True Positive Cases Research Articles

Diagnostic Accuracy of Ultrasonography Using U Classification of Thyroid Nodules in Detection of Malignant Thyroid

Ultrasonography (US) helps diagnose malignant thyroid nodules based on various characteristics, including echogenicity, margins, microcalcifications, size, form, and aberrant neck lymph nodes. The study aimed to determine the diagnostic accuracy of ultrasonography for cancer diagnosis in thyroid nodules, using Histopathology as the gold standard. To minimize morbidity and death from the condition and the number of solely invasive procedures biopsies, the results of our research will give patients and physicians with a noninvasive, cost-effective, and conveniently accessible diagnostic technique for differentiating cancerous from benign nodules. A cross-sectional analytical study was designed to collect data prospectively from July 2022 to October 2022 in the Department of Radiology at Nuclear Medicine, Oncology and Radiotherapy Institute Islamabad. Patients in the age range of 18-60 years, both genders were enrolled. Th data was entered into SPSS 24. The frequencies and percentages of categorical factors such as sex and malignancy in thyroid nodules were determined using descriptive analysis. For numerical variables such as age, the mean and standard deviation were computed. We evaluated the sensitivity, specificity, PPV, and NPV with a 95% confidence interval for the U-classification of malignant thyroid nodules and represented as Two by Two tables. In addition, Histopathology was used to evaluate U's efficacy as a diagnostic tool for finding malignant thyroid nodules. The study sample comprised 34 (68%) female and 16 (32%) male patients. On Biopsy, cancerous nodules were diagnosed in only 19 (38.5%) patients, and the remaining 31 (62%) had benign lesions. The prevalence of thyroid malignancy in our sample was 38%. On ultrasonography, malignancy was diagnosed in 15(30%) lesions, while the remaining 35(70%) patients were diagnosed with benign lesions. Histopathology confirmed malignant thyroid nodules in 15 (true positive) cases, whereas 6 (false positive) had no malignant lesion on Histopathology. In US negative patients, 27 were true negative, while 2 were false negative. The sensitivity of ultrasound U-score in diagnosing malignant thyroid nodules was 88.2%, specificity was 81.8%, PPV was 71.4%, and NPV was 93% Diagnostic accuracy is high when the US is used to detect thyroid problems, making it the preferred noninvasive technique. We recommend that thyroid lesions be routinely assessed clinically, imaged radiographically, and analyzed histo-pathologically. U Classification system for identifying potentially cancerous thyroid nodules is a valuable tool. It allows for a more prudent choice of nodules to undergo FNAC, reducing the number of needless procedures.

Diagnostic Accuracy Of Contrast Enhanced Ct For Detection Of Renal Cell Carcinoma Taking Histopathology As Gold Standard.

Renal cell carcinoma being the commonest primary renal malignancy of adulthood accounts for approximately 80-90% renal malignant lesions. The purpose of radiological imaging modalities when devising the treatment options for renal masses is crucial as it significantly influence the clinical outcome and prognosis of the disease. Subjective impression by a radiologist for diagnosing a mass lesion is known to be critical and its precision is improved by contrast enhanced CT as demonstrated by certain retrospective analyses. We aimed to ascertain the diagnostic accuracy of contrast enhanced computed tomography to diagnose renal cell cancers by verifying through histopathology reported diagnoses. This Cross-sectional (validation) study was carried out in Radiology and Urology departments of Ayub Teaching Hospital; Abbottabad, from 1st November 2020 to 30th April 2022. The study population included all admitted symptomatic patients with age range 18-70 years of either gender. The patients were subjected to detailed clinical examination and history and an ultrasound and contrast enhanced CT abdomen and pelvis. CT scans were reported under supervision of single consultant radiologist. Data was analysed in SPSS version 20.0. Mean age of the patients was 38.88±11.62 years ranging from 18-70 years and mean duration of symptoms was 54.64±49.171 ranging from 3-180 days. All of the total 113 patients underwent contrast enhanced CT scan and later operated to confirm the diagnoses by histopathology. The comparison yielded true positive (TP) cases to be 67, True Negative (TN) 16, False Positive (FP) 26, and 4 False Negative (FN) as per CT scan diagnoses. CT scan had a diagnostic Accuracy of 73.45% with 94.37% sensitivity and 38.10% specificity. Contrast-enhanced CT has a high sensitivity for making the diagnosis of renal cell carcinoma; however, its specificity is low. A multidisciplinary approach is necessary to overcome the low specificity. Therefore, collaboration between radiologists and urologic oncologists should be considered while devising treatment plan for patients.

The role of non-invasive prenatal testing and ultrasound in prenatal screening of fetal chromosomal abnormalities in singleton: a retrospective study.

Non-invasive prenatal testing (NIPT) has good screening performance for common chromosomes, but it may have false positive (FP) and false negative (FN) results for various reasons. For abnormal NIPT results, the combination of fetal ultrasound phenotypes will provide more fetal information for prenatal diagnosis. The aim of this study was to combine NIPT and ultrasound phenotypes to analyze their complementary roles in prenatal screening of fetal chromosome abnormalities. From January 2018 to December 2021, 12,803 pregnant women with singleton who successfully underwent NIPT/expanded NIPT (NIPT-Plus) at Xiangya Hospital of Central South University, of which 111 cases were positive results and one case was FN result. We retrospectively collected the clinical features, ultrasonographic findings, prenatal diagnosis, and pregnancy outcomes of these 112 pregnant women and analyzed the ultrasonic manifestations of different chromosomal abnormalities in detail. The positive predictive values (PPVs) of NIPT/NIPT-Plus for trisomy (T)21, T18, sex chromosome abnormality (SCA), microdeletion/microduplication syndrome (MMS), T13, and rare autosomal trisomy (RAT) were 100.0%, 85.7%, 57.1%, 44.4%, 40.0%, and 7.7%, respectively. The total termination rates of pregnancy for T21, T18, T13, SCA, pathogenic MMS, and RAT were 93.5%, 100.0%, 100.0%, 66.7%, 100.0%, and 100.0%, respectively. From the karyotypes of SCA live-born fetuses, 47,XYY and 47,XXX were more likely to be selected for continued pregnancy. The ultrasound phenotypes of T21 were diverse, including normal, soft marker, and structural malformation. Both T18 and T13 had structural malformations as the main phenotypes. Most ultrasound phenotypes of FP T21, T18, and T13 were normal but occasionally manifested as fetal growth restriction (FGR). The ultrasound phenotypes of SCA, MMS, and RAT were relatively mild and manifested as normal, soft marker, FGR, or polyhydramnios, and the ultrasound phenotypes were similar between FP and true positive (TP) cases. Ultrasound phenotypes are helpful in identifying FP NIPT/NIPT-Plus results, especially for T18 and T13. Given its mild ultrasound phenotypes, NIPT-Plus has important clinical significance in reducing the missed diagnosis of SCA, MMS, and RAT, but its screening performance needs to be further improved.

A comparative study of conventional cytology and cell block in the diagnosis of pleural effusion with special reference to immunohistochemistry

Background: Body cavity fluids are evaluated by cell block (CB) technique. In conventional cytological smears (CS), appropriate identification of the cells as either reactive mesothelial cells or malignant cells is a diagnostic problem. In CB method, there is increase in cellularity, so it gives more morphological details of cells and improving the sensitivity of diagnosis. Sections obtained by CB method are also can be stored for future study like immunohistochemistry (IHC). Aims and Objectives: The aim of the study was to determine the diagnostic efficacy of CB technique over conventional CS and to study of IHC in CB of malignant pleural effusion. Materials and Methods: This will be institution-based, cross-sectional, and observational study. The pleural fluid (except blood and pus) obtained by thoracocentesis from both male and female patient (>18 years of age) 100 cases was included in the study. Pleural fluid mixed with blood/pus, fluid from cystic lesion, and inadequate sample (<15 ml vol.) were excluded in the study. Results: Association between architectural pattern in CB versus architectural pattern in cytology smear showed statistically significant value Chi-square: 201.7417, P < 0.0001. Conclusion: We may conclude that CB technique is better than conventional cytology smear technique especially in case of malignant pleural effusion. It increases true positive cases and decreases false negative cases. It also increases cellularity, maintain architectural pattern, and cellular morphology.

Identifying Nonpatient Authors of Patient Portal Secure Messages in Oncology: A Proof-of-Concept Demonstration of Natural Language Processing Methods.

Patient portal secure messages are not always authored by the patient account holder. Understanding who authored the message is particularly important in an oncology setting where symptom reporting is crucial to patient treatment. Natural language processing has the potential to detect messages not authored by the patient automatically. Patient portal secure messages from the Memorial Sloan Kettering Cancer Center were retrieved and manually annotated as a predicted unregistered proxy (ie, not written by the patient) or a presumed patient. After randomly splitting the annotated messages into training and test sets in a 70:30 ratio, a bag-of-words approach was used to extract features and then a Least Absolute Shrinkage and Selection Operator (LASSO) model was trained and used for classification. Portal secure messages (n = 2,000) were randomly selected from unique patient accounts and manually annotated. We excluded 335 messages from the data set as the annotators could not determine if they were written by a patient or proxy. Using the remaining 1,665 messages, a LASSO model was developed that achieved an area under the curve of 0.932 and an area under the precision recall curve of 0.748. The sensitivity and specificity related to classifying true-positive cases (predicted unregistered proxy-authored messages) and true negatives (presumed patient-authored messages) were 0.681 and 0.960, respectively. Our work demonstrates the feasibility of using unstructured, heterogenous patient portal secure messages to determine portal secure message authorship. Identifying patient authorship in real time can improve patient portal account security and can be used to improve the quality of the information extracted from the patient portal, such as patient-reported outcomes.

Diagnostic Accuracy of Elastography to Differentiate Between Malignant and Benign Lymph Nodes of Neck and Head Region Taking Histopathology as Gold Standard

Background: The analysis of superficial lymphadenopathy in the cervical, axillary, and inguinal regions is vital in planning therapy for patients. Elastography is a technique currently being used for the evaluation of lymph nodes by means of evaluating tissue elasticity. In medical practice, shear wave-based and strain elastography techniques are being utilized. Strain elastography can be used to assess types of elasticity. Colors inside and around the nodes are estimated in the first place and then a 4-5 scale scoring system is used to score them visually. The present study aimed to assess the diagnostic accuracy of elastography in distinction between malignant and benign lymph nodes of the neck and head region, taking histopathology as the gold standard. Methods: This study was carried out on ninety-six (96) patients of either gender with lymph nodes in the head and neck region admitted to Children Hospital and University of Child Health Sciences Lahore and Mardan Medical Complex. Patients with proven histopathology and gone through surgery in the head and neck region were excluded from the study. Each patient was subjected to the high-resolution elastography with a 7.5 MHz linear array probe. A consultant radiologist performed the elastography in the presence of the researcher and noted the lymph node types. The histopathology report was compared with the findings of elastography. Results: High-resolution elastography was conducted on each patient enrolled in this study and their results were categorized into two distinct groups’ namely positive elastography and negative elastography. In the positive group, malignant lymph node diagnoses were supported in 51 patients by elastography. Out of which 46 were true positive cases and 5 were false-positive cases with no malignant histopathology. Similarly, in elastography, negative patients, only 3 cases were false negative and 42 cases were true negative. The overall diagnostic precision, specificity, negative predictive value, positive predictive value, and sensitivity of elastography was found to be 92%, 89.10%, 92.80%, 89.40%, and 94%, respectively, in order to differentiate malignant lymph nodes from benign lymph nodes in the neck and head region, taking histopathology as the gold standard. Conclusions: The present study demonstrated that elastography is a favorable and invasive technique for the diagnosis and differentiation of malignant lymph nodes from benign lymph nodes with high diagnostic accuracy. It may help in selecting surgical procedures for lymph nodes in the neck and head region. Keywords: Elastography, Sensitivity, Malignant Lymph Nodes.

Accuracy of CT-Guided Core-Needle Biopsy in Diagnosis of Thoracic Lesions Suspicious for Primitive Malignancy of the Lung: A Five-Year Retrospective Analysis.

Lung cancer represents a heterogeneous group of neoplasms, with the highest frequency and mortality in both sexes combined. In a clinical scenario characterized by the widespread of multidetector-row spiral CT, core-needle biopsy under tomographic guidance is one of the main and safest methods to obtain tissue specimens, even though there are relatively high rates of pneumothorax (0-60% incidence) and pulmonary hemorrhage (4-27% occurrence rates). The aim of this retrospective study is to assess the diagnostic accuracy of CT-guided core-needle biopsy in the diagnosis of primary lung malignancies and to compare our results with evidence from the literature. Our analysis included 350 thoracic biopsies, performed from 2017 to 2022 with a 64-row CT guidance and 16/18 G needles mounted on a biopsy gun. We included in the final cohort all samples with evidence of primary lung malignancies, precursor lesions, and atypia, as well as inconclusive and negative diagnoses. There was sensitivity of 90.07% (95% CI 86.05-93.25%), accuracy of 98.87% (95% CI 98.12-99.69%), positive predictive value of 100%, and negative value of 98.74% (95% CI 98.23-99.10%). Specificity settled at 100% (93.84-100%). The AUC was 0.952 (95% CI 0.924-0.972). Only three patients experienced major complications after the procedure. Among minor complications, longer distances from the pleura, the presence of emphysema, and the lower dimensions of the lesions were correlated with the development of pneumothorax after the procedure, while longer distances from the pleura and the lower dimensions of the lesions were correlated with intra-alveolar hemorrhage. Immunohistochemistry analysis was performed in 51% of true positive cases, showing TTF-1, CK7, and p40 expression, respectively, in 26%, 24%, and 10% of analyzed samples. The CT-guided thoracic core-needle biopsy is an extremely accurate and safe diagnostic procedure for the histological diagnosis of lung cancer, a first-level interventional radiology exam for peripheral and subpleural lesions of the lung, which is also able to provide adequate samples for advanced pathologic assays (e.g., FISH, PCR) to assess molecular activity and genetic sequencing.

Efficiency of expanded noninvasive prenatal testing in the detection of fetal subchromosomal microdeletion and microduplication in a cohort of 31,256 single pregnancies

Noninvasive prenatal testing (NIPT) is widely used to screen for common fetal chromosomal aneuploidies. However, the ability of NIPT-Plus to detect copy number variation (CNV) is debatable. Accordingly, we assessed the efficiency of NIPT-Plus to detect clinically significant fetal CNV. We performed a prospective analysis of 31,260 singleton pregnancies, included from June 2017 to December 2020. Cell-free fetal DNA was directly sequenced using the semiconductor sequencing platform for women with high-risk CNV with clinically significant results. Fetal karyotyping and chromosomal microarray analysis (or next-generation sequencing) are recommended for invasive diagnostic procedures. Women at low risk with no other abnormal results continued their pregnancies. We analyzed the expanded NIPT results, diagnostic test results, and follow-up information to evaluate its performance in detecting fetal CNV. Of the 31,260 pregnant women who received NIPT-Plus, 31,256 cases were tested successfully, a high risk of clinically significant CNV was detected in 221 cases (0.71%); 18 women refused further diagnosis; 203 women underwent invasive prenatal diagnosis; and 78 true positive cases and 125 false positive cases, with an overall positive predictive value (PPV) of 38.42% and a false positive rate of 0.40%. For known microdeletion/microduplication syndromes (n = 27), the PPVs were 75% DiGeorge syndrome (DGS), 80% 22q11.22 microduplication, 50% Prader–Willi syndrome, and 50% cri-du-chat. For the remaining clinically significant fetal CNVs (n = 175), the combined PPVs were 46.5% (CNVs > 10 Mb) and 28.57% (CNVs ≤ 10 Mb). NIPT-Plus screening for CNV has certain clinical value. NIPT-Plus yielded relatively high PPVs for 22q11.2 microduplication syndrome and DGS, and low to moderate PPVs for other CNVs.

New CMC Algorithm for Evaluation of Lupus Anticoagulant

Introduction: Lupus Anticoagulant (LA) is an autoantibody that in vitro inhibit phospholipid-dependent coagulation reactions in the absence of specific coagulation factor inhibition Primary laboratory criteria for LA detection include prolonged clotting time of a phospholipid dependent test, failure of correction on mixing study, shortening of the clotting time in the presence of high phospholipid concentrations & absence of other inhibitors. (1) According to guidelines,for diagnosing LA two tests based on different principles should be used- dRVVT(Dilute Russel's Viper Venom Time) should be the first test considered. Second test should be a sensitive aPTT (Activate Partial Thromboplastin Time).LA is a multistep procedure with screening, mixing and confirmation tests. Devreese et al recently concluded that integration of screening and confirmation in a single procedure and skipping the mixing tests result in a poor diagnostic efficacy for LA (2).LA is an in-vitro inhibitor and elevated Screening test without mixing studies does not prove inhibitor effect & it wastes time & resources to perform confirmatory tests skipping the mixing. Hence, we devised a new algorithm- Christian Medical College (CMC) Algorithm as shown in figure-1 which starts with DRVVT Screen Mix. To identify interferences due to anticoagulants like heparin and fibrin degradation products (FDP) thrombin time (TT) was also included. If Screen Mix is normal APTT Screen Mix was performed. Aim of our new algorithm was to reduce false positives and avoid interferences in LA Materials and methods: Four hundred and ninety-one (491) samples were analysed retrospectively for a period of 5 months from January 2022 to May 2022. The new algorithm was incorporated into STA R Max2 (Diagnostica Stago) analyser and automatic calculation of ratios and interpretation of results were done based on flow charts. LA testing was performed using DRVVT screen and confirm reagents (STA-Staclot DRVV Screen and STA-Staclot DRVV Confirm) and/or APTT reagent (STA-PTT Synthasil). LA test was considered positive when Screen/ Confirm(S/C) ratio was >1.2. We compared this result to the three hundred forty seven(347) samples, over a period of 4 months(September 2021 - December 2021) analyzed in old algorithm where DRVVT screen & APTT were done as the initial steps instead of DRVVT mixing studies as the 1st step. Results: In the new algorithm result were classified into 7 categories. Category 1 had normal DRVVT screen Mix and normal APTT; these represent true negative cases comprising 68.8 % of the cases. Category 2 had normal DRVVT screen Mix, prolonged APTT Screen Mix with normal TT. 1 case in this category had other Antiphosholipid Antibody (APLA) negative & repeat testing for LA was advised. Category 3 had normal DRVVT Screen mix, prolonged APTT Screen Mix with prolonged TT. There was 1 case in this category, who was on heparin, APLA antibody was negative. Repeat testing was advised at a later date. Category 4 had prolonged DRVVT Screen Mix, normal S/C ratio , with normal TT. There were 61 cases (12%) in this category among which 5 cases had normal DRVVT Screen with prolonged Mix Category 5 had Prolonged DRVVT Screen Mix, with normal S/C Ratio, prolonged TT and this category had 13 (2 %) cases. On further evaluation they were found to be on anticoagulants. Category 6 had prolonged S/C Ratio with normal TT, which are the true positive cases, n=67 (13.6%). There were 4 cases where Screen mix was more prolonged than Screen, and Screen fell below the cut off & could have been missed if mixing step was not done Category 7 had prolonged S/C ratio with prolonged TT. There were 10 cases (2%) in this category. On further evaluation 6 patients had history of anticoagulants and 2 had features of DIC. These 8 patients could represent false positive LA and would have been misclassified if TT was not done. Old algorithm had 20 % positive cases & 80 % negative cases. Since the algorithm were incorporated into STA R Max2 hands on time decreased from 240 minutes to 80 minutes. Cost of the reagents were similar by 2 algorithms. Conclusion: The new algorithm gives better clarity in classification of patients into true positive and true negative & detection of interference due to heparin as thrombin time is also done in parallel. Possible false positive cases could be identified at the onset even before repeat confirmatory lupus testing. This study concludes the importance of mixing studies in avoiding false negatives. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical evaluation of true and false positive Z values among high-risk cases screened by non-invasive prenatal testing

To analyze the Z values of true and false positive cases by non-invasive prenatal testing (NIPT) in order to improve its accuracy in clinical practice. Results of 24 384 NIPT tests were reviewed. For cases with high risks for trisomies 21, 18 and 13, the range of Z values in true and false positive cases was analyzed and discussed. A total of 335 high-risk cases were identified by NIPT, among which 256 had elected prenatal diagnosis, 153 (59.77%) were verified as true positives, and 103 (40.23%) were false positives, and the area under the curve (AUC) was 0.9994. For NIPT screening, the positive predictive value (PPV) for trisomy 21 was 100% when Z>13, regardless if the pregnant woman was over 35. When 3<Z<13, the PPV for trisomy 21 was 80% (8/10) for those>35 and about 41.6% (5/12) for those<35. For trisomy 18, the PPV was 100% when Z>13, and only 14.3% (1/7) when 3<Z<13. NIPT showed that the positive predictive value of trisomy 13 was only 6.67% (1/15) when the trisomy 13 Z value was more than 20, the positive predictive value was 100% , and the trisomy 13 Z value was 3<Z<20. NIPT is a technique similar to prenatal diagnosis and has a high positive predictive value for trisomies 18 and 21. Proper classification and division of the high-risk Z value of NIPT can further improve the positive predictive values for trisomies 21, 18 and 13 in different intervals, and is more helpful to guide clinicians in genetic counseling for high-risk pregnant women. Meanwhile, the compliance of prenatal diagnosis in high risk NIPT pregnant women with Z value between 3~13 was improved.

The Performance of Antigen-detecting Rapid Diagnostic Test Among COVID-19 Outbreaks in North-Eastern Peninsular Malaysia

Background and aims: Accurate and timely diagnosis is crucial for coronavirus disease 2019 (COVID-19) outbreaks. Antigen-detecting rapid diagnostic tests (Ag-RDTs) are easily accessible and affordable, producing rapid results. They are an alternative to the limited gold-standard real-time reverse-transcription polymerase chain reaction (rRT-PCR) tests. This study assessed the performance of Ag-RDTs for COVID-19 outbreaks in institutional settings with high disease prevalence in Kelantan State, Malaysia. Methods: This study analyzed a total of 303 individuals from five institutional outbreaks with paired nasopharyngeal specimens tested for COVID-19 by Ag-RDTs and rRT-PCR. The diagnostic performance of Ag-RDTs was evaluated through rRT-PCR as the gold standard based on cycle threshold (Ct) value, disease prevalence, and manufacturers. Results: There was a moderate agreement between Ag-RDTs and RT-PCR (κ=0.603; 95% CI: 0.520- 0.686; P&lt;0.001). The overall specificity was 97.9% (95% CI: 94.1%-99.6%), sensitivity was 63.3% (95% CI: 55.3%-70.8%), accuracy Ag-RDTs was 81.2% (95% CI: 76.4%-85.5%), while positive and negative predictive value was 96.6% (95% CI: 90.2%-98.9%) and 74.1% (95% CI: 70.0%-77.9%), respectively. Further, lower median Ct was reported in 100 (33.0%) true-positive cases compared to 58 (19.1%) false-negative cases (20.3 vs 31.4, P&lt;0.001). The sensitivity was higher (P&lt;0.001) in those with high viral load (Ct value≤25.0) with better performance and a prevalence&gt;10%. In addition, no significant difference was observed between the studied manufacturers. Conclusion: The Ag-RDTs performed well in diagnosing COVID-19 among outbreaks with higher viral load and disease prevalence. High-risk cases tested negative by Ag-RDTs may have low viral load and require confirmation by rRT-PCR.

Perinatal outcomes of prenatal cases testing positive for trisomy 9 by noninvasive prenatal testing

ObjectivesTo evaluate the performance of non-invasive prenatal testing (NIPT) for the detection of fetal trisomy 9 in prenatal screening and to investigate the prenatal appearances and genetic counseling of trisomy 9 fetuses. Materials and methodsThe ultrasonography information, laboratory detection and pregnancy outcome of 16 cases of single pregnancy with trisomy 9 identified by NIPT who received amniocentesis in our prenatal diagnosis center from January 2018 to December 2020 were retrospectively analyzed. ResultsAmong the 16 cases, 2 cases of trisomy 9, 3 cases of trisomy 9 mosaicism, 2 cases reporting of regions of homozygosity and 9 cases of false positive were diagnosed. Among the true positive cases, 4 cases showed abnormal ultrasonic finding: 3 cases terminated pregnancy and 1 case was lost to follow-up. Another 1 case was in utero fetal demise in the second trimester without structural abnormality, and 2 cases were normal live birth without developmental abnormalities. In the 9 cases with normal kayrotyping, 1 case had termination of pregnancy and 1 case with mental retardation and poor cognitive ability, other 7 had good pregnancy outcomes. ConclusionOur results may be helpful for the selection of prenatal diagnostic strategies and genetic counseling for pregnant women with trisomy 9 revealed by NIPT.

Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors.

Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above ("high") and below ("low") the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with "high" CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with "low" CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce "high" IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce "low" IRT CFFNs.

Application of long non-coding RNA RBAT1 in improving diagnosis and prognosis of ovarian carcinoma.

Tumorigenesis of bladder cancer and retinoblastoma is correlated with long non-coding RNA (lncRNA) RBAT1. However, the role of RBAT1 in ovarian carcinoma (OC) is unclear. Thus, the study explored the role of RBAT1 in OC. This research enrolled patients with OC ( n = 68), irritable bowel disease (IBD, n = 68, females), digestive tract inflammation (DTI, n = 68, females), urinary tract infection (UTI, n = 68, females), endometriosis (EM, n = 68, females), and healthy controls (HCs, n = 68) to collect plasma sampled. OC and paired non-tumor tissues were collected from patients with OC. RBAT1 accumulation in all samples was analyzed using RT-qPCR. The role of plasma RBAT1 in OC diagnosis was examined using the ROC curves with OC patients as the true positive cases and other patients and HCs as the true negative cases. The role of RBAT1 in predicting the survival of OC patients was analyzed using the survival curve study. RBAT1 was overexpressed in both OC plasma and tissues. Plasma RBAT1 levels were correlated with RBAT1 levels in OC tissues but not in non-tumor tissues. Plasma RBAT1 could distinguish OC patients from other patients and HCs. Patients with high plasma RBAT1 levels had a shorter survival. RBAT1 is overexpressed in OC and might be applied to improve the diagnosis and prognosis of OC.

Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.

To assess the outcomes of pregnancies at high-risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell-free DNA (cfDNA) screening. A retrospective study of women who underwent cfDNA screening between September 2019 and July 2021 at three ultrasound services in Australia. Positive predictive values (PPVs) were calculated using fetal chromosomal analysis. Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p=0.022) and 9.8% (p=0.004), respectively), which was not observed in the SI group (2.9%<10th (p=0.168) and 0.0% <3rd (p=0.305)). The PPVs for SI and RAT results are low, except when a structural abnormality is also present. Discordant positive RATs are associated with growth restriction.

Comparison between Immunocytochemistry, FISH and NGS for ALK and ROS1 Rearrangement Detection in Cytological Samples.

The detection of ROS1 and ALK rearrangements is performed for advanced-stage non-small cell lung cancer. Several techniques can be used on cytological samples, such as immunocytochemistry (ICC), fluorescence in situ hybridization (FISH) and, more recently, next-generation sequencing (NGS), which is gradually becoming the gold standard. We performed a retrospective study to compare ALK and ROS1 rearrangement results from immunocytochemistry, FISH and NGS methods from 131 cytological samples. Compared to NGS, the sensitivity and specificity of ICC were 0.79 and 0.91, respectively, for ALK, and 1 and 0.87 for ROS1. Regarding FISH, the sensitivity and specificity were both at 1 for ALK and ROS1 probes. False-positive cases obtained by ICC were systematically corrected by FISH. When using ICC and FISH techniques, results are very close to NGS. The false-positive cases obtained by ICC are corrected by FISH, and the true-positive cases are confirmed. NGS has the potential to improve the detection of ALK and ROS1 rearrangements in cytological samples; however, the cost of this technique is still much higher than the sequential use of ICC and FISH.

Diagnostic Accuracy of Ultrasound for Small Bowel Obstruction in Paediatric Population Undergoing Laparotomy Keeping Surgical Findings as the Gold Standard

Objective: To analyze the diagnostic accuracy of ultrasound in small bowel obstruction in the paediatric population and compare it with surgical findings.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Radiology Department, Pakistan Institute of Medical Sciences, Islamabad Pakistan from Jun 2018 to Jun 2019.&#x0D; Methodology: This study enrolled 84 paediatric small bowel obstruction cases who underwent exploratory laparotomy at the Pakistan institute of medical sciences from Jun 2018 to Jun 2019. The clinically suspected cases of small bowel obstruction were referred by paediatric surgery to the Radiology department, where an ultrasound abdomen was performed by a senior resident, exclusively targeting the bowel. The clinical, sonological, and per-operative findings were recorded on a proforma.&#x0D; Results: The mean age in our study was 3.5±2.7 years. A male gender predominance was noted. The most consistent greyscale feature favouring bowel obstruction was dilated bowel loops, found among 98.7% (76 out of 77) of surgically confirmed cases of bowel obstruction. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of ultrasound were 98.7%, 71.4%, 97.4%, 83.4% and 94.6% respectively. The sonological cause of obstruction was readily demonstrated among 51 (67%) out of 76 true positive cases. The most common site of obstruction was the distal ileum, with intussusception being the leading cause found among 32% of true positive cases.&#x0D; Conclusion: The overall diagnostic accuracy of ultrasound in revealing small bowel obstruction is high among the paediatric population.

Circular reasoning, confessions and abusive head trauma: A critical analysis of Edwards et al. (2020)

AbstractA major issue in current clinical research regarding shaken baby syndrome (SBS) and abusive head trauma (AHT) has been described as circular reasoning. Circular reasoning in this context means that a child protection team makes the SBS/AHT diagnosis, and that this diagnosis is also used as the reference test (gold standard) when researchers classify SBS/AHT cases as true positive cases. Circular reasoning results in a high risk of bias. In order to avoid this, videotaped, witnessed and spontaneously confessed shaking has been suggested as the currently least problematic means to avoid circular reasoning. Against this backdrop it is welcomed that Edwards et al. (2020) have conducted a systematic literature review in order to identify studies where someone has confessed to have shaken a baby with or without signs of impact. Even though Edwards et al. dismissed the risk of bias due to false confessions, false confessions can occur, e.g. if an expert witness convinces police and/or prosecutor that, in a case of isolated retino‐dural haemorrhages (i.e. without signs of impact), violent shaking is the only possible mechanism. In such cases circular reasoning can hardly be avoided. In the best world, circumstances under which confessions are provided should be documented by video recording to allow critical assessment.Edwards et al., and Adamsbaum et al. (2010), explicitly make an important distinction between two major stated reasons for shaking a baby: a) shaking after a baby's collapse as a revival attempt, and b) shaking due to anger, frustration due to colicky crying, etc. Based on this distinction, we propose that these two major stated reasons for shaking actually should be separated, and that a caregiver who claims that he/she did shake the infant but as a revival attempt can be telling the truth. This hypothesis could be tested, e.g. by analysing the effect of AHT preventive interventions after separating the two categories of stated reason for shaking. Edwards et al. criticised the Swedish SBU report for having included only two (2) confession studies and claimed that they themselves, with their systematic literature review, ‘clearly refute the argument that there are insufficient data within the published literature to support shaking as an important cause of AHT’. The correctness and relevance of this criticism depends on the research question, the difference between ‘data’ and ‘evidence’, as well as if the inclusion criteria, the exclusion criteria and the applied quality assessment are in accordance with the accepted principles of systematic literature reviews and evidence‐based medicine.

Cut-off dilemma: Differences from the forensic and clinic perspective

Opioids are a major concern in many countries due to the serious health consequences associated with their use. The United Nations Office on Drugs and Crime (UNODC) opioid crisis strategy report states that the number of people using opioids for non-medical purposes around the world has nearly doubled in the last decade and the prevalence of opioid use has increased by 76% in the same period. The same report stated that opioid use is responsible for approximately two-thirds of deaths attributed to substance use disorders worldwide. Opiates are one of the five classes of abused drugs mandated for testing in the Drug Testing Program of the Substance Abuse and Mental Health Services Administration (SAMHSA). SAMHSA regulated opiate cut-off value from 300 ng/mL to 2000 ng/mL for clinical cases only in 2010. In our country, similar legislation was made in 2016 and unfortunately, the cut-off value was increased to 2000 ng/mL not only for clinical but also for forensic cases. In this study, it is aimed to examine the effects of the opiate cut-off values of 300 and 2000 ng/mL on the toxicological analysis results. Opiate results were evaluated in terms of 300 and 2000 ng/mL cut-off values in the urine samples of the cases who applied to Ege University BATI Institute, Addiction Toxicology Laboratory between 2014–2021 with illegal substance analysis. Urine samples were accepted to the laboratory and urine integrity test was performed before analysis. Urine samples were first subjected to pre-screening analysis by immunoassay method. Confirmation analysis was performed with gas chromatography-mass spectrometry (GC-MS, Agilent 7890B) of the samples that were positive after the pre-scan analysis. A total of 11,348 cases were screened in terms of opiates and the mean age of the cases is 25.4. Of the total cases, 3.45% ( n = 392) were opiate positive. Of the total cases, 83.7% ( n = 328) were male and 16.1% ( n = 64) of them were female. When the cases were classified according to the admitted reasons for the analysis request; alcohol, substance and drug use reason were 67,3%, psychiatric disorders 20.9% and 1.5% due to war & injury and falling, 7,4% for other reasons. According to the cut-off value of 300 ng/mL, the rate of opiate positive cases between 300 < n < 2000 were 39.8%. The cut-off value of 2000 ng/mL, the rate of 2000 < n opiate positive cases were 60.2%. According to the results, if the cases between 2014 and 2021 were evaluated according to the 300 ng/mL cut-off value, treatment and/or forensic proceedings would have been applied to 156 people because they were opiate positive. However, the presence of morphine in the urine samples of forensic toxicological cases, which may cause opiate positivity can be caused by legal prescription drugs, oral use of poppy seeds, or drug use. As the intake of some codeine-containing drugs even at therapeutic amounts and ingestion of food products containing poppy seeds can give a positive opiate result with the 300 ng/mL screening cut-off value, the most appropriate thresholds should extensively studied. The cut-off values used in forensic toxicological analyzes should be paid special attention in clinical and forensic analyzes. Since the cut-off values used in clinical and forensic cases are the same, awareness is the responsibility of forensic toxicologists and the physician who evaluates them medico-legally. Even in the presence of heroin and morphine in the urine matrix, too many true positive cases can be overlooked, since the threshold value used for forensic purposes is the same as that used for clinical purposes and remains below this value.

Deep Learning Algorithms for Diagnosis of Lung Cancer: A Systematic Review and Meta-Analysis.

Simple SummaryLung cancer screening has been shown to help reduce mortality in selected populations of smokers; however, performing screening programs at a larger scale with high accuracy is still a challenge. The use of artificial intelligence (AI) has been investigated to improve large scale screening. We have performed a meta-analysis of the diagnostic accuracy of deep learning (DL) algorithms to diagnose lung cancer. Combining six eligible studies, the pooled sensitivity and specificity of DL algorithms were 0.93 (95% CI 0.85–0.98) and 0.68 (95% CI 0.49–0.84), respectively. Despite remaining challenges in the field, AI is likely to play an important role in disease screening in the future.We conducted a systematic review and meta-analysis of the diagnostic performance of current deep learning algorithms for the diagnosis of lung cancer. We searched major databases up to June 2022 to include studies that used artificial intelligence to diagnose lung cancer, using the histopathological analysis of true positive cases as a reference. The quality of the included studies was assessed independently by two authors based on the revised Quality Assessment of Diagnostic Accuracy Studies. Six studies were included in the analysis. The pooled sensitivity and specificity were 0.93 (95% CI 0.85–0.98) and 0.68 (95% CI 0.49–0.84), respectively. Despite the significantly high heterogeneity for sensitivity (I2 = 94%, p < 0.01) and specificity (I2 = 99%, p < 0.01), most of it was attributed to the threshold effect. The pooled SROC curve with a bivariate approach yielded an area under the curve (AUC) of 0.90 (95% CI 0.86 to 0.92). The DOR for the studies was 26.7 (95% CI 19.7–36.2) and heterogeneity was 3% (p = 0.40). In this systematic review and meta-analysis, we found that when using the summary point from the SROC, the pooled sensitivity and specificity of DL algorithms for the diagnosis of lung cancer were 93% and 68%, respectively.