Prospective Diagnostic Cohort Study Research Articles

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): A prospective multicenter diagnostic cohort study in Asia.

196 Background: The benefit of standard esophagectomy in patients with clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is disputable and the alternative of active surveillance should be studied. PreSANO study demonstrated that clinical response evaluations (CREs) are accurate to detect residual tumor after nCRT in patients with mainly adenocarcinoma, however, its applicability to esophageal squamous cell carcinoma (ESCC) is unknown. The preSINO trial (NCT03937362) aimed to assess the accuracy of CREs based on bite-on-bite biopsy, endoscopic ultrasonography with fine needle aspiration (EUS-FNA) of suspected lymph nodes, PET-CT in patients with ESCC, and to provide a basis for organ-sparing strategy of ESCC in Asia. Methods: Patients were eligible when they were planned for nCRT (CROSS regimen) followed by standard surgery. Patients received the first CRE (bite-on-bite biopsies) 4-6 weeks after completion of nCRT. Patients with locoregional residual tumor and without distant metastases underwent immediate surgery. In patients with a cCR at CRE-1, a second CRE (CRE-2) was done 10-12 weeks after completion of nCRT using PET-CT, bite-on-bite biopsies and EUS-FNA of suspicious lymph nodes. All patients underwent surgery irrespective of the outcome of CRE-2, in the absence of distant metastases. Circulating tumor DNA (ctDNA) analyses based on tumor-informed assay were performed at baseline and CREs for exploratory analysis. Primary endpoint was the accuracy of CREs for detecting TRG3-4 or TRG1-2 with ypN+ residual tumor. A false-negative rate (FNR) of 19.5% was considered acceptable according to the study protocol. Results: From Aug 20, 2019, to Jan 15, 2023, 309 patients were included of whom 250 patients underwent nCRT plus surgery. Eighteen of 133 patients with TRG3-4 or TRG1-2 with ypN+ residual tumor were not detected by bite-on-bite biopsies and EUS-FNA (FNR: 13.5%). Sensitivity, specificity, negative predictive value and positive predictive value of detecting any residual tumor were 82%, 93%, 69% and 97%, respectively. PET-CT detected interval distant metastases in 13 (5%) of 268 patients prior to surgery. Postoperative distant recurrence rate among patients with ctDNA-positive and ctDNA-negative during CREs were 15.1% (11/73) and 3.3% (2/59), respectively. Conclusions: Bite-on-bite biopsies and EUS-FNA for lymph nodes were accurate for detecting locoregional residual disease after nCRT in patients with ESCC. Post-nCRT ctDNA-positive during CREs may indicate an increased risk of long-term distant metastasis, potentially serving as a diagnostic tool to identify patients who would benefit from postponement of surgery and additional systemic therapy. The long-term follow-up results of this trial will further answer this question. Clinical trial information: NCT03937362 .

Development of tuberculosis treatment decision algorithms in children below 5 years hospitalised with severe acute malnutrition in Zambia and Uganda: a prospective diagnostic cohort study

In children with severe acute malnutrition (SAM) tuberculosis is common, challenging to diagnose, and often fatal. We developed tuberculosis treatment decision algorithms (TDAs) for children under the age of 5 years with SAM. In this prospective diagnostic study, we enrolled and followed up children aged <60 months hospitalised with SAM at three tertiary hospitals in Zambia and Uganda from 4 November 2019 to 20 June 2022. We included children aged 2-59 months with SAM as defined by WHO and hospitalised following the WHO clinical criteria. We excluded children with current or history of antituberculosis treatment within the preceding 3 months. They underwent tuberculosis symptom screening, clinical assessment, chest X-ray, abdominal ultrasound, Xpert MTB/RIF Ultra (Ultra) and culture on respiratory and stool samples with 6 months follow-up. Tuberculosis was retrospectively defined using the 2015 standard case definition for childhood tuberculosis. We used logistic regression to develop diagnostic prediction models for a one-step diagnosis and a two-step screening and diagnostic approaches. We derived scores from models using WHO-recommended thresholds for sensitivity and proposed TDAs. This study is registered with ClinicalTrials.gov, NCT04240990. Of 1906 children hospitalised with SAM during the study period, 1230 were screened, 1152 were eligible and 603 were enrolled. Of the 603 children enrolled-median age 15 (inter-quartile range (IQR): 11-20) months and 65 (11.0%) living with HIV-114 (18.9%) were diagnosed with tuberculosis, including 51 (8.5%) with microbiological confirmation and 104 (17.2%) initiated treatment at a median of 6(IQR: 2-10) days after inclusion. 108 children were retrospectively classified as having tuberculosis resulting in a prevalence of 17.9% (95% confidence intervals (CI): 15.1; 21.2). 75 (69.4%) children with tuberculosis reported cough of any duration, 32 (29.6%) cough ≥2 weeks and 11 (10.2%) tuberculosis contact history. 535 children had complete data and were included in the diagnostic prediction model. The one-step diagnostic model had 15 predictors, including Ultra, clinical, radiographic, and abdominal features, an area under the receiving operating curve (AUROC) of 0.910, and derived TDA sensitivity of 86.14% (95% CI: 78.07-91.56) and specificity of 80.88% (95% CI: 76.91-84.30). The two-step model had AUROCs of 0.750 and 0.912 for screening and diagnosis, respectively, and derived combined TDA sensitivity of 79.21% (95% CI: 70.30-85.98) and a specificity of 83.64% (95% CI: 79.87-86.82). Tuberculosis prevalence was high among hospitalised children with SAM, with atypical clinical features. TDAs achieved satisfactory diagnostic accuracy and could be used to improve diagnosis in this vulnerable group. Unitaid.

The predictive value and reliability of ultrasound-guided synovial aspiration and biopsies for diagnosing periprosthetic shoulder infections.

Preoperative diagnosis of periprosthetic shoulder infections (PSI) is difficult. Infections are mostly caused by low virulence bacteria and patients do not show typical signs of infection. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination with multiplex polymerase chain reaction (mPCR), serum markers, and/or synovial markers for the preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. A prospective explorative diagnostic cohort study was performed including 55 patients undergoing revision shoulder replacement surgery. A shoulder puncture was performed preoperatively before incision to collect synovial fluid for mPCR analysis and for measurement of interleukin-6, calprotectin, white blood cell count (WBC), and polymorphonuclear cells. Also prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two for mPCR analysis. A blood sample was obtained to determine serum C-reactive protein, WBC, and erythrocyte sedimentation rate. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; the primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, blood and synovial markers, mPCR, and combinations thereof. Routine tissue cultures were positive for infection in 24 patients. Cultures from ultrasound-guided biopsies diagnosed infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively. The best diagnostic value was found for the combination of ultrasound-guided biopsies for culture, synovial WBC, and calprotectin with a sensitivity of 69.2%, specificity of 80.0%, PPV of 69.2%, and NPV of 80.0%. Ultrasound-guided biopsies for cultures alone and in combination with mPCR, and/or blood and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of PSI. Diagnostic study level II.

Comparison of a point-of-care and a core lab high-sensitivity cardiac troponin I assay: Analysis of an international prospective diagnostic cohort study

Comparison of a point-of-care and a core lab high-sensitivity cardiac troponin I assay: Analysis of an international prospective diagnostic cohort study

Diagnostic accuracy of pocket-size lung ultrasound for etiological definition of pneumonia and surveillance of complications in children hospitalized: a prospective diagnostic cohort study

Background: Pneumonia, the leading infectious cause of death in children worldwide, often requires a chest radiograph (CXR) for diagnosis, involving radiation exposure. Point-of-Care Ultrasound (POCUS) offers a radiation-free alternative and, specifically the pocket-size variant, enhances convenience at the patient's bedside. While evidence supports ultrasound's accuracy in detecting community-acquired pneumonia (CAP) in children comparable to CXR, few studies have explored its ability to distinguish pneumonia etiology, especially utilizing pocket-size POCUS devices. Methods: In this prospective diagnostic cohort study conducted over a year in a tertiary pediatric referral center, we aim to assess the diagnostic accuracy of a pocket-size POCUS device compared to CXR for determining the etiology of CAP in pediatric patients (aged &gt;6 months and &lt;18 years). At least 76 participants diagnosed with CAP will undergo independent POCUS examinations at various intervals, complemented by CXRs when necessary, independently classified by a third investigator. The General Electrics Vscan AirTM®, featuring Bluetooth connectivity to smartphone/tablet, will be employed for POCUS. Data collection will include systematized POCUS and CXR descriptions, alongside sociodemographic, clinical, and therapeutic variables. Statistical analysis using SPSS® version 28 will evaluate the diagnostic accuracy of the POCUS device. Conclusions: This trial's outcomes hold significant promise in unveiling unknown data about the diagnostic accuracy of pocket-size POCUS for pediatric CAP etiological diagnosis. Utilizing a device meeting technical recommendations, featuring a dual-headed probe and Bluetooth connectivity, this study has the potential to bring innovation to clinical practice, improving patient care and creating scientific value. Trial Registration Number: NCT06296693.

The value of lung ultrasound score in neonatal respiratory distress syndrome: a prospective diagnostic cohort study.

The accurate diagnosis of critically ill patients with respiratory failure can be achieved through lung ultrasound (LUS) score. Considering its characteristics, it is speculated that this technique might also be useful for patients with neonatal respiratory distress syndrome (NRDS). Thus, there is a need for precise imaging tools to monitor such patients. This double-blind randomized cohort study aims to investigate the impact of LUS and related scores on the severity of NRDS patients. This study was conducted as a prospective double-blind randomized study. Bivariate correlation analysis was conducted to investigate the relationship between LUS score and Oxygenation Index (OI), Respiratory Index (RI), and Sequential Organ Failure Assessment (SOFA) score. Spearman's correlation coefficient was used to generate correlation heat maps, elucidating the associations between LUS and respective parameters in different cohorts. Receiver Operating Characteristic (ROC) curves were employed to calculate the predictive values, sensitivity, and specificity of different scores in determining the severity of NRDS. This study ultimately included 134 patients admitted to the intensive care unit (ICU) between December 2020 and June 2022. Among these patients, 72 were included in the NRDS cohort, while 62 were included in the Non-NRDS (N-NRDS) cohort. There were significant differences in the mean LUS scores between NRDS and N-NRDS patients (p < 0.01). The LUS score was significantly negatively correlated with the OI (p < 0.01), while it was significantly positively correlated with the RI and SOFA scores (p < 0.01). The correlation heatmap revealed the highest positive correlation coefficient between LUS and RI (0.82), while the highest negative correlation coefficient was observed between LUS and OI (-0.8). ROC curves for different scores demonstrated that LUS score had the highest area under the curve (0.91, 95% CI: 0.84-0.98) in predicting the severity of patients' conditions. The combination of LUS and other scores can more accurately predict the severity of NRDS patients, with the highest AUC value of 0.93, significantly higher than using a single indicator alone (p < 0.01). Our double-blind randomized cohort study demonstrates that LUS, RI, OI, and SOFA scores can effectively monitor the lung ventilation and function in NRDS. Moreover, these parameters and their combination have significant predictive value in evaluating the severity and prognosis of NRDS patients. Therefore, these results provide crucial insights for future research endeavors.

Development and Validation of a Clinical Prediction Model for Venous Thromboembolism Following Neurosurgery: A 6-Year, Multicenter, Retrospective and Prospective Diagnostic Cohort Study.

Based on the literature and data on its clinical trials, the incidence of venous thromboembolism (VTE) in patients undergoing neurosurgery has been 3.0%~26%. We used advanced machine learning techniques and statistical methods to provide a clinical prediction model for VTE after neurosurgery. All patients (n = 5867) who underwent neurosurgery from the development and retrospective internal validation cohorts were obtained from May 2017 to April 2022 at the Department of Neurosurgery at the Sanbo Brain Hospital. The clinical and biomarker variables were divided into pre-, intra-, and postoperative. A univariate logistic regression (LR) was applied to explore the 67 candidate predictors with VTE. We used a multivariable logistic regression (MLR) to select all significant MLR variables of MLR to build the clinical risk prediction model. We used a random forest to calculate the importance of significant variables of MLR. In addition, we conducted prospective internal (n = 490) and external validation (n = 2301) for the model. Eight variables were selected for inclusion in the final clinical prediction model: D-dimer before surgery, activated partial thromboplastin time before neurosurgery, age, craniopharyngioma, duration of operation, disturbance of consciousness on the second day after surgery and high dose of mannitol, and highest D-dimer within 72 h after surgery. The area under the curve (AUC) values for the development, retrospective internal validation, and prospective internal validation cohorts were 0.78, 0.77, and 0.79, respectively. The external validation set had the highest AUC value of 0.85. This validated clinical prediction model, including eight clinical factors and biomarkers, predicted the risk of VTE following neurosurgery. Looking forward to further research exploring the standardization of clinical decision-making for primary VTE prevention based on this model.

Preoperative diagnosis of knee cartilage, meniscal, and ligament injuries by magnetic resonance imaging

PurposeThe purpose of the study was to report on the current accuracy measures specific to 1.5-Tesla MRI of the knee in the patient population prone to injuries of the anterior cruciate ligament (ACL), the menisci, and the articular cartilage.MethodsWe accrued patients between January 2018 through August 2021 who underwent a preoperative MRI and were diagnosed with an articular cartilage injury either due to unevenness of articular cartilage in T2-weighted sequences or due to the irregularity of subchondral bone in T1-weighted sequences. All patients were treated arthroscopically. Sensitivity, specificity, and accuracy were calculated for the detection of ACL, meniscus, and cartilage injuries. A P-value of < 0.05 represented statistical significance.ResultsOne-hundred and forty-seven cases which included 150 knee joints were enrolled in this study. The mean age at the time of surgery was 42.9 years-old. The sensitivity in the diagnosis of ACL injuries was significantly greater than that in the diagnosis of cartilage injuries (P = 0.0083). The ratios of the equality of operative indication in 6 recipient sites were found to be between 90.0% and 96.0%. The diagnostic critical point was within a 1 cm in diameter.ConclusionThe diagnostic sensitivity in cartilage injuries was significantly lower than ones of ACL and meniscal injuries. The ratios of the equality of operative indication was determined to be between 90.0% and 96.0%, if we consider the unevenness of articular cartilage or the irregularity of subchondral bone.Level of evidenceLevel III, Prospective diagnostic cohort study.

Study protocol of the GLOW study: maximising treatment options for recurrent glioblastoma patients by whole genome sequencing-based diagnostics—a prospective multicenter cohort study

BackgroundGlioblastoma (GBM), the most common glial primary brain tumour, is without exception lethal. Every year approximately 600 patients are diagnosed with this heterogeneous disease in The Netherlands. Despite neurosurgery, chemo -and radiation therapy, these tumours inevitably recur. Currently, there is no gold standard at time of recurrence and treatment options are limited. Unfortunately, the results of dedicated trials with new drugs have been very disappointing. The goal of the project is to obtain the evidence for changing standard of care (SOC) procedures to include whole genome sequencing (WGS) and consequently adapt care guidelines for this specific patient group with very poor prognosis by offering optimal and timely benefit from novel therapies, even in the absence of traditional registration trials for this small volume cancer indication.MethodsThe GLOW study is a prospective diagnostic cohort study executed through collaboration of the Hartwig Medical Foundation (Hartwig, a non-profit organisation) and twelve Dutch centers that perform neurosurgery and/or treat GBM patients. A total of 200 patients with a first recurrence of a glioblastoma will be included. Dual primary endpoint is the percentage of patients who receive targeted therapy based on the WGS report and overall survival. Secondary endpoints include WGS report success rate and number of targeted treatments available based on WGS reports and number of patients starting a treatment in presence of an actionable variant. At recurrence, study participants will undergo SOC neurosurgical resection. Tumour material will then, together with a blood sample, be sent to Hartwig where it will be analysed by WGS. A diagnostic report with therapy guidance, including potential matching off-label drugs and available clinical trials will then be sent back to the treating physician for discussing of the results in molecular tumour boards and targeted treatment decision making.DiscussionThe GLOW study aims to provide the scientific evidence for changing the SOC diagnostics for patients with a recurrent glioblastoma by investigating complete genome diagnostics to maximize treatment options for this patient group.Trial registration: ClinicalTrials.gov Identifier: NCT05186064.

Sensitivity and specificity of waveform analysis for assessing postoperative epidural function

Study objectivesTo characterize the accuracy of epidural waveform analysis (EWA) in assessing the functionality of thoracic epidural catheters in the immediate postoperative period (primary objective), and to determine the inter-rater reliability between EWA waveform observers (secondary outcome). DesignSingle center, prospective diagnostic accuracy cohort study. SettingPost-anesthetic care unit of a university teaching hospital. Patients84 adult patients undergoing elective thoracic, gynecologic, vascular, urologic, or general surgery with preoperative placement of a thoracic epidural catheter for perioperative analgesia. InterventionsEWA tracings were video recorded in the immediate postoperative period through the epidural catheter in the post-anesthetic care unit. MeasurementsPostoperative EWA tracings were compared with clinical assessments of the sensory block to ice produced by epidural local anesthetic in the immediate postoperative period. Additionally, intra-class correlation analysis of agreement between 3 independent (and blinded) EWA waveform observers was carried out. ResultsAmong 80 patients with thoracic epidurals who completed the study protocol, 73 demonstrated postoperative functional epidurals with sensory block to ice and 7 demonstrated non-functional epidurals. EWA yielded 65 true positives, 6 true negatives, 8 false negatives, and 1 false positive. Postoperative EWA sensitivity, specificity, positive predictive value and negative predictive value, along with the 95% confidence intervals (CI) were 89% (79–95%), 86% (42–100%), 98% (92–100%), and 43% (18–71%) respectively. Intra-class correlation between waveform assessors was 0.870 (95% CI 0.818–0.910, p < 0.001). ConclusionsEWA is useful in assessing the position of thoracic epidural catheters in the immediate postoperative period, demonstrating high sensitivity and specificity as well as robust inter-rater reliability. For patients in whom sensory block to ice cannot be reliably assessed postoperatively, EWA may provide a useful adjunct for assessing epidural functionality.

Evaluating the Sensitivity and Specificity of Siemens Clinitest Lateral Flow Test and the Simple AMplification-Based Assay (SAMBA)-2 PCR Test for SARS-CoV-2 Infection.

IntroductionAccurate point-of-care testing for SARS-CoV-2 could quickly identify which patients need to be isolated and improve flow for patients being admitted as an emergency to the hospital. We evaluated two diagnostic tests with shorter turnaround times, the Siemens Clinitest Lateral Flow (Siemens Healthineers AG, Erlangen, Germany) and the Simple AMplification-Based Assay (SAMBA)-2 PCR test against a standard laboratory PCR test.MethodsWe conducted a prospective diagnostic cohort study in a single English emergency department. Adult participants underwent three swabs: the Siemens Clinitest Lateral Flow Test, the SAMBA-2 and a standard laboratory PCR test.ResultsA total of 212 participants were recruited. The sensitivity and specificity of the Siemens Clinitest Lateral Flow Test against the laboratory PCR test was 55.6% (95% CI 30.8-78.5) and 100% (95% CI 98.1-100) respectively. The sensitivity and specificity of the SAMBA-2 PCR test against the laboratory PCR test was 60.0% (95% CI 32.3-83.7) and 100% (95% CI 97.9-100) respectively.ConclusionNeither the Siemens Clinitest Lateral Flow Test nor the SAMBA-2 PCR test demonstrated sufficient sensitivity to rule out active SARS-CoV-2 infection. Both tests demonstrated high specificity.

Differentiating central from peripheral causes of acute vertigo in an emergency setting with the HINTS, STANDING, and ABCD2 tests: A diagnostic cohort study.

Diagnosing stroke in dizzy patients remains a challenge in emergency medicine. The accuracy of the neuroophthalmologic examination HINTS performed by emergency physicians (EPs) is unknown. Our objective was to determine the accuracy of the HINTS examination performed by trained EPs for diagnosing central cause of acute vertigo and unsteadiness and to compare it with another bedside clinical tool, STANDING, and with the history-based score ABCD2. This was a prospective diagnostic cohort study among patients with isolated vertigo and unsteadiness seen in a single emergency department (ED). Trained EPs performed HINTS and STANDING tests blinded to attending physicians. ABCD2≥4 was used as the threshold and was calculated retrospectively. The criterion standard was diffusion-weighted brain magnetic resonance imaging (MRI). Peripheral diagnoses were established by a normal MRI, and etiologies were further refined by an otologic examination. We included 300 patients of whom 62 had a central lesion on neuroimaging including 49 strokes (79%). Of the 238 peripheral diagnoses, 159 were vestibulopathies, mainly benign paroxysmal positional vertigo (40%). HINTS and STANDING tests reached high sensitivities at 97% and 94% and NPVs at 99% and 98%, respectively. The ABCD2 score failed to predict half of central vertigo cases and had a sensitivity of 55% and a NPV of 87%. The STANDING test was more specific and had a better positive predictive value (PPV; 75% and 49%, respectively; positive likelihood ratio [LR+]= 3.71, negative likelihood ratio [LR-]= 0.09) than the HINTS test (67% and 44%, respectively; LR+= 2.96, LR-= 0.04). The ABCD2 score was specific (82%, LR+= 3.04, LR-= 0.56) but had a very low PPV (44%). In the hands of EPs, HINTS and STANDING tests outperformed ABCD2 in identifying central causes of vertigo. For diagnosing peripheral disorders, the STANDING algorithm is more specific than the HINTS test. HINTS and STANDING could be useful tools saving both time and costs related to unnecessary neuroimaging use.

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study

To evaluate the diagnostic and predictive ability of lung ultrasound at 3 time points in the first 2weeks after birth for predicting bronchopulmonary dysplasia (BPD) among infants <29weeks of gestational age. This was a prospective, diagnostic cohort study. Lung ultrasound was performed on days 3, 7, and 14 after birth and lung ultrasound scores (LUS) were calculated in blinded fashion. Diagnostic test characteristics and area under receiver operating characteristic (AUROC) curves were calculated. A total of 152 infants were enrolled with mean (SD) gestational age of 25.8 (1.5) weeks gestation. Of them, 87 (57%) infants were diagnosed with BPD. The LUS were significantly higher in infants diagnosed with BPD compared with those without BPD at all scan time points (P<.01). The score of >10 at all 3 time points had higher sensitivity (0.89, 0.89, and 0.77), specificity (0.87, 0.90, and 0.92), and corresponding clinically important positive and negative likelihood ratios. The AUROC for LUS at the 3 time points were 0.96, 0.97, and 0.95 on day 3, 7, and 14, respectively. Compared with the model using clinical characteristics, LUS alone had higher AUROC (P<.05 for all 3 time points). In this cohort, LUS in the first 2weeks after birth had a very high predictive value for the diagnosis of BPD among infants of <29weeks of gestation. ClinicalTrials.govNCT04756297.

Validation of a Machine Learning Brain Electrical Activity–Based Index to Aid in Diagnosing Concussion Among Athletes

An objective, reliable indicator of the presence and severity of concussive brain injury and of the readiness for the return to activity has the potential to reduce concussion-related disability. To validate the classification accuracy of a previously derived, machine learning, multimodal, brain electrical activity-based Concussion Index in an independent cohort of athletes with concussion. This prospective diagnostic cohort study was conducted at 10 clinical sites (ie, US universities and high schools) between February 4, 2017, and March 20, 2019. A cohort comprising a consecutive sample of 207 athletes aged 13 to 25 years with concussion and 373 matched athlete controls without concussion were assessed with electroencephalography, cognitive testing, and symptom inventories within 72 hours of injury, at return to play, and 45 days after return to play. Variables from the multimodal assessment were used to generate a Concussion Index at each time point. Athletes with concussion had experienced a witnessed head impact, were removed from play for 5 days or more, and had an initial Glasgow Coma Scale score of 13 to 15. Participants were excluded for known neurologic disease or history within the last year of traumatic brain injury. Athlete controls were matched to athletes with concussion for age, sex, and type of sport played. Classification accuracy of the Concussion Index at time of injury using a prespecified cutoff of 70 or less (total range, 0-100, where ≤70 indicates it is likely the individual has a concussion and >70 indicates it is likely the individual does not have a concussion). Of 580 eligible participants with analyzable data, 207 had concussion (124 male participants [59.9%]; mean [SD] age, 19.4 [2.5] years), and 373 were athlete controls (187 male participants [50.1%]; mean [SD] age, 19.6 [2.2] years). The Concussion Index had a sensitivity of 86.0% (95% CI, 80.5%-90.4%), specificity of 70.8% (95% CI, 65.9%-75.4%), negative predictive value of 90.1% (95% CI, 86.1%-93.3%), positive predictive value of 62.0% (95% CI, 56.1%-67.7%), and area under receiver operator characteristic curve of 0.89. At day 0, the mean (SD) Concussion Index among athletes with concussion was significantly lower than among athletes without concussion (75.0 [14.0] vs 32.7 [27.2]; P < .001). Among athletes with concussion, there was a significant increase in the Concussion Index between day 0 and return to play, with a mean (SD) paired difference between these time points of -41.2 (27.0) (P < .001). These results suggest that the multimodal brain activity-based Concussion Index has high classification accuracy for identification of the likelihood of concussion at time of injury and may be associated with the return to control values at the time of recovery. The Concussion Index has the potential to aid in the clinical diagnosis of concussion and in the assessment of athletes' readiness to return to play.

How Does Spinopelvic Mobility and Sagittal Functional Cup Orientation Affect Patient-Reported Outcome 1 Year after THA?—A Prospective Diagnostic Cohort Study

BackgroundThis prospective cohort study aimed to characterize how spinopelvic characteristics change post-total hip arthroplasty (THA) and determine how patient-reported outcome measures are associated with 1) individual spinopelvic mobility and 2) functional sagittal cup orientation post-THA. MethodsOne hundred consecutive patients who received unilateral THAs for end-stage hip osteoarthritis, without spinal pathology were studied. Preoperatively and postoperatively, patients underwent clinical and radiographic evaluations. Patient-reported outcomes were collected using the hip disability and osteoarthritis outcome score - physical function shortform (HOOS-PS). Radiographic parameters measured from standing and relaxed-seated radiographs, included the lumbar lordosis angle, pelvic tilt, pelvic femoral angle and cup orientation in the coronal (inclination/anteversion) and sagittal (anteinclination) planes. Spinopelvic mobility was characterized (ΔPT: “stiff” [<10°], “normal” [10°-30°], and “hypermobile” [>30°]). ResultsPreoperative spinopelvic characteristics were not associated with HOOS-PS. Post-THA, the spinopelvic characteristics changed, with less patients having spinopelvic hypermobility (7%) compared with preop (14%). Postoperatively, patients with spinopelvic hypermobility showed significantly worse HOOS-PS scores (21 ± 17 vs 21 ± 22 vs 41 ± 23; ANOVA P = .037). Sagittal but not coronal cup orientation was associated with postoperative spinopelvic characteristics. Cup anteinclination was less in the patients with postoperative spinopelvic hypermobility (27 ± 7° vs 36 ± 8° vs 36 ± 10°; ANOVA: P = .035). ConclusionWe hypothesize that spinopelvic hypermobility is secondary to impingement and reduced hip flexion; to achieve a seated position, impinging hips require more posterior pelvic tilt. Patients with spinopelvic hypermobility are likely impinging secondary to the low cup anteinclination (sagittal malorientation despite optimum coronal orientation) and thus have lower HOOS-PS compared. Sagittal assessments are thus important to adequately study hip mechanics. Level of EvidenceLevel II, diagnostic study.

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: A Prospective Diagnostic Cohort Study

Background: Bronchopulmonary dysplasia (BPD) remains a common and serious complication of preterm birth. Early prediction of BPD can be useful to alter its course using clinical, quality improvement and research strategies. Our aim is to evaluate the diagnostic and predictive ability of lung ultrasound at three time points in the first two weeks after birth for predicting BPD among infants less than 29 weeks gestational age. Methods: This was a prospective, diagnostic cohort study conducted between July 2019 and December 2020 at two Neonatal Intensive Care Units. Eligible infants were enrolled after parental consent. Lung ultrasound was performed on days 3, 7 and 14 after birth and lung ultrasound scores (LUS) were calculated in blinded fashion. Diagnostic test characteristics and area under receiver operating characteristic (AUROC) curves were calculated and compared with values obtained from clinical predictors. Findings: A total of 152 infants were enrolled with mean (SD) gestational age of 26·5 (1.5) weeks and mean (SD) birth weight of 923 (250) grams. Of them, 87 (57%) infants were diagnosed with BPD. The LUS were significantly higher in infants diagnosed with BPD compared to those without BPD at all scan time points (p 10 at all 3 timepoints had higher sensitivity (0·89, 0·89, and 0·77) with specificity (0·87, 0·90, and 0·92) and corresponding clinically important positive and negative likelihood ratios. The AUROC for LUS at the three time points were 0·96, 0·97 and 0·95 on day 3, 7 and 14 respectively. Compared to the model using clinical characteristics, LUS alone had higher AUROC (p<0·05 for all three time points). Interpretation: In this cohort, LUS in the first 2 weeks after birth had a very high predictive value for the diagnosis of BPD among infants of <29 weeks’ gestation. Trial Registration: Study was registered at http:// www.clinicaltrials.gov (registration # NCT04756297). Funding: No specific funding was received. Declaration of Interests: The authors have no conflicts of interest or potential conflicts of interest relevant to this article to disclose. Ethics Approval Statement: Research Ethics Board (REB) approvals were obtained from both participating institutions. An informed consent was obtained from parents prior to patient’s enrollment.

Evaluation of the 0h/1h high-sensitivity cardiac troponin T algorithm in diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) in Han population.

A rapid 0h/1h algorithm using high-sensitivity cardiac troponin T (hs-cTnT) for rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) is recommended by the European Society of Cardiology. We aim to prospectively evaluate the diagnostic performance of the algorithm in Chinese Han patients with suspected NSTEMI. In this prospective diagnostic cohort study, 577 patients presenting to the emergency department with suspected NSTEMI and recent (<12h) onset of symptoms were enrolled. The levels of serum hs-cTnT were measured on admission, 1h later and 4-14h later. All patients underwent the initial clinical assessment and were triaged into three groups (rule-out, rule-in and observe) according to the 0h/1h algorithm. The major cardiovascular events (MACE) were evaluated at the 7-day and 30-day follow-ups. Among 577 enrolled patients, NSTEMI was the final diagnosis for 106 (18.4%) patients. Based on the hs-cTnT 0h/1h algorithm, 148 patients (25.6%) were classified as rule-out, 278 patients (48.2%) as rule-in and 151 patients (26.2%) were assigned to the observe group. The rule-out approach resulted in a sensitivity of 100% and negative predictive value of 100%. The rule-in approach resulted in a specificity of 62.9% [95% CI (58.5-67.2%)] and positive predictive value of 37.1% [95%CI (31.3-42.8%)]. No MACE was observed in the rule-out group within 30-day follow-up. The hs-cTnT 0h/1h algorithm is a safe tool for early rule-out of NSTEMI, while probably not an effective strategy for accurate rule-in of NSTEMI in Chinese Han population.

Association between self-reported functional capacity and major adverse cardiac events in patients at elevated risk undergoing noncardiac surgery: a prospective diagnostic cohort study

BackgroundPerioperative cardiovascular guidelines endorse functional capacity estimation, based on ‘cut-off’ daily activities for risk assessment and climbing two flights of stairs to approximate 4 metabolic equivalents. We assessed the association between self-reported functional capacity and postoperative cardiac events. MethodsConsecutive patients at elevated cardiovascular risk undergoing in-patient noncardiac surgery were included in this predefined secondary analysis. Self-reported ability to walk up two flights of stairs was extracted from electronic charts. The primary endpoint was a composite of cardiac death and cardiac events at 30 days. Secondary endpoints included the same composite at 1 yr, all-cause mortality, and myocardial injury. ResultsAmong the 4560 patients, mean (standard deviation) age 73 (SD 8 yr) yr, classified as American Society of Anesthesiologists physical status ≥3 in 61% (n=2786/4560), the 30-day and 1-yr incidences of major adverse cardiac events were 5.7% (258/4560) and 11.2% (509/4560), respectively. Functional capacity less than two flights of stairs was associated with the 30-day composite endpoint (adjusted hazard ratio 1.63, 95% confidence interval [CI] 1.23–2.15) and all other endpoints. The addition of functional capacity information to the revised cardiac risk index (RCRI) significantly improved risk classification (functional capacity plus RCRI vs RCRI: net reclassification improvement [NRI]Events 6.2 [95% CI 3.6–9.9], NRINonevents19.2 [95% CI 18.1–20.0]). ConclusionsIn patients at high cardiovascular risk undergoing noncardiac surgery, self-reported functional capacity less than two flights of stairs was independently associated with major adverse cardiac events and all-cause mortality at 30 days and 1 yr. The addition of self-reported functional capacity to surgical and clinical risk improved risk classification. Clinical trial registrationINCT 02573532.

Outcomes of a Telephone-Based Questionnaire for Follow-up of Patients Who Have Completed Curative-Intent Treatment for Oral Cancers

Follow-up assessment of patients who had treatment for head and neck cancer is critical and an important part of the overall treatment program. During each visit to the hospital, patients are evaluated by a physician and may undergo additional tests. Because it has been observed that the symptoms mentioned by patients often guide the treating clinicians in identifying cancer recurrence, an appropriately constructed questionnaire can help clinicians determine which patients need further testing as a result of a recurrence and which patients can continue to be monitored remotely. To evaluate the role of a symptom-based telephone questionnaire in detecting recurrences in patients with radically treated oral cancer. This prospective diagnostic cohort study was conducted from October 1, 2018, to February 28, 2019. This study took place at Tata Memorial Centre, an apex referral cancer center in India. A total of 615 consecutive patients with oral cancer were screened, of whom 400 patients consented to be a part of the study. After completion of curative treatment, these patients were followed up for 2 months to 2 years. We excluded patients younger than 18 years or older than 80 years, those with Eastern Cooperative Oncology Group status greater than 2, and those who had already been diagnosed with recurrent disease. The patients were contacted 2 weeks before their clinic appointment, and a telephone interview was conducted using a predefined questionnaire. Based on patients' responses to these questions, their disease status was estimated. Subsequently, during the actual follow-up visit, a trained head and neck surgeon, who was blinded to the questionnaire result, examined them. The sensitivity and specificity of the telephone questionnaire were calculated by comparing its results with those of the trained head and neck surgeon after the clinical evaluation. Of the 615 patients screened, 400 consented to be part of the study. Participants had a median (interquartile range) age of 49 (41-56) years, and 334 (83.5%) were men. Recurrence was noted in 20 patients (5.0%). The telephone-based questionnaire was found to have sensitivity of 90.0%, specificity of 74.2%, positive predictive value of 15.5%, and negative predictive value of 99.3%. Clinical examination values were 100.0%, 92.9%, 42.5%, and 100.0%, respectively. A total of 124 patients (31.0%) said that they would prefer such a telephone follow-up compared with an actual physical follow-up visit. This diagnostic cohort study found that a symptom-based telephone questionnaire had good sensitivity and negative predictive value for detecting recurrences in patients with oral cancer on follow-up evaluation after completion of definitive treatment.

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study

BackgroundAfter neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC.MethodsOperable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10–12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value.DiscussionIf the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial).Trial registrationThe preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).