Background: An adjunctive infiltration between popliteal artery and capsule of the posterior knee (iPACK) block—an infiltration between the popliteal artery and posterior knee capsule—has been used in knee surgery to address posterior knee pain, complementing the anterior and medial sensory coverage of an adductor canal block (ACB). Its benefit in all-inside anterior cruciate ligament reconstruction (ACL-R) using quadriceps tendon (QT) autograft remains uncertain. Purpose: To compare acute postoperative pain, opioid consumption, and 6-week knee range of motion between patients receiving continuous ACB alone and continuous ACB plus a single-shot iPACK block. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Patients undergoing primary all-inside ACL-R with QT autograft were randomized to either continuous ACB with placebo skin wheal (ACB group) or continuous ACB with iPACK (ACB-iPACK group). Demographic and surgical data were collected prospectively. The primary outcome was visual analog scale (VAS) pain scores during the first 72 postoperative hours. Secondary outcomes included opioid use (morphine milligram equivalents), achievement of full knee extension, and difference in maximal flexion between the surgical and nonsurgical limb at 6 weeks. Results: A total of 71 patients were analyzed (ACB, n = 33; ACB-iPACK, n = 38), with no significant group differences in baseline characteristics. Median VAS scores at discharge were significantly lower in the ACB-iPACK group (20 mm) versus the ACB group (32.5 mm) ( P = .049). No further differences occurred between 12 and 72 hours postoperatively. Perioperative and postoperative opioid consumption did not differ between groups (perioperative, P = .52; postoperative, P = .47 to ≥.99). Rates of achieving full extension were similar. At 6 weeks, the difference in knee flexion between limbs was significantly smaller in the ACB-iPACK group (37.7°) compared with the ACB group (47.6°) (mean difference, 9.9°; P = .02). No perioperative regional anesthesia complications occurred. Conclusion: Adding an iPACK block to continuous ACB for all-inside ACL-R with QT autograft provided a slight reduction in pain at discharge (VAS difference, 12.5 mm) and improved knee flexion at 6 weeks. However, pain scores and opioid use beyond the immediate postoperative period were not significantly different between groups. These findings may help guide patient counseling regarding the expected benefits of incorporating an iPACK block in this surgical setting. Registration: NCT05498870 (ClinicalTrials.gov identifier).

Retrospective evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with retained gastric contents (RGC) after standard 8-hr fasting, possibly increasing aspiration risk. The primary aim of this study was to compare the incidence of RGC on upper endoscopy after appropriate preoperative fasting in patients taking GLP-1 RAs vs patients not taking GLP-1 RAs. We conducted prospective observational study of 256 patients scheduled for elective endoscopy involving stomach visualization. The primary outcome was RGC, defined as solid content or liquid-only content > 1.5 mL·kg−1 body weight. Control patients followed standard 8-hr fasting, while patients taking GLP-1 RAs were instructed to hold this medication 1 week prior and were limited to a preprocedural 24-hr clear liquid diet. We measured RGCvia suctioning whenever possible and recorded subjective physician impressions. Secondary outcomes included aspiration events, procedure abortion, and conversion to general anesthesia. We evaluated the differences between groups using two-sample t tests or Wilcoxon rank-sum test for continuous and ordinal variables and Chi square tests or Fisher’s exact test for categorical variables. We analyzed potentially confounding variables via logistic regression. There was no statistically significant difference in the incidence of RGC between patients taking GLP-1 RAs (8

Background:The Precision rEsearCh pArticipatioN (PECAN) study aims to explore factors that influence perceptions of precision health research participation, focusing on diverse communities in South Carolina. The objective is to identify both positive and negative factors affecting participation, enabling the development of strategies to enhance understanding and reduce barriers, particularly within a population facing significant health disparities. Methods:To ensure the effectiveness of the survey instrument for the PECAN study, researchers conducted a cognitive study through guided group discussions with community members. These discussions were designed to pinpoint survey questions that participants found difficult to understand, hard to answer, or unclear. The insights gained from this cognitive evaluation were used to refine and improve the survey, ensuring it is clear, uniform, and effective for gathering meaningful data. Results:The cognitive interview study identified several survey items that participants found challenging or ambiguous, particularly due to complex wording, culturally irrelevant content, and questions requiring extensive recall. Participants emphasized the need for clearer language, reassurance about anonymity, and the use of biological terms, as well as greater cultural representation. Based on this feedback, researchers revised the survey to simplify language, provide contextual disclaimers about specimen collection, depersonalize genetic testing questions, and restructure redundant items. Conclusions:The cognitive interview study was instrumental in enhancing the PECAN survey's clarity and effectiveness. By addressing participants' feedback, the researchers were able to create a more accessible survey instrument. These improvements are expected to facilitate better data collection, ultimately contributing to a deeper understanding of factors influencing precision health research participation among diverse populations. This methodology highlights the importance of participant feedback in developing research tools that are both inclusive and effective.

BACKGROUND:Precision health research uses genomic, environmental, and lifestyle data to tailor disease prevention, health promotion, and treatment strategies. While it offers potential for improved diagnoses and personalized care, recruitment and retention remain challenging. METHODS:The Precision rEsearCh pArticipatioN (PECAN) study used an exploratory qualitative design, guided by the socioecological model, to examine barriers and facilitators to participation in precision health research among diverse South Carolina residents. Ten focus groups were conducted with 23 participants, exploring individual, interpersonal, and community-level influences. RESULTS:Barriers included mistrust in the medical system, limited awareness of research opportunities, and logistical issues such as transportation and scheduling. Facilitators included perceived health benefits, monetary incentives, ease of participation, and strong communication with the research team. Recommendations to address barriers included inclusive outreach, transparent communication about data use and participant expectations, leveraging provider relationships, and offering flexible scheduling and locations. CONCLUSION:The PECAN study highlights how mistrust, logistical barriers, and historical inequities-such as medical exploitation and limited rural research infrastructure-impede participation in precision health research. Facilitators like health benefits and effective communication can support engagement. Despite a small sample size, findings underscore the need for systemic change, including policy-level solutions to expand rural research infrastructure, enhance provider engagement, and ensure transparent data practices. These insights from rural and diverse communities emphasize the urgency of structural changes to promote equitable participation in precision health research.

Aim: We aimed to compare Quan and colleagues (2011) established weights for the Charlson Comorbidity Index (CCI) conditions to autism-specific weights for predicting mortality risk in autistic older adults. Materials & methods: We used inpatient healthcare claims from autistic older adults (aged 65+; n = 2829) using the Medicare Standard Analytic Files from 2021 to 2023. We used a machine learning technique called stochastic hill climbing to assign weights to the 12 CCI conditions to maximize predictive ability for 30-day and 1-year mortality. We then compared the resulting area under the curve (AUC) against the established weights. Results: The established weights had poor predictive ability for 30-day (AUC: 0.68; 95% CI: 0.62–0.74) and 1-year mortality (AUC: 0.67; 95% CI: 0.63–0.72). The autism-specific weights also had poor predictive ability for 30-day (AUC: 0.67; 95% CI: 0.61–0.73) and 1-year mortality (AUC: 0.67; 95% CI: 0.62–0.71). Conclusion: The established and autism-specific CCI weights performed similarly in predicting mortality among autistic older adults. Findings may suggest adjusting CCI weights alone is insufficient to accurately predict mortality risk in autistic older adults, and additional health conditions not currently captured by the CCI may need to be added to better predict mortality in this population. Future studies on developing an autism-specific mortality risk index are warranted.

BackgroundImmune dysregulation years prior to a clinical diagnosis of systemic lupus erythematosus (SLE) may include a range of asymptomatic autoantibody positivity to clinically evident disease. The effect of this spectrum of immune dysregulation on pregnancy outcomes, including pregnancies in women prior to a diagnosis of SLE, is poorly understood. We sought to identify associations of adverse pregnancy outcomes across groups along this spectrum.MethodsUtilizing a large longitudinal cohort at a single center, we evaluated pregnancy outcomes among the following four groups: antinuclear antibody (ANA) negative controls, ANA-positive controls, pregnancies before a diagnosis of SLE, and pregnancies after a diagnosis of SLE. The pregnancy outcomes considered were live birth rate, preeclampsia, low birth weight, premature birth, spontaneous abortion, and stillbirth. Generalized estimating equation models were used to evaluate key associations and confounders.ResultsWe included 811 participants and 2,209 pregnancies. Of these, 198 participants were ANA-positive controls and 369 were diagnosed with SLE, with their first pregnancy occurring before diagnosis. Overall, 81.5% self-identified as Black and 31% had resided in areas with high social vulnerability. The median number of pregnancies between the groups was similar, with the majority of participants having at least one live birth. The lowest median number of pregnancies occurred in the pregnancy after SLE diagnosis group. The adverse outcome rate did not differ between the ANA-positive and ANA-negative controls. The risk of any adverse outcome was greatest in those with pregnancies after an SLE diagnosis [OR (95% CI): 3.33 (2.35, 4.71)], but was also increased in those with pregnancies before a diagnosis of SLE as compared to the ANA-positive controls [OR (95% CI): 1.78 (1.28, 2.47)]. When grouped by time prior to diagnosis, the risk of any adverse outcome remained increased in pregnancies occurring both 2–5 years or greater than 5 years prior to SLE diagnosis as compared to the ANA-positive controls [OR (95% CI): 1.64 (1.01, 2.67) and OR (95% CI): 1.65 (1.17, 2.32), respectively].ConclusionThe risk of adverse pregnancy outcomes appears to increase along the SLE spectrum, with the highest risk occurring after diagnosis. ANA positivity alone is not sufficient to impact pregnancy outcomes.

Effective opioid-sparing analgesia is essential in pediatric cleft palate repair, as infants and young children are vulnerable to opioid-related adverse effects. Ultrasound-guided suprazygomatic maxillary nerve (SZMN) blocks have emerged as a promising regional anesthesia technique, but evidence supporting their effectiveness remains limited. We conducted a retrospective observational cohort study of pediatric patients younger than 18 years who underwent cleft palate repair at a single tertiary academic medical center between January 2020 and February 2023. The primary outcome was total perioperative opioid consumption, measured as morphine milligram equivalents per kilogram (MME/kg). Secondary outcomes included intraoperative and postoperative opioid use, time to first successful feeding, and length of hospital stay. Multivariable linear regression was used to adjust for potential confounders, including cleft type and perioperative factors. Seventy-four patients met inclusion criteria, of whom 28 received an ultrasound-guided SZMN block. Patients who did not receive an SZMN block consumed more opioids (56%; 95% confidence interval [CI] 12.1-117.3; p = 0.010). After adjustment for cleft type and perioperative variables, absence of an SZMN block remained independently associated with higher opioid consumption (44.9%; 95% CI 3.39-103.2; p = 0.035). Reduction in intraoperative opioid use in the SZMN block group also reached statistical significance. No differences were observed in postoperative opioid use, time to first feeding, or hospital length of stay. Ultrasound-guided SZMN blocks were associated with reduced perioperative opioid consumption in pediatric cleft palate repair without prolonging recovery. Prospective studies are warranted to confirm these findings.

Background Effective opioid-sparing analgesia is essential in pediatric cleft palate repair, as infants and young children are vulnerable to opioid-related adverse effects. Ultrasound-guided suprazygomatic maxillary nerve (SZMN) blocks have emerged as a promising regional anesthesia technique, but evidence supporting their effectiveness remains limited. Methods We conducted a retrospective observational cohort study of pediatric patients younger than 18 years who underwent cleft palate repair at a single tertiary academic medical center between January 2020 and February 2023. The primary outcome was total perioperative opioid consumption, measured as morphine milligram equivalents per kilogram (MME/kg). Secondary outcomes included intraoperative and postoperative opioid use, time to first successful feeding, and length of hospital stay. Multivariable linear regression was used to adjust for potential confounders, including cleft type and perioperative factors. Results Seventy-four patients met inclusion criteria, of whom 28 received an ultrasound-guided SZMN block. Patients who did not receive an SZMN block consumed significantly more opioids (57% higher; 95% confidence interval [CI], 11.7–121.5; P = 0.012). After adjustment for cleft type and perioperative variables, absence of an SZMN block remained independently associated with higher opioid consumption (48.9% increase; 95% CI, 4.41–112.4; P = 0.031). Intraoperative opioid use was also significantly lower in the SZMN block group. No differences were observed in postoperative opioid use, time to first feeding, or hospital length of stay. Conclusions Ultrasound-guided SZMN blocks were associated with significantly reduced perioperative opioid consumption in pediatric cleft palate repair without prolonging recovery. Prospective studies are warranted to confirm these findings.

IntroductionBoth the quadratus lumborum block (QLB) and the pericapsular nerve group (PENG) block provide effective postoperative analgesia after hip surgery while minimizing the impact on motor function. This study aimed to compare QLB and PENG in patients undergoing primary total hip arthroplasty (THA).MethodsThis superiority trial randomized patients scheduled for elective THA to receive a lateral QLB or a PENG with a lateral femoral cutaneous nerve (LFC) block for postoperative analgesia. Perioperative analgesic protocols were standardized. The primary outcome was postoperative cumulative opioid consumption measured over time up to 72 hours. Secondary outcomes included postoperative pain scores in the first 72 hours, time to ambulation, length of stay, and patient-reported functional outcome measures (Hip disability and Osteoarthritis Outcome Score for Joint Replacement and Patient-Reported Outcome Measures Information System-10 scores).ResultsThis trial consented and randomized 106 subjects and 101 were included in the analysis: PENG (n=50), QLB (n=51). Mean (95% CI) opioid consumption in intravenous morphine milligram equivalents differed at 36 hours (mean difference (95% CI), 18.0 (0.80, 35.1); p=0.040), 48 hours (23.0 (5.20, 40.8); p=0.011), 60 hours (28.0 (9.24, 46.7); p=0.004), and 72 hours (33.0 (13.0, 53.0); p=0.001). There were no significant differences between treatment arms in average resting pain score, time to ambulation, rate of same-day discharge, length of stay, or patient-reported functional outcomes.ConclusionWhile both lateral QLB and PENG block+LFC block are effective analgesic methods for patients undergoing THA, patients receiving lateral QLB had decreased cumulative opioid consumption from 36 to 72 hours postoperative and lower pain scores with movement compared with patients receiving PENG+LFC blocks.Trial registration numberNCT05710107.

OBJECTIVES:Chest tube thoracostomy is a core skillset within pediatric emergency medicine (PEM); however, few PEM physicians perform this procedure regularly. Site selection is typically performed through landmark identification of the fifth intercostal space (ICS), and incorrect placement can result in serious morbidity. The aims of this study were to evaluate the accuracy of safe thoracostomy site selection among PEM providers, and to identify relationships between provider demographics and experience with performance in this selection process. METHODS:This was a single-center observational study using a convenience sample of pediatric emergency department (PED) patients. Providers marked the fifth ICS bilaterally using the landmark technique, and the ICS and diaphragm levels were subsequently confirmed using point-of-care ultrasound (POCUS). Descriptive statistics were calculated for patient and provider characteristics. Associations between provider characteristics with location of the ICS mark were evaluated using a generalized estimating equation approach. RESULTS:Fifteen participating PEM providers performed 120 bilateral landmark-based ICS identifications. Among all identified sites (n=240), only 37.1% (n=89) were accurately confirmed as the fifth ICS, with 12.9% (n=31) being below the fifth ICS. Furthermore, 9.2% (n=22) of all sites were located below the diaphragm during resting breathing. Providers with longer tenure, more PED experience, greater number of chest tubes placed, and greater comfort with identifying the fifth ICS were more likely to mark below the fifth ICS (P=0.004, 0.026, <0.001, <0.001, respectively). CONCLUSIONS:This study demonstrates a considerable gap in thoracostomy site selection accuracy among PEM physicians. A significant number of chosen sites were found to be below the fifth ICS, and there was a surprising discordance between provider experience and accuracy. These findings highlight a critical gap in performance and the need for ongoing training. Incorporating POCUS into standard practice may improve site selection accuracy and patient outcomes in the PED setting.

Introduction Concerns about potential side effects remain a barrier to uptake of Food and Drug Administration-approved smoking cessation pharmacotherapy (ie, varenicline, bupropion, nicotine replacement therapy [NRT]). However, use of pharmacotherapy can double the odds of successful quitting. Knowledge of an individual's likelihood of side effects while taking smoking cessation pharmacotherapy could influence treatment planning discussions and monitoring.Methods We conducted a secondary, post hoc analysis to predict an individual's likelihood of adverse events (AEs) using the Evaluating Adverse Events in a Global Smoking Cessation Study data from 4209 adults in the United States who smoked. Participants were randomized to receive 12 weeks of treatment with varenicline, bupropion, NRT patch, or placebo. Our models predicted the likelihood of moderate to severe psychiatric and nonpsychiatric AEs during treatment.Results Using pretreatment demographic and clinical data, multivariable logistic regression models yielded acceptable areas under the receiver operating characteristic curve for an individual's likelihood of moderate to severe (1) psychiatric AEs for bupropion and NRT and (2) nonpsychiatric AEs for varenicline and bupropion. Once we adjusted for demographic and baseline characteristics, medication was not associated with psychiatric AEs. Varenicline differed from placebo with regards to nonpsychiatric AEs.Conclusions It is possible to predict person-specific likelihood of moderate to severe psychiatric and nonpsychiatric AEs during smoking cessation treatment, though the probability of psychiatric AEs did not differ by medication. Future work should consider factors related to implementation in clinical settings, including determining whether lower burden assessment protocols can be equally accurate for AE prediction.Implications Using data from a large dataset people who smoke in the United States, it is possible to predict an individual's likelihood of psychiatric and nonpsychiatric AEs during smoking cessation treatment prior to initiating treatment. These predictive models provide a starting point for future work addressing how best to modify and integrate such clinical decision support algorithms into treatment for smoking cessation.

Background/Objectives: The role of double-lumen endotracheal tube (DLT) versus single-lumen endotracheal tube (SLT) use during lung transplantation (LTx) and its effects on postoperative dysphagia have not yet been studied. It has been shown that new-onset oropharyngeal dysphagia (OPD) is common after various thoracic surgeries including lung transplantation and that OPD is associated with increased postoperative complications. Methods: A single-center, retrospective cohort study was performed using a data exploration tool in the electronic medical record. Data included demographic characteristics, medical history, postoperative dysphagia measured by Functional Oral Intake Scale (FOIS) via modified barium swallow study (MBSS) within 5 days of surgery, and other secondary outcomes. Results: In univariate analysis, participants who had a DLT (49 patients) had significantly higher FOIS scores (indicating better swallowing function) as compared to those with an SLT (21 patients) (p = 0.035). Lumen type remained significant in a multivariable model, with use of a DLT showing more than a 5-fold increase in the odds of a higher FOIS score after controlling for other factors (p = 0.004; cumulative OR (95% CI): 5.2 (1.7-15.9)). Participants who had a DLT had shorter hospital length of stay (LOS) (p = 0.017; single 18 days (IQR = 13), double 14 days (IQR 7)). Those who had a DLT experienced significantly greater ventilator-free time at postoperative day 30 compared to those who received an SLT (p = 0.018). ICU LOS was similar between those who received a DLT vs. SLT. Conclusions: Overall, DLT seems to confer reduced new-onset OPD after lung transplantation surgery when compared with SLT. The use of DLT instead of SLT for lung isolation for LTx may have the potential to reduce morbidity and mortality in this population.

Youth substance use increases risk for developing substance use disorders. Previous work using the longitudinal ABCD Study® found distinct neurocognitive factors contribute to youth tobacco and alcohol initiation. Using data for 7776 ABCD Study® participants, this study expands prior work to examine prospective associations between early neurocognitive factors (general ability, executive function, learning and memory, and visuospatial and mental rotation) at ages 9-10 years (sample enrolled 2016-2018) and cannabis use by ages 13-14 years. We also test whether positive and negative tobacco smoking, alcohol, and cannabis expectancies mediate associations between neurocognitive factors and substance use initiation. Higher performance in general ability was associated with increased risk [OR = 1.23, 95 % CI 1.07-1.42] for cannabis use; positive cannabis expectancies mediated 72.6 % (p-value = 0.003) of the effect [Indirect effect: OR = 1.16, 95 % CI 1.12-1.20] and negative expectancies mediated -10.2 % (p-value = 0.04) of the effect [Indirect effect: OR = 0.98, 95 % CI 0.97-0.99]. Accuracy in visuospatial reasoning was protective [OR = 0.83, 95 % CI 0.73-0.95)] for cannabis use; the effect was not mediated by expectancies. Positive alcohol use expectancy mediated 36.3 % of the association between general ability and early alcohol use [OR = 1.15, 95 % CI 1.05-1.25; Indirect effect: OR = 1.05, 95 % CI 1.03-1.07]. Associations with early tobacco use were independent of tobacco expectancies. Developmentally appropriate expectancy-based interventions lowering positive expectancies and bolstering negative expectancies may be effective for preventing youth cannabis initiation. Interventions lowering positive alcohol expectancies may help prevent youth alcohol use.

BACKGROUND:Deep learning approaches have tremendous potential to improve the predictive power of traditional suicide prediction models to detect and predict intentional self-harm (ISH). Existing research is limited by a general lack of consistent performance and replicability across sites. We aimed to validate a deep learning approach used in previous research to detect and predict ISH using clinical note text and evaluate its generalizability to other academic medical centers. METHODS:We extracted clinical notes from electronic health records (EHRs) of 1,538 patients with International Classification of Diseases codes for ISH and 3,012 matched controls without ISH codes. We evaluated the performance of two traditional bag-of-words models (i.e., Naïve Bayes, Random Forest) and two convolutional neural network (CNN) models including randomly initialized (CNNr) and pre-trained Word2Vec initialized (CNNw) weights to detect ISH within 24 hours of and predict ISH from clinical notes 1-6 months before the first ISH event. RESULTS:In detecting concurrent ISH, both CNN models outperformed bag-of-words models with AUCs of.99 and F1 scores of 0.94. In predicting future ISH, the CNN models outperformed Naïve Bayes models with AUCs of 0.81-0.82 and F1 scores of 0.61-.64. CONCLUSIONS:We demonstrated that leveraging EHRs with a well-defined set of ISH ICD codes to train deep learning models to detect and predict ISH using clinical note text is feasible and replicable at more than one institution. Future work will examine this approach across multiple sites under less controlled settings using both structured and unstructured EHR data.

This systematic review evaluates the accuracy of citations to a landmark study on premature mortality among autistic people.

BACKGROUND:Preoperative gastric ultrasound allows non-invasive qualitative and quantitative assessment of gastric contents aiding in preoperative risk assessment. We hypothesized that appropriately fasted diabetic surgical patients taking GLP-1 agonists would have higher gastric volumes than those not taking GLP-1 agonists. METHODS:This prospective, observational cohort study enrolled diabetic patients undergoing elective surgery, comparing those taking (n = 106) and not taking (n = 100) GLP-1 agonists. The primary outcome was gastric volume assessed via gastric ultrasound in the right lateral decubitus position. Secondary outcomes included presence of a full stomach (solids/thick liquids or greater than 1.5 mL/kg clear liquid), need for surgery delay, Perlas grade, and occurrence of intraoperative aspiration. The impact of GLP-1 agonist type, duration of use, and timing of last dose on gastric volume was also examined. RESULTS:Diabetic patients on GLP-1 agonists had significantly higher median gastric volumes compared to patients not on GLP-1 agonists (0.61 mL/kg vs 0.16 mL/kg, P < 0.001) and increased odds of a full stomach (OR 11.3, 95 % CI 5.2-24.7, P < 0.0001). GLP-1 agonist use correlated with higher Perlas grades (P < 0.001). Gastric volumes were significantly higher with GLP-1 agonist use within 7 days of surgery relative to use within 7-14 days or more than 14 days from surgery (P < 0.001 for both comparisons). CONCLUSIONS:GLP-1 agonist therapy was associated with higher residual gastric volumes and higher risks of full stomachs in fasted diabetic patients. GLP-1 agonist use within 7 days of surgery was also associated with higher gastric volumes relative to holding therapy for over 7 days, supporting current consensus-based guidelines.

Background Demand for same-day discharge pathways and early ambulation following knee arthroplasty continues to increase. While spinal anesthesia with mepivacaine versus bupivacaine may promote return of motor function and ambulation, there are limited randomized trials evaluating this in knee arthroplasty patients. This study hypothesized that spinal mepivacaine would result in earlier return of motor function, promoting ambulation and same-day discharge. Methods Patients undergoing primary total knee arthroplasty (n=163) were enrolled and randomized patients to mepivacaine (60 mg) or isobaric bupivacaine (10 mg) for spinal anesthesia. The primary outcome was time to return of motor function. Additional outcomes included time to first ambulation, distance at first ambulation, same-day discharge rate, length of stay, postoperative pain, opioid consumption, and side effects. Results Patients receiving a mepivacaine spinal anesthetic had faster median (95% CI) time to return of motor function, (210 min (200, 216) vs 229 (223, 237) min, p<0.001) and lower rates of urinary retention (36% vs 57%, p=0.007). Mepivacaine patients exhibited higher pain scores in the post-anesthesia care unit (32.4 vs 9.5 mm, p<0.001) but no differences at 6, 24, or 48 hours postoperative. Opioid consumption did not differ at any time point (p=0.769). There were no differences in time to first ambulation, distance at first ambulation, same-day discharge rate, length of stay, nausea, vomiting, pruritus, or transient neurological symptoms between groups. Conclusions Although mepivacaine expedited return of motor function after knee arthroplasty, a clinically relevant 20% reduction was not observed. Ambulation times and same-day discharge rates did not differ. Trial registration number NCT05765682 .

OBJECTIVE:We assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc). METHODS:Association of NCF1-H90 with SSc was performed in case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry by time-of-flight. RESULTS:The NCF1-H90 allele is associated with risk for diffuse cutaneous SSc (dcSSc) in Chinese and European Americans, and lung fibrosis in Chinese patients with SSc (OR=2.09, p=7.96E-10). Low copy number of NCF1 associated with lung fibrosis in European Americans (OR=4.33, p=2.60E-2). BLM-treated KI mice demonstrated increased pulmonary fibrosis, exhibiting activated type I interferon signature, elevated Spp1, Ccl2, Arg1, Timp1 and Il6 expression, enriched macrophage scores in lung tissues. In a longitudinal observation cohort, homozygous H90 patients with SSc at baseline had increased anti-nuclear antibody titres, anti-topoisomerase antibody seropositivity and anti-centromere antibody seronegativity, increased incidence of lung fibrosis and Gender-Age-lung Physiology index, elevated modified Rodnan Skin Score (mRSS) and elevated plasma osteopontin (OPN, SPP1), CCL2, ARG1, TIMP-1 and IL-6. These H90 patients with SSc sustained elevated mRSS during follow-up years with decreased survival. The 0, 1 and 2 copies of H90 carriage in SSc PBMCs exhibited dose-dependent increases in profibrotic CD14+CD68+CD11b+Tim3+monocytes. Elevated OPN, CCL2 and ARG1 in CD68+CD11b+monocyte-derived macrophages from H90 patients were decreased after co-culturing with anti-CCL2 antibody. CONCLUSION:Low NCF1 activity increases the risk for the development of dcSSc and lung fibrosis via expanding profibrotic SPP1+MoMs in a CCL2-dependent manner, contributing to the severity of lung fibrosis in both BLM-treated mice and patients with SSc.