Negative Predictive Value For Detection Research Articles

Reproducibility of Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT) as a screening test for the detection of b thalassemia and Hemoglobin E traits with the variation of reading time

Background: Though 0.36% NaCl buffered solution has been used as an effective reagent for carrying out Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT) as a screening test for the detection of b thalassemia and Hemoglobin E traits, reading time for its interpretation is yet to be settled. Methods: This cross -sectional analytic study was done at Department of Pediatric Hematology and Oncology, BSMMU from January 2006-June 2007. NESTROFT was performed in 3 separate tubes for each of the 100 subjects (with â thalassemia trait and HbE trait and normal hemoglobin) with 0.36% NaCl buffered solution and reading was taken at different time at 5-minute, 15-minuteand 30-minute. Results were recorded as positive and negative. Hb electrophoresis, Hemogram with RBC indices for each sample and iron profile of selected subjects were done. Results: Among the 100 study subjects, 48 were carriers (18 were â thalassemia traits, 30 were Hb E traits). Age range was 1 to 52 yrs. Mean Hemoglobin concentration, MCV, MCH of both b thalassemia and Hb E carrier were significantly lower than normal subjects (p values <. 001). At 5-minute observation, NESTROFT was positive in 17 out of 18 â thalassemia traits with a sensitivity of 94.4%, 24 out of 30 HbE traits gave positive result with a sensitivity of 80%. Among the 52 normal subjects 35 gave negative result with a specificity of 67%. Positive predictive value and negative predictive value for detection of b thalassemia traits and HbE traits were 50% & 97% and 58% and 85%respectively. Result of NESTROFT interpreted at 15-minute and 30-minute did not show any change. Conclusion: From this study it may be concluded that for interpretation of NESTROFT reading at 5-minute would be optimum. BANGLADESH J CHILD HEALTH 2022; VOL 46 (3) : 130-137

Evaluation of MRI in the diagnostic accuracy of extrahepatic metastases in neuroendocrine tumors in comparison with the reference standard somatostatin-receptor-PET/CT.

The aim of this study was to compare the diagnostic performance of different sets of MR sequences in detecting extrahepatic disease of NETs on routine liver magnetic resonance imaging (MRI). One hundred twenty-seven patients with NETs with and without hepatic and extrahepatic metastases who underwent liver MRI and SSTR-PET/CT were retrospectively analyzed. Two radiologists evaluated in consensus in four sessions: (1) non-contrast T1w+T2w (NC), (2) NC+DWI, (3) NC+ contrast-enhanced T1w (CE), and (4) NC+DWI+CE the presence and number of metastases (lymph nodes, bone, peritoneal surface, lung base, and abdominal organ). Sensitivity, specificity, positive, and negative predictive value for detection of metastases were calculated for each session in a patient-based manner; detection and error rates were calculated for lesion-based analysis. Comparison between the MR-sessions and positron emission tomography-computed tomography (PET/CT) was performed with the McNemar test. Regarding all 1,094 lesions detected in PET/CT, NC+DWI, and NC, CE+DWI identified most true-positive lesions 779 (71%) and 775 (71%), respectively. Patient-based analysis revealed significantly higher sensitivity by NC+DWI (85%) than NC and NC+CE (p = 0.011 and 0.004, respectively); the highest specificity was reached by NC+CE+DWI (100%). Site-based analysis revealed highest detection rates for lymph node metastases for NC+DWI and NC, CE+DWI (73 and 76%, respectively); error rates were lower for NC, CE+DWI with 5% compared with 17% (NC+DWI). Detection rates for bone metastases were similarly high in NC+DWI and NC, CE+DWI (75 and 74%, respectively), while CE showed no benefit. For peritoneal metastases highest sensitivity was reached by NC+DWI (67%). The combination of NC+DWI showed better sensitivities than the combination of NC+CE. NC+DWI showed similar, sometimes even better sensitivities than NC+CE+DWI, but with lower specificities.

Diagnostic ultrasound of the chest wall in the symptomatic patient after mastectomy

BackgroundLack of standardized imaging recommendations among mastectomy patients has led to variability in how recurrences are detected. ObjectiveTo describe the findings and assess the diagnostic efficacy of ultrasound in the evaluation of symptomatic post-mastectomy patients. Materials and methodsThis single institution, retrospective study included 749 consecutive diagnostic chest wall ultrasound examinations performed in mastectomy patients, from January 2016 to June 2017. Chest wall ultrasound evaluated the mastectomy bed with or without reconstruction. Electronic health records were queried for the primary breast cancer histology prior to mastectomy, clinical symptoms prompting the diagnostic ultrasound, ultrasound findings, subsequent cytology and pathology, and follow-up data. Excluded were patients with a known recurrence, asymptomatic patients, and those with <2 years of clinical or imaging follow-up. Descriptive and comparative statistical analyses were performed. ResultsAmong the 749 ultrasounds performed, 58 malignancies were identified for a 7.7% (58/749) malignancy rate, with a median tumor size of 20 mm.Patients diagnosed with a malignancy most often presented with a palpable abnormality (79.3%, 46/58) or skin changes (13.8%, 8/58) and rarely with pain (1.7%, 1/58). Patients who underwent a biopsy yielding a benign result most often presented with a palpable abnormality (41.5%, 287/691), pain (25.6%,177/691), or postoperative swelling/suspected fluid collection (17.8%, 123/691).Diagnostic ultrasound yielded a 91.4% sensitivity (95% CI 81.0, 97.1), 96.1% specificity (95% CI 94.4, 97.4), 66.3% PPV3 (95% CI 57.4, 74.1), and 99.3% negative predictive value (95% CI 98.3, 99.7) for cancer detection. There were 5 false negative ultrasound cases after a skin punch biopsy was performed due to clinically suspicious skin changes. ConclusionsChest wall ultrasound has a high sensitivity and negative predictive value for detection of breast cancer recurrence in symptomatic patients after mastectomy. Skin changes remain an important clinical manifestation of a cancer recurrence.

Tumor Fraction Correlates With Detection of Actionable Variants Across > 23,000 Circulating Tumor DNA Samples.

Profiling of circulating tumor DNA (ctDNA) is increasingly adopted in the management of solid tumors, concurrent with increased availability of more comprehensive ctDNA panels. However, variable ctDNA shed can result in variable assay sensitivity. We studied the relationship between ctDNA tumor fraction (TF) and detection of actionable alterations across cancer types. A total of 23,482 liquid biopsies (LBx) submitted between September 2020 and October 2021 were sequenced using a hybrid capture panel that reports genomic alterations (GAs) and genomic biomarkers across 324 cancer-related genes. The primary end points were the prevalence of targetable GAs by cancer type and detection in relationship to ctDNA TF. Sensitivity of detection in LBx was assessed in 1,289 patients with available tissue results. 94% (n = 22,130) of LBx had detectable ctDNA, with a median TF of 2.2%. LBx profiling detected GAs in National Comprehensive Cancer Network category 1 genes in 37% of lung, 30% of prostate, 36% of breast, and 51% of colon cancer cases. Potential germline GAs flagged on clinical reports were detected in genes including BRCA1/2, PALB2, CHEK2, and ATM. Polyclonal mutations in genes associated with resistance such as AR, ESR1, RB1, and NF1 were detected. The sensitivity of LBx to detect driver alterations identified in tissue biopsy from the same patient ranged from 58% to 86% but was consistently at or near 100% in cases with TF ≥ 10%. Elevated ctDNA shed is associated with both high sensitivity and negative predictive value for detection of actionable GAs. The presence of elevated TF suggests adequate tumor profiling and may reduce the value of subsequent reflex to confirmatory tissue testing in patients with negative LBx results.

Global longitudinal strain for detection of cardiac iron overload in patients with thalassemia: a meta-analysis of observational studies with individual-level participant data

BackgroundAlthough cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO).MethodsWe searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist.ResultsA total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76–2.4], p = 0.001, I2 = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91–3.5], p = 0.001, I2 = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6–0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO.ConclusionsAccording to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients.Graphical

A Rapid Cytological Screening as pre-Endoscopy Screening for Early Esophageal Squamous Cell Lesions: A Prospective Pilot Study from a Chinese Academic Center.

Background: Cytological detection of early esophageal squamous cell carcinoma (ESCC) remains challenging. Therefore, we introduced a rapid cytological screening method and evaluated its efficacy as a pre-endoscopy screening for early ESCC and precursor lesions. Methods: This method consisted of a sponge sample retrieval, automatic liquid-based cytological treatment and slides preparation, computer-assisted screening and manual diagnosis. Efficacy for detection of early ESCC and precursor lesions was evaluated. Also, diagnostic efficiency was compared with manual diagnosis. Results: Eighty-three patients with early ESCC and precursor lesions and 2,090 asymptomatic participants with high risks of ESCC were enrolled. Whole procedure was accomplished within two working days. Abnormal cells were detected in all 83 patients, and in 272 (13.01%) subjects among 2,090 asymptomatic participants. Early ESCC, high-grade intraepithelial neoplasia, low-grade intraepithelial neoplasia and reflux esophagitis and normal endoscopic findings were detected in 8, 13, 11, 187 and 53 participants with abnormal cells, respectively. The calculated sensitivity, specificity, positive predictive value and negative predictive value for detection of early ESCC and precursor lesions were 100%, 88.34%, 11.76%, and 100%, respectively. Compared with manual diagnosis, this method was accomplished in a shorter time duration (5.4 ± 0.45 min vs 320.2 ± 132.4 min, p < 0.001), a higher diagnostic accuracy (96.7% vs74.4%, p = 0.015) and a better inter-observer agreement (93.3% vs66.7%, K = 0.286, p < 0.001). Conclusions: Our study provides a promising methodology as pre-endoscopy screening for early ESCC and precursor lesions.

The prediction of right atrial pressure using electrocardiogram: a novel approach.

AimsPulmonary hypertension (PH) is a serious disorder that can complicate pulmonary and cardiovascular diseases. Right atrial (RA) pressure is a robust predictor of the pulmonary hypertension severity, which is measured via right heart catheterization. Limited studies have been carried out to assess the association between electrocardiogram data and the RA pressure as a prognostic factor of PH. In this study, the relation between P wave and PR segment changes with RA pressure was evaluated.Methods and resultsIn this study, 94 patients in PH groups of 1, 3, and 4, based on the World Health Organization classification, were entered. RA pressure was measured using the right heart catheterization. PR segment and P wave morphology in leads II and V1 were evaluated in patient's electrocardiogram. The median age of the patients was 35.5 years old in which 64.9% of them were female. The distribution of patients in groups 1, 3, and 4 PH were 77.7%, 5.3%, and 17%, respectively. Among the studied P wave and PR segment changes, PR segment depression in lead II and pulmonary P wave in lead V1 had significant relation with the RA pressure (P‐value <0.001). The sensitivity, specificity, and negative predictive values of PR segment depression for detection of patients with high RA pressure (RA pressure > 14 mmHg) were 80%, 84%, and 94%. The specificity and negative predictive values of pulmonary P wave in lead V1 were determined 89% and 88%.ConclusionsIt was found that the PR segment depression in lead II and pulmonary P wave in lead V1 associate with the RA pressure in patients with precapillary PH. PR segment depression had useful sensitivity, specificity, and negative predictive values, and the pulmonary P wave in lead V1 had acceptable specificity and negative predictive values for detection of patients with high RA pressure. Therefore, the electrocardiogram can be used as a screening tool for determination of pulmonary hypertension severity.

Artificial Intelligence-Enabled Electrocardiography to Screen Patients with Dilated Cardiomyopathy

Undiagnosed dilated cardiomyopathy (DC) can be asymptomatic or present as sudden cardiac death, therefore pre-emptively identifying and treating patients may be beneficial. Screening for DC with echocardiography is expensive and labor intensive and standard electrocardiography (ECG) is insensitive and non-specific. The performance and applicability of artificial intelligence-enabled electrocardiography (AI-ECG) for detection of DC is unknown. Diagnostic performance of an AI algorithm in determining reduced left ventricular ejection fraction (LVEF) was evaluated in a cohort that comprised of DC and normal LVEF control patients. DC patients and controls with 12-lead ECGs and a reference LVEF measured by echocardiography performed within 30 and 180 days of the ECG respectively were enrolled. The model was tested for its sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) based on the prevalence of DC at 1% and 5%. The cohort consisted of 421 DC cases (60% males, 57±15 years, LVEF 28±11%) and 16,025 controls (49% males, age 69 ±16 years, LVEF 62±5%). For detection of LVEF≤45%, the area under the curve (AUC) was 0.955 with a sensitivity of 98.8% and specificity 44.8%. The NPV and PPV were 100% and 1.8% at a DC prevalence of 1% and 99.9% and 8.6% at a prevalence of 5%, respectively. In conclusion AI-ECG demonstrated high sensitivity and negative predictive value for detection of DC and could be used as a simple and cost-effective screening tool with implications for screening first degree relatives of DC patients.

The place of transvagınal ultrasonography saline infusion sonohysterography and hysteroscopy in the diagnosis of abnormal uterine bleedings

Aim: To establish the accuracy oftransvaginal ultrasonography, saline infusion sonohysterography and hysteroscopy in diagnosing uterine pathology in patients with abnormal uterine bleeding. &#x0D; Material Metod : In our study, Transvaginalultrasonography (TVUSG), Saline infusion sonohystygraphy (SIS) and Hysteroscopy were applied to 60 patients in the reproductive period, who did not use any contraception method other than condom, who did not have chronic and systemic diseases, who applied to our clinic with abnormal uterine bleeding. Dilatation &amp; Curettage (D&amp;C) was applied to all patients after the procedure. Histopathology results obtained with D&amp;C were compared with those obtained with TVUSG, SIS and Hysteroscopy.&#x0D; Results: Histopathologically,28 patients (46.7%) endometrial polyp, 4 patients (6.7%) submucomyomia, 10 patients (16.7%) endometrial hyperplasia was in the form of endometrial changes due to cycle irregularities in 18 patients (30%). The sensitivity, specifieity, positive and negative predictive values for detection of intracavitary pathology by transvaginal sonography were 71,42%, 77,78%, 88,23%, 83,85%. The value s determined by saline infusion sonohysterography were respeetively 88.89%, 90,48%, 80.00%, 95.0% and the values determined by hysteroseopy were respeetively 100%,90.00%,95,24%, 100%. &#x0D; Conclusion: TVUSG and SIS is a cheaper, easier and highly diagnostic value procedure for detecting endometrial pathologies such as endometrial polyps and submucous myomas. However, due to the high diagnostic values, low complication rates, direct biopsy and simultaneous treatment, we believe that hysteroscopy will maintain its 'gold standard' feature in the diagnosis and treatment of endometrial pathologies for many years.

Observer agreement and accuracy of 18F-sodium fluoride PET/computed tomography in the diagnosis of skull-base bone invasion and osseous metastases in newly diagnosed nasopharyngeal carcinoma.

To evaluate the interobserver agreement and the diagnostic performance in F-sodium fluoride (F-NaF) PET/computed tomography (CT) for the detection of skull-base bone invasion (SBBI) and osseous metastases in patients with newly diagnosed nasopharyngeal carcinoma (NPC). One hundred seventeen patients with newly diagnosed NPC between 2017 and 2019 who underwent F-NaF PET/CT was in included. Two experienced observers independently evaluated the F-NaF PET/CT of SBBI and osseous metastases on a patient level using a two-category scale present on a dichotomous scale, respectively. On a patient level, the diagnostic performance was calculated using a sensitivity analysis. The interobserver agreement on a patient level of SBBI and osseous metastases were perfect on a patient-level (κ: 0.85), (κ: 0.808), respectively. On a lesion level of detection of osseous metastases, the observers agreed on the number as well as the location of osseous metastases in 101 (86.3%) patients. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of detection of SBBI and osseous metastases were ranged 0.911-0.962, 0.921-0.974, 0.932-0.957, 0.962-0.986, and 0.841-0.923, and ranged 0.917-0.958, 0.899-0.957, 0.906-0.949, 0.863-0.936, and 0.939-0.970, respectively. The interobserver agreement of F-NaF PET/CT for the detection of SBBI and osseous metastases in patients with NPC were both very high among trained observers. Moreover, the diagnostic performance of NaF PET/CT was satisfactory, rendering NaF PET/CT a robust tool in the diagnostic armamentarium.

Evaluation of the performance of DiaSorin molecular Pneumocystis jirovecii-CMV multiplex real-time PCR assay from bronchoalveolar lavage samples

The aim of this study was to evaluate the performance of the DiaSorin Molecular PJ-CMV multiplex real-time PCR (PJ-CMV PCR) assay (DiaSorin Molecular LLC, USA) in bronchoalveolar lavage (BAL) samples compared to direct immunofluorescence assay (IFA) for the detection of Pneumocystis jirovecii and assess CMV and P. jirovecii co-infection rate in immunosuppressed patients with suspected pneumonia. A total of 125 BAL samples from immunosuppressed patients submitted for PJP-IFA were tested. Surplus samples were saved and further tested by using the PJ-CMV PCR assay. Among the 125 samples, P. jirovecii was detected in 31.2% (39/125) and in 40% (50/125) of the specimens using IFA and PJ-CMV PCR respectively. Eleven of the PJ-CMV PCR positive samples were negative by direct IFA for P. jirovecii. All samples positive by direct IFA were also positive by PJ-CMV PCR. Using the direct IFA as a gold standard, the PJ-CMV PCR sensitivity, specificity, positive predictive value and negative predictive value for detection of P. jirovecii were 100%, 87.2%, 78% and 100%, respectively. However, after reviewing the clinical diagnosis, the specificity and PPV increased to 100%. Of the 50 P. jirovecii samples positive by PJ-CMV PCR, 18 (36%) were also positive for CMV by the PJ-CMV PCR. The co-infection rate was found to be 37.5% (6/16) and 35.2% (12/34) in HIV infected and non-HIV infected patients. This study indicated that the DiaSorin Molecular PJ-CMV multiplex real-time PCR assay has higher sensitivity than direct IFA for detection of P. jirovecii and provides rapid detection of PJ and CMV infection in BAL samples.

Fetal structural anomalies diagnosed during the first, second and third trimesters of pregnancy using ultrasonography: a retrospective cohort study.

The prevalence of congenital abnormalities in general populations is approximately 3-5%. One of the most important applications of obstetric ultrasound is in detection of fetal structural defects. To assess fetal structural anomalies diagnosed using ultrasound in the three trimesters of pregnancy. Retrospective cohort study at the Mário Palmério University Hospital of the University of Uberaba (Universidade de Uberaba, UNIUBE), from March 2014 to December 2016. Ultrasound data at gestational weeks 11-13 + 6, 20-24 and 32-36 were recorded to identify fetal anomalies in each trimester and in the postnatal period. The primary outcome measurements were sensitivity, specificity, positive predictive value and negative predictive value for detection of fetal anomalies and their prevalence. The prevalence of anomalies detected using ultrasound was 2.95% in the prenatal period and 7.24% in the postnatal period. The fetal anomalies most frequently diagnosed using ultrasound in the three trimesters were genitourinary tract anomalies, with a prevalence of 27.8%. Cardiac anomalies were diagnosed more often in the postnatal period, accounting for 51.0% of all cases. High specificity, negative predictive value and accuracy of ultrasound were observed in all three trimesters of pregnancy. Ultrasound is safe and has utility for detecting fetal anomalies that are associated with high rates of morbidity and mortality. However, the low sensitivity of ultrasound for detecting fetal anomalies in unselected populations limits its utility for providing reassurance to examiners and to pregnant women with normal results.

Improved Detection of Benign and Malignant Rib Lesions in the Routine Computed Tomography Workup of Oncological Patients Using Automated Unfolded Rib Image Postprocessing.

The aim of this study was to evaluate the performance of the automated computed tomography (CT) postprocessing software unfolded rib images for improved detection of both benign and malignant rib lesions during routine diagnostic workup of oncological patients. One thousand eight in-patients and out-patients (63.66 ± 14.25 years; range, 18.67-95.67 years; 405 females and 603 males), undergoing chest CT between July 2018 to January 2019 at our institution, were retrospectively evaluated. Patients underwent chest CT alone or as part of a whole-body CT staging/restaging. The CT protocol consisted of the following: 120 kV; 100 mAs; matrix, 512 × 512; collimation, 0.6 mm; reconstructed section thickness of 3 mm and 1 mm using a soft tissue spatial resolution kernel (I30f) and a sharp kernel (B70f). Both transversal image data sets were used for "conventional" diagnosis including coronal reformates with 3-mm slice thickness. One-millimeter slice thickness image data sets of all patients were additionally directed from the scanner to a computational server where they were automatically postprocessed to 3-dimensional unfolded ribs. The "unfolding" of the rib using the centerline as an axis allows a synchronous display and rotation of all ribs by mouse scrolling. These postprocessed image data sets were evaluated in a separate reading session (approximately 4 weeks later). The readers had no information about the underlying medical history or clinical presentation. They were asked to record the lesion number, site of involvement along the rib (proximal, body, distal), number of the involved ribs, and the character of the lesion in terms of lytic versus sclerotic versus mixed lytic/sclerotic. The standard of reference was F-FDG PET, Ga-DOMITATE PET/CT, bone scan, or imaging follow-up (>6 months). From a total of 1008 evaluated patients, 763 (73.02%) were hemato-oncologic patients. A total of 104 rib lesions were found by transversal CT image reading, whereas the unfolded rib image reading detected 305 lesions. Eighty-nine were classified malignant, and 202 were classified benign. Detection of malignant rib lesions proved significant both for less than 1 cm (P < 0.02) and more than 1 cm in diameter (P < 0.007). The sensitivity, specificity, positive predictive value, and negative predictive value for detection of malignant rib lesions were 97.7%, 98.5%, 96.6%, and 99% for unfolding ribs, and 76.4%, 100%, 92.7%, and 90.5% for conventional (transversal) image reading, respectively. Detection of sclerotic rib lesions and lesions greater than 1 cm in diameter were significantly better (P < 0.01) for the unfolding rib algorithm. The "unfolded rib" reformates are significantly superior for rib lesion detection compared with conventional transversal CT scan reading and should therefore be used in all patients, particularly those with an oncologic background.

Validation of a two-gene mRNA urine test for detection of high-grade prostate cancer in German men.

96 Background: There is an unmet need for non-invasive methods that can accurately identify patients at increased risk for clinically significant prostate cancer (PCa). SelectMDx is a urine-based molecular test that has been clinically validated for the detection of high-grade PCa. We evaluated SelectMDx clinical performance in a cohort of German men undergoing initial prostate biopsy. Methods: The study population consisted of 443 men sequentially enrolled men who underwent initial prostate biopsy between July 2009 and December 2014 due to suspected PCa. Post-DRE urine was collected from all subjects prior to biopsy, and samples stored at -70C. Urinary HOXC6 and DLX-1 mRNAs were quantified by PCR in May 2018, and RNA results combined with clinical risk factors to determine the likelihood that biopsy would identify ISUP grade group (GG) ≥ 2 (Gleason Score ≥ 7) PCa. We assessed SelectMDx performance for detection of GG ≥ 2 PCa, compared to the PCPT Risk Calculator Version 2.0 (PCPTRC, http://myprostatecancerrisk.com , accessed Oct 7, 2018). Results: For the 443 subjects enrolled, average age was 66 years (median 66, interquartile range 61 to 71), and average serum PSA level 8.8 ng/mL (6.4, 4.8 to 9.7). Cancer was detected in 243/443 (55%) men biopsied (43% GG1, 36% GG2, 9% GG3 and 12% GG4-5). The prevalence of GG2-5 PCa in this population was 31.4% (139/443). For detection of GG2 or higher PCa versus GG1 or no PCa at biopsy, SelectMDx AUC was 0.82 (95% C.I. 0.78-0.86) and the PCPTRC yielded AUC 0.75 (0.70-0.80), P &lt; 0.001. SelectMDx sensitivity was 94% (89-98%), specificity 46% (40-52%), positive predictive value 45% (42-47%) and negative predictive value (NPV) 95% (90-97%). If the initial biopsy had been performed based on SelectMDx results alone, 46% of potentially unnecessary biopsies and 34% of all biopsies would have been avoided, while 5.8% of men with biopsy-detectable high-grade PCa (seven GG2, one GG3) may have had their diagnosis delayed. Conclusions: In this first validation study of SelectMDx in German men, the test’s clinical performance was comparable to the published EU validation study, showing a high NPV for detection of GG2 or higher PCa. These results provide further evidence for the clinical validity of SelectMDx.

Abstract P2-07-08: Standardized prediction of Oncotype DX® risk classes by local RT-qPCR

Abstract Background: Recent results from the prospective validation of the Oncotype DX® recurrence score (RS) have underlined the clinical validity of the assay for the prediction of chemotherapy benefit in ER+/HER2- early stage breast cancer patients. Due to health economic restrictions, some patients have no easy access to the test. A pre-selection of tumor samples may help identify patients with a high likelihood to be spared chemotherapy. Histology and semi-quantitative IHC are hence used to select samples for Oncotype testing, but these suffer from intra- and inter-observer variability, especially for Ki-67 which is a main factor in most RS prediction algorithms. We have established and validated a tool for the prediction of RS risk classes (TAILORx cutoff RS ≤25) based on highly standardized, reproducible and locally performed RT-qPCR measurements of ERBB2, ESR1, PGR and MKI67 mRNA using the CE-marked IVD MammaTyper®. Methods: Total RNA was extracted from whole surface 10μm sections from FFPE breast cancer samples with a known RS result and a tumor cell content ≥20%. ERBB2, ESR1, PGR and MKI67 mRNA expression was measured by RT-qPCR on a CFX96 qPCR cycler using the MammaTyper® kit. A prediction model for an RS ≤25 result was established using multivariable logistic regression. Based on this model and the training data two cutoffs for confident prediction of low chemotherapy benefit patients in a clinical setting were established at 95% and 97.5% specificity. The model and the cutoffs were then fixed and validated in a second, separate set of breast cancer samples. ROC analysis was used to characterize predictive power of the continuous values resulting from the prediction model. Positive and negative predictive values for detection of an RS ≤25 result were also determined on the validation samples using the two pre-defined cutoffs. Results: The sample set for training of the prediction model encompassed 202 samples including 29 samples (14.4%) with an RS &amp;gt;25. In an initial multivariable model with all four markers, PGR and MKI67 were the strongest predictors while the influence of ESR in the model was lower, but still significant. ERBB2 was no significant predictor in this set of ERBB2 negative samples and was therefore excluded from the final model which was based on three markers only. This three marker model achieved an AUC of 0.920 (95% CI: 0.871-0.968) in the training samples. When applying the fixed model from the training dataset to a second separately collected set of 104 samples containing 20 samples (19.2%) with an RS &amp;gt;25, an AUC of 0.883 (95% CI: 0.810-0.955) was documented. When further applying the two predefined cutoffs established in the training set, 45 and 36 of the 104 validation samples (43.3% and 34.6%) had a predicted low chemotherapy benefit result (RS ≤25). Even with the less stringent cutoff, not a single one of the RS &amp;gt;25 cases from the validation cohort was falsely predicted as RS ≤25 sample. Conclusion: We have established a highly reliable method for prediction of Oncotype DX® low chemotherapy benefit results based on local and cost effective mRNA measurements. This method enables local pathologies to pre-assess routine samples using a highly precise molecular tool and thereby reserve the Oncotype DX® test for cases with ambiguous cancer biology. Citation Format: Lehr H-A, Aulmann S, Etzrodt A, Laible M, Hartmann K, Gürtler C, Wirtz RM, Sahin U, Varga Z. Standardized prediction of Oncotype DX® risk classes by local RT-qPCR [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-08.

The significance of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography in detection of pelvic nodal metastases in endometrial cancer

Objective This study was conducted to assess the accuracy of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG PET-CT) in detection of pelvic nodal metastases in endometrial cancer. Methods Patients with endometrial cancer from January 2015 to June 2017 confirmed by the postoperative pathology were retrospectively analyzed. 30 patients finished PET-CT before operation. The findings on histopathology were compared with 18FDG-PET/CT findings to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 18FDG-PET/CT. To analyze the efficacy of maximum standardized uptake (SUVmax) and lymph node maximum standardized uptake (LN-SUVmax) of PET-CT in the diagnosis of pelvic lymph node metastasis. Results For detection of pelvic nodes, based on patient analysis, 18FDG-PET/CT had a sensitivity of 75.0%, specificity of 88.5%, PPV of 50.0%, NPV of 95.8% and accuracy of 86.7%. Based on a nodal region analysis, 18FDG-PET/CT had a sensitivity of 83.3%, specificity of 98.3%, PPV of 55.0%, NPV of 99.6%, and accuracy of 98.3%. When maximum standardized uptake values (SUVmax)>8, area under curve (AUC)=0.64, Yonden Index=0.42. When maximum standardized uptake values of lymphonodus (LN -SUVmax)>3 (AUC=0.79, Yonden Index=0.63), the sensitivity and specificity of diagnosis of lymph node metastasis were 100%, 42.31%, and 75.0%, 88.5%, but without statistically significant difference. Although AUC of LN-SUVmax was higher than SUVmax of primary lesion, but the difference was not statistically significant (P>0.05). Conclusions 18FDG-PET/CT has high specificity, NPV for detection of pelvic LN metastasis area in endometrial cancer, which can provide preoperative basis for patients with endometrial cancer to avoid lymph node resection, thereby reducing the risk of early endometrial cancer surgery and improving the quality of life after surgery.We concluded that, there were no exact cutoffs of SUVmax for the prediction of lymph node metastases, neither primary lesion, nor lymph node. There is clearly a need for multicenter, large-scale trials to find out better parameters in judging metastasis of lymphnodes. Key words: Fluorodeoxyglucose F18; Positron-emission tomography; Endometrial neoplasms; Lymphatic metastasis

Heart Rate Characteristic Index Monitoring for Early Detection of Infections in Very Low Birth Weight Infants

The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate characteristics (HRC) monitoring in detection of infections and 2) to evaluate whether HRC monitoring detects infections prior to onset of clinical symptoms in very low birth weight (VLBW) infants. A retrospective cohort study was conducted analyzing HRC scores and episodes of infection for VLBW infants in the Neonatal Intensive Care Unit (NICU) at Cincinnati Children’s Hospital Medical Center from January 2015 through May 2016. HRC scores were acquired using the HRC monitor system and entered into the electronic medical record by bedside staff. Culture-positive and culture-negative clinical infections were recorded. Positive HRC scores were defined as an increase 1 point above the baseline or the first rise above 2. HRC scores within 24 hours and also within the 5-day period before the start of antibiotics for infections were analyzed for sensitivity, specificity, positive predictive value and negative predictive value for detection of neonatal infection. The HRC score increase 1 point above the baseline or the first rise above 2 in the 24 hours before the start of antibiotics for infectious events had a sensitivity of 68.0%, a specificity of 10.8%. Positive predictive value (PPV) and negative predictive value (NPV) were 34.0% and 33.3%, respectively. The PPV and NPV were modestly higher for elevated HRC scores during the 5-day period before infections, 41.1% and 66.7%, respectively. In our single-center retrospective study, elevated HRC scores had limited ability to detect infection. More than half of the positive monitor events were not related to infection. The potential clinical impact of the monitor to detect infection before the onset of clinical symptoms was limited and the risk for unnecessary evaluation and treatment was high.

Amobile one-lead ECG device incorporated in asymptom-driven remote arrhythmia monitoring program. The first 5,982 Hartwacht ECGs.

BackgroundIn recent years many mobile devices able to record health-related data in ambulatory patients have emerged. However, well-organised programs to incorporate these devices are sparse. Hartwacht Arrhythmia (HA) is such a program, focusing on remote arrhythmia detection using the AliveCor Kardia Mobile (KM) and its algorithm.ObjectivesThe aim of this study was to assess the benefit of the KM device and its algorithm in detecting cardiac arrhythmias in a real-world cohort of ambulatory patients.MethodsAll KM ECGs recorded in the HA program between January 2017 and March 2018 were included. Classification by the KM algorithm was compared with that of the Hartwacht team led by a cardiologist. Statistical analyses were performed with respect to detection of sinus rhythm (SR), atrial fibrillation (AF) and other arrhythmias.Results5,982 KM ECGs were received from 233 patients (mean age 58 years, 52% male). The KM algorithm categorised 59% as SR, 22% as possible AF, 17% as unclassified and 2% as unreadable. According to the Hartwacht team, 498 (8%) ECGs were uninterpretable. Negative predictive value for detection of AF was 98%. However, positive predictive value as well as detection of other arrhythmias was poor. In 81% of the unclassified ECGs, the Hartwacht team was able to provide a diagnosis.ConclusionsThis study reports on the first symptom-driven remote arrhythmia monitoring program in the Netherlands. Less than 10% of the ECGs were uninterpretable. However, the current performance of the KM algorithm makes the device inadequate as a stand-alone application, supporting the need for manual ECG analysis in HA and similar programs.

Evaluation of an Epigenetic Assay for Predicting Repeat Prostate Biopsy Outcome in African American Men

To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) ≤6 PCa and 27 (33%) with GS ≥7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS ≥7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS ≥7 PCa were 78.8% and 94.2%, respectively. In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy.

Near-Infrared Lymphatic Mapping of the Recurrent Laryngeal Nerve Nodes in T1 Esophageal Cancer

It is still unclear that dissection of recurrent laryngeal nerve nodes is mandatory in patients with cT1 middle or lower thoracic esophageal squamous cell carcinoma when the nodes are negative in preoperative staging workup. We aimed to evaluate the feasibility of near-infrared image-guided lymphatic mapping of bilateral recurrent laryngeal nerve nodes. The day before operation, we injected indocyanine green (ICG) into the submucosal layer by endoscopy. At the time of upper mediastinal dissection, ICG-stained basins were identified along the bilateral recurrent laryngeal nerves and retrieved under guidance of the Firefly system. After the operation, remnant ICG-unstained basins were dissected from the specimen to assess the presence of metastasis. Of 29 patients enrolled, ICG-stained basins could be identified in 25 patients (86.2%), and 6 of them (24.0%) had nodal metastasis; 4 in the right recurrent laryngeal nerve chain, 1 in the left recurrent laryngeal nerve chain, and 1 in both recurrent laryngeal nerve chains. On pathologic examination of 345 recurrent laryngeal nerve nodes, two metastatic nodes were identified in ICG-unstained basins along the left recurrent laryngeal nerve in a patient who had lymph node metastases in ICG-stained basins along both recurrent laryngeal nerves. Negative predictive value in detection of nodal metastasis was 100% for the right recurrent laryngeal nerve chain and 98.2% for the left recurrent laryngeal nerve chain. Real-time assessment of recurrent laryngeal nerve nodes with near-infrared image was technically feasible, and we could detect lymphatic basins that most likely have nodal metastasis. Our technique might be useful in determining the optimal extent of lymphadenectomy.