prior to thoracic stage of surgery and assessed for duct visualization. Control group was formed by propensity score matching using retrospectively collected data regarding patients who underwent esophagectomy. RESULTS: A total of 25 patients were included in analysis, compared to a control of 50 patients after matching. Thoracic duct was visualized in 60% of patients in the study group (15/25 patients). Significant differences were found between study and control groups (p < 0.05) with regards to median operative time (422 vs. 285 min, respectively), overall complications (16 vs. 34%, respectively), and median postoperative length of stay (13.5 vs. 10 days, respectively). There was a difference in rate of chyle leak between study and control groups; however, this was not significant (0 vs. 12%, respectively, p = 0.17). CONCLUSION: Patent blue injection represents a simple method for thoracic duct visualization during minimally invasive esophagectomy which may improve surgical outcomes.

Real-World Dalbavancin Use for Serious Gram-Positive Infections: Comparing Outcomes Between People Who Use and Do Not Use Drugs.

Background: Dalbavancin has been used off-label to treat invasive bacterial infections in vulnerable populations like people who use drugs (PWUD) because of its broad gram-positive coverage and unique pharmacological properties. This retrospective, multisite study examined clinical outcomes at 90 days in PWUD versus non-PWUD after secondary treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, septic arthritis, and epidural abscesses. Methods: Patients at 3 teaching hospitals who received dalbavancin for an invasive infection between March 2016 and May 2022 were included. Characteristics of PWUD and non-PWUD, infection highlights, hospital stay and treatment, and outcomes were compared using χ2 for categorical variables, t test for continuous variables, and nonparametric tests where appropriate. Results: There were a total of 176 patients; 78 were PWUD and 98 were non-PWUD. PWUD were more likely to have a patient-directed discharge (26.9% vs 3.1%; P < .001) and be lost to follow-up (20.5% vs 7.14%; P < .01). Assuming loss to follow-up did not achieve clinical cure, 73.1% of PWUD and 74.5% of non-PWUD achieved clinical cure at 90 days (P = .08). Conclusions: Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient-directed discharge and loss to follow-up, PWUD had similar rates of clinical cure at 90 days compared to non-PWUD.

Esophagectomy in the Older Adult: A Systematic Review.

Current management of esophageal carcinoma (EC) involves combining different modalities, offering the opportunity of personalized strategies. This is particularly enticing in the geriatric population, where tailoring treatment modalities remains key to achieve good outcomes in terms of both quality of life and survival. Primary outcomes of our review included (1) evidence on short-term outcomes following esophagectomy, and (2) evidence on long-term outcomes following esophagectomy. Secondary review questions compared outcomes of (1) neoadjuvant treatment versus upfront surgery for locally advanced esophageal carcinoma, (2) endoscopic submucosal dissection versus esophagectomy for early esophageal carcinoma, and (3) definitive radiation with or without chemotherapy versus surgery. Twenty-six articles were included in the review for the main review questions. Our systematic review underscores the need for comprehensive geriatric evaluations to guide decision-making. Despite concerns about perioperative risks, well-selected older patients can derive survival benefits from surgical intervention.

Association of the multi-biomarker disease activity score with arterial 18-fluorodeoxyglucose uptake in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would associate with changes in arterial inflammation in an interventional trial. METHODS: In the TARGET Trial, RA patients with active disease despite methotrexate were randomly assigned to the addition of either a TNF inhibitor or sulfasalazine+hydroxychloroquine (triple therapy). Baseline and 24-week follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans were assessed for change in arterial inflammation measured as the maximal arterial target-to-blood background ratio of FDG uptake in the most diseased segment of the carotid arteries or aorta (MDS-TBRmax). The MBDA test, measured at baseline and weeks 6, 18, and 24, was assessed for its association with the change in MDS-TBRmax. RESULTS: Interpretable scans were available at baseline and week 24 for n = 112 patients. The MBDA score at week 24 was significantly correlated with the change in MDR-TBRmax (Spearman's rho = 0.239; p= 0.011) and remained significantly associated after adjustment for relevant confounders. Those with low MBDA at week 24 had a statistically significant adjusted reduction in arterial inflammation of 0.35 units vs no significant reduction in those who did not achieve low MBDA. Neither DAS28-CRP nor CRP predicted change in arterial inflammation. The MBDA component with the strongest association with change in arterial inflammation was serum amyloid A (SAA). CONCLUSIONS: Among treated RA patients, achieved MBDA predicts of changes in arterial inflammation. Achieving low MBDA at 24 weeks was associated with clinically meaningful reductions in arterial inflammation, regardless of treatment.

Operative Volumes and Postoperative Outcomes After Elective Resection of Congenital Lung Malformations in Infants.

OBJECTIVE: To determine whether hospital- and surgeon-level operative volumes are associated with differences in postoperative outcomes among infants undergoing elective lung surgery for a congenital lung malformation (CLM). SUMMARY BACKGROUND DATA: Infant lung surgery is a relatively uncommon procedure performed by pediatric surgeons nationwide. The relationship between surgical volume and postoperative outcomes remains unknown. METHODS: A retrospective cohort study of asymptomatic infants who underwent elective lung resection of a CLM was conducted using the Pediatric Health Information System database (2016-2020). Multivariable linear and poisson regressions were performed based on annual lung resection tertiles. RESULTS: There were 1420 infants managed by 48 hospitals and 309 primary surgeons. Institutions that performed seven or fewer CLM resections per year (56%) were associated with significantly higher postoperative complication rates compared to medium- and high-volume hospitals (low: 134 [34%], medium: 110 [21%], high: 144 [29%]; P<0.001). Surgeons who performed one or fewer CLM resections per year (82%) were associated with significantly higher complication rates compared to medium- and high-volume surgeons (low: 171 [31%], medium: 75 [26%], high: 119 [24%]; P=0.02). Multivariable analyses confirmed that low-volume hospitals were associated with higher complications (OR 1.81, CI 1.38-2.37; P<0.001), and low-volume surgeons had an increased risk of complications (overall: OR 1.37, CI 1.01-1.84; P=0.04). CONCLUSIONS: In this cohort study of infants undergoing elective lung resection for a CLM, lower volume providers were associated with higher postoperative patient morbidity. These findings represent an opportunity to inform quality improvement initiatives on pediatric lung resection and the debate on surgical subspecialization for this unique patient population.

Editorial Commentary: Magnetic Resonance Arthrogram Is More Accurate and Precise Than Conventional Magnetic Resonance Imaging for Evaluating Labral Tears After First-Time Shoulder Dislocation.

Recent research shows that magnetic resonance arthrogram offers better definition of certain shoulder pathology, especially labral tears, compared with magnetic resonance imaging (MRI). Conventional MRI accuracy and precision deteriorate after 2 weeks, and few health delivery environments achieve MRI within 14 days of a shoulder dislocation. Moreover, further loss of MRI accuracy is time dependent. Although magnetic resonance arthrogram should be considered a first-line imaging study when evaluating shoulder instability more than 2 weeks after the patient's injury, one must also consider clinical value and cost-effectiveness.

Changes in alcohol intake and serum urate changes: longitudinal analyses of annual medical examination database.

INTRODUCTION: Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change. METHOD: We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates. RESULTS: We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day). CONCLUSIONS: This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

Biomarkers of Cardiovascular Risk in Patients With Rheumatoid Arthritis: Results From the TARGET Trial.

Cardiovascular disease remains an important comorbidity in patients with rheumatoid arthritis (RA), but traditional models do not accurately predict cardiovascular risk in patients with RA. The addition of biomarkers could improve prediction. METHODS AND RESULTS: The TARGET (Treatments Against RA and Effect on FDG PET/CT) trial assessed whether different treatment strategies in RA differentially impact cardiovascular risk as measured by the change in arterial inflammation on arterial target to background ratio on fluorodeoxyglucose positron emission tomography/computed tomography scans conducted 24 weeks apart. A group of 24 candidate biomarkers supported by prior literature was assessed at baseline and 24 weeks later. Longitudinal analyses examined the association between baseline biomarker values, measured in plasma EDTA, and the change in arterial inflammation target to background ratio. Model fit was assessed for the candidate biomarkers only, clinical variables only, and models combining both. One hundred nine patients with median (interquartile range) age 58 years (53-65 years), RA duration 1.4 years (0.5-6.6 years), and 82% women had biomarkers assessed at baseline and follow-up. Because the main trial analyses demonstrated significant target to background ratio decreases with both treatment strategies but no difference across treatment groups, we analyzed all patients together. Baseline values of serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-40, and osteoprotegerin were associated with significant change in target to background ratio. When selected candidate biomarkers were added to the clinical variables, the adjusted R2 improved from 0.20 to 0.33 (likelihood ratio P=0.0005). CONCLUSIONS: A candidate biomarker approach identified several promising biomarkers that associate with baseline and treatment-associated changes in arterial inflammation in patients with RA. These will now be tested in an external validation cohort.