Blinded Cohort Research Articles

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis

ObjectivesThe differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic...

Atlantoaxial bands in small breed dogs: influence of external pressure by the endotracheal tube tie.

To determine the prevalence of dorsal cervical spinal compression in a population of dogs susceptible to caudal occipital dysplasia. To determine whether endotracheal tube ties iatrogenically alter the dorsal compression ratio in the atlantoaxial region. Prospective, randomised, controlled, cross-over, blinded cohort study of dogs weighing <15 kg and presenting for neurologic signs localised to the cervical region. In mid-sagittal T2-weighted MR images, dorsal cervical compression and cerebellar compression were evaluated. Dorsal cervical compression ratios were calculated and compared to determine the effect of the endotracheal tube tie on the atlantoaxial region depending on whether dogs were in extended or flexed neck position. Prevalence of dorsal cervical spinal compression consistent with an atlantoaxial band was 32/44 (73%) dogs without tie pressure and 37/44 (84%) dogs with tie pressure. Significantly higher compression ratios were found with tie placement over the craniocervical region. Dorsal compression ratios of dogs with cerebellar compression were significantly greater than those without it. The location of the endotracheal tube tie can influence interpretation of MR images of the craniocervical region of small breed dogs. These breeds more often had greater dorsal cervical spinal compression with tie pressure, especially when they had cerebellar compression.

Point-of-care bedside ultrasound examination for the exclusion of clinically significant ankle and fifth metatarsal bone fractures; a single blinded prospective diagnostic cohort study

ObjectiveThe aim of this study was to assess the diagnostic value of point-of-care bedside ultrasound (PoCUS) as in usual clinical practice in suspected ankle and fifth metatarsal bone fractures, compared to the standard of radiographic imaging.MethodsThis prospective study included patients ≥17 years presenting to the Emergency Department with ankle trauma and positive Ottawa Ankle Rules. All patients underwent PoCUS of the ankle by a (resident) emergency physician, the images were assessed by an ultrasound expert. Both were blinded for the medical history and clinical findings of the patients. Radiography of the ankle followed, evaluated by a radiologist blinded from the PoCUS findings. Primary outcome measures were sensitivity and specificity of PoCUS.ResultsA total of 242 patients were included, with 35 (22%) clinically significant (non-avulsion) fractures observed with radiography. The sensitivity of PoCUS in detecting clinically significant fractures by all sonographers was 80.0% (95% Confidence Interval (CI) 63.0 to 91.6%), specificity 90.3% (95% CI 83.7 to 94.9%), positive predictive value 70.0% (95% CI 57.0 to 80.3%) and the negative predictive value 94.1% (95% CI 89.1 to 96.9%). The sensitivity of PoCUS in detecting clinically significant fractures by the expert was 82.8% (95% CI 66.3 to 93.4%), specificity 99.2% (95% CI 95.5 to 99.9%), positive predictive value 96.7% (95% CI 80.3 to 99.5%) and the negative predictive value 95.3% (95% CI 91.0 to 98.2%).ConclusionPoCUS combined with the OAR has a good diagnostic value in usual clinical practice in the assessment of suspected ankle and fifth metatarsal bone fractures compared to radiographic imaging. More experience with PoCUS will improve the diagnostic value.Trial registrationRegistered in the local Research Register, study number 201500597.

Stimulated Raman histology for rapid and accurate intraoperative diagnosis of CNS tumors: prospective blinded study.

In some centers where brain tumor surgery is performed, the opportunity for expert intraoperative neuropathology consultation is lacking. Consequently, surgeons may not have access to the highest quality diagnostic histological data to inform surgical decision-making. Stimulated Raman histology (SRH) is a novel technology that allows for rapid acquisition of diagnostic histological images at the bedside. The authors performed a prospective blinded cohort study of 82 consecutive patients undergoing resection of CNS tumors to compare diagnostic time and accuracy of SRH simulation to the gold standard, i.e., frozen and permanent section diagnosis. Diagnostic accuracy was determined by concordance of SRH-simulated intraoperative pathology consultation with a blinded board-certified neuropathologist, with official frozen section and permanent section results. Overall, the mean time to diagnosis was 30.5 ± 13.2 minutes faster (p < 0.0001) for SRH simulation than for frozen section, with similar diagnostic correlation: 91.5% (κ = 0.834, p < 0.0001) between SRH simulation and permanent section, and 91.5% between frozen and permanent section (κ = 0.894, p < 0.0001). SRH-simulated intraoperative pathology consultation was significantly faster and equally accurate as frozen section.

Ultrasound in labor admission to predict need for emergency cesarean section: a prospective, blinded cohort study

Objective To assess whether assessment with ultrasound could improve the detection of emergency cesarean section (ECS) in laboring women. Methods Women who presented with symptoms of active labor or women in need of labor induction were invited to participate in the study. Women included in the study were evaluated with ultrasonography for fetal biometry and vaginal examinations for Bishop score assessment. The main aim in this study was determining factors associated with ECS due to fetal distress and obstructed labor. Results No fetal biometry variable was associated with ECS due to any indication (fetal distress and obstructed labor combined) in the univariate analysis. In multivariate analyses, biometry variables were adjusted for Bishop score at admission and only abdominal circumference percentile showed a significant association with the odds of ECS due to any indication (OR:1.02, 95% CI: 1.01–1.03). Biparietal diameter and abdominal circumference variables were associated with the odds of ECS due to obstructed labor in both univariate and multivariate analyses (p < .05 for all). However, the predictive accuracy of biparietal diameter percentile (area under the curve (AUC): 0.55, 95% CI: 0.46–0.63) and abdominal circumference percentile (AUC: 0.56, 95% CI: 0.48–0.64) without adjunct variables were poor. Moreover, the addition of fetal biometry parameters to Bishop score did not improve the predictive accuracy of Bishop score. Conclusion Ultrasound assessment at admission, in addition to Bishop score assessment, did not significantly improve the prediction of ECS. Also, the fetal biometry alone had poor predictive capability for ECS. Routine ultrasound assessment at labor admission appears to be ineffective for predicting ECS. Precis Fetal biparietal diameter and abdominal circumference showed an association with emergency cesarean due to obstructed labor but the predictive accuracy of fetal biometry was low. Routine ultrasound examination at admission, in addition to Bishop score assessment, may not useful for assessing the risk of emergency section in unselected populations.

LEV 2. Comparison of the Recanalization Rate and Post-thrombotic Syndrome in Patients With Deep Venous Thrombosis Treated With Rivaroxaban or Warfarin

In this paper, we report the outcomes of patients with deep venous thrombosis (DVT) in the lower limbs treated with the oral anticoagulant rivaroxaban or warfarin, focusing on the recanalization rate (measured with duplex ultrasound) and the incidence of post-thrombotic syndrome (PTS). This was a prospective, consecutive, randomized, blind cohort study of patients admitted with DVT to the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018. The patients were randomized into two groups and treated with oral anticoagulation for 6 months: either rivaroxaban (group 1) or warfarin (group 2). The study was registered at ClinicalTrials.gov under NCT02704598. Eighty-eight patients with DVT were admitted to the vascular surgery department and randomized into the two groups. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. Four patients were excluded from the study during follow-up because of a diagnosis of ovarian cancer (one patient), head and neck cancer (one patient), lung cancer (one patient), and stomach cancer (one patient). Therefore, 84 patients were evaluated: 46 patients in group 1 and 38 in group 2. The incidence of PTS (Table I) was 17.9% (15 cases) in the total cohort but was significantly higher in group 2 (11 cases [28.9%]) than in group 1 (4 cases [8.7%]; P < .001; odds ratio, 4.278). The rate of total venous recanalization at 360 days was 40.5% (34 patients) in the total cohort but was significantly higher in group 1 (35 patients [76.1%]) than in group 2 (5 patients [13.2%]; P < .001). The incidence of partial venous recanalization was 46.4% and was significantly higher in group 2 (28 patients [73.7%]) than in group 1 (11 patients [23.9%]; P = .016). Five patients in the total cohort (6%) showed no venous recanalization, all of them in group 2 (P = .016; Table II). In this study, patients who received oral rivaroxaban displayed a lower incidence of PTS and a better total vein recanalization rate after 6 and 12 months than patients who received warfarin.Table IVillalta score and post-thrombotic syndrome (PTS) at 6 months and 12 monthsVariableTotal (N = 84)Group 1 (n = 46 [54.7%])Group 2 (n = 38 [45.3%])P valueVillalta score <566 (78.5)42 (91.3)24 (63.1).025 5-914 (16.6)4 (8.7)10 (26.3).012 10-144 (4.9)04 (10.5).007PTS at 6 months <518 (21.4)4 (8.7)14 (37.8)<.001 5-969 (82.1)42 (91.3)27 (71.1).025 10-1411 (13.1)4 (8.7)7 (18.4).012PTS at 12 months4 (4.8)04 (10.5).007Segment affected and PTS at 12 monthsa15 (17.9)4 (8.7)11 (28.9)<.001 Femoropopliteal10 (14)3 (8.6)8 (22.2)<.001 Iliofemoral4 (28.6)1 (9.1)3 (100)<.001Values are reported as number (%).aPercentage refers to the incidence of deep venous thrombosis in the segment. Open table in a new tab Table IIUltrasound data on venous flow at admission and at 3 months, 6 months, and 360 daysVariableTotal (N = 84)Group 1 (n = 46 [54.7%])Group 2 (n = 38 [45.3%])P valueAt admission Occlusion78 (92.9)43 (93.5)35 (92.1).56 Partial flow6 (7.1)3 (6.5)3 (7.9).56At 3 months Occlusion8 (9.5)1 (2.2)7 (18.4).006 Partial flow60 (71.4)33 (71.7)27 (71.1).006 Total flow16 (19)12 (26.1)4 (10.5).006At 6 months Occlusion5 (6)05 (13.5).001 Partial flow50 (59.5)21 (45)29 (76.3).001 Total flow25 (29.8)22 (47.8)3 (7.9).001At 360 days Occlusion5 (6)05 (13.2)<.001 Partial flow38 (45.2)10 (21.7)28 (73.7)<.001 Total patency41 (48.8)36 (78.3)5 (13.2)<.001Values are reported as number (%). Open table in a new tab

EP23.07: Ultrasound in labour to predict a need for emergency Caesarean section (ECS): a prospective, blinded cohort study

EP23.07: Ultrasound in labour to predict a need for emergency Caesarean section (ECS): a prospective, blinded cohort study

Deep Neural Networks for Radiographic Risk Stratification of Gliomas

Deep learning algorithms allow for non-invasive risk stratification of gliomas based on radiographic data, which may help guide clinical decision making and further our understanding of glioma subtypes. The aim of this study was to accurately classify histopathologic grade based on quantitative imaging features on MRI through the development a convolutional neural network, as well as determine radiographic signatures predictive of survival outcomes across tumor grades. We analyzed T1 post-contrast MRI sequences for 111 patients diagnosed with high or low grade glioma within The Cancer Genome Atlas. Our training cohort consisted of 80 gliomas (20 high grade, 60 low grade). An 8-layer 3D convolutional neural network (3D CNN) was constructed to classify low grade versus high grade gliomas. Stacked denoising auto-encoders were used for pre-training to initialize weights within the 3D CNN. Data augmentation was implemented to increase training sample size. Regularization and dropout were employed to prevent overfitting of the data. Our blinded validation cohort consisted of 31 gliomas. Performance of the model was evaluated using AUC and accuracy. The relationship between class predictions generated by the 3D CNN output and survival was studied using Kaplan Meier curves and the log rank test. Within our training cohort the 3D CNN achieved an accuracy of 95.0% and AUC of 0.90 (95% CI: 0.81-0.99). When tested on the validation cohort the 3D CNN achieved an accuracy of 80.6% and AUC of 0.81 (95% CI 0.69-0.92). Among low grade gliomas those with a high-grade glioma class prediction >30% were associated with a poorer overall survival (p<.001). Among high grade gliomas those with a low-grade glioma class prediction >25% were associated with an improved overall survival (p<.001). We developed a 3D CNN to accurately predict histopathologic grade based on MRI imaging features in patients with high and low grade gliomas. Additionally, we identified radiographic signatures predictive of survival across grade groups in our analysis, suggesting that radiographic features can be used in conjunction with clinical and molecular information to classify gliomas beyond histopathological grade.

Comparison of the recanalization rate and postthrombotic syndrome in patients with deep venous thrombosis treated with rivaroxaban or warfarin

BackgroundIn this article, we report the outcomes of patients with deep venous thrombosis in the lower limbs treated with the oral anticoagulant rivaroxaban or warfarin, focusing on the recanalization rate (measured with duplex ultrasound) and the incidence of postthrombotic syndrome. MethodsThis was a prospective, consecutive, randomized, blind cohort study of patients admitted with deep venous thrombosis to the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018. The patients were randomized into 2 groups and treated with oral anticoagulation for 6 months: either rivaroxaban (group 1) or warfarin (group 2). The study was registered at clinicaltrials.gov under NCT 02704598. ResultsEighty-eight patients with deep venous thrombosis were admitted to the Vascular Surgery Department and randomized into the 2 groups. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. Four patients were excluded from the study during follow-up because of a diagnosis of ovarian cancer (1 patient), head and neck cancer (1 patient), lung cancer (1 patient), and stomach cancer (1 patient). Therefore, 84 patients were evaluated: 46 patients in group 1 and 38 in group 2. The incidence of postthrombotic syndrome was 17.9% (15 cases) in the total cohort, but was significantly higher in group 2 (11 cases, 28.9%) than in group 1 (4 cases, 8.7%; P < .001; odds ratio, 4.278). The rate of total venous recanalization at 360 days was 40.5% (34 patients) in the total cohort, but was significantly higher in group 1 (35 patients, 76.1%) than in group 2 (5 patients, 13.2%; P < .001). The incidence of partial venous recanalization was 46.4% and was significantly higher in group 2 (28 patients, 73.7%) than in group 1 (11 patients, 23.9%; P = .016). Five patients in the total cohort (6%) showed no venous recanalization, all of them in group 2 (P = .016). ConclusionIn this study, patients who received oral rivaroxaban displayed a lower incidence of postthrombotic syndrome and a better total vein recanalization rate after 6 and 12 months than patients who received warfarin.

Persistent cardiac dysfunction on echocardiography in African American women with severe preeclampsia.

Cardiovascular disease (CVD) and preeclampsia both disproportionally affect African American women. Evidence continues to grow linking a history of preeclampsia to future CVD. Therefore, we sought to determine whether abnormalities in cardiac function, as determined by echocardiography, could be identified at the time of preeclampsia diagnosis in African American women, and if they persist into the early postpartum period. This prospective blinded longitudinal cohort study was performed from April 2015 to May 2017. We identified African American women diagnosed with preterm (<37 weeks) preeclampsia with severe features and compared them to control normotensive pregnant women matched on race, gestational age, maternal age, and body mass index. We obtained transthoracic echocardiograms on cases and controls at time of diagnosis and again 4-12 weeks postpartum. We quantified the systolic function with longitudinal strain, ventricular-arterial coupling parameters and diastolic function. There were 29 matched (case-control) pairs of African American women for a total of 58 women. At time of preeclampsia diagnosis, there was more abnormal cardiac function as evidenced by worse cardiac systolic function (longitudinal strain), increased chamber stiffness (end systolic elastance), and worse diastolic function (E/e') in preeclampsia cases compared to controls. These findings persisted 4-12 weeks postpartum. There were additional notable abnormalities in E/A, and Ea (arterial load) postpartum, indicative of potentially worse diastolic function and increased arterial stiffness in the postpartum period. Among African American women, we found notable cardiac function differences between women with severe preeclampsia and healthy pregnant controls that persist postpartum.

Predicting the non-survival outcome of large hemispheric infarction patients via quantitative electroencephalography: Superiority to visual electroencephalography and the Glasgow Coma Scale

BackgroundQuantitative electroencephalography (QEEG) data are useful to predict outcomes of cerebral infarction patients. This study was performed to establish the value of QEEG in the prediction of outcomes in patients with large hemispheric infarction (LHI). MethodsA prognostic blinded cohort study was conducted on patients diagnosed with LHI in our neurocritical care unit. The electroencephalography (EEG) was recorded at the bedside within 3 days of LHI onset. Each EEG expert scored the raw EEG, and QEEG parameters including the absolute power, (delta + theta)/ (alpha + beta) ratio and brain symmetry index were obtained afterwards. Baseline data including Glasgow Coma Scale (GCS) was recorded at the meantime. Outcomes included survival or non-survival at the time of discharge and 6 months after the onset of LHI. ResultsA total of 50 patients entered into the final analysis. There were no differences in baseline data or visual EEG grades between survival and non-survival groups. QEEG analysis showed that the absolute theta power of all of the electrodes and the contralateral electrodes was significantly higher in the non-survival group than in the survival group at discharge. Multivariable logistic regression analysis demonstrated that theta power of the contralateral electrodes was an independent predictor of death at discharge and at 6 months. Compared to the GCS and EEG grading, the QEEG index exhibited higher accuracy in predicting non-survival outcomes. ConclusionsAmong QEEG indices, theta power is valuable in predicting non-survival outcome in participants and is superior to visual EEG and GCS.

Upfront PET/CT affects management decisions in patients with recurrent head and neck squamous cell carcinoma

PurposeTo compare multidisciplinary team conference (MDTC) decisions regarding treatment intent based on either chest X-ray + MRI of the head and neck (CXR/MRI) or 18F-FDG-PET/CT (PET/CT) in patients with recurrent head and neck squamous cell carcinoma (HNSCC). MethodsProspective blinded cohort study based on paired data. Consecutive patients with suspected recurrent HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging data was conducted as per standard practice. After at least three months (to eliminate recall bias in the team), the first project MDTC, based on either CXR/MRI or PET/CT, was conducted, and the tumor board made conclusions regarding treatment. After an additional three months, a second project MDTC was conducted using the complementary imaging strategy. The separate treatment strategies were compared using McNemar’s test. ResultsA total of 110 patients (90 males and 20 females, median age 66 years, range 40–87) were included. The initial primary tumor originated from the pharynx in 56 (51%) patients, oral cavity in 17 (15%) patients, and larynx in 37 (34%) patients. Based on CXR/MRI, 87 patients (79%) were recommended curative treatment and 23 (21%) palliative treatment. Based on PET/CT, the MDTC decided that 52 (47%) patients were suitable for curative treatment and 58 (53%) for palliative treatment. The absolute difference of 32% was statistically significant (95% CI: 22–42%, p < 0.001). ConclusionsPET/CT affected MDTC decisions in patients with recurrent HNSCC towards less curative and more palliative treatment.

Relationship between Perioperative Hypotension and Perioperative Cardiovascular Events in Patients with Coronary Artery Disease Undergoing Major Noncardiac Surgery.

Perioperative hypotension is associated with cardiovascular events in patients having noncardiac surgery. It is unknown if the severity of preexisting coronary artery disease determines susceptibility to the cardiovascular risks of perioperative hypotension. In this retrospective exploratory analysis of a substudy of an international prospective blinded cohort study, 955 patients 45 yr of age or older with history or risk factors for coronary artery disease underwent coronary computed tomographic angiography before elective inpatient noncardiac surgery. The authors evaluated the potential interaction between angiographic findings and perioperative hypotension (defined as systolic blood pressure less than 90 mmHg for a total of 10 min or more during surgery or for any duration after surgery and for which intervention was initiated) on the composite outcome of time to myocardial infarction or cardiovascular death up to 30 days after surgery. Angiography assessors were blinded to study outcomes; patients, treating clinicians, and outcome assessors were blinded to angiography findings. Cardiovascular events (myocardial infarction or cardiovascular death within 30 days after surgery) occurred in 7.7% of patients (74/955), including in 2.7% (8/293) without obstructive coronary disease or hypotension compared to 6.7% (21/314) with obstructive coronary disease but no hypotension (hazard ratio, 2.51; 95% CI, 1.11 to 5.66; P = 0.027), 8.8% (14/159) in patients with hypotension but without obstructive coronary disease (hazard ratio, 3.85; 95% CI, 1.62 to 9.19; P = 0.002), and 16.4% (31/189) with obstructive coronary disease and hypotension (hazard ratio, 7.34; 95% CI, 3.37 to 15.96; P < 0.001). Hypotension was independently associated with cardiovascular events (hazard ratio, 3.17; 95% CI, 1.99 to 5.06; P < 0.001). This association remained in patients without obstructive disease and did not differ significantly across degrees of coronary disease (P value for interaction, 0.599). In patients having noncardiac surgery, perioperative hypotension was associated with cardiovascular events regardless of the degree of coronary artery disease on preoperative coronary computed tomographic angiography.

The utility of magnetic resonance imaging results in physician decision-making before initial lumbar spinal injection

BACKGROUND CONTEXTThe need for advanced imaging before spinal intervention is an area of ongoing debate. Many studies have demonstrated the accuracy of magnetic resonance imaging (MRI) results in evaluating structural pathology in the lumbar spine, but few have addressed how frequently MRI findings change clinical management. A randomized controlled trial showed that viewing MRI results did not impact outcomes in patients with radiculopathy undergoing epidural steroid injection (ESI). The results suggested ESIs that correlated with both imaging and clinical findings experienced slightly more benefit than the blinded cohort, although statistically insignificantly. PURPOSEThree related studies were conducted to (1) increase understanding of the opinions of interventional spine physicians regarding the utility of viewing imaging before injection and (2) evaluate the impact of viewing MRI results on injection planning (retrospective and prospective analyses). STUDY DESIGNSurvey, prospective, and retrospective analysis. PATIENT SAMPLEPatients presenting to a university-based spine center for initial evaluation of back or leg pain who were candidates for spinal intervention. OUTCOME MEASURESSelf-reported measures from a clinical practice questionnaire distributed to interventional spine physicians to determine rates and rationale for utilization of MRI before spine injection, physiologic measures including MRI results, functional measures including physician decision-making regarding type and location of injection performed. METHODSThis study was funded by the University of Colorado Health and Welfare Trust. A survey was sent to interventional spine physicians to assess their utilization of MRI results before spine procedures. A retrospective analysis of patients who were candidates for ESI was conducted to evaluate how initial injection plan compared with the postviewing of MRI results on injection performed. In a prospective analysis, injection plans pre- and post-MRI were compared among patients presenting for initial evaluation of low back or leg pain. RESULTSSurvey responses showed that specialists order MRI studies to correlate with physical exam (91%) and to detect the presence of synovial cysts (68%), whereas tumor/infection (93%) was most likely to cause a change in their approach. In the retrospective review, the physician's planned approach before viewing the MRI was concordant with the actual procedure 49% of the time. A different type of procedure was performed in 15% of planned injections. In such cases, the initial treatment plan was altered (ie, same procedure at a different or additional level or side) in 35% of planned injections. In the prospective data collection, 43% of injections were different from the initial physician decision. The most common reasons for altering the injection was different level affected (36%), facet pathology (22%), and different nerve root affected (16%). CONCLUSIONSIn clinical practice, MRI before injection frequently changes management decisions in the planning and delivery of lumbar spine injections.

The role of laryngeal ultrasound in the assessment of pediatric dysphonia and stridor

ObjectivesDysphonia and stridor are not infrequent in the pediatric population. Awake nasolaryngoscopy (ANL) is the primary diagnostic procedure used to evaluate a child with stridor and/or dysphonia. The major limitation of this technique is poor cooperation in children, resulting in inadequate visualization of the larynx. Ultrasound is a widely used noninvasive imaging modality that has yet to be applied to the laryngeal examination. Our goal was to investigate the feasibility and diagnostic potential of laryngeal ultrasound (LUS) in cases of pediatric stridor and/or dysphonia. MethodsProspective blinded cohort study of infants and children 0–16 years of age referred for ANL due to voice disorders and/or stridor. Prior knowledge of the etiology was considered an exclusion criterion. ResultsLUS concurred with the ANL in the diagnosis of abnormal vs normal larynx in 28/32 children that were recruited. LUS had a sensitivity and specificity of 87% (95% CI: 69%–96%) and 100% (95% CI: 16%–100%) respectively, for diagnosing overall laryngeal disorders in comparison to ANL. LUS also had an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93, (P = 0.04, 95% CI: 0.84–1). ConclusionLUS may be applied as an adjuvant diagnostic tool for ruling in laryngeal pathologies in children including dysphonia and stridor. As further experience is acquired the value of LUS in diagnosis will be better understood.

High-intensity interval ergometer training improves aerobic capacity and fatigue in patients with multiple sclerosis

Moderate endurance training leads to a significant improvement of aerobic fitness and fatigue in patients with multiple sclerosis (MS). However, the effects of high-intensity interval training (HIIT) have not systematically investigated. To determine the effects of short-term HIIT on aerobic fitness and fatigue in MS patients. Prospective monocentric, randomized, simple blinded cohort study. Participants exercised for 8 weeks on a bicycle ergometer three times weekly for 8 weeks. Forty patients with relapsing–remitting MS and an extended disability status score (EDSS) of < 3.5 participated. For 8 weeks, participants exercised three times weekly for 30 min according to two different protocols (HIIT versus moderate endurance training). Measurements were taken at baseline and after 8 weeks of training. Individual aerobic fitness (VO2peak) was assessed via a stepwise ramp protocol, fatigue by the Fatigue Severity Scale (FSS), and ambulation was measured by the Timed 25-Foot Walk Test (T25-FW). Data were analysed according to the intention-to-treat (ITT) approach. Aerobic fitness increased significantly in the HIIT group (pre: 26.7 ± 6.1, post: 29.7 ± 6.6 ml/min/kg; p < 0.04). No changes with regard to FSS and T25FW were detected in both groups. However, sub-group analysis revealed a significant decrease of fatigue in patients with elevated baseline fatigue (pre: 5.00 ± 0.7, post: 4.7 ± 1.2; p = 0.03). HIIT is a promising time-efficient approach in subjects with MS leading to rapid improvement of aerobic fitness.

SA135MIR-9, MIR-153 AND MIR-124 ARE DOWN-REGULATED BY COCAINE IN A DOPAMINERGIC CELL MODEL AND CONTRIBUTE TO COCAINE DEPENDENCE

Dysphonia and stridor are not infrequent in the pediatric population. Awake nasolaryngoscopy (ANL) is the primary diagnostic procedure used to evaluate a child with stridor and/or dysphonia. The major limitation of this technique is poor cooperation in children, resulting in inadequate visualization of the larynx. Ultrasound is a widely used noninvasive imaging modality that has yet to be applied to the laryngeal examination. Our goal was to investigate the feasibility and diagnostic potential of laryngeal ultrasound (LUS) in cases of pediatric stridor and/or dysphonia.Prospective blinded cohort study of infants and children 0–16 years of age referred for ANL due to voice disorders and/or stridor. Prior knowledge of the etiology was considered an exclusion criterion.LUS concurred with the ANL in the diagnosis of abnormal vs normal larynx in 28/32 children that were recruited. LUS had a sensitivity and specificity of 87% (95% CI: 69%–96%) and 100% (95% CI: 16%–100%) respectively, for diagnosing overall laryngeal disorders in comparison to ANL. LUS also had an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93, (P = 0.04, 95% CI: 0.84–1).LUS may be applied as an adjuvant diagnostic tool for ruling in laryngeal pathologies in children including dysphonia and stridor. As further experience is acquired the value of LUS in diagnosis will be better understood.

Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis.

Surgical wound infiltration with local anesthetics is common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacaine can provide up to 92hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults. It is also commonly used by pediatric surgeons, but its safety profile in this age group has not been described. The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal bupivacaine compared to plain bupivacaine for surgical wound infiltration. We conducted a retrospective, single center, assessor blinded cohort study of pediatric surgical inpatients having open or laparoscopic surgery in the Cleveland Clinic between 2013 and 2017 and receiving wound infiltration with local anesthetics. We compared the incidence of local anesthetic systemic toxicity among those who received any dose of liposomal bupivacaine and those who received plain bupivacaine. Groups were matched 1:2 according to procedure type, age, and physical status score. Local anesthetic systemic toxicity was primarily defined as at least two signs or symptoms possibly related to anesthetic toxicity, as judged by two independent adjudicators blinded to the type of local anesthetic. A sensitivity analysis compared the incidence of a single sign/symptom possibly related to anesthetic toxicity. A total of 924 surgical cases were included in the final analysis (356 liposomal bupivacaine and 568 plain bupivacaine cases). The primary outcome did not occur in any patient. The sensitivity analysis found three cases in the liposomal bupivacaine group and two cases in the plain bupivacaine group having a single sign/symptom possibly related to local anesthetic administration (relative risk 2.4, 95% CI 0.4-14.0, P=0.38). In a cohort of pediatric surgical patients receiving wound infiltration with either plain or liposomal bupivacaine, we identified no cases of local anesthetic systemic toxicity syndrome, and only few patients with any sign or symptom that could potentially be related to local anesthetic toxicity.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology

Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

Aptamer-based proteomics of serum and plasma in acquired aplastic anemia

Single-stranded oligonucleotides containing deoxyuridine are aptamers (SOMAmers) that can bind proteins with high specificity and affinity and slow dissociation rates. SOMAscan, an aptamer-based proteomic technology, allows measurement of more than 1,300 proteins simultaneously for the identification of new disease biomarkers. The aim of the present study was to identify new serum and plasma protein markers for diagnosis of acquired aplastic anemia (AA) and response to immunosuppressive therapies (IST). SOMAscan was used to screen 1,141 serum proteins in 28 AA patients before and after therapy and 1,317 plasma proteins in seven SAA patients treated with standard IST and a thrombopoietin receptor agonist. From our analysis, 19 serum and 28 plasma proteins were identified as possible candidate diagnostic and prognostic markers. A custom immunobead-based multiplex assay with five selected serum proteins (BMP-10, CCL17, DKK1, HGF, and SELL) was used for validation in a verification set (n = 65) of samples obtained before and after IST and in a blinded validation cohort at baseline (n = 16). After technical validation, four biomarkers were employed to predict diagnosis (accuracy, 88%) and long-term response to IST (accuracy, 79%). In conclusion, SOMAscan is a powerful tool for the identification of new biomarkers. We propose further larger studies to validate new candidate serum and plasma diagnostic and prognostic markers of AA.