Incremental Yield Research Articles

S0423 “WATS” the Incremental Yield of Wide-Area Transepithelial Sampling for Dysplasia Detection in Barrett’s Esophagus? A Systematic Review and Meta-Analysis

INTRODUCTION: Seattle protocol forceps biopsies (FB) are currently recommended for surveillance in Barrett’s esophagus (BE). Dysplasia detection is limited by sampling error. Wide-area transepithelial sampling (WATS) utilizes computer-aided diagnosis of esophageal brushings to increase dysplasia detection. We assessed the incremental yield of WATS compared to FB and limitations of published data in a systematic review and meta-analysis. METHODS: We queried multiple scientific databases for studies utilizing WATS with FB from 2000–2020. We utilized the arcsine transformation with a fixed-effects meta-analysis of single arm proportions for analysis given the small number of studies. Primary outcome was the incremental yield of WATS over FB for dysplastic BE (IND/LGD + HGD + EAC) as a composite. Secondary outcomes were incremental yield of WATS for HGD/EAC, and the rate of reconfirmation of incremental WATS dysplasia on subsequent FB. RESULTS: We included 6 full-length manuscripts (from 2011 to 2020), studying 37,468 patients (6 included data for dysplastic BE, and 4 for HGD/EAC), Study characteristics are shown in the Table. All WATS samples were read by pathologists at CDx Diagnostics (Suffern, NY). BE histology was confirmed by 2 expert GI pathologists in only 2 (33%) studies. Meta-analysis of 6 studies demonstrated that FB diagnosed dysplasia in 5.8% (95% CI: 5.1%–6.6%) of cases, while WATS added an incremental yield of 4.5% (95% CI: 3.9%–5.2%; Figure 1). Meta-analysis of 4 studies demonstrated that FB diagnosed HGD/EAC in 0.6% (95% CI 0.4%–0.9%) of patients, while WATS added an incremental yield of 0.4% (95% CI: 0.2%–0.6%; Figure 2). Notably, WATS was negative in 1%–45% of cases where FB identified dysplasia. Only 1 study reported reconfirmation of WATS dysplasia on subsequent endoscopy: only 7 of 23 (30%) WATS dysplasia (+) patients had dysplasia on subsequent FB. In 3 studies the incremental yield of WATS dysplasia was reported in several cases with FB histology negative for intestinal metaplasia (85% of cases). No endoscopic data was available in these cases. CONCLUSION: WATS appears to increase the yield of dysplastic BE and HGD/EAC as an adjunct to FB. However, in most studies, this incremental yield is not reconfirmed by FB, WATS reads are done only by CDx pathologists and FB dysplasia is not confirmed by expert GI pathologists. Long-term follow up is required to ascertain dysplasia outcomes in patients with dysplasia based solely on WATS.Figure 1Figure 2Table 1

Chromosomal Abnormalities Detected by Karyotyping and Microarray Analysis in Twins With Structural Anomalies

Objectives To evaluate the incidence and types of chromosomal abnormalities detected in twins with structural anomalies and compare their distribution according to chorionicity and amnionicity and by structural-anomaly type. The added value of chromosomal microarray analysis (CMA) over conventional karyotyping in twins was also estimated. Methods This was a single-center, retrospective analysis of 534 twin pregnancies seen over an 11-year period, in which one or both fetuses were diagnosed with congenital structural anomalies on ultrasound. The ultrasound findings and invasive prenatal diagnostic results were reviewed. Twin pregnancies were categorized as monochorionic monoamniotic (MCMA), monochorionic diamniotic (MCDA) or dichorionic diamniotic (DCDA). Chromosomal abnormalities detected by G-banding karyotyping and/or CMA were analyzed by chorionicity and amnionicity and by structural-anomaly type. Results The 534 twin pairs analyzed comprised 25 pairs of MCMA, 112 pairs of MCDA and 397 pairs of DCDA twins. Of the 549 fetuses affected by structural anomalies, 432 (78.7%) underwent invasive prenatal testing and cytogenetic results were obtained. The incidence of overall chromosomal abnormalities in the DCDA fetuses (25.4%) was higher than that in the MCMA (3.7%) and MCDA (15.3%) fetuses. The incidence of aneuploidy was significantly higher in the DCDA group (22.8%) than in the MCMA (0.0%) and MCDA (12.4%) groups. The incidence of chromosomal abnormalities detected in fetuses, with anomalies of the cardiovascular, faciocervical, musculoskeletal, genitourinary and gastrointestinal systems, was higher in the DCDA group than in the MCDA group. In both the DCDA and MCDA groups, hydrops fetalis was associated with the highest incidence of chromosomal abnormality; of these fetuses, 67.6% had Turner syndrome (45,X). Pathogenic copy-number variations (CNVs) undetectable by karyotyping were identified by CMA in five (2.0%; 95% CI, 0.3-3.7%) DCDA fetuses. No pathogenic CNVs were found in MCMA and MCDA twins. Conclusions Dichorionic twins with structural anomalies have a higher risk of chromosomal abnormalities, especially aneuploidies, than do monochorionic twins. The incremental diagnostic yield of CMA over karyotyping seems to be lower (2.0%) in twins than that reported in singleton pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction

PurposeTo test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA). MethodsWe selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters. ResultsOverall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (−20.1 ± 3.1% vs −21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (−19.7 ± 2.9% vs −21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was −21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was −16.4%. ConclusionsAt CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.

Partially automated whole-genome sequencing reanalysis of previously undiagnosed pediatric patients can efficiently yield new diagnoses

To investigate the diagnostic and clinical utility of a partially automated reanalysis pipeline, forty-eight cases of seriously ill children with suspected genetic disease who did not receive a diagnosis upon initial manual analysis of whole-genome sequencing (WGS) were reanalyzed at least 1 year later. Clinical natural language processing (CNLP) of medical records provided automated, updated patient phenotypes, and an automated analysis system delivered limited lists of possible diagnostic variants for each case. CNLP identified a median of 79 new clinical features per patient at least 1 year later. Compared to a standard manual reanalysis pipeline, the partially automated pipeline reduced the number of variants to be analyzed by 90% (range: 74%-96%). In 2 cases, diagnoses were made upon reinterpretation, representing an incremental diagnostic yield of 4.2% (2/48, 95% CI: 0.5–14.3%). Four additional cases were flagged with a possible diagnosis to be considered during subsequent reanalysis. Separately, copy number analysis led to diagnoses in two cases. Ongoing discovery of new disease genes and refined variant classification necessitate periodic reanalysis of negative WGS cases. The clinical features of patients sequenced as infants evolve rapidly with age. Partially automated reanalysis, including automated re-phenotyping through CNLP, has the potential to identify molecular diagnoses with reduced expert labor intensity.

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study.

Objective:To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms.Summary of Background Data:Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown.Methods:This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia.Results:A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8–2.1]. Individual yields were 0.7% (95% CI: 0.2–1.1) for chest CT and 1.1% (95% CI: 0.6–1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence.Conclusions:One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures.

Chromosomal Microarray Analysis for the Fetuses with Aortic Arch Abnormalities and Normal Karyotype.

BackgroundAortic arch abnormalities (AAA) are abnormal embryologic developments of the aorta and its branches. Their outcomes often depend on their association with other congenital diseases and genetic testing results.ObjectiveThis study aimed to evaluate the yield of chromosomal microarray analysis (CMA) in fetuses with different patterns of AAA and normal karyotype.MethodsData from 158 pregnancies referred for prenatal CMA testing due to fetal AAA were obtained between April 2016 and April 2019. Fetuses with isolated AAA, AAA accompanied by soft ultrasound markers, and AAA with other ultrasound malformations were classified into groups A, B, and C, respectively. Cases with detectable karyotype aberrations were excluded from the study.ResultsTwenty cases (12.7%) of submicroscopic anomalies were detected in 158 cases with normal karyotype, comprising 16 cases (10.1%) of clinically significant variants, two cases (1.3%) of variants of unknown significance, and two variants (1.3%) that were likely benign. Microdeletion of 22q11.2 accounted for 25% (4/16) of the clinically significant variants. The overall incremental yields by CMA in group A, group B, and group C were 1.8%, 2.3%, and 24.1%, respectively. Except for double aortic arch, the incremental yield of clinical significant findings for each type of AAA in group C was much higher than that in group A and group B. In group A, a clinically significant variant was only detected in one fetus with right aortic arch (RAA) (1.8%, 1/57).ConclusionsIn addition to 22q11.2 microdeletion, many other clinically significant submicroscopic variants are present in fetuses with AAA, especially in fetuses with other ultrasound malformations. Although CMA is always recommended in the presence of any malformation in many countries, our results suggest insufficient evidence to recommend CMA in fetuses with isolated AAA, except for isolated RAA.

Incremental yield of ECG screening repeated annually over 4 years in an adult Japanese population without prior atrial fibrillation: a retrospective cohort study

ObjectivesInternational guidelines recommend opportunistic screening for atrial fibrillation (AF); however, there is no current data to inform how often to repeat screening. We aimed to investigate the incremental annual yield...

Prenatal exome sequencing in fetuses with congenital heart defects.

The genetic diagnosis of congenital heart defects (CHDs) is challenging because of genetic and phenotypic heterogeneity. The aim of our study was to evaluate the clinical value of whole exome sequencing (WES) in the prenatal diagnosis of CHDs in a large cohort. Trio-based WES was performed in 260 fetuses with CHDs negative for karyotype and chromosome microarray analysis results. WES produced a diagnostic yield of 10% (26/260) in the entire cohort. Relative high diagnostic rate was observed in cases with cardiac rhabdomyoma (60%), complex CHDs (16.7%), septal defect (14.0%), and conotruncal defect (9.9%). There was no significant difference between the diagnostic yields in simple and complex CHDs groups (9.9% vs 16.7%), and in non-isolated and isolated CHDs groups (15.7% vs 7.9%). The diagnostic yields in cases with CHDs with soft markers, CHDs with fetal growth restriction, and CHDs with other structural anomalies (syndromic CHDs) were 0 (0/13), 50% (1/2) and 18.2% (10/55), respectively. Variants of unknown significance were detected in 16 (6.2%) fetuses, and secondary findings in 7 (2.7%) cases. Variants in 14 candidate genes were identified. Our study demonstrates an incremental diagnostic yield by trio-based WES in the prenatal diagnosis of CHDs after routine tests, not as high as expected.

Su1541 DIAGNOSIS OF BILIARY STRICTURES USING SPYGLASS DIRECTED BIOPSIES – INTENTION TO TREAT ANALYSIS AT A TERTIARY CARE CENTER

Diagnosis of biliary strictures remains clinically arduous and challenging. We aimed to evaluate the utility of single-operator cholangioscopy (SOC)-system SpyGlass with and without cytology versus cold biopsies performed during endoscopic retrograde cholangiopancreatography (ERCP) in a single tertiary care center to diagnose biliary strictures. We conducted a retrospective analysis of all biliary strictures that underwent biopsies for diagnosis in an intention to treat analysis. A total of 42 patients (51% males) are included over a period of 3 years. Follow up was complete in 37 patients. The patients were divided into 4 groups – bile duct biopsies only using the SpyGlass system (n=19), bile duct biopsies using the SpyGlass system with cytology brushings (n=8), bile duct biopsies using cold biopsy forceps alone (n=6) and only cytology brushings (n=4). The objective was to obtain the diagnostic accuracy of each method for malignant, and for all lesions combined. Biliary stricture was located in the common bile duct in 55% patients and the common hepatic duct in 32% patients. The median length was 14.5±8 mm with a mean bilirubin of 10+8 mg/dl. The biopsy site corroborated with the site of the stricture except in patients with right or left hepatic duct strictures (n=5) where right hepatic duct biopsies could be obtained only in 1 patient. Spyglass was successful in all patients except 1. Twenty-five (68%) patients were found to have malignant and 12 (32%) patients had benign lesions. SpyGlass with cytology accurately detected malignancies in 67% of patients with total diagnostic accuracy for all lesions was 75%. SpyGlass biopsies alone accurately diagnosed 64% malignancies, and 79 % all lesions. When both these groups were combined, diagnostic accuracy for malignant lesions was 65% and for all lesions was 78%. Diagnostic accuracy for cold biopsy forceps was 75% for malignant lesions and 83% for all lesions. Cytology accurately diagnosed 50% of malignant lesions and 50% of all lesions. One patient diagnosed initially with benign stricture on SpyGlass was later diagnosed as having malignancy when biopsied again using SpyGlass. The outcomes are provided in table 2. There were no episodes of post-ERCP pancreatitis. Retrospective analysis at a single center. The number of biopsies using SpyGlass was variable (3-6) and not uniformly reported. Performing SpyGlass biopsies has a high rate of technical success. SpyGlass directed biopsies accurately predict diagnosis in 79% of patients. The addition of cytology does not add much incremental yield in the diagnosis of bile duct strictures. Cold biopsy forceps are not always technically feasible, but when possible offers excellent diagnostic yield, although our sample size is limited. Future prospective randomized studies with a larger dataset are recommended.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Tablet‐based electroencephalography diagnostics for patients with epilepsy in the West African Republic of Guinea

Epilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established. Tablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility. There were 149 participants (41% female; median age 17.9years; 66.6% ≤21years of age; mean seizures per month 5.7±SD 15.5). The mean duration of EEG1 was 53±12.3min and that of EEG2 was 29.6±12.8min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n=53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n=23, 24.2%), 12 (52.1%) did not have EDs at EEG2. Tablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.

PGI17 COST EFFECTIVENESS ANALYSIS OF ENDOSCOPIC CAPSULE FOR DIAGNOSIS OF OBSCURE GASTROINTESTINAL BLEEDING IN THE BRAZILIAN PRIVATE HEALTHCARE SYSTEM

To evaluate the cost-effectiveness of endoscopic capsule (EC) as enteroscopic diagnostic technique, compared to diagnostic procedures currently included in Brazilian private healthcare system, specifically, push enteroscopy using a standard probe and a double-balloon enteroscopy A decision tree model was developed from private payer perspective. The study population was adult patients diagnosed with gastrointestinal bleeding of obscure origin. The primary clinical outcome was diagnostic yield of each comparator; complications were included as a secondary outcome. Clinical data was identified through a literature review and final outcomes were calculated using a meta-analysis. Direct medical costs were included, taken from 2018 private insurance pricing charts (CBHPM) and presented in 2019 BRL and USD. Time horizon adopted was disease diagnosis and complications/adverse events timeframe. There was no discount rate. An univariate sensitivity analysis was conducted. A cost-effectiveness ratio was calculated two scenarios: 1) EC vs push enteroscopy and 2) EC vs double ballon enteroscopy. In the first analysis, EC presents an incremental diagnostic yield of 0.14 and an incremental cost of BRL 1,099 (USD 274), resulting in an ICER of BRL 7,931 (USD 1,982). In comparison to double ballon enteroscopy, EC results in an incremental diagnostic yield of -0.04 and an incremental cost of BRL 2,451 (USD 612). As such, EC is a dominant therapy compared to double balloon enteroscopy. Sensitivity analysis indicated that the results were robust to variations in both cost and effectiveness variables. Cost of EC and push enteroscopy were the varibles with the greatest impact on results. The analysis indicates that enteroscopy with endoscopic capsule has lower costs and a better diagnostic yield when compared to double balloon enteroscopy, making it a dominant alternative. Compared to push enteroscopy, EC may be considered a cost-effectiveness therapy that considerably improves the diagnostic yield.

Addition of an online, validated family history questionnaire to the Dutch FIT-based screening programme did not improve its diagnostic yield

BackgroundFaecal immunochemical testing (FIT) is suboptimal in detecting advanced neoplasia (AN). To increase the sensitivity and yield of a FIT-based screening programme, FIT could be combined with risk factors for AN. We evaluated the incremental yield of adding a family history questionnaire (FHQ) on colorectal cancer (CRC) and Lynch syndrome-associated tumours to the Dutch FIT-based screening programme.MethodsSix thousand screen-naive individuals, aged 59–75 years, were invited to complete a FIT (FOB-Gold, cut-off 47 µg Hb/g faeces) and a validated online FHQ. Participants with a positive FIT and/or positive FHQ, confirmed after genetic counselling, were referred for colonoscopy. Yield of detecting AN per 1000 invitees for the combined strategy was compared with the FIT-only strategy.ResultsOf the 5979 invitees, 1952 (32.6%) completed the FIT only, 2379 (39.8%) completed both the FIT and FHQ and 95 (1.6%) completed the FHQ only. Addition of the FHQ to FIT-based screening resulted in one extra case of AN detected after 16 additional colonoscopies, resulting in a yield of 19.6 (95% CI, 16.4–23.5) for the combined strategy versus 19.5 (95% CI, 16.3–23.3) for the FIT-only strategy (p = 1.0).ConclusionsThe addition of an FHQ to one round of FIT screening did not increase the detection of AN compared with FIT only (ClinicalTrials.gov NCT02698462).

Establishing and Coordinating a Nationwide Multidisciplinary Study Group: Lessons Learned by the Dutch Pancreatic Cancer Group.

Establishing and Coordinating a Nationwide Multidisciplinary Study Group: Lessons Learned by the Dutch Pancreatic Cancer Group.

Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis

PurposeEmerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of low-pass GS compared with CMA is warranted. MethodsA total of 1023 women undergoing prenatal diagnosis were enrolled. Each sample was subjected to low-pass GS and CMA for CNV analysis in parallel. CNVs were classified according to guidelines of the American College of Medical Genetics and Genomics. ResultsLow-pass GS not only identified all 124 numerical disorders or pathogenic or likely pathogenic (P/LP) CNVs detected by CMA in 121 cases (11.8%, 121/1023), but also defined 17 additional and clinically relevant P/LP CNVs in 17 cases (1.7%, 17/1023). In addition, low-pass GS significantly reduced the technical repeat rate from 4.6% (47/1023) for CMA to 0.5% (5/1023) and required less DNA (50 ng) as input. ConclusionIn the context of prenatal diagnosis, low-pass GS identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform used. This study provides strong evidence for applying low-pass GS as an alternative prenatal diagnostic test.

Predictive Value of In Vivo MR Spectroscopy With Semilocalization by Adiabatic Selective Refocusing in Differentiating Clear Cell Renal Cell Carcinoma From Other Subtypes.

OBJECTIVE. The purpose of this study is to evaluate the diagnostic value of in vivo MR spectroscopy (MRS) with semilocalization by adiabatic selective refocusing (semi-LASER MRS) in differentiating clear cell renal cell carcinoma (RCC) from the non-clear cell subtype. SUBJECTS AND METHODS. Sixteen patients with biopsy-proven RCC or masses highly suspicious for RCC were prospectively recruited to participate in the study. Single-voxel 1H spectra were acquired using a 3-T MRI system, with a semi-LASER sequence acquired for renal tumors in 14 patients and for healthy renal tissue (control tissue) in 12 patients. Offline processing of the MR spectra was performed. MRI and spectra analysis were performed independently by radiologists who were blinded to the reference histopathologic findings. RESULTS. Semi-LASER MRS was diagnostic for nine of 11 patients (82%) with histopathologically proven clear cell RCC, showing a strong lipid peak in seven patients and a weaker lipid resonance in two others, whereas control spectra showed weakly positive findings in only one patient. MRS findings were negative for lipid resonance in two of three patients (67%) with non-clear cell tumors and were weakly positive in another patient. Semi-LASER MRS had a high sensitivity and positive predictive value of 82% and 90%, respectively, in addition to a specificity of 67%, a negative predictive value of 50%, and overall accuracy of 79% for the detection of clear cell RCC. Lipid resonance was detected by MRS for four of six clear cell RCCs with no intravoxel fat on chemical-shift MRI. CONCLUSION. The preliminary results of the present study show that semi-LASER MRS is promising for the noninvasive discrimination of clear cell RCC from non-clear cell RCC on the basis of detection of lipid resonance and that it provides an incremental yield compared with chemical-shift MRI.

Utility of chromosomal microarray for diagnosis in cases of nonimmune hydrops fetalis.

Chromosomal microarray (CMA) is recommended in the diagnostic evaluation of cases with fetal structural anomalies when invasive testing is pursued. However, the utility of CMA for nonimmune hydrops fetalis (NIHF) specifically is not well known. Our objective was to describe the overall yield of CMA in the diagnostic evaluation of NIHF, comparing isolated cases to those with concurrent structural anomalies. This was a retrospective cohort study of all prenatally diagnosed NIHF cases evaluated at the University of California, San Francisco from 2008 to 2018. NIHF due to twin-twin transfusion syndrome was excluded. There were 131 cases of prenatally diagnosed NIHF. In 43/44 cases with a CMA performed, results were categorized as normal or likely benign. One case was found on CMA to have a large pathogenic duplication of 21p11.2q22.3, which could have been detected by karyotype and was consistent with a diagnosis of Down syndrome. There was no incremental yield demonstrated for CMA over karyotype. Among a cohort of prenatally diagnosed NIHF cases, CMA did not identify any copy number variants beyond those detectable by karyotype, and the vast majority of CMAs were normal. These results suggest that CMA has low diagnostic utility for NIHF.

Generation and expulsion process of the Chang 7 oil shale in the Ordos Basin based on temperature-based semi-open pyrolysis: Implications for in-situ conversion process

There is a substantial amount of oil shale resources in the seventh member of the Triassic Yanchang Formation (abbreviated as Chang 7) in the Ordos Basin, and its geological and geochemical characteristics are highly suitable for in-situ conversion process (ICP). A comprehensive characterization of its hydrocarbon generation, expulsion and retention features will help determine the optimum conditions for future field tests. However, typical thermal simulation experiments based on either open-system or closed-system are not applicable to provide data to construct the models. Therefore, in this study, eight parallel thermal simulation experiments, which were based on the newly designed temperature-based semi-open pyrolysis experiments were performed on the Chang 7 oil shale. The yields (including cumulative yields and net incremental yields) and compositional characteristics of the expelled oil, expelled gas, and retained oil were analyzed. Results show that the hydrocarbon expulsion has a coupling relationship with hydrocarbon generation that can be divided into four stages: (1) Slow hydrocarbon generation stage (300–320 °C, 0.53–0.55 %Ro). Minimal amounts of oil and gas are generated in this stage. The hydrocarbon expulsion efficiency increases rapidly. (2) Quick oil-generation stage (320–380 °C, 0.55–1.09 %Ro). The fast cracking of kerogen and thermal bitumen generates a large amount of oil. The hydrocarbon expulsion efficiency remains relatively stable. (3) The secondary oil cracking and quick gas-generation stage (380–420 °C, 1.09–1.66 %Ro). The oil yield begins to decrease after reaching its maximum and a large amount of hydrocarbon gas is generated. The oil generation capability of kerogen is basically exhausted. The hydrocarbon expulsion efficiency and gas/oil ratio increase rapidly at this stage. (4) The heavy hydrocarbon gas cracking stage (after 420 °C, 1.66 %Ro). The oil yield continues to decline, accompanied by the onset decline in the gas yield (except methane). At this time, the hydrocarbon expulsion efficiency continues to increase but at a rather low speed. Under the experimental conditions in this study, 1.24–1.66% Ro is considered a favorable thermal maturity interval, in which maximum oil production with relatively light components can be obtained and the hydrocarbon gas is abundant.

The yield of chromosomal microarray analysis among pregnancies terminated due to fetal malformations

Background Chromosomal microarray analysis (CMA) is preferred for genetic work-up when fetal malformations are detected prenatally. Objectives To assess the detection rate of CMA after pregnancy termination due to abnormal ultrasound findings. Methods CMA was successfully performed in 71 pregnancies using fetal DNA (mainly from skin) or placenta. Data regarding clinical background, pregnancy work-up, and CMA were analyzed. Results Findings were abnormal in 17 cases (23.9%), of which 13 were detectable by karyotype. The incremental yield of CMA was 4/71 (5.6%); 1/32 (3.1%) for cases with an isolated anomaly and 3/39 (7.7%) for cases with nonisolated anomalies. Conclusions CMA yield from terminated pregnancies was 23.9%. Although most chromosomal abnormalities are detectable by karyotype, CMA does not require viable dividing cells; hence, it is more practical for work-up after termination. In most cases, the diagnosis was followed by consultation regarding the risk of recurrence and recommendations for testing in subsequent pregnancies.

Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens.

Rationale: Microbiological confirmation of pulmonary tuberculosis in children is desirable.Objectives: To investigate the diagnostic accuracy and incremental yield of Xpert MTB/RIF Ultra (Ultra; Cepheid), a new rapid test, on repeated induced sputum, nasopharyngeal aspirates, and combinations of specimens.Methods: Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled.Measurements and Main Results: Induced sputum (IS) and nasopharyngeal aspirates (NPAs) were obtained. NPAs were frozen; IS underwent liquid culture, and an aliquot was frozen. Ultra was performed on thawed NPAs and IS specimens individually. Children were categorized as confirmed, unconfirmed, or unlikely tuberculosis according to NIH consensus case definitions. The diagnostic accuracy of Ultra was compared with liquid culture on IS. In total, 195 children (median age: 23.3 mo; 32 [16.4%] HIV-infected) had one IS and NPA, and 130 had two NPAs. There were 40 (20.5%) culture-confirmed cases. Ultra was positive on NPAs in 26 (13.3%) and on IS in 31 (15.9%). Sensitivity and specificity of Ultra on one NPA were 46% and 98%, respectively, and similar by HIV status. Sensitivity and specificity of Ultra on one IS were 74.3% and 96.9% respectively. Combining one NPA and one IS increased sensitivity to 80%. Sensitivity using Ultra on two NPAs was 54.2%, increasing to 87.5% with an IS Ultra.Conclusions: IS provides a better specimen than repeated NPA for rapid diagnosis using Ultra. However, Ultra testing of combinations of specimens provides a novel strategy that can be adapted to identify most children with confirmed pulmonary tuberculosis.

Implementation of Incremental Yield Condition for Continual Problems with Singularity

The limit elastic state of an infinitely large half-plane under the action of concentrated vertical and horizontal forces has been considered. The gradient yield condition specifying the elasto-plastic material yielding initial moment at non-uniform stress state is used as the limit state criterion. The analytical expressions allowing to interpret the result in the singular point have been derived.