Accuracy of contrast-enhanced CT in liver neoplasms in children under 2 years age.

BACKGROUND: Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases. OBJECTIVE: To evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years. METHODS: Eighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed. RESULTS: The mean age of the sample was 11.4 months (95% CI, 10.9-11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2-89.2%), which increased to 92.1% (95% CI, 84.3-96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4-99.9%). CONCLUSION: CT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients.

Malnutrition screening tool and nutritional screening tool for classification of nutritional risk in patients with cancer upon hospital admission: Comparison of diagnostic performance using Global Leadership Initiative on malnutrition criteria as reference.

BACKGROUND & AIMS: Tools for screening of nutrition risk in patients with cancer are usually validated against other screening instruments. Here with the performance of Malnutrition Screening Tool (MST) and Nutritional Screening Tool (NUTRISCORE) to identify the risk of malnutrition was assessed. A full nutritional evaluation and diagnosis following criteria from the Global Leadership Initiative of Malnutrition (GLIM) was the reference standard for the classification of malnutrition. METHODS: Diagnostic test prospective analysis of adult patients with a confirmed diagnosis of cancer. MST, NUTRISCORE and nutritional evaluation and diagnosis by GLIM criteria were independently performed within 24 h of admission to a 4th tier hospital in Bogotá, Colombia. RESULTS: From 439 patients the sensitivity and specificity of MST was 75% and 94% and of NUTRISCORE 45% and 97% respectively. The area under receiver operating characteristic (ROC) curves were 0.90 for MST and 0.85 for NUTRISCORE (p = 0.003). CONCLUSION: The MST showed a significantly better diagnostic performance over NUTRISCORE for detection of malnutrition risk at admission to hospital of patients with cancer.

Value of turbo spin echo-based diffusion-weighted imaging in the differential diagnosis of benign and malignant solitary pulmonary lesions.

To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)-based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE-based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann-Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = - 4.522, p < 0.001). Additionally, the ADC800, ADCtotal, and D values were all significantly lower in lung cancer than in the benign lesions (Z = - 5.054, -5.370, and -6.047, respectively, all p < 0.001), whereas the f values did not exhibit any statistically significant difference between the two groups. D had the highest area under the curve (AUC = 0.887), followed by ADCtotal (AUC = 0.844), ADC800 (AUC = 0.824), and LSR (AUC = 0.789). The LSR, ADC800, ADCtotal, and D values did not differ statistically significantly in diagnostic effectiveness. Lung DWI using TSE is feasible for differentiating SPLs. The LSR method, conventional DWI, and IVIM have comparable diagnostic efficacy for assessing SPLs.

Performance of the first-trimester Fetal Medicine Foundation competing risks model for preeclampsia prediction: an external validation study in Brazil.

BACKGROUND: The current version of the Fetal Medicine Foundation competing risks model for preeclampsia prediction has not been previously validated in Brazil. OBJECTIVE: This study aimed (1) to validate the Fetal Medicine Foundation combined algorithm for the prediction of preterm preeclampsia in the Brazilian population and (2) to describe the accuracy and calibration of the Fetal Medicine Foundation algorithm when considering the prophylactic use of aspirin by clinical criteria. STUDY DESIGN: This was a cohort study, including consecutive singleton pregnancies undergoing preeclampsia screening at 11 to 14 weeks of gestation, examining maternal characteristics, medical history, and biophysical markers between October 2010 and December 2018 in a university hospital in Brazil. Risks were calculated using the 2018 version of the algorithm available on the Fetal Medicine Foundation website, and cases were classified as low or high risk using a cutoff of 1/100 to evaluate predictive performance. Expected and observed cases with preeclampsia according to the Fetal Medicine Foundation-estimated risk range (≥1 in 10; 1 in 11 to 1 in 50; 1 in 51 to 1 in 100; 1 in 101 to 1 in 150; and <1 in 150) were compared. After identifying high-risk pregnant women who used aspirin, the treatment effect of 62% reduction in preterm preeclampsia identified in the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial was used to evaluate the predictive performance adjusted for the effect of aspirin. The number of potentially unpreventable cases in the group without aspirin use was estimated. RESULTS: Among 2749 pregnancies, preterm preeclampsia occurred in 84 (3.1%). With a risk cutoff of 1/100, the screen-positive rate was 25.8%. The detection rate was 71.4%, with a false positive rate of 24.4%. The area under the curve was 0.818 (95% confidence interval, 0.773-0.863). In the risk range ≥1/10, there is an agreement between the number of expected cases and the number of observed cases, and in the other ranges, the predicted risk was lower than the observed rates. Accounting for the effect of aspirin resulted in an increase in detection rate and positive predictive values and a slight decrease in the false positive rate. With 27 cases of preterm preeclampsia in the high-risk group without aspirin use, we estimated that 16 of these cases of preterm preeclampsia would have been avoided if this group had received prophylaxis. CONCLUSION: In a high-prevalence setting, the Fetal Medicine Foundation algorithm can identify women who are more likely to develop preterm preeclampsia. Not accounting for the effect of aspirin underestimates the screening performance.

Predictive validity of the Developmental Coordination Disorder Questionnaire as a screening tool to identify motor skill problems: A systematic review and meta-analysis.

BACKGROUND: The Developmental Coordination Disorder Questionnaire (DCDQ) has been used to screen children who probably have developmental coordination disorder (DCD). AIMS: We systematically reviewed studies on the predictive validity of the DCDQ and performed a meta-analysis on its diagnostic accuracy. METHODS AND PROCEDURES: Literature was searched through four electronic databases: MEDLINE, Embase, CINAHL, and PsycArticles. A total of 27 studies was selected based on the inclusion criteria. The sensitivity and specificity of the DCDQ were assessed using summary receiver operating characteristic (sROC) curves. Subgroup analyses were conducted according to the DCDQ type, reference standard, and participant type. OUTCOMES AND RESULTS: Overall, the DCDQ has a sensitivity of 0.70 and a specificity of 0.77, showing moderate diagnostic accuracy (area under the curve, 0.80). Subgroup analysis showed that the revised version of the DCDQ had higher diagnostic accuracy than the original version. When the reference standard was the Diagnostic and Statistical Manual of Mental Disorders, the sensitivity and specificity of the DCDQ were 0.87 and 0.83, respectively. The diagnostic accuracy was higher in clinical samples compared to the general population. CONCLUSIONS AND IMPLICATIONS: This study demonstrated that the DCDQ has adequate diagnostic accuracy, suggesting it can help screen children with motor skill deficits.

Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Diagnostic Efficacy Study Comparing Tzanakis Scoring System With Alvarado Scoring System in Effective Diagnosis of Acute Appendicitis.

Objective Among the common causes of abdominal emergencies, acute appendicitis ranks at the top, particularly in the young population. While negative appendectomy is not uncommon, the risk of appendicular perforation is substantial if the diagnosis is missed or delayed. This study evaluated the diagnostic efficacy of the Tzanakis scoring system for acute appendicitis, comparing it with the Alvarado scoring system, considering the histopathological finding as the gold standard. Materials and methods This prospective observational study, conducted in the General Surgery department in a tertiary care hospital in India, included clinically diagnosed acute appendicitis cases posted for open or laparoscopic appendicectomy. Results The mean age for the 60 participants included in the study was 30.97±13.44, and the median was 24.5 yrs. The sensitivity of ultrasonography (USG) in diagnosing histopathological positive acute appendicitis was 89%, and the specificity was 50%. The sensitivity, specificity, positive, and negative predictive values of the Tzanakis score were 87%, 50%, 96%, and 22%, respectively, and those of the Alvarado score were 54%, 75%, 96%, and 10%, respectively. Conclusion The receiver operator characteristic (ROC) curve for the Alvarado and Tzanakis scores showed that the area under the curve (AUC) was greater for the Tzanakis scoring system (0.670) than for the Alvarado scoring system (0.598). Differences between the AUCs were not statistically significant. Although the Tzanakis scoring system is more sensitive than the Alvarado scoring system in diagnosing acute appendicitis, studies with larger samples are needed to show the superiority of this scoring system over the Alvarado scoring system.

Comparison of the Prognostic Accuracy of Full Outline of Unresponsiveness (FOUR) Score with Glasgow Coma Scale (GCS) Score among Patients with Traumatic Brain Injury in a Tertiary Care Center.

Objectives The Glasgow Coma Scale (GCS) is widely used and considered the gold standard in assessing the consciousness of patients with traumatic brain injury. However, some significant limitations, like the considerable variations in interobserver reliability and predictive validity, were the reason for developing the Full Outline of Unresponsiveness (FOUR) score. The current study aims to compare the prognostic accuracy of the FOUR score with the GCS score for in-hospital mortality and morbidity among patients with traumatic brain injury. Materials and Methods A prospective cohort study was conducted, where 237 participants were selected by consecutive sampling from a tertiary care center. These patients were assessed with the help of GCS and FOUR scores within 6 hours of admission, and other clinical parameters were also noted. The level of consciousness was checked every day with the help of GCS and FOUR scores until their last hospitalization day. Glasgow Outcome Scale was used to assess their outcome on the last day of hospitalization. The GCS and FOUR scores were compared, and data were analyzed by descriptive and inferential statistics. The chi-square test, independent Student's t -test, and receiver operating characteristic analysis were used for inferential analysis. Results The area under the curve (AUC) for the GCS score at the 6th hour for predicting mortality was 0.865 with a cutoff value of 5.5, and it yields a sensitivity of 87% and a specificity of 64%. The AUC for FOUR scores at the 6th hour for predicting the mortality was 0.893, with a cutoff value of 5.5, and it yields a sensitivity of 87% and a specificity of 73%. Conclusion The current study shows that, as per the AUC of GCS and FOUR scores, their sensitivity was equal, but specificity was higher in the FOUR score. So, the FOUR score has higher accuracy than the GCS score in the prediction of mortality among traumatic brain injury patients.

Urinary methotrexate dosage in rheumatoid arthritis, in patients treated for at least 6 months: a potential marker of adherence.

OBJECTIVES: Non-adherence to rheumatoid arthritis (RA) treatments must be identified. A methotrexate (MTX) urinary dosage (METU) was recently developed. The aim of our study was to assess adherence to MTX in RA using METU in real-life conditions and to compare it with indirect adherence measurement technics. METHODS: We performed a cross-sectional study at Reims University Hospital. We included over 18-year-old patients with RA treated by MTX for more than 6 months. Patients were invited to complete demographic, clinical and psychological questionnaires and adherence measurement technics (Compliance Questionnaire of Rheumatology (CQR) and Medication Possession Ratio (MPR)). A urinary sample was collected to measure MTX and information about tolerance was evaluated through Methotrexate Intolerance Severity Score. RESULTS: 84 patients were included, 26 using oral MTX, 58 subcutaneous (SC) MTX. Among them, 73% were female, mean age was 61.5 years, MTX mean dose was 15 mg/week and 61.9% were treated by biological DMARDs (Disease Modifying Antirheumatic Drugs). 77 patients (91.7%) were adherent to treatment according to METU, whereas MPR and CQR reported less adherence (69.5% and 61.9%, respectively). MPR and METU were not significantly different in SC MTX users (p=0.059). Non-adherent patients had a higher number of tender joints and C reactive protein value (p<0.05). CONCLUSION: This is the first largest study evaluating MTX adherence in patients with RA using a urinary dosage. We identified that indirect adherence measurements did not reflect real-life adherence. It would be appreciable to realise METU, in a new study, in patients with RA with unexplained response to treatment, to consider it before escalating therapeutic strategy.

Beneath the surface: A systematic review on intraoperative imaging techniques for deep margin assessment in oral squamous cell carcinoma.

Resection margins of oral squamous cell carcinoma (SCC) are often inadequate. A systematic review on clinical intraoperative whole-specimen imaging techniques to obtain adequate deep resection margins in oral SCC is lacking. Such a review may render better alternatives for the current insufficient intraoperative techniques: palpation and frozen section analyses (FSA). This review resulted in ten publications investigating ultrasound (US), four investigating fluorescence, and three investigating MRI. Both US and fluorescence were able to image the tumor intraorally and perform ex-vivo imaging of the resection specimen. Fluorescence was also able to image residual tumor tissue in the wound bed. MRI could only be used on the ex-vivo specimen. The 95 % confidence intervals for sensitivity and specificity were large, due to the small sample sizes for all three techniques. The sensitivity and specificity of US for identifying < 5 mm margins ranged from 0 % to 100 % and 60 % to 100 %, respectively. For fluorescence, this ranged from 0 % to 100 % and 76 % to 100 %, respectively. For MRI, this ranged from 7 % to 100 % and 81 % to 100 %, respectively. US, MRI and fluorescence are the currently available imaging techniques that can potentially be used intraoperatively and which can image the entire tumor-free margin, although they have insufficient sensitivity for identifying < 5 mm margins. Further research on larger cohorts is needed to improve the sensitivity by determining cut-off points on imaging for inadequate margins. This improves the number of adequate resections of oral SCC's and pave the way for routine clinical implementation of these techniques.

Distinguishing thymic cysts from low-risk thymomas via [18F]FDG PET/CT.

BACKGROUND: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. METHODS: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). CONCLUSIONS: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings.

Evaluation of magnetic resonance imaging to detect cholesteatoma in clinical healthcare.

BACKGROUND: Non-Echo-Planar Diffusion Weighed Magnetic Resonance Imaging (non-EPI DW MRI) plays a role in the planning of cholesteatoma surgery. OBJECTIVES: To outline the usage of Non-EPI DW MRI in cholesteatoma diagnostics and to determine its accuracy, using otosurgery diagnostics as reference standard. MATERIAL AND METHODS: A retrospective descriptive study. All subjects operated, with suspicion of cholesteatoma as indication, that had a preceding examination with non-EPI DW MRI, between October 2010 and March 2019. Calculating sensitivity, specificity, predicative values, and likelihood ratios, using non-EPI DW MRI as index test and diagnosis from otosurgery as reference standard. RESULTS: Fifty-two subject episodes were included. Non-EPI DW MRI had a sensitivity of 0.50, specificity of 0.75, positive and negative predictive values of 0.74 and 0.52 and, positive and negative likelihood ratios of 2.0 and 0.67 respectively. CONCLUSIONS AND SIGNIFICANCE: There is a clear annual trend with increased numbers of executed examinations during the study period. The diagnostic accuracy of non-EPI DW MRI does not reach acceptable levels in the existing everyday routine practice conditions. The accuracy of the examination increases when interpreted by an experienced radiologist and when using the definition of cholesteatoma recommended by EAONO/JOS.

Validity of Prescription-Defined and Hospital-Diagnosed Hypertension Compared with Self-Reported Hypertension in Denmark.

Purpose: Hypertension is an important risk factor in cardio-epidemiological research, but data quality remains a concern. We validated different registry-based definitions of hypertension. Patients and Methods: The cohort included all first-time responders of the Danish National Health Surveys (2010, 2013, or 2017). Prescription-defined hypertension was defined as ≥1 or ≥2 filled prescriptions of antihypertensive specific drugs in ≥1 or ≥2 different antihypertensive drug classes within 90, 180, or 365 days before survey response. Hospital-diagnosed hypertension was defined from hypertension diagnoses within five years before the survey response. Considering self-reported hypertension as the reference, we calculated the positive predictive value (PPV), the negative predictive value (NVP), the sensitivity, and the specificity of prescription-defined and hospital-diagnosed hypertension. Results: Among 442,490 survey responders, 127,247 (29%) had self-reported hypertension. For prescription-defined hypertension with 365-day lookback, the PPV was highest for ≥2 prescriptions in ≥2 drug classes (94%) and lowest for ≥1 prescription in ≥1 drug class (85%). The NPV was highest for ≥1 prescription in ≥2 drug classes (94%) and lowest for ≥1 prescription in ≥2 drug classes (80%). The sensitivity was highest for ≥1 prescription in ≥1 drug class (79%) and lowest for ≥2 prescriptions in ≥2 drug classes (30%). The specificity was ≥94% for all algorithms. The PPV and specificity did not change noteworthy with length of lookback period, whereas the NPV and the sensitivity generally were higher for longer lookback. The algorithm ≥1 prescription in ≥2 drug classes with 365-day lookback was among the best balanced across all measures of validity (PPV=88%, NPV=94%, sensitivity=75%, specificity=96%). For hospital-diagnosed hypertension, the PPV was 90%, the NPV was 76%, the sensitivity was 22%, and the specificity was 99%. Conclusion: Compared with self-reported hypertension, the algorithms for prescription-defined and hospital-diagnosed hypertension had high predictive values and specificity, but low sensitivity.

[Importance of aspirin challenges in patients with NSAID-exacerbated respiratory disease]. / Stellenwert von ASS-Provokationen beim Analgetika-Intoleranz-Syndrom.

BACKGROUND: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is often characterized by a severe course of chronic rhinosinusitis with nasal polyps (CRSwNP), comorbid asthma, and NSAID hypersensitivity. The gold standard for N-ERD diagnosis is challenge with acetylsalicylic acid (ASA). In expert recommendations, the diagnosis of N-ERD is established based on a plausible positive history of NSAID hypersensitivity and CRSwNP with asthma. OBJECTIVE: The following review describes the performance of ASA challenges and their sensitivity and specificity. It also examines the extent to which a positive history of NSAID hypersensitivity correlates with ASA challenge results in clinical trials and when ASA challenges should be performed. RESULTS AND CONCLUSION: ASA challenges have high sensitivity and specificity. In clinical ASA challenge studies, there is a high concordance between a positive history of NSAID hypersensitivity obtained by rhinologists and the measured data of ASA challenge in patients with CRSwNP and comorbid asthma. Therefore, ASA challenge is primarily indicated in patients with an unclear history of NSAID hypersensitivity.

Validation of the Cervical Torsion Test and Head Neck Differentiation Test in Patients with Peripheral Vestibular Hypofunction.

OBJECTIVE: This study compared adults with peripheral vestibular hypofunction (VH) to healthy controls and assessed the sensitivity and specificity of the Cervical Torsion Test (CTT) and the Head Neck Differentiation Test (HNDT). This study aimed to determine whether neck problems affected primary outcomes. METHODS: This cross-sectional study included adults from a specialist consultation for dizziness. VH had been diagnosed with the video Head Impulse Test. Exclusion criteria were conditions following head or neck trauma and diseases of the central nervous system. Sensitivity and specificity of the index tests were calculated, and regression analyses were performed to test for contributing factors. RESULTS: A total of 19 patients with VH and a historical cohort of 19 matched healthy controls were included. Most patients with VH (84.2%) experienced symptoms in at least 1 test component, compared to 5.2% of the control group. Of patients with VH, 78.9% had symptoms during the HNDT "en bloc" (en bloc = head and trunk rotated together) whereas only 26.3% reported symptoms during the CTT en bloc. Best discriminatory validity was found for the HNDT en bloc, with a sensitivity of 0.79 (95% CI = 0.54-0.94), a specificity of 0.86 (95% CI = 0.65-0.97), and a positive likelihood ratio of 5.79 (95% CI = 1.97-17.00). The number of symptoms of CTT "in torsion" (in torsion = trunk rotated actively with fixed head) was increased by a factor of 1.13 (95% CI = 1.01-1.27) for every additional point on the Neck Disability Index. CONCLUSIONS: The CTT and HNDT can serve as nonlaboratory tests in patients with dizziness. The HNDT en bloc has the best discriminatory validity, finding those with and those without VH. Symptom reproduction during torsion may help to identify when neck problems may contribute to dizziness. IMPACT: The HNDT en bloc may be useful for ruling VH in or out in patients with dizziness. Positive CTT and HNDT in torsion components may verify the likelihood of additional neck involvement.

CAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT.

BACKGROUND: Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (IKr) and thereby regulate the late repolarization phase. There is an important interindividual susceptibility to develop diLQT, which is of unknown origin but can be reproduced in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). We aimed to investigate the dynamics of hERG channels in response to sotalol and to identify regulators of the susceptibility to developing diLQT. METHODS: We measured electrophysiological activity and cellular distribution of hERG channels after hERG blocker treatment in iPS-CMs derived from patients with highest sensitivity (HS) or lowest sensitivity (LS) to sotalol administration in vivo (ie, on the basis of the measure of the maximal change in QT interval 3 hours after administration). Specific small interfering RNAs and CAVIN1-T2A-GFP adenovirus were used to manipulate CAVIN1 expression. RESULTS: Whereas HS and LS iPS-CMs showed similar electrophysiological characteristics at baseline, the late repolarization phase was prolonged and IKr significantly decreased after exposure of HS iPS-CMs to low sotalol concentrations. IKr reduction was caused by a rapid translocation of hERG channel from the membrane to the cytoskeleton-associated fractions upon sotalol application. CAVIN1, essential for caveolae biogenesis, was 2× more highly expressed in HS iPS-CMs, and its knockdown by small interfering RNA reduced their sensitivity to sotalol. CAVIN1 overexpression in LS iPS-CMs using adenovirus showed reciprocal effects. We found that treatment with sotalol promoted translocation of the hERG channel from the plasma membrane to the cytoskeleton fractions in a process dependent on CAVIN1 (caveolae associated protein 1) expression. CAVIN1 silencing reduced the number of caveolae at the membrane and abrogated the translocation of hERG channel in sotalol-treated HS iPS-CMs. CAVIN1 also controlled cardiomyocyte responses to other hERG blockers, such as E4031, vandetanib, and clarithromycin. CONCLUSIONS: Our study identifies unbridled turnover of the potassium channel hERG as a mechanism supporting the interindividual susceptibility underlying diLQT development and demonstrates how this phenomenon is finely tuned by CAVIN1.

Reliability of IL-6 Alone and in Combination for Diagnosis of Late Onset Sepsis: A Systematic Review.

Diagnosis of neonatal sepsis is difficult due to nonspecific signs and symptoms. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in neonates after 72 h of life in case of late onset sepsis (LOS). We searched for studies regarding IL-6 accuracy for the diagnosis of LOS between 1990 and 2020 using the PubMed database. Following study selection, the reported IL-6 sensitivities and specificities ranged between 68% and 100% and 28% and 100%, with median values of 85.7% and 82% and pooled values of 88% and 78% (respectively) in the 15 studies including 1306 infants. Subgroup analysis revealed a better sensitivity (87% vs. 82%), but not specificity (both 86%), in preterm infants compared to term infants or mixed populations. Early sample collection revealed the highest sensitivity (84%), but had the lowest specificity (86%). To assess quality, we used a STARD checklist adapted for septic neonates and the QUADAS criteria. Limitations of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarkers. We concluded that IL-6 demonstrated good performance especially in the preterm infant population and the best results were achieved by measurements at the time of LOS suspicion.

Two-stage stratified designs with survival outcomes and adjustment for misclassification in predictive biomarkers.

Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.

¿Cómo detectar a los pacientes mayores no institucionalizados en riesgo de malnutrición durante su hospitalización? Comparación de 8 herramientas de cribado de malnutrición o de riesgo nutricional / How to detect non-institutionalized older patients at risk of malnutrition during their hospitalization? Comparison of 8 screening tools for malnutrition or nutritional risk

Antecedentes: La prevalencia de malnutrición es elevada entre la población mayor. El ingreso hospitalario es una ventana de oportunidad para su detección. Objetivo: Valorar la concordancia de distintas escalas nutricionales en pacientes hospitalizados.Método: Estudio prospectivo en pacientes mayores de 65años no institucionalizados ingresados en un servicio de Medicina Interna. Se compararon 5 encuestas de cribado de malnutrición (MNA, MST, MUST, NRS-2000 y CONUT) y 3 encuestas de cribado de riesgo nutricional (SCREEN3, 8 y 14). Como patrón de referencia se utilizó la definición de malnutrición de la Iniciativa Global para el Liderazgo en Malnutrición (GLIM). Resultados: Se incluyeron 85 pacientes (37% mujeres, mediana de edad 83años). El 48% (IC95%: 38-59%) de los pacientes fueron clasificados como malnutridos según criterios GLIM. La escala SCREEN3 fue la más sensible (93%; IC95%: 87-98) y MUST la más específica (91%; IC95%: 85-99). La escala más eficaz para excluir la sospecha de malnutrición fue SCREEN3 (LR− 0,17; IC95%: 0,05-0,53) y la mejor para confirmarla fue MST (LR+ 7,08; IC95%: 3,06-16,39). La concordancia entre las distintas escalas fue baja o muy baja, con índices kappa entre 0,082 y 0,465.Conclusiones: Se precisa un abordaje integral para detectar la malnutrición en adultos mayores ingresados. Las escalas más sensibles son más útiles en el cribado inicial. Las herramientas de riesgo nutricional podrían ser eficaces en esta etapa. En un segundo paso se debe confirmar la malnutrición de acuerdo con criterios establecidos como los de la GLIM.(AU)

Background: The prevalence of malnutrition is high among the elderly population. Hospital admission is a window of opportunity for its detection. Objective: To assess the concordance of different nutritional scales in hospitalized patients. Methods: Prospective study in non-institutionalized patients over 65years of age admitted to an internal medicine department. Five malnutrition screening surveys (MNA, MST, MUST, NRS-2000 and CONUT) and three nutritional risk screening surveys (SCREEN3, 8 and 14) were compared. As gold standard we use the Global Leadership Initiative for Malnutrition (GLIM) definition of malnutrition. Results: Eighty-five patients (37% female, median age 83years) were included. Forty-eight percent (95%CI: 38-59%) of patients were classified as malnourished according to GLIM criteria. The SCREEN3 scale was the most sensitive (93%; 95%CI: 87-98) and MUST the most specific (91%; 95%CI: 85-99). The most effective scale for excluding suspected malnutrition was SCREEN3 (LR− 0.17; 95%CI: 0.05-0.53) and the best for confirming it was MST (LR+ 7.08; 95%CI: 3.06-16.39). Concordance between the different scales was low or very low with kappa indices between 0.082 and 0.465. Conclusions: A comprehensive approach is needed to detect malnutrition in hospitalized patients. More sensitive scales are more useful in initial screening. Nutritional risk tools could be effective at this stage. In a second step, malnutrition should be confirmed according to established criteria such as GLIM.(AU)

Valor diagnóstico del índice de masa corporal en comparación con impedancia bioeléctrica para identificar sobrepeso u obesidad en jóvenes adultos mexicanos / Diagnostic value of body mass index versus bioelectrical impedance analysisfor detection of overweight and obesity among Mexican young adults

Introducción: El índice de masa corporal (IMC) es am-pliamente utilizado para diagnosticar estado de nutrición;pero tiene limitaciones porque no evalúa la grasa corporal. Objetivo: Determinar el valor diagnóstico del IMC en com-paración con impedancia bioeléctrica para identificar sobre-peso y obesidad (SpyOb) en adultos jóvenes mexicanos.Material y métodos: Estudio de validación en adultos jó-venes mexicanos. Se midió talla con estadímetro SECA 215,peso y composición corporal con InBody 270 por personal en-trenado. Se realizaron comparaciones por sexo con U deMann Whitney y Chi2; y correlaciones de Spearman para IMCy porcentaje de grasa corporal total (%GCT). Se calculó sen-sibilidad (s) y especificidad (e) con curvas ROC comparandoIMC y %GCT para diagnosticar SpyOb. Análisis se realizó conStata 14 y valores p<0.05 fueron considerados significativos. Resultados: Se evaluaron 351 universitarios con medianade edad de 19 años. El 42.4% fue diagnosticado con SpyObde acuerdo al IMC, y 48.1% fue identificado en esa mismacondición mediante %GCT; con diferencias significativas porsexo sólo en el diagnóstico por %GCT. La correlación entre IMC y %GCT fue alta para la muestra en general (r=0.68) ymuy alta por sexo (r=0.85 hombres y r=0.81 mujeres). ElAUC para diagnosticar obesidad en mujeres fue de 0.90, conalta sensibilidad (100%) y alta especificidad (80.4%), y paradiagnosticar sobrepeso el AUC fue de 0.52 con baja sensibili-dad (31.5%) y especificidad regular (73.1%). El AUC paradiagnosticar obesidad en hombres fue de 0.84, con alta sen-sibilidad (80%) y alta especificidad (88.9%), y para diagnos-ticar sobrepeso el AUC fue de 0.63, con baja sensibilidad(32.5%) y alta especificidad (94.3%).Conclusiones: Se encontró alta y muy alta correlaciónentre IMC y %GCT, tanto en hombres como en mujeres. ElIMC es un indicador útil y confiable para diagnosticar obesi-dad, pero no para diagnosticar sobrepeso en jóvenes adultos mexicanos.(AU)

Background:The Body Mass Index (BMI) is widely usedfor nutritional status assessment; nevertheless, it has limita-tions due to the fact that it doesn’t evaluate the body fat.Objective: Identify the diagnostic value of the BMI versusBioelectrical Impedance to determinate overweight and obe-sity in young Mexican adults.(AU)