Positive Predictive Value For Detection Research Articles

Elucidating vaccine efficacy using a correlate of protection, demographics, and logistic regression

BackgroundVaccine efficacy (VE) assessed in a randomized controlled clinical trial can be affected by demographic, clinical, and other subject-specific characteristics evaluated as baseline covariates. Understanding the effect of covariates on efficacy is key to decisions by vaccine developers and public health authorities.MethodsThis work evaluates the impact of including correlate of protection (CoP) data in logistic regression on its performance in identifying statistically and clinically significant covariates in settings typical for a vaccine phase 3 trial. The proposed approach uses CoP data and covariate data as predictors of clinical outcome (diseased versus non-diseased) and is compared to logistic regression (without CoP data) to relate vaccination status and covariate data to clinical outcome.ResultsClinical trial simulations, in which the true relationship between CoP data and clinical outcome probability is a sigmoid function, show that use of CoP data increases the positive predictive value for detection of a covariate effect. If the true relationship is characterized by a decreasing convex function, use of CoP data does not substantially change positive or negative predictive value. In either scenario, vaccine efficacy is estimated more precisely (i.e., confidence intervals are narrower) in covariate-defined subgroups if CoP data are used, implying that using CoP data increases the ability to determine clinical significance of baseline covariate effects on efficacy.ConclusionsThis study proposes and evaluates a novel approach for assessing baseline demographic covariates potentially affecting VE. Results show that the proposed approach can sensitively and specifically identify potentially important covariates and provides a method for evaluating their likely clinical significance in terms of predicted impact on vaccine efficacy. It shows further that inclusion of CoP data can enable more precise VE estimation, thus enhancing study power and/or efficiency and providing even better information to support health policy and development decisions.

A New Method for 2D-Adapted Wavelet Construction: An Application in Mass-Type Anomalies Localization in Mammographic Images

This contribution presents a wavelet-based algorithm to detect patterns in images. A two-dimensional extension of the DST-II is introduced to construct adapted wavelets using the equation of the tensor product corresponding to the diagonal coefficients in the 2D discrete wavelet transform. A 1D filter was then estimated that meets finite energy conditions, vanished moments, orthogonality, and four new detection conditions. These allow, when performing the 2D transform, for the filter to detect the pattern by taking the diagonal coefficients with values of the normalized similarity measure, defined by Guido, as greater than 0.7, and α=0.1. The positions of these coefficients are used to estimate the position of the pattern in the original image. This strategy has been used successfully to detect artificial patterns and localize mass-like abnormalities in digital mammography images. In the case of the latter, high sensitivity and positive predictive value in detection were achieved but not high specificity or negative predictive value, contrary to what occurred in the 1D strategy. This means that the proposed detection algorithm presents a high number of false negatives, which can be explained by the complexity of detection in these types of images.

Abstract 17700: Double Trouble With Identification of Isolated Sub-Segmental Pulmonary Embolism Using ICD-10 Discharge Diagnosis Codes: The PE-EHR+ Study

Introduction: International Classification of Diseases 10 th revision (ICD-10) discharge diagnosis codes are widely used for research studies that use electronic databases. The accuracy of the codes for identifying patients with isolated sub-segmental pulmonary embolism (issPE) is unknown. Methods: We used data from the Mass General Brigham (MGB) health system (01/2016-12/2021) and included 1,734 patients randomly selected from 3 groups: Patients with ICD-10 Principal Discharge Diagnosis codes for PE, patients with secondary Discharge Diagnosis codes for PE, and patients with no ICD-10 codes for PE. Weighted estimates were obtained by considering the total number of hospitalizations in each category at MGB hospitals. Accuracy of the codes was assessed by two independent physicians who reviewed discharge summaries, daily notes, and radiology reports. Results: Of 1,734 records reviewed, 1,712 were included (age: 60.6±17.8 years, 52.3% female). Manual chart review found 865 patients with acute PE, including 104 (12.0%) with issPE. Of these 104 patients, 103 (98.3%) had ICD-10 codes for PE. However, only in 15 (14.6%) cases, PE codes were specified as being limited to subsegmental vessels (issPE). In turn, in another 43 cases, Principal-or-secondary ICD-10 codes for issPE were listed but the patients did not have acute issPE during index hospitalization per review of records. The sensitivity and specificity for issPE codes in Principal or secondary discharge position were 14.4% and 97.3% (Table, panel A). Positive predictive value in the weighted sample was only 26.2% (Table, panel B). Conclusions: ICD-10 codes are insensitive and have a poor positive predictive value for detection of isolated subsegmental PE and should not be used for case identification for research purposes or quality improvement initiatives.

Utility of Ultrasound Imaging Features in Diagnosis of Breast Cancer

Background Currently, breast cancer (BC) is considered one of the most prevalent cancer worldwide in women and represents a global health challenge. Early diagnosis is the keystone in the management of BC patients. This study aims to assess the utility of ultrasonography (US) features of malignancy in the diagnosis of BC. Methods This retrospective cross-sectional study involved the electronic records of 326 female patients who were diagnosed with BC. A cross-tabulation test was performed to identify the association between the presence of each US feature (yes/no), and the final US diagnosis (benign/malignant). The strength of association of each feature was measured using the odds ratio (OR) which was assumed to be significant when > 1, with a 95% confidence interval (CI). Results The mean age of the female patients involved in this study was 45.36 ±12.16 years old (range, 17-90 years). Cross-tabulation test showed a significant association between the malignancy tumor and the irregular shape of the lesion (p < 0.001, OR=7.162, CI 2.726-18.814), non-circumscribed margins (p < 0.001, OR = 9.031, CI 3.200-25.489), tissue distortion (p < 0.001, OR = 18.095, CI 5.944-55.091), and the lymph node enlargement (p < 0.001, OR = 5.705, CI 2.332-13.960). Conclusion US imaging features of malignancy have a high sensitivity and positive predictive value for detection of the BC. However, the specificity of breast US imaging features is much lower because of the overlapping features in benign and malignant breast lesions. Breast lesions with an irregular shape, not circumscribed irregular or spiculated margins, hypo-echogenicity, tissue distortion, and those with lymphadenopathy have the highest likelihood of malignancy despite the low specificity. US is a highly valuable, safe, and affordable imaging modality with high diagnostic accuracy for BC.

Visual Inspection of Cervix wiih Acetic Acid as A Method of Cervical Cancer Screening in Tertiary Hospital

Background: Cervical cancer belongs to a glorious natural history which favors well implemented secondary prevention. Considering the various constraints in our country, our study aimed to evaluate Visual Inspection of Cervix with Acetic Acid (VIA) as an alternative or adjunct to cervical cytology (Pap smear) in early detection of cervical cancer and also to assess its effectiveness as a screening method in a tertiary center outside of low resource settings.
 Materials and methods: This cross-sectional descriptive study was carried out at Gynae OPD of Chittagong Medical College Hospital (CMCH) from January to December 2012. A total of 1600 sexually active women with 21 to 60 years old were enrolled in this study by purposive sampling technique. The women underwent a complete clinical evaluation, including Pap smear and VIA. Any positive test was referred to colposcopy and directed biopsy. Finally, data were analyzed with the help of SPSS 16 software.
 Results: Out of 1600, VIA was positive in 135(8.4%) and cytology was positive in 74(4.6%) cases of the true positive 48 cases. The sensitivity of VIA (75%) was much higher than that of Pap smear (48%). The sensitivity ratio 1.54 (p<0.001). The positive predictive value for detection of CIN2 and above was 17% for VIA and 16% for pap (p=0.5). Moreover, patients of lost to follow-up before colposcopy and biopsy were only 4.44% with VIA positive cases while 28.38% with positive Pap smear (p<0.0001).
 Conclusions: The high sensitivity of VIA indicates that it may be a feasible alternative test for detection of precancerous lesions of the cervix not only in limited-resource settings but also in a well-equipped tertiary hospital.
 IAHS Medical Journal Vol 4(2), June 2021; 22-26

Intrapartum cardiotocographic monitoring and its correlation with neonatal outcome.

Despite the advancements in perinatal care in past decades, perinatal asphyxia remains a serious problem leading to significant perinatal morbidity and mortality. Therefore, foetal monitoring during the intrapartum period is of paramount importance. Among various methods of fetal monitoring, cardiotocography is a form of electronic foetal monitoring in which there is simultaneous recording of foetal heart rate and uterine contractions. This cross-sectional observational study was done in the labour room and neonatal intensive care unit (NICU) of a teaching Municipal Hospital in North India including 500 pregnant women of age group 18-45 years with singeleton fetus of gestation ≥36 weeks without any known congenital anomaly. Intrapartum cardiotocography (CTG) for 20 minutes was done within 12 hours prior to delivery and babies born to them were observed for birth asphyxia as Apgar score <7 at 1 minute as per using APGAR score less than 7 at 1 minute as per south east asia regional neonatal perinatal database (SEAR-NPD), world health organization (WHO) working definition. CTG tracing was normal/reassuring in 92% of pregnant women, nonreassuring in 7% and was abnormal in only 1%. In patients with abnormal and nonreassuring CTG, delivery by lower segment cesarian section (LSCS) was significantly high (P < .0001). APGAR scoring was done at 1 minute and 5 minutes of life, it was found that 4% babies were having score less than 7 at 1 minute with incidence of birth asphyxia 40 per 1,000 live births Neonatal seizure was significantly more in nonreassuring and abnormal CTG group (P value <.0001). Abnormal CTG tracings result in higher incidence of operative interventions for deliveries. Abnormal CTG pattern during intrapartum CTG has high specificity and negative predictive value but has low sensitivity and positive predictive value for detection of birth asphyxia and need for NICU admission.

Comparison of initial and second opinion reads of multiparametric magnetic resonance imaging of the prostate for transperineal template-guided biopsies with MRI-Ultrasound fusion

PurposeTo investigate the value of second-opinion evaluation of multiparametric prostate magnetic resonance imaging (MRI) by subspecialised uroradiologists for the detection of significant cancer in transperineal fusion prostate biopsy. MethodsThe evaluated data included age, PSA (ng/ml), PSA density, Gleason score, digital rectal examination (DRE), prostate volume of 149 patients. Twenty-seven patients (18%) had no previous prostate biopsy, 114 patients (77%) had a previous negative biopsy, and 8 patients (5%) were on active surveillance. Using PI-RADS v2 scores for mpMRI a second report was performed by a specialist uroradiologist. In all cases a subsequent transperineal biopsy was performed with at least 2 cores per target and additional background systemic cores. Initial and second-opinion radiology reports were evaluated for detection of any cancer and Gleason score (GS) 7-10 cancer, including positive predictive value and negative (NPV) and compared by Fisher's exact test. ResultsAt transperineal biopsy, 51 % (76/149) of patients had a GS 6-10 prostate cancer (PCa), 27 % (40/149) of patients had a GS 3 + 3 PCa and 12 % (18/149) a GS 3 + 4 and 12 % (18/149) had a GS ≥4 + 3 PCa. Agreement between initial and second-opinion reads was observed in 57.7% (86/149; kappa value = 0.32). The detection of clinically significant cancers with second-opinion reads was significantly higher (0.61; 17/28) compared to initial reads (0.35; 17/49); P = 0.034. ConclusionsSecond reading of prostate mpMRIs by subspecialised uroradiologists significantly improved the positive predictive value for detection of clinically significant prostate cancer and showed a trend towards improved NPV for MRI-negative cases where biopsy could be safely avoided. Urologists should be aware that the experience of the reporter will affect the report when making decisions if and how to obtain biopsies. Reporter experience may help to reduce overcalling and avoid over-targeting of lesions.

Diagnostic value of [18F]Fluorocholine PET/CT in detection of primary medullary thyroid cancer.

Medullary thyroid cancer (MTC) is a challenging neuroendocrine malignancy where the role of nuclear medicine imaging is currently limited. This paper investigates the potential diagnostic value of [18F]Fluorocholine PET/CT in primary MTC. We prospectively enrolled 25 patients (10 male, 15 female) with suspicion for primary MTC based on fine-needle aspiration biopsy (FNAB). All patients had a baseline three phase [18F]Fluorocholine PET/CT (2.5MBq/kg): two regional head and neck and upper mediastinum studies at 5min (first phase) and 120min (third phase) and a whole-body PET/CT (from the skull vertex to mid-thighs) at 60min (second phase). Any non-physiological radiotracer uptake was regarded as MTC positive. All patients referred to surgery had a preoperative neck-US. True lesion status was assessed using either histopathology, FNAB results or follow-up imaging and laboratory (calcitonin, CEA) results. Results with p < 0.05 were considered statistically significant. Nineteen of 25 patients (76%) were surgically treated and histopathology reports were obtained. Patient-based sensitivity and positive predictive value for detection of any MTC lesion using [18F]Fluorocholine PET/CT were both 100%. Neck-US was more specific (100% vs 70%; p = 0.002) and had a higher positive predictive value than [18F]Fluorocholine PET/CT (100% vs 55%; p = 0.018) for N1a and N1b staging. [18F]Fluorocholine PET/CT had a higher sensitivity (100% vs 50%; p = 0.025) and higher negative predictive value (100% vs 81%; p = 0.026) than neck-US for N1b staging. The optimal SUVmax cut-off to differentiate malignant from benign neck lesions at 60 and 120min was 2.56. Patients with M1 stage on PET/CT had higher calcitonin (median of 5,372 vs 496.6pg/ml; p = 0.005) and CEA concentrations (median of 95.8 vs 18.65µg/l; p = 0.034) compared to patients with M0 disease. [18F]Fluorocholine PET/CT appears to be a promising radiotracer for primary staging of MTC by increasing diagnostic accuracy for N staging and detecting possible distant metastatic sites at initial presentation of disease.

Reflex cytology for triage of high-risk human papillomavirus positive self-sampled material in cervical cancer screening: a prospective cohort study.

ObjectiveHigh‐risk human papillomavirus (HrHPV)‐positive women detected by self‐sampling require an extra visit at the general practitioner for additional cytology testing, but the loss to follow up within this triage is substantial. The aim of this study was to evaluate the clinical utility of reflex cytology on hrHPV‐positive self‐samples for immediate stratification of women who need referral for colposcopy.DesignA prospective cohort study.SettingTwo Dutch cervical cancer‐screening laboratories.Population1014 screenees who tested hrHPV‐positive on self‐samples between 1 December 2018 and 1 August 2019.MethodsSelf‐samples were directly used for cytological analysis. Cytological and histological outcomes during follow up were obtained from the Dutch Pathology Registry (PALGA).Main outcome measuresTest performance of reflex cytology on self‐samples was determined for different thresholds and compared with physician‐taken cytology and histological outcomes.ResultsReflex cytology on self‐samples for detecting abnormal cytology showed a sensitivity of 26.4% (95% CI 21.8–31.3) and specificity of 90.5% (95% CI 87.7–92.8). Of all ≥CIN2 cases, 29.4% (95% CI 22.5–37.1) were detected with reflex cytology on self‐samples. The positive predictive value for detection of ≥CIN2 was higher with cytology on self‐collected samples than on physician‐collected samples. Of women who were lost to follow up, 12.9% were found to have abnormal cytology on their self‐sampled material.ConclusionCytology testing is achievable on hrHPV‐positive self‐samples, could decrease the loss to follow up in screening and is easily implementable in the current clinical practice. Of all hrHPV‐positive women with abnormal cytology on additional physician‐collected samples, 26.4% could have been directly referred for colposcopy if triage with reflex cytology on self‐sampled material had been performed.Tweetable abstractReflex cytology for triage of hrHPV+ self‐samples is of added value for direct referral of women for colposcopy.

Peri-thrombus vascular hyperintensity sign: detection of intracranial thrombus location and length in acute ischemic stroke.

The aim of the study was to investigate the diagnostic accuracy of peri-thrombus vascular hyperintensity sign (PVHS) on three-dimensional (3D) black-blood (BB) contrast-enhanced MRI for the detection of intracranial thrombus location and length in acute ischemic stroke (AIS) patients. Consecutive AIS patients who underwent MRI including 3D BB contrast-enhanced MRI sequence within 8h of clinical onset were prospectively evaluated. Two readers independently reviewed the 3D BB contrast-enhanced MRI data to assess the presence and location of PVHS. Findings were compared with those of contrast-enhanced MR angiography (CE-MRA) as the reference standard. The PVHS was identified in 49% (63/129) of AIS patients with good agreement. The PVHS had 100% specificity, 88% negative predictive value, 89% sensitivity, and 100% positive predictive value for detection of acute arterial occlusions. Eight patients showed discordant thrombus locations between 3D BB contrast-enhanced MRI and CE-MRA. Median thrombus length in patients with complete occlusion was 9.61mm. The PVHS on 3D BB contrast-enhanced MRI is a highly specific tool for evaluating the location and length of a thrombus in AIS patients.

Bivartect: accurate and memory-saving breakpoint detection by direct read comparison.

MotivationGenetic variant calling with high-throughput sequencing data has been recognized as a useful tool for better understanding of disease mechanism and detection of potential off-target sites in genome editing. Since most of the variant calling algorithms rely on initial mapping onto a reference genome and tend to predict many variant candidates, variant calling remains challenging in terms of predicting variants with low false positives.ResultsHere we present Bivartect, a simple yet versatile variant caller based on direct comparison of short sequence reads between normal and mutated samples. Bivartect can detect not only single nucleotide variants but also insertions/deletions, inversions and their complexes. Bivartect achieves high predictive performance with an elaborate memory-saving mechanism, which allows Bivartect to run on a computer with a single node for analyzing small omics data. Tests with simulated benchmark and real genome-editing data indicate that Bivartect was comparable to state-of-the-art variant callers in positive predictive value for detection of single nucleotide variants, even though it yielded a substantially small number of candidates. These results suggest that Bivartect, a reference-free approach, will contribute to the identification of germline mutations as well as off-target sites introduced during genome editing with high accuracy.Availability and implementationBivartect is implemented in C++ and available along with in silico simulated data at https://github.com/ykat0/bivartect.Supplementary information Supplementary data are available at Bioinformatics online.

Human papillomavirus (HPV) DNA and mRNA primary cervical cancer screening: Evaluation and triaging options for HPV-positive women.

Objective Cervical cancer is the second most common cancer in Thai women; human papillomavirus (HPV) is the main cause. This study aimed to determine the clinical performance of HPV mRNA compared with HPV DNA testing. Methods Cervical specimens were collected from women aged 35 to 60 who attended the routine organized screening programme. We compared accuracy parameters of standalone HPV mRNA and HPV DNA tests, and those of triaging with liquid-based cytology or HPV genotyping and liquid-based cytology for those positive only for the less oncogenic HPV types. Test accuracy parameters were estimated using latent class analysis using Bayesian models. Results Of the 5046 women enrolled, 174 (3.4%) were HPV DNA positive and 141 (2.8%) HPV mRNA positive. Colposcopy compliance was 95.4% ( n = 166) among HPV DNA-positive women and 94.3% ( n = 133) among those HPV mRNA positive. The estimated sensitivity, specificity, and positive predictive value for detection of CIN2 or worse were 67.4%, 97.1%, 12.1% for HPV DNA testing, and 73.1%, 97.8%, 16.3% for HPV mRNA testing. These estimates for triaging of HPV DNA-positive women with liquid-based cytology were 64.4%, 98.8%, and 19.0%, respectively, and slightly better for liquid-based cytology triage of HPV mRNA-positive women, at 71.8%, 98.9%, and 22.1%. Conclusion A triaging strategy based on HPV genotyping and liquid-based cytology for those positive only for the less oncogenic HPV types had test characteristics comparable with that of liquid-based cytology triage. The HPV mRNA detection-based strategies had non-significant advantages over the HPV DNA detection-based strategies.

Author Reply

We appreciate the thoughtful response to our study findings and agree that the medical community should re-evaluate the American Academy of Pediatrics guidelines for febrile urinary tract infections. While the guidelines rely on the use of renal and bladder ultrasound findings to determine the need for VCUGs, several previous investigations have shown that ultrasound findings are a poorly predictive of VCUG abnormalities. Hoberman et al determined that identification of urinary tract dilation on renal ultrasound following the first febrile urinary tract infection had only a 10% sensitivity and 40% positive predictive value for detection of vesicoureteral reflux on VCUG among 302 children. 1 Hoberman A Charron M Hickey RW Baskin M Kearney DH Wald ER Imaging studies after a first febrile urinary tract infection in young children. N. Engl. J. Med. 2003; 348: 195-202 Crossref PubMed Scopus (562) Google Scholar These results were corroborated by Juliano et al, who reported evidence of dilating vesicoureteral reflux among 23/84 children with a normal renal ultrasound. 2 Juliano TM Stephany HA Clayton DB et al. Incidence of abnormal imaging and recurrent pyelonephritis after first febrile urinary tract infection in children 2 to 24 months old. J. Urol. 2013; 190: 1505-1510 Crossref PubMed Scopus (40) Google Scholar A larger study by Logvinenko et al revealed that renal ultrasound had a sensitivity of only 32% for detecting grade 3-5 vesicoureteral reflux among nearly 4000 patients. The group concluded that ultrasound was a poor screening tool for diagnosis of high-grade vesicoureteral reflux. 3 Logvinenko T Chow JS Nelson CP Predictive value of specific ultrasound findings when used as a screening test for abnormalities on VCUG. J Pediatr Urol. 2015; 11 (e171-177): 176 Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar The use of renal ultrasound findings to guide VCUG administration, therefore, should be called into question. It is perhaps for this reason that guideline adherence did not improve vesicoureteral reflux detection among children aged 2-24 months in our patient cohort.

Diagnostic Accuracy of a MR Protocol Acquired with and without Endorectal Coil for Detection of Prostate Cancer: A Multicenter Study

Introduction: The purpose of this study was to compare diagnostic accuracy of a prostate multiparametric magnetic resonance imaging (mpMRI) protocol for detection of prostate cancer between images acquired with and without en-dorectal coil (ERC). Materials: This study was approved by the regional ethics committee. Between 2014 and 2015, 33 patients (median age 51.3 years; range 42.1-77.3 years) who underwent prostate-MRI at 3T scanners at 2 different institutions, acquired with (mpMRI_ERC) and without (mpMRI_PPA) ERC and who received radical prostatectomy, were included in this retrospective study. Two expert readers (R1, R2) attributed a PI-RADS version 2 score for the most suspect (i. e. index) lesion for mpMRI_PPA and mpMRI_ERC. Sensitivity and positive predictive value for detection of index lesions were assessed using 2 × 2 contingency tables. Differences between groups were tested using the McNemar test. Whole-mount histopathology served as reference standard. Results: On a quadrant-basis cumulative sensitivity ranged between 0.61-0.67 and 0.76-0.88 for mpMRI_PPA and mpMRI_ERC protocols, respectively (p > 0.05). Cumulative positive predictive value ranged between 0.80-0.81 and 0.89-0.91 for mpMRI_PPA and mpMRI_ERC protocols, respectively. The differences were not statistically significant for R1 (p = 0.267) or R2 (p = 0.508). Conclusion: Our results suggest that there may be no significant differences for detection of prostate cancer between images acquired with and without an ERC.

Siewert type I and II oesophageal adenocarcinoma: sensitivity/specificity of computed tomography, positron emission tomography and endoscopic ultrasound for assessment of lymph node metastases in groups of thoracic and abdominal lymph node stations.

In Siewert type I/II oesophageal adenocarcinoma, the sensitivity and specificity of computed tomography (CT), positron emission tomography (PET)-CT and endoscopic ultrasound (EUS) for assessment of the N descriptor in defined groups of lymph nodes were investigated. CT, PET/CT, EUS images and the pathological data of 101 oesophageal adenocarcinomas submitted to primary resection were compared. The lymph nodes were identified as (a) right paratracheal/subcarinal/pulmonary ligament; (b) paraoesophageal; (c) paracardial; (d) left gastric artery, lesser curvature; (e) coeliac trunk, hepatic/splenic artery. Of the 2451 lymph nodes identified, 273 (11.1%) were histologically positive. Overall sensitivity, specificity and negative and positive predictive value for detection of lymph nodes metastatic were respectively: CT sensitivity 39%, specificity 86%, negative 58% and positive 74% predictive value; PET/CT sensitivity 30%, specificity 98%, negative 58% and positive 93% predictive value; EUS sensitivity 50%, specificity 81%, negative 72% and positive 62% predictive value. The sensitivity of CT, PET/CT and EUS in the thoracic nodal groups (a) and (b) was, respectively, 58.3%, 7.1% and 87.5% and 33.3%, 20% and 80%. Sensitivity was below 47% for all tests in the abdominal nodal groups. In contrast, specificity (88.6-100%) was super imposable in all nodal groups. The strength of agreement among the 3 imaging techniques was poor (kappa < 0.30) for the thoracic anatomical groups of interest: (a) lower paratracheal/subcarinal/pulmonary ligament and (b) paraoesophageal; it was moderate/good (kappa >0.30) for the abdominal N groups of interest: c, d and e. The diagnostic performance of CT, PET and EUS for assessing the N descriptor in the paracardial and abdominal stations close to the primary tumour is not satisfactory. EUS can efficiently assess the presence/absence of nodal metastases in the thoracic stations. ClinicalTrials.gov number: NCT03529968.

Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory

Since its debut in 2011, cell-free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex-chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre- and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. The objective of this study was to determine the positive predictive value and false-positive rates for different chromosomal abnormalities identified by cell-free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. We tested 712 patient samples sent to our laboratory to confirm a cell-free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell-free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome-wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false-positive rates were calculated from tabulated data. The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for 1p36 deletion syndrome and 21% for 22q11.2 deletion syndrome. Detection of sex chromosomal aneuploidies had positive predictive values of 26% for monosomy X, 50% for 47,XXX, and 86% for 47,XXY. The positive predictive values for detection of common autosomal and sex chromosomal aneuploidies by cell-free fetal DNA screening were comparable with other studies. Identification of microdeletions was associated with lower positive predictive values and higher false-positive rates, likely because of the low prevalence of the individual targeted microdeletion syndromes in the general population. Although the obtained positive predictive values compare favorably with those seen in traditional screening approaches for common aneuploidies, they highlight the importance of educating clinicians and patients on the limitations of cell-free fetal DNA screening tests. Improvement of the cell-free fetal DNA screening technology and continued monitoring of its performance after introduction into clinical practice will be important to fully establish its clinical utility. Nonetheless, our data provide valuable information that may aid result interpretation, patient counseling, and clinical decision making/management.

Clinical value of fluorine-18\u03b1-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

BackgroundWe investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (18F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (18F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs).ResultsMedian T/N ratio of 18F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs (p = 0.006). Both T/N ratio (p = 0.016) and maximum standardized uptake value (p = 0.033) of 18F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cut-off of 3.37 for the T/N ratio of 18F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of 18F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of 18F-FDG PET was positively correlated (rs = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of 18F-FDG and 18F-FAMT (rs = 0.454, p = 0.004), but median T/N ratio of 18F-FAMT PET was significantly higher than that of 18F-FDG PET in all grades of glioma.ConclusionsThe T/N ratio of 18F-FAMT uptake has high positive predictive value for detection of HGGs. 18F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to 18F-FDG PET in both LGGs and HGGs. Therefore, 18F-FAMT is a useful radiotracer for the preoperative visualization of gliomas.

Pitfalls in the identification of Enterococcus species and the detection of vanA and vanB genes.

The aims were to assess the performance of Vitek 2 in identifying enterococcal species and the implementation of GeneXpert(®) vanA/vanB PCR for the detection of vancomycin-resistant enterococci (VRE). Gram-positive cocci from clinical and environmental specimens (n=431) suspicious of being enterococci by conventional methods were evaluated by Vitek 2. This system identified 296 Enterococcus faecium, 87 Enterococcus faecalis, 10 Enterococcus villorum, 9 Enterococcus gallinarum, 9 Enterococcus durans, 5 Enterococcus casseliflavus, 1 Enterococcus spp. and 14 isolates as Non-Enterococcus. All strains were submitted to pulsed field gel electrophoresis (PFGE) analysis showing 64 banding patterns. Representative strains from each banding pattern were further characterized to species level by 16S rDNA sequencing. The misidentification rate by Vitek 2 to species level among 429 molecularly identified enterococci was 6% (26 isolates). Additionally, 372 rectal swabs were obtained from critically ill patients. They were evaluated for the presence of VRE by ChromID VRE combined with in-house PCR vs GeneXpert(®) . GeneXpert(®) showed high (>92%) sensitivity, specificity, accuracy for vanA-positive Enterococcus detection, as well as, sensitivity and specificity for vanB-positive strains. Positive predictive value for detection of vanB-positive enterococci by GeneXpert(®) vanA/vanB was low (30%). GeneXpert(®) showed the same efficacy as ChromID VRE in detecting vanA-positive enterococci, but lower for vanB-gene detection. The study shows that even though the performance of Vitek 2 Advanced Expert System was good in identifying enterococci to species level, it is important to verify results by a molecular method when phenotypic findings are discordant with epidemiologic patterns. Furthermore, GeneXpert(®) vanA/vanB PCR and ChromID VRE combined with in-house PCR were applied in rectal samples for the detection of VRE colonization among critically ill patients. GeneXpert(®) showed an excellent performance in detecting vanA-positive enterococci, but false-positive results for vanB-gene detection render its application problematic in departments with high incidence of vanB-positive enterococci.

Positive predictive value of endometrial polyps in Pipelle aspiration sampling: a histopathological study of 195 cases

ObjectiveTo estimate the positive predictive value of Pipelle endometrial sampling in detecting the presence of an underlying endometrial polyp. The secondary objective is to examine the histologic features that can predict the presence of endometrial polyps. Study designThis is a retrospective case review study. 195 women who had undergone diagnostic hysteroscopy and/or polypectomy were identified in a University teaching hospital. All patients had a prior polyp diagnosis in the Pipelle endometrial sample. The histology of these samples were compared and analyzed with subsequent DH findings and final hysteroscopic biopsies. Slides were reviewed by 2 gynaecological pathologists. Results162 women were premenopausal (mean age 46.1, SD=4.6) and 33 were postmenopausal (mean age 57.2, SD=8.1). The commonest indication for a Pipelle endometrial sampling was abnormal uterine bleeding. Presence of polyp was confirmed by DH in 56.3% (111/195) cases. Of these, 81.1% (90/111) were confirmed histologically. The positive predictive value of detection of polyps in Pipelle endometrial samples for premenopausal and postmenopausal women was 53.7% and 72.7%, respectively (p=.05). The most reliable histologic features that can predict the presence of an underlying polyp was fibrous stroma (p=.01) and focal glandular clustering (p=.03). The prevalence of endometrial hyperplasia and carcinoma in women who was confirmed to have polyp was 11.7% (13/111). ConclusionThe positive predictive value of Pipelle endometrial samples in detecting endometrial polyps was 56.3%. It was higher in the postmenopausal women (72.7%) compared to premenopausal women (53.7%). The prevalence of endometrial hyperplasia and carcinoma in women who was confirmed to have polyp was consistent with the rate reported in the literature. Using ultrasonography as an adjunct maybe helpful in diagnosing endometrial polyps.

Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100% specificity and 100% positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92% for SLe(a) and 64 and 70% for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78%, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.