Development and clinical application of bioelectrical impedance analysis method for body composition assessment.

Obesity, which is characterized by excessive body fat, increases the risk of chronic diseases, such as type 2 diabetes, cardiovascular diseases, and certain cancers. Sarcopenia, a decline in muscle mass, is also associated with many chronic disorders and is therefore a major concern in aging populations. Body composition analysis is important in the evaluation of obesity and sarcopenia because it provides information about the distribution of body fat and muscle mass. It is also useful for monitoring nutritional status, disease severity, and the effectiveness of interventions, such as exercise, diet, and drugs, and thus helps assess overall health and longevity. Computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry are commonly used for this purpose. However, they have limitations, such as high cost, long measurement time, and radiation exposure. Instead, bioelectrical impedance analysis (BIA), which was introduced several decades ago and has undergone significant technological advancements, can be used. It is easily accessible, affordable, and importantly, poses no radiation risk, making it suitable for use in hospitals, fitness centers, and even at home. Herein, we review the recent technological developments and clinical applications of BIA to provide an updated understanding of BIA technology and its strengths and limitations.

Trunk-to-leg volume and appendicular lean mass from a commercial 3-dimensional optical body scanner for disease risk identification.

BACKGROUND & AIMS: Body shape expressed as the trunk-to-leg volume ratio is associated with diabetes and mortality due to the associations between higher adiposity and lower lean mass with Metabolic Syndrome (MetS) risk. Reduced appendicular muscle mass is associated with malnutrition risk and age-related frailty, and is a risk factor for poor treatment outcomes related to MetS and other clinical conditions (e.g.; cancer). These measures are traditionally assessed by dual-energy X-ray absorptiometry (DXA), which can be difficult to access in clinical settings. The Shape Up! Adults trial (SUA) demonstrated the accuracy and precision of 3-dimensional optical imaging (3DO) for body composition as compared to DXA and other criterion measures. Here we assessed whether trunk-to-leg volume estimates derived from 3DO are associated with MetS risk in a similar way as when measured by DXA. We further explored if estimations of appendicular lean mass (ALM) could be made using 3DO to further improve the accessibility of measuring this important frailty and disease risk factor. METHODS: SUA recruited participants across sex, age (18-40, 40-60, >60 years), BMI (under, normal, overweight, obese), and race/ethnicity (non-Hispanic [NH] Black, NH White, Hispanic, Asian, Native Hawaiian/Pacific Islander) categories. Each participant had whole-body DXA and 3DO scans, and measures of cardiovascular health. The 3DO measures of trunk and leg volumes were calibrated to DXA to express equivalent trunk-to-leg volume ratios. We expressed each blood measure and overall MetS risk in quartile gradations of trunk-to-leg volume previously defined by National Health and Nutrition Examination Survey (NHANES). Finally, we utilized 3DO measures to estimate DXA ALM using ten-fold cross-validation of the entire dataset. RESULTS: Participants were 502 (273 female) adults, mean age = 46.0 ± 16.5y, BMI = 27.6 ± 7.1 kg/m2 and a mean DXA trunk-to-leg volume ratio of 1.47 ± 0.22 (females: 1.43 ± 0.23; males: 1.52 ± 0.20). After adjustments for age and sex, each standard deviation increase in trunk-to-leg volume by 3DO was associated with a 3.3 (95% odds ratio [OR] = 2.4-4.2) times greater risk of MetS, with individuals in the highest quartile of trunk-to-leg at 27.4 (95% CI: 9.0-53.1) times greater risk of MetS compared to the lowest quartile. Risks of elevated blood biomarkers as related to high 3DO trunk-to-leg volume ratios were similar to previously published comparisons using DXA trunk-to-leg volume ratios. Estimated ALM by 3DO was correlated to DXA (r2 = 0.96, root mean square error = 1.5 kg) using ten-fold cross-validation. CONCLUSION: Using thresholds of trunk-to-leg associated with MetS developed on a sample of US-representative adults, trunk-to-leg ratio by 3DO after adjustments for offsets showed significant associations to blood parameters and MetS risk. 3DO scans provide a precise and accurate estimation of ALM across the range of body sizes included in the study sample. The development of these additional measures improves the clinical utility of 3DO for the assessment of MetS risk as well as the identification of low muscle mass associated with poor cardiometabolic and functional health.

Advancing body composition assessment in patients with cancer: First comparisons of traditional versus multicompartment models.

BACKGROUND AND AIMS: Measurement of body composition using computed tomography (CT) scans may be a viable clinical tool for low muscle mass assessment in oncology. However, longitudinal assessments are often infeasible with CT. Clinically accessible body composition technologies can be used to track changes in fat-free mass (FFM) or muscle, though their accuracy may be impacted by cancer-related physiological changes. The purpose of this study was to examine the agreement among accessible body composition method with criterion methods for measures of whole-body FFM measurements and, when possible, muscle mass for the classification of low muscle in patients with cancer. METHODS: Patients with colorectal cancer were recruited to complete measures of whole-body DXA, air displacement plethysmography (ADP), and bioelectrical impedance analysis (BIA). These measures were used alone, or in combination to construct the criterion multicompartment (4C) mode for estimating FFM. Patients also underwent abdominal CT scans as part of routine clinical assessment. Agreement of each method with 4C model was analyzed using mean constant error (CE = criterion - alternative), linear regression including root mean square error (RMSE), Bland-Altman limits of agreement (LoA) and mean percentage difference (MPD). Additionally, appendicular lean soft tissue index (ALSTI) measured by DXA and predicted by CT were compared for the absolute agreement, while the ALSTI values and skeletal muscle index by CT were assessed for agreement on the classification of low muscle mass. RESULTS: Forty-five patients received all measures for the 4C model and 25 had measures within proximity of clinical CT measures. Compared to 4C, DXA outperformed ADP and BIA by showing the strongest overall agreement (CE = 1.96 kg, RMSE = 2.45 kg, MPD = 98.15 ± 2.38%), supporting its use for body composition assessment in patients with cancer. However, CT cutoffs for skeletal muscle index or CT-estimated ALSTI were lower than DXA ALSTI (average 1.0 ± 1.2 kg/m2) with 24.0% to 32.0% of patients having a different low muscle classification by CT when compared to DXA. CONCLUSIONS: Despite discrepancies between clinical body composition assessment and the criterion multicompartment model, DXA demonstrates the strongest agreement with 4C. Disagreement between DXA and CT for low muscle mass classification prompts further evaluation of the measures and cutoffs used with each technique. Multicompartment models may enhance our understanding of body composition variations at the individual patient level and improve the applicability of clinically accessible technologies for classification and monitoring change over time.

Changes in lung cancer staging and emergency presentations during the first year of the COVID-19 pandemic.

Aim: This study retrospectively analyses the impact of the 1st year of the COVID-19 pandemic on route of presentation and staging in lung cancer compared to the 2 years before and after implementation of the Leicester Optimal Lung Cancer Pathway (LOLCP) in Leicester, United Kingdom. Method: Electronic databases and hospital records were used to identify all patients diagnosed with lung cancer in 2018 (pre-LOLCP), 2019 (post-LOLCP), and March 2020-2021 (post-COVID-19 lockdown). Information regarding patient characteristics, performance status, stage, and route of diagnosis was documented and analysed. Emergency presentation was defined as diagnosis of new lung cancer being made after unscheduled attendance to urgent or emergency care facility. Results: Following implementation of the LOLCP pathway, there was a significant decrease in emergency presentations from 26.8 to 19.6% (p = 0.002) with a stage shift from 33.9% early stage disease to 40.3%. These improved outcomes were annulled during the COVID-19 pandemic, with emergency presentations increasing to 38.9% (p < 0.001) and a reduction in early-stage lung cancer diagnoses to 31.5%. There was a 61% decline in 2 week wait referrals but no significant decline in the LOLCP direct-to-CT referrals. Conclusion: We have demonstrated a significant increase in late-stage lung cancer diagnoses and emergency presentations during the first year of the COVID-19 pandemic. The causes for these changes are likely to be multifactorial. The long-term effect on lung cancer mortality remains to be seen and is an important focus of future study.

Accuracy and Precision of 3-dimensional Optical Imaging for Body Composition by Age, BMI, and Ethnicity.

BACKGROUND: The obesity epidemic brought a need for accessible methods to monitor body composition, as excess adiposity has been associated with cardiovascular disease, metabolic disorders, and some cancers. Recent 3-dimensional optical (3DO) imaging advancements have provided opportunities for assessing body composition. However, the accuracy and precision of an overall 3DO body composition model in specific subgroups are unknown. OBJECTIVES: This study aimed to evaluate 3DO's accuracy and precision by subgroups of age, body mass index, and ethnicity. METHODS: A cross-sectional analysis was performed using data from the Shape Up! Adults study. Each participant received duplicate 3DO and dual-energy X-ray absorptiometry (DXA) scans. 3DO meshes were digitally registered and reposed using Meshcapade. Principal component analysis was performed on 3DO meshes. The resulting principal components estimated DXA whole-body and regional body composition using stepwise forward linear regression with 5-fold cross-validation. Duplicate 3DO and DXA scans were used for test-retest precision. Student's t tests were performed between 3DO and DXA by subgroup to determine significant differences. RESULTS: Six hundred thirty-four participants (females = 346) had completed the study at the time of the analysis. 3DO total fat mass in the entire sample achieved R2 of 0.94 with root mean squared error (RMSE) of 2.91 kg compared to DXA in females and similarly in males. 3DO total fat mass achieved a % coefficient of variation (RMSE) of 1.76% (0.44 kg), whereas DXA was 0.98% (0.24 kg) in females and similarly in males. There were no mean differences for total fat, fat-free, percent fat, or visceral adipose tissue by age group (P > 0.068). However, there were mean differences for underweight, Asian, and Black females as well as Native Hawaiian or other Pacific Islanders (P < 0.038). CONCLUSIONS: A single 3DO body composition model produced accurate and precise body composition estimates that can be used on diverse populations. However, adjustments to specific subgroups may be warranted to improve the accuracy in those that had significant differences. This trial was registered at clinicaltrials.gov as NCT03637855 (Shape Up! Adults).

Early surgical stabilization of rib fractures for flail chest is associated with improved patient outcomes: An ACS-TQIP review.

BACKGROUND: Rib fractures are a common in thoracic trauma. Increasingly, patients with flail chest are being treated with surgical stabilization of rib fractures (SSRF). We performed a retrospective review of the Trauma Quality Improvement Program database to determine if there was a difference in outcomes between patients undergoing early SSRF (≤3 days) versus late SSRF (>3 days). METHODS: Patients with flail chest in Trauma Quality Improvement Program were identified by CPT code, assessing those who underwent SSRF between 2017 and 2019. We excluded those younger than 18 years and Abbreviated Injury Scale head severity scores greater than 3. Patients were grouped based on SSRF before and after hospital Day 3. These patients were case matched based on age, Injury Severity Score, Abbreviated Injury Scale head and chest, body mass index, Glasgow Coma Scale, and five modified frailty index. All data were examined using χ2, one-way analysis of variance, and Fisher's exact test within SPSS version 28.0. RESULTS: For 3 years, 20,324 patients were noted to have flail chest, and 3,345 (16.46%) of these patients underwent SSRF. After case matching, 209 patients were found in each group. There were no significant differences between reported major comorbidities. Patients with early SSRF had fewer unplanned intubations (6.2% vs. 12.0%; p = 0.04), fewer median ventilator days (6 days Q1: 3 to Q3: 10.5 vs. 9 Q1: 4.25 to Q3: 14; p = 0.01), shorter intensive care unit length of stay (6 days Q1: 4 to Q3: 11 vs. 11 Q1: 6 to Q3: 17; p < 0.01), and hospital length of stay (15 days Q1: 11.75 to Q3: 22.25 vs. 20 Q1: 15.25 - Q3: 27, p < 0.01. Early plating was associated with lower rates of deep vein thrombosis and ventilator-acquired pneumonia. CONCLUSION: In trauma-accredited centers, patients with flail chest who underwent early SSRF (<3 days) had better outcomes, including fewer unplanned intubations, decreased ventilator days, shorter intensive care unit LOS and HLOS, and fewer DVTs, and ventilator-associated pneumonia. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Evaluation of Microvascular Rarefaction in Vascular Cognitive Impairment and Heart Failure (CRUCIAL): Study Protocol for an Observational Study.

INTRODUCTION: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel-related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these comorbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity. METHODS: The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis, and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment. DISCUSSION: CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow preclinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets.

Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.

BACKGROUND: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037). CONCLUSIONS: Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

Serious Bacterial Infections in Young Febrile Infants With Positive Urinalysis Results.

It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL. CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.

Validation of the Rule of 7's for Identifying Children at Low-risk for Lyme Meningitis.

BACKGROUND: The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease. METHODS: We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis. RESULTS: Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I2 = 71%], specificity 40% (95% CI: 30%-50%, I2 = 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I2 = 55%). CONCLUSIONS: The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.

Rapid Detection of Significant Traumatic Brain Injury Requiring Emergency Intervention.

Moderate and severe traumatic brain injuries (TBI) are a major cause of severe morbidity and mortality; rapid diagnosis and management allow secondary injury to be minimized. Traumatic brain injury is only one of many potential causes of altered mental status; head computed tomography (HCT) is used to definitively diagnose TBI. Despite its widespread use and obvious importance, interpretation of HCT images is rarely covered by formal didactics during general surgery or even acute care surgery training. The schema illustrated here may be applied in a rapid and reliable fashion to HCT images, expediting the diagnosis of clinically significant traumatic brain injury that warrants emergent medical and surgical therapies to reduce intracranial pressure. It consists of 7 normal anatomic structures (cerebrospinal fluid around the brain stem, open fourth ventricle, "baby's butt," "Mickey Mouse ears," absence of midline shift, sulci and gyri, and gray-white differentiation). These 7 features can be seen even as the CT scanner obtains images, allowing the trauma team to expedite medical management of intracranial hypertension and pursue neurosurgical consultation prior to radiologic interpretation if the features are abnormal.

Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study.

BACKGROUND: Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE is a negative predictor of the need for revision surgery. Further optimization of testing protocols, evaluation in multiple centers, and integration with clinical and imaging impressions prompted the current study. OBJECTIVE: To compare the diagnostic accuracy of 2 TFE protocols, with micropumper (TFE+MP) or without (TFE-only), to neuro-imaging in patients emergently presenting with symptoms concerning for shunt malfunction. METHODS: We performed a prospective multicenter operator-blinded trial of a consecutive series of patients who underwent evaluation for shunt malfunction. TFE was performed, and preimaging clinician impressions and imaging results were recorded. The primary outcome was shunt obstruction requiring neurosurgical revision within 7 d. Non-inferiority of the sensitivity of TFE vs neuro-imaging for detecting shunt obstruction was tested using a prospectively determined a priori margin of -2.5%. RESULTS: We enrolled 406 patients at 10 centers. Of these, 68/348 (20%) evaluated with TFE+MP and 30/215 (14%) with TFE-only had shunt obstruction. The sensitivity for detecting obstruction was 100% (95% CI: 88%-100%) for TFE-only, 90% (95% CI: 80%-96%) for TFE+MP, 76% (95% CI: 65%-86%) for imaging in TFE+MP cohort, and 77% (95% CI: 58%-90%) for imaging in the TFE-only cohort. Difference in sensitivities between TFE methods and imaging did not exceed the non-inferiority margin. CONCLUSION: TFE is non-inferior to imaging in ruling out shunt malfunction and may help avoid imaging and other steps. For this purpose, TFE only is favored over TFE+MP.

Two-Tier Lyme Disease Serology Test Results Can Vary According to the Specific First-Tier Test Used.

BACKGROUND: Variability in 2-tier Lyme disease test results according to the specific first-tier enzyme immunoassay (EIA) in children has not been examined rigorously. In this study, we compared paired results of clinical 2-tier Lyme disease tests to those of the C6 peptide EIA followed by supplemental immunoblotting (C6 2-tier test). METHODS: We performed a prospective cohort study of children aged ≥1 to ≤21 years who were undergoing evaluation for Lyme disease in the emergency department at 1 of 6 centers located in regions in which Lyme disease is endemic. The clinical first-tier test and a C6 EIA were performed on the same serum sample with supplemental immunoblotting if the first-tier test result was either positive or equivocal. We compared the results of the paired clinical and C6 2-tier Lyme disease test results using the McNemar test. RESULTS: Of the 1714 children enrolled, we collected a research serum sample from 1584 (92.4%). The clinical 2-tier EIA result was positive in 316 (19.9%) children, and the C6 2-tier test result was positive or equivocal in 295 (18.6%) children. The clinical and C6 2-tier test results disagreed more often than they would have by chance alone (P = .002). Of the 39 children with either a positive clinical or C6 2-tier test result alone, 2 children had an erythema migrans (EM) lesion, and 29 had symptoms compatible with early disseminated Lyme disease. CONCLUSIONS: Two-tier Lyme disease test results differed for a substantial number of children on the basis of the specific first-tier test used. In children for whom there is a high clinical suspicion for Lyme disease and who have an initially negative test result, clinicians should consider retesting for Lyme disease.

Detecting direct oral anticoagulants in trauma patients using liquid chromatography-mass spectrometry: A novel approach to medication reconciliation.

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSION: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. LEVEL OF EVIDENCE: Diagnostic Test, level III.

Higher C6 enzyme immunoassay index values correlate with a diagnosis of noncutaneous Lyme disease.

The correlation between the Food and Drug Administration-cleared C6 enzyme immunoassay (EIA) C6 index values and a diagnosis of Lyme disease has not been examined. We used pooled patient-level data from 5 studies of adults and children with Lyme disease and control subjects who were tested with the C6 EIA. We constructed a receiver operating characteristic curve using regression clustered by study and measured the area under the curve (AUC) to examine the accuracy of the C6 index values in differentiating between patients with noncutaneous Lyme disease and control subjects. In the 4821 included patients, the C6 index value had excellent ability to distinguish between patients with noncutaneous Lyme disease and control subjects [AUC 0.99; 95% confidence interval (CI) 0.99-1.00]. An index value cut point of ≥3.0 had a sensitivity of 90.9% (95% CI, 87.8-93.3) and specificity of 99.0% (95% CI, 98.6-99.2%) for Lyme disease.

Positive 2-Tiered Lyme Disease Serology is Uncommon in Asymptomatic Children Living in Endemic Areas of the United States.

Knowing the frequency of positive Lyme disease serology in children without signs of infection facilitates test interpretation. Of 315 asymptomatic children from Lyme disease endemic regions, 32 had positive or equivocal C6 enzyme-linked immunoassays, but only 5 had positive IgG or IgM supplemental immunoblots (1.6%; 95% confidence interval: 0.7%-3.7%).

Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf).

Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma. Manufactured carbon nanotubes (CNTs) are similar to asbestos in terms of their fibrous shape and biopersistent properties and thus may pose an asbestos-like inhalation hazard. Here we show that instillation of either long CNTs or long asbestos fibers into the pleural cavity of mice induces mesothelioma that exhibits common key pro-oncogenic molecular events throughout the latency period of disease progression. Sustained activation of pro-oncogenic signaling pathways, increased proliferation, and oxidative DNA damage form a common molecular signature of long-CNT- and long-asbestos-fiber-induced pathology. We show that hypermethylation of p16/Ink4a and p19/Arf in CNT- and asbestos-induced inflammatory lesions precedes mesothelioma; this results in silencing of Cdkn2a (Ink4a/Arf) and loss of p16 and p19 protein, consistent with epigenetic alterations playing a gatekeeper role in cancer. In end-stage mesothelioma, silencing of p16/Ink4a is sustained and deletion of p19/Arf is detected, recapitulating human disease. This study addresses the long-standing question of which early molecular changes drive carcinogenesis during the long latency period of mesothelioma development and shows that CNT and asbestos pose a similar health hazard.

Change in Angular Alignment Is Associated With Early Dysphagia After Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective analysis of a prospective cohort. OBJECTIVE: Change in cervical angular alignment may be associated with dysphagia. SUMMARY OF BACKGROUND DATA: Bony deformities of the cervical spine may be associated with secondary contractures of soft tissues in the neck. Acute surgical deformity correction causes in changes in soft tissue tension in the anterior neck, resulting in dysphagia. METHODS: The study population included patients undergoing 1 and 2 level elective anterior cervical discectomy and fusion for cervical myelopathy or radiculopathy. Preoperative and postoperative radiographs at 2 weeks were measured by a blinded observer for C2-C7 endplate angle, C2-C7 posterior vertebral body length, and occipital condyle plumb line distance on upright lateral radiographs at 2, 6, and 12 weeks postoperatively. Patients were prospectively queried about dysphagia incidence and severity using a numeric rating scale. Multiple linear regression analysis was used to determine the effect of change in radiographic parameters controlling for demographic characteristics. RESULTS: The study population included 25 patients with complete radiographs. The mean change in C2-C7 angle was -0.6 degrees (SD 9), the mean change in C2-C7 length was 1.7 mm (SD 26), the mean change in occipital condyle plumb line distance was 2.3 mm (SD 20).Multiple linear regression analysis was performed including operative time, age, sex, number of levels, and change in radiographic parameters as independent variables and using dysphagia score as the dependent variable. The change in C2-C7 angle and operative time were the only statistically significant predictors of change in dysphagia at 2 and 6 weeks postoperatively. CONCLUSIONS: These results indicate that lordotic change in spinal alignment and longer operative times are associated with increased postoperative dysphagia. Surgeons should counsel patients in whom a large angular correction is expected about the possibility for postoperative dysphagia. Furthermore, future studies on dysphagia incidence should include radiographic alignment as an independent predictor of dysphagia.

Successful combined management for ruptured superior rectal artery aneurysm in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomally dominant inherited disorder characterized by neurocutaneous and bony lesions with multisystem vasculopathy in the form of stenotic and aneurysmal disease. The multisystemic nature of NF1 aneurysmal disease can have potentially serious clinical sequelae and complicated management. A 55-year-old woman with NF1 presented acutely with severe abdominal and back pain, diarrhea, and hypotension with a delayed fall in her hemoglobin. Imaging demonstrated a retroperitoneal bleed from a superior rectal artery aneurysm. The inferior mesenteric artery was coiled with cessation of bleeding. She became unstable again and underwent a successful laparotomy for aneurysm exclusion and evacuation of hematoma. Vessel position and relatively nonspecific symptoms on presentation make awareness among front-line clinicians critical. Endovascular management can be difficult, and the clinician should be prepared for open surgery if the patient displays signs of recurrent bleeding.