Cumulative Time Research Articles

Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors.

Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes. Methods We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality. Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR]: 108.0-337.0 minutes). Components were as follows: 72.5 minutes (IQR: 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR: 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR: 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval [CI]: 1.2-2.0, p = 0.002). Gastrointestinal or other critical bleeding (ratio 2.59, 95% CI: 1.67-4.02, p < 0.001), and tertiary/academic center treatment (ratio 1.58, 95% CI: 1.15-2.18, p = 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6, 12.0, and 22.9% of patients, respectively. Conclusions In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.

The Association of Oxygen Delivery and Transfusion on Cardiopulmonary Bypass with Acute Kidney Injury

ObjectivesWe sought to estimate whether the association of transfusion and AKI has a threshold of oxygen delivery below which transfusion is beneficial, but, above which it's harmful. DesignRetrospective study SettingCardiovascular operating room and intensive care unit. ParticipantsPatients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass. InterventionsNone Measurements and Main ResultsWe used logistic regression to estimate the association between oxygen delivery (mean, cumulative deficit, and bands of oxygen delivery), transfusion, and their interaction and AKI. A subgroup analysis using transfused and non-transfused patients with exact matching on cumulative oxygen deficit and time on bypass with adjustment for propensity to receive a transfusion using logistic regression. 991 of 4,203 patients developed AKI within 7 days. After adjustment for confounders, lower mean oxygen delivery (OR=0.968, 95% CI=0.949, 0.988, p=0.002) and transfusions (OR=1.442, 95% CI=1.077, 1.932, p=0.014) were associated with increased odds of kidney injury by 7 days. As oxygen delivery decreased, the risk of AKI increased, with the slope of the odds ratio steeper below <160 mL/m2/min. In the subgroup analysis, matched transfused patients were more likely to develop AKI (145 [45%] v 101 [31%], p <0.001) than matched non-transfused patients. However, after propensity scoring adjustment, this was non-significant (OR=1.181, 95% CI=0.796, 1.752; p=0.406). ConclusionsWe found a non-linear relationship between oxygen delivery and AKI. We found no level of oxygen delivery at which transfusion was associated with a lessening of the risk of AKI.

Factors Affecting Gross Enrollment Rates in Higher Education in Indonesia

A statistical indicator that expresses educational achievement in a nation as a percentage is the gross enrollment rate. The number of people enrolled in postsecondary education, regardless of age, is compared to the number of individuals between the ages of 19 and 23 in GER HE. Finding the impact of the units under analysis—the Economic Gini Ratio, the Ratio of Lecturers, and the Ratio of the Number of Universities—on the GER of HEs in Indonesia between 2020 and 2022 is the main goal of the research. A quantitative approach using secondary data is the research methodology employed. A saturated sample from the total population of 102 samples was used. Regression analysis of data panels is the method of data analysis. The cumulative time series data from three years, specifically 2020–2022, make up the data panel that is used. Next, data from several objects (cross section) is utilized, namely data from 34 Indonesian provinces. The study's findings, which were derived using the Fixed Effect Model (FEM), indicate that, for higher education institutions, the economic Gini ratio has a substantial negative impact on GER by -2.038873 between 2020 and 2022. Meanwhile, the ratio of universities to teachers and the ratio of lecturers to universities has no discernible impact on the GER of HEIs in Indonesia between 2020 and 2022.

Delay-adaptive compensation for 3-D formation control of leader-actuated multi-agent systems

This paper focuses on the control of collective dynamics in large-scale multi-agent systems (MAS) operating in a 3-D space, with a specific emphasis on compensating for the influence of an unknown delay affecting the actuated leaders. The communication graph of the agents is defined on a mesh-grid 2-D cylindrical surface. We model the agents’ collective dynamics by a complex- and a real-valued reaction–advection–diffusion 2-D partial differential equations (PDEs) whose states represent the 3-D position coordinates of the agents. The leader agents on the boundary suffer unknown actuator delay due to the cumulative computation and information transmission time. We design a delay-adaptive controller for the 2-D PDE by using PDE backstepping combined with a Lyapunov functional method, where the latter is employed to design an update law that generates real-time estimates of the unknown delay. Capitalizing on our recent result on the control of 1-D parabolic PDEs with unknown input delay, we use Fourier series expansion to bridge the control of 1-D PDEs to that of 2-D PDEs. To design the update law for the 2-D system, a new target system is defined to establish the closed-loop local boundedness of the system trajectories in H2 norm and the regulation of the states to zero assuming a measurement of the spatially distributed plant’s state. We illustrate the performance of the delay-adaptive controller by numerical simulations.

Venous disorders as an occupational disease - a systematic review on epidemiology, pathophysiology, and modification strategies.

Forced postures are common in the workplace. Work in the primary economic sector is characterised by a high degree of physical activity and movement; however, activities in the secondary and tertiary sectors commonly require workers to stand or sit. An expansion of the tertiary sector in recent decades has meant that people in industrialised and emerging economies primarily sit or stand at work. The aim of the systematic review was to identify occupational factors relating to the presence of chronic venous disease (CVD), to place these in the context of developments in the workplace, and to determine whether measures are in place to prevent CVD. We performed a systematic literature review to analyse studies assessing work-related risk factors for CVD. We searched for publications in the PubMed database, the clinic library of BG Hospital Bergmannstrost Halle, and the registry of the German Statutory Accident Insurance. Using occupation-specific keyword combinations, we identified 27,522 publications. The publications underwent an automatic and manual filtering process according to the PRISMA guidelines and 81 publications qualified for the review. Ultimately 25 studies were included in the systematic review. All of the subjects of the studies worked in the secondary and tertiary sectors. No studies looked at the relationship between venous disorders and primary sector occupations. Standing at work for more than four hours a day, repeated heavy lifting, and cumulative time working in a sitting or standing position are risk factors for the development of CVD. Sitting is less of a risk factor than standing or walking. Occupational history and the patient's activity profile are important diagnostic tools which can help confirm a diagnosis and justify treatment when findings are inconsistent. Compression therapy is the primary form of secondary and tertiary prevention. There continues to be a lack of primary preventive measures related to workplace design.

Accelerating Adversarially Robust Model Selection for Deep Neural Networks via Racing

Recent research has introduced several approaches to formally verify the robustness of neural network models against perturbations in their inputs, such as the ones that occur in adversarial attacks. At the same time, this particular verification task is known to be computationally challenging. More specifically, assessing the robustness of a neural network against input perturbations can easily take several hours of compute time per input vector, even when using state-of-the-art verification approaches. In light of this, it becomes challenging to select from a given set of neural network models the one that is best in terms of robust accuracy, i.e., the fraction of instances for which the model is known to be robust against adversarial perturbations, especially when given limited computing resources. To tackle this problem, we propose a racing method specifically adapted to the domain of robustness verification. This racing method utilises Delta-values, which can be seen as an efficiently computable proxy for the distance of a given input to a neural network model to the decision boundary. We present statistical evidence indicating significant differences in the empirical cumulative distribution between robust and non-robust inputs as a function of Delta-values. Using this information, we show that it is possible to reliably expose vulnerabilities in the model with relatively few input iterations. Overall, when applied to selecting the most robust network from sets of 31 MNIST and 27 CIFAR-10 networks, our proposed method achieves speedups of a factor of 108 and 42, respectively, in terms of cumulative running time compared to standard local robustness verification on the complete testing sets.

Accumulating Sedentary Time and Physical Activity From Childhood to Adolescence and Cardiac Function in Adolescence.

Increased physical activity (PA) may mitigate the negative cardiovascular health effects of sedentary behavior in adolescents. However, the relationship of PA and sedentary time from childhood with cardiac function in adolescence remains underexplored. Therefore, we investigated the associations of cumulative sedentary time and PA from childhood to adolescence with cardiac function in adolescence. Participants were 153 adolescents (69 girls) who were aged 6 to 8 years at baseline, 8 to 10 years at 2-year follow-up, and 15 to 17 years at 8-year follow-up. Cumulative sedentary time and PA exposure between baseline and 2-year follow-up and between baseline and 8-year follow-up were measured using a combined accelerometer and heart rate monitor. Cardiac function was assessed using impedance cardiography at 8-year follow-up. The data were analyzed using linear regression analyses adjusted for age and sex. Cumulative moderate to vigorous PA (standardized regression coefficient [β]=-0.323 [95% CI, -0.527 to -0.119]) and vigorous PA (β=-0.295 [95% CI, -0.508 to -0.083]) from baseline to 8-year follow-up were inversely associated with cardiac work at 8-year follow-up. Conversely, cumulative sedentary time had a positive association (β=0.245 [95% CI, 0.092-0.398]). Cumulative vigorous PA from baseline to 8-year follow-up was inversely associated with cardiac work index at 8-year follow-up (β=-0.218 [95% CI, -0.436 to 0.000]). Higher levels of sedentary time and lower levels of PA during childhood were associated with higher cardiac work in adolescence, highlighting the importance of increasing PA and reducing sedentary time from childhood.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range, elevated alanine aminotransferase (ALT) levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively. METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected. The incidence rate, cumulative times, and equally and unequally weighted cumulative effects of excess high-normal ALT levels (ehALT) were measured. Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD. RESULTS A total of 83.13% of participants with MAFLD had normal ALT levels. The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group. Compared with those in the low-normal ALT group, the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651 [95% confidence interval (CI): 1.199-2.273] and 1.535 (95%CI: 1.119-2.106) in the third quartile and 1.616 (95%CI: 1.162-2.246) and 1.580 (95%CI: 1.155-2.162) in the fourth quartile, respectively. CONCLUSION Most participants with MAFLD had normal ALT levels. Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Association of cumulative health status with subsequent mortality in patients with acute heart failure.

We aim to examine the association between long-term cumulative health status and subsequent mortality among patients with acute heart failure (HF). Based on a national prospective cohort study of patients hospitalized for HF, we measured health status by Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 at 4 time points, i.e. admission, 1-,6- and 12-month after discharge. Cumulative health status was interpreted by cumulative KCCQ-12 score and cumulative times of good health status. Outcomes included subsequent all-cause and cardiovascular mortality. Multivariable Cox proportional hazard models were performed to examine the association between cumulative health status and subsequent mortality. Totally, 2328 patients (36.7% women and median age 66 [IQR: 56-75] years) were included, the median follow-up was 4.34 (IQR: 3.93-4.96) years. Compared with Quartile 4, the lowest Quartile 1 had the highest HR for all-cause mortality (2.96; 95% CI: 2.26-3.87), followed by Quartile 2 (1.79; 95% CI: 1.37-2.34) and Quartile 3 (1.62; 95% CI: 1.23-2.12). Patients with 0-time of good health status had the highest risk of all-cause mortality (HR: 2.41, 95% CI: 1.69-3.46) compared with patients with 4-times of good health status. Similar associations persisted for cardiovascular mortality. A greater burden of cumulative health status indicated worse survival among patients hospitalized for HF. Repeated KCCQ measurements could be helpful to monitor long-term health status and identify patients vulnerable to death. Clinical Trial Registration: www.clinicaltrials.gov (NCT02878811).

The Interactive Effects of Sedentary Time, Physical Activity, and Fat Mass on Insulin Resistance in the Young Population.

Recent evidence in 9-year-old children with overweight/obesity followed up for 7 years until late adolescence concluded that increased physical activity (PA) decreased the risk of high fasting glucose, low insulin sensitivity, and secretion. However, whether this effect persists until young adulthood is unknown. This observational study examined the effects of cumulative sedentary time (ST), light PA (LPA), and moderate-to-vigorous (MVPA) on glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) in 11-year-old children followed up for 13 years until young adulthood. Altogether 792 children from the Avon Longitudinal Study of Parents and Children, UK who had data on at least two measures of accelerometer-based movement behaviour during ages 11, 15, and 24 years follow-up clinic visits with complete fasting glucose, insulin, and HOMA-IR measures at ages 15, 17, and 24 years were included. ST, LPA, and MVPA were measured with an accelerometer. Cumulative ST from ages 11-24 years was associated with increased odds (odds ratio 1.20 [95% CI 1.00-1.44] p=0.047) and cumulative LPA was associated with the decreased odds of hyperinsulinemia (0.80 [0.66-0.96] p=0.017) among participants with overweight/obesity. Cumulative MVPA was inversely associated with insulin but after accounting for the mediating role of fat mass, MVPA effect on lowering insulin decreased by 58% resulting in statistical non-significance. In the temporal path analyses, among participants with overweight/obesity, higher glucose at age 15 years was associated with lower LPA and MVPA at 24 years. Higher LPA at 15 years was associated with lower insulin and HOMA-IR at 24 years and vice-versa. Promoting LPA while decreasing body fat mass and ST may be considered crucial intervention targets to attenuate the risk of hyperinsulinemia and insulin resistance from childhood through young adulthood.

The association of cumulative vasoactive drugs and neurodevelopmental outcomes in preterm Infants

To assess the effect of cardiovascular medications on the neurodevelopment of preterm infants, as measured by calculated cumulative time of vasoactive-inotropic score (VISct). A retrospective study was conducted on preterm infants who developed significant hypotension defined as a mean BP more than 2SDs below the mean for GA and received treatment with duration > 6 hours for each hypotensive episode, we calculated the vasoactive inotropic score (VIS) and cumulative exposure to cardiovascular medications over time (VISct). The composite Bayley III was reported from the high-risk follow-up clinic for the surviving infants between 18 to 21 months corrected age. VISct was significantly higher in infants with abnormal neurodevelopment. Cognitive Bayley was the most affected component with median (IQR) VISct 882.5(249,2047) versus 309(143,471) (p-value 0.012), followed by language function with VISct 786(261,1563.5), versus 343(106.75,473.75) (p-value 0.016) when those with Bayley III <85 were compared with those with normal Bayley IIIs. High VISct scores may have negative effect on cognitive and language neurodevelopmental outcomes.

Liver impairment status toward workers exposed to vinyl chloride under different techniques

To analyse potential differences towards liver impairment status on vinyl chloride monomer(VCM) exposed population from technique under acetylene hydrochlorination to the one of ethylene oxychlorination respectively and to explore the possible reasons, which will pave the way for occupational health promotion in terms of hazard reduction. a cross-sectional study was initiated between June and September in 2022 towards 2 groups of VCM exposed population from the facility of acetylene hydrochlorination(n=78) and the one of ethylene oxychlorination(n=69) in a PVC petrochemical complex enterprise(abbreviation of H) in Tianjin City. The demographic information concerning age, gender, messages on occupational history, field investigation were inquired through questionnaire interview. Then, venous blood(4 mL/person) and urine(10-50 mL/person) were collected during the physical exam phase and indices of 8-hydroxy-2 deoxyguanosine(8-OHdG) in blood and thiodiglycolic acid(TDGA) in urine were detected through ELISA and solid phase extraction-ion chromatography respectively. The 2 groups of population were matched well in terms of average age distribution and gender composition ratio, with significant differences on population composition ratio were found on variables of working years, alcohol consumption and daily sleeping duration(P&lt;0.01 or P&lt;0.05). It was found that the average content of TDGA in acetylene hydrochlorination group was(0.81±0.05)mg/L while the content in ethylene oxychlorination group reached to(0.83±0.06)mg/L, noteworthy differences were only found among 6 posts in the acetylene hydrochlorination group and 5 others in the ethylene oxychlorination group after classification for specific posts, however, the average concentration of 8-OHdG in acetylene hydrochlorination group(122(78.3, 168.8) μg/m~3) was different from the one in ethylene oxychlorination group(101.7(79.6, 149.7) μg/m~3)(Z=6.82, P&lt;0.05). Moreover, a series of positive correlations in moderate intensity between 8-OHdG concentration and TDGA content were observed among posts of polymerization cleaners(r=0.53), aggregation operators(r=0.47), maintenance repairers(r=0.45), sampling operators(r=0.41) in acetylene hydrochlorination group(P&lt;0.05) and posts of cracking reactants(r=0.64), DCS operators(r=0.51), oxychlorination operators(r=0.50) and chemical loaders(r=0.44) in ethylene oxychlorination group(P&lt;0.05). Liver function indices such as content on ALT(χ~2=15.41, P&lt;0.01), AST(χ~2=9.95, P&lt;0.01) and ALP(χ~2=3.79, P&lt;0.01) were different in the 2 groups population with statistical significance, then proportions on population composition ratio that exceeded normal ranges of indices on ALT, AST, AST/ALT ratio, ALP and Alb/Glb ratio were higher in acetylene hydrochlorination group than ones in ethylene oxychlorination group with great significance(P&lt;0.05), so as to the abnormalities in liver B altrosonography test between groups(χ~2=17.33, P&lt;0.01). Binary logistic regression model indicated that 8-OHdG concentration in blood that exceed 90 μg/m~3, TDGA content in urine that exceed 0.60 mg/L, working years that were over 10a, alcohol consumption, sleeping duration less than 6 h per day and male workers were potential risky factors for liver impairment(P&lt;0.05). The degree on liver impairment status was higher in acetylene hydrochlorination group than ones in in ethylene oxychlorination group under the same PVC factory, which might be associated with the oxidative stress injury induced from the combination of higher VCM concentration at workplaces, longer cumulative exposure time, longer working years, alcohol consumption habits and sleep shortage caused by shift work patterns.

Safety, efficacy, and clinical utility of the 5.1-mm debridement catheter for treatment of walled-off pancreatic necrosis (with video)

Background and AimsDirect endoscopic necrosectomy (DEN) is a recommended strategy for treatment of walled-off-necrosis (WON). DEN uses a variety of devices including the EndoRotor (Interscope, Inc.) debridement catheter. Recently, a 5.1 mm EndoRotor with increased chamber size and rate of tissue removal was introduced. The aim of this study was to assess the efficacy and safety of this device. MethodsA multi-center cohort study was conducted at eight institutions including patients who underwent DEN with the 5.1 mm EndoRotor. The primary outcome was the number of DEN sessions needed for WON resolution. Secondary outcomes included the average percent reduction in solid WON debris and decrease in WON area per session, total time spent performing EndoRotor therapy for WON resolution, and adverse events. Results64 procedures in 41 patients were included. For patients in which the 5.1 mm EndoRotor catheter was the sole therapeutic modality, an average of 1.6 DEN sessions resulted in WON resolution with an average cumulative time of 85.5 minutes. Of the 21 procedures with data regarding percent of solid debris, the average reduction was 85% +/- 23% per session. Of the 19 procedures with data regarding WON area, the mean area significantly decreased from 97.6 +/- 72.0 cm2 to 27.1 +/- 35.5 cm2 (p<0.001) per session. Adverse events included two intra-procedural LAMS dislodgements managed endoscopically and three perforations none of which were related to EndoRotor. Bleeding was reported in seven cases, none required embolic or surgical therapy and two required blood transfusions. ConclusionsThis is the first multi-center retrospective study to investigate the efficacy and safety of the 5.1 mm EndoRotor catheter for WON. Results from this study showed an average of 1.6 DEN sessions were needed to achieve WON resolution with an 85% single session reduction in solid debris and a 70% single session decrease in WON area with minimal adverse events.

Experimental study on the life and performance of an improved DC arc plasma torch

A novel DC arc plasma torch is designed in this paper in order to reduce the electrode erosion, and a series of experiments are carried out to investigate how to improve the lifetime and performance of the nitrogen DC arc plasma torch. The analysis of voltage characteristics of the plasma torch indicates that the interelectrode insert can increase the average arc voltage and the sudden expansion structure can reduce the voltage fluctuation, which is helpful to improve the working stability to some extent. The spectrum characteristics at the plasma torch outlet and the cold flow simulations show that the dual shielding gas mainly act near the anode and can effectively cover the entire anode wall. Combining the shielding gas distribution with anode heat transfer processes in argon and nitrogen plasma torch, it is inferred that argon shielding gas plays an important role on reducing the anode heat transfer processes in nitrogen plasma torch, which can effectively suppress the anode erosion. The life testing experimental results find that there is no significant erosion of the cathode, anode, and interelectrode insert after cumulative working time exceeding 20 h. The maximum nitrogen plasma jet length can reach ∼35 mm with the outlet jet temperature of about 20 000 K at the current of 100 A and nitrogen gas flow rate of 10 slm. The maximum average specific enthalpy and thermal efficiency are respectively about 14 MJ kg−1 and 75% in the nitrogen plasma torch. Therefore, this newly designed DC arc plasma torch not only can suppress the electrode erosion but also has good working performance, which is expected to have excellent application prospects.

Research on correlation between metal oxide semiconductor target and magnetron sputtered film based on TFT application

The research on the intrinsic relationship between target quality and TFT (thin film transistor) performance is not perfect for magnetron sputtering processes. The systematic analysis of target-film-device still needs to be improved. This paper studied the internal relationship between metal oxide semiconductor targets, thin films, and TFT devices for the deterioration problem of device performance caused by the failure of the aging target. The experimental results showed that the target surface with a long cumulative sputtering time had apparent macroscopic concave, related to the electromagnetic field distribution. The concave region was the primary source of thin film composition, so the research object of this work was mainly the concave region. A multi-oxide target was used in this work, and its selective sputtering phenomenon was serious, mainly reflected in the sputtering rate of In2O3 grains with higher electrical conductivity than other components. There were many failure sites on the surface of the target, including nodules, holes, coating layers, and cracks. The failure sites would hinder the normal sputtering process and eventually form a vicious circle, failing the target. Due to the decline of target quality, sputtering particles would be in a state of insufficient kinetic energy, resulting in particle agglomeration, element segregation, weak M-O (metal-oxide) bonds, loose accumulation, and surface or block defects. Ultimately, the TFT performance with the aging target showed lower mobility, larger subthreshold swing, increased off-state current, and poorer stability. Clarifying the relationship between target quality and device performance is beneficial for the development of electronic devices.

IL-17 expression and prognosis of laryngeal squamous cell carcinoma.

Objective: To investigate the roles of proinflammatory cytokine IL-17 in the prognosis of laryngeal squamous cell carcinoma (LSCC). Methods: In all, 67 LSCC patients were enrolled to evaluate the expression of IL-17, IL-23, CD8, CD31, and vascular endothelial growth factor by immunohistochemical staining. Cumulative survival time was determined by the Kaplan-Meier approach, and prognostic variables for overall survival (OS) were identified by Cox proportional-hazards models. Results: The expression of IL-17 and IL-23 was remarkably higher in LSCC tissue than in adjacent normal (AN) tissue (P < .001). The Kaplan-Meier analysis indicated that patients with cervical lymph node metastasis (CLNM), advanced tumor node metastasis (TNM) stage, poor-differentiated grade, high microvessel density (MVD) in LSCC tissues, and high IL-17 expression in AN tissues had poorer OS (all P < .05). Cox regression analysis revealed that CLNM (HR = 7.246; 95% CI: 2.598-20.208; P < .001), high MVD in tumor tissues (HR = 4.233; 95% CI: 1.482-12.092; P = .007), and low CD8 expression in AN tissues (HR = 3.996; 95% CI: 1.442-11.074; P = .008) were significantly associated with poorer OS in LSCC, while IL-17 expression in AN tissue was not. Conclusion: High IL-17 expression in AN tissues could indicate poor prognosis and may be a prognostic marker for LSCC. Low CD8 expression in AN tissues may represent poor frontline antitumor immunity and be associated with poor prognosis.

Institutional Variability in Anesthesia Time for Mehta Casting in Early-Onset Scoliosis (EOS).

Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors. An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used. Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46min; P <0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P =0.008). Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times. Prognostic Level II.

Influence of loneliness burden on cardio-cerebral vascular disease among the Chinese older adult: a national cohort study.

Adverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult. A total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017-2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018-2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD. Among participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096-1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62-72 years or in those with diabetes. The cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term.

The association of an elevated Th/Ts ratio and lupus anticoagulant with symptomatic osteonecrosis in systemic lupus erythematosus patients.

This study aimed to assess the risk factors for symptomatic osteonecrosis (ON) in systemic lupus erythematosus (SLE) and identify clinical characteristics and laboratory markers for predicting symptomatic ON occurrence in SLE patients. Seventy (6.0%) of 1175 SLE patients diagnosed with symptomatic ON were included in this study. An equal number of SLE patients without symptomatic ON, matched in terms of age and gender, were enrolled in the control group. Clinical symptoms, routine laboratory examinations, lymphocyte subsets, and treatments of these patients were retrospectively reviewed and compared between the two groups. Logistic regression analysis was employed to identify risk factors associated with symptomatic ON in SLE. Among the 70 cases in the symptomatic ON group, 62 (88.6%) patients experienced femoral head necrosis, with bilateral involvement observed in 58 patients. Bone pain was reported in 32 cases (51.6%), and 19 cases (30.6%) presented with multiple symptoms. Univariate analysis revealed significant differences between the two groups in various factors, including disease duration (months), cumulative steroid exposure time, history of thrombosis, neurological involvement, the number of affected organs, myalgia/myasthenia, and the use of medications such as glucocorticoids, immunosuppressants, aspirin, and statins (P<0.05). Moreover, lupus anticoagulant (LA) levels were significantly higher in the symptomatic ON group than in the control group (P<0.05). Furthermore, notable distinctions were observed in peripheral blood immune cells, including an elevated white blood cell count (WBC), a decreased percentage of Ts cells (CD3+CD8+), and an elevated Th/Ts ratio. Logistic regression analysis revealed that a history of thrombosis, LA positivity, and an elevated Th/Ts ratio remained positive factors associated with symptomatic ON (P<0.05). Decreased Ts cells and changes in the T lymphocyte subset play an important regulatory role in the development of symptomatic ON. A history of thrombosis and LA are associated with an increased probability of symptomatic ON in SLE and may serve as potential predictors.

Abstract 108: Gut Microbiota Composition Modifies Behavioral Phenotypes Into Adulthood Following Neonatal Hypoxic-Ischemia in Mice

Neonatal hypoxic ischemic encephalopathy (HIE) increases the risk for attention deficit disorder and autism spectrum disorders in children. Perturbations in the gut microbiome are associated with behavioral changes in pre-clinical models of neurological injury and development. However, the role of the gut microbiome in behavior after HIE has not been investigated. Also, the therapeutic potential of gut microbiota modification after HIE remains unexplored. We hypothesize that altering the gut microbiome after HIE can improve chronic behavioral deficits in mice. The Rice Vannucci Model (RVM) was used to model HIE on 9-day old C57BL/6 mice. 2 months after injury, fecal samples were collected for 16s rRNA sequencing and behavioral tests were performed. We treated HIE and sham mice with fecal microbiota transfers (FMT) from naïve donors. To determine if the microbiota from HIE mice drives behavioral deficits, we also gave FMT from HIE or sham donors into naïve. Tests were repeated 1 and 3 months after FMT, and mice were sacrificed at 5 months of age. 2 months after injury, baseline open field tests revealed a hyperactive phenotype in HIE mice. There was increased mean velocity, distance moved, and cumulative time in border coupled with decreased cumulative time in center compared to shams (P&amp;lt0.0001, P&amp;lt0.0001, P=0.0168, P=0.025; T test, two cohorts, n=14-18). PCoA on calculated weighted UniFrac distances reveal a significant difference in β-diversity in males (P=0.015) and females (P=0.033) at 2 months. At 5 months, HIE mice with a naïve FMT had normalization of their hyperactive phenotype, measured by a reduction in mean velocity and distance moved (P=0.028 and P=0.0322; Repeated Measures One-way ANOVA, Dunnett’s test), while sham mice had no change. Surprisingly, naïve mice given a FMT from HIE donors became hypoactive with reduced mean velocity and distance moved (P=0.0004 and P=0.0004; Mixed effects Model, Tukey’s test, 2 cohorts n=6-11), while Naive mice with sham FMT had no change. In conclusion, gut microbiota modification through FMT in adult mice with a history of HIE reduced the severity of their hyperactive phenotype. Conversely, FMT from HIE mice into naïve mice induced mild behavioral changes but did not reproduce the hyperactivity seen in HIE mice.