Diagnostic performance of p16/Ki-67 dual immunostaining at different number of positive cells in cervical smears in women referred for colposcopy

Abstract Background The aim of the study was to evaluate the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/ Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population. Subjects and methods We performed an analysis on a subset cohort of 174 women enrolled within a large-scale randomised controlled human papillomavirus (HPV) self-sampling project organised as part of the population-based Cervical Cancer Screening Programme ZORA in Slovenia. This subset cohort of patients was invited to the colposcopy clinic, underwent p16/Ki-67 DS cervical cytology and had the number of p16/Ki-67 positive cells determined. Results Among analysed women, 42/174 (24.1%) had histologically confirmed CIN2+. The risk for CIN2+ was increasing with the number of positive cells (p < 0.001). The sensitivity of p16/Ki-67 DS for detection of CIN2+ was 88.1%, specificity was 65.2%, positive predictive value was 44.6% and negative predictive value was 94.5%. Conclusions Dual p16/Ki-67 immunostaining for the detection of CIN2+ has shown high sensitivity and high negative predictive value in our study, which is comparable to available published data. The number of p16/Ki-67 positive cells was significantly associated with the probability of CIN2+ detection. We observed a statistically significant and clinically relevant increase in specificity if the cut-off for a positive test was shifted from one cell to three cells.

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Predicting the risk of respiratory distress in newborns with congenital pulmonary malformations

European Respiratory Journal ◽

10.1183/13993003.00949-2021 ◽

2021 ◽

pp. 2100949

Author(s):

Christophe Delacourt ◽

Nathalie Bertille ◽

Laurent J. Salomon ◽

Makan Rashenas ◽

Alexandra Benachi ◽

...

Keyword(s):

Respiratory Distress ◽

Negative Predictive Value ◽

Predictive Value ◽

Volume Ratio ◽

Predictive Ability ◽

Population Based ◽

Term Infants ◽

Predictive Variable ◽

Study Results ◽

Roc Area

ObjectivesMost children with prenatally diagnosed congenital pulmonary malformations (CPM) are asymptomatic at birth. We aimed to develop a parsimonious prognostic model for predicting the risk of neonatal respiratory distress (NRD) in preterm and term infants with CPM, based on the prenatal attributes of the malformation.MethodsMALFPULM is a prospective population-based nationally representative cohort including 436 pregnant women. The main predictive variable was the CPM volume ratio (CVR) measured at diagnosis (CVR first) and the highest CVR measured (CVR max). Separate models were estimated for preterm and term infants and were validated by bootstrapping.ResultsIn total, 67 of the 383 neonates studied (17%) had NRD. For infants born at term (>37 weeks, N=351), the most parsimonious model included CVR max as the only predictive variable (ROC area: 0.70±0.04, negative predictive value: 0.91). The probability of NRD increased linearly with increasing CVR max and remained below 10% for CVR max<0.4. In preterm infants (N=32), both CVR max and gestational age were important predictors of the risk of NRD (ROC area: 0.85±0.07). Models based on CVR first had a similar predictive ability.ConclusionsPredictive models based exclusively on CVR measurements had a high negative predictive value in infants born at term. Our study results could contribute to the individualised general risk assessment to guide decisions about the need for newborns with prenatally diagnosed CPM to be delivered at specialised centers.

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Evaluating Specivity, Sensitivity, Positive and Negative Predictive Values of CA125 for Diagnosing Ovarian Cancer

Journal of Arak University of Medical Sciences ◽

10.32598/jams.24.2.6002.1 ◽

2021 ◽

Vol 24 (2) ◽

pp. 196-203

Author(s):

Elahe Fini ◽

◽

Neda Nasirian ◽

Bahram Hosein Beigy ◽

◽

...

Keyword(s):

Ovarian Cancer ◽

Positive Predictive Value ◽

Tumor Marker ◽

Negative Predictive Value ◽

Predictive Value ◽

Screening Test ◽

High Sensitivity ◽

Medical Community ◽

Cross Sectional ◽

Predictive Values

Background and Aim: Ovarian cancer is among the most common cancers in women worldwide. CA125 is the most frequent biomarker used in the screening for ovarian cancer. CA125 has no high sensitivity and specificity as a screening test in the medical community; however, because of being simple and noninvasive, it is almost always requested for evaluation and ruling out cancer. It plays an important role in the treatment and post-treatment process, the prediction of prognosis, and the relapse of the disease. The present study aimed to determine the relationship between a high level of CA125 tumor marker and ovarian cancer by detecting spesivity, sensivity, positive and negative predictive values. Methods & Materials: In this cross-sectional study, all cases undergoing CA125 test in Velayat Hospital in 2017-1028 were evaluated for having ovarian cancer. In addition, the CA125 level was compared between healthy individuals and patients with ovarian cancer. Finally, the obtained data were analyzed using SPSS. Ethical Considerations: The present study was approved by the Qazvin University of Medical Sciences (Ethics Code: IR.QUMS.REC.1396.316). Results: In this study, 35.3% of the study participants received a definite diagnosis of ovarian cancer. Generally, CA125 values were negative in 41.8% and positive in.58.2% of the study subjects. The sensitivity of the test was measured as 80.1%, the specivity as 53.6%, the positive predictive value equaled 48.4%, and the negative predictive value was measured as 83%. There was a significant relationship between age and the presence of ovarian cancer, and serum CA125 levels. Conclusion: The present study suggested that age and the serum level of CA125 were statistically significant. Finally, CA125 levels were significantly related to ovarian cancer. It provided moderate specivity and specivity as well as low positive predictive value and high negative predictive value as a tumor marker; it is valuable for ruling out of tumor but not appropriate as a screening test.

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Role of MRI in the Diagnosis of Injury to the Lisfranc Ligament Complex

Foot & Ankle Orthopaedics ◽

10.1177/2473011418s00297 ◽

2018 ◽

Vol 3 (3) ◽

pp. 2473011418S0029

Author(s):

Christopher Kreulen ◽

Eric Giza ◽

Eva Escobedo ◽

Cyrus Bateni ◽

Michael Doherty

Keyword(s):

Magnetic Resonance ◽

Mr Imaging ◽

Negative Predictive Value ◽

Predictive Value ◽

High Sensitivity ◽

Lisfranc Injury ◽

Radiology Reports ◽

Lisfranc Ligament ◽

Sensitivity Specificity

Category: Sports Introduction/Purpose: Subtle Lisfranc ligamentous injuries are difficult to diagnose and magnetic resonance is becoming a useful tool. The purpose of this study is to evaluate the efficacy of magnetic resonance (MR) imaging for the diagnosis of injuries of the Lisfranc ligament complex. Methods: The radiology database was searched between Jan 1, 2010 and Mar 10, 2015 to identify patients over the age of 18 years who had MR imaging of the foot for suspected injury of the Lisfranc ligament complex. MR images were reviewed by 2 fellowship trained musculoskeletal radiologists, whom were blinded to the original radiology reports. Findings were categorized as: no injury or injury present. Injury was deemed to be present if 2 of the 3 components of C1-M2 ligament showed disruption or signal alterations on T1 and T2 weighted images. Disagreements were resolved by consensus. Correlation was made with surgical findings whenever performed. In patients not undergoing surgery, the presence or absence of injury was determined by clinical examination performed by an orthopedic surgeon and follow-up. Sensitivity, specificity, positive predictive value(PPV), and negative predictive value (NPV) of MR for diagnosis of Lisfranc ligament complex injury was determined. Results: Of 60 patients, 9 were excluded due to a lack of follow-up. Lisfranc injury was determined to be present on MR in 26 patients and 18 underwent surgery. Injury was confirmed in 16, and 2 were intact. 2 patients underwent closed reduction and were clinically determined to be injured. 6 of the injured 26 patients were sprained and not injured/torn on clinical evaluation. Of the 25 patients determined to have no injury on MR, 24 were intact clinically. 1 patient had a Lisfranc injury on follow-up. Sensitivity, specificity, PPV and NPV of MR for detection of significant Lisfranc injury were 94.7% (CI: 73.9% to 99.9%), 75% (CI: 56.6% to 88.5%), 69.2% (CI: 55% to 80.5%) and 96% (CI: 77.9% to 99.4%) respectively. Conclusion: MR has a high sensitivity and negative predictive value for diagnosis of injury to the Lisfranc ligament complex. MR of the foot should be considered in patients with clinical suspicion of injury to the Lisfranc ligament complex, and it is highly accurate in excluding such injuries.

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Investigating the impact of disease and health record duration on the eMERGE algorithm for rheumatoid arthritis

Journal of the American Medical Informatics Association ◽

10.1093/jamia/ocaa014 ◽

2020 ◽

Vol 27 (4) ◽

pp. 601-605

Author(s):

Vanessa L Kronzer ◽

Liwei Wang ◽

Hongfang Liu ◽

John M Davis ◽

Jeffrey A Sparks ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Predictive Value ◽

Index Date ◽

Model Performance ◽

Area Under The Curve ◽

Population Based ◽

Health Record ◽

The Impact

Abstract Objective The study sought to determine the dependence of the Electronic Medical Records and Genomics (eMERGE) rheumatoid arthritis (RA) algorithm on both RA and electronic health record (EHR) duration. Materials and Methods Using a population-based cohort from the Mayo Clinic Biobank, we identified 497 patients with at least 1 RA diagnosis code. RA case status was manually determined using validated criteria for RA. RA duration was defined as time from first RA code to the index date of biobank enrollment. To simulate EHR duration, various years of EHR lookback were applied, starting at the index date and going backward. Model performance was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC). Results The eMERGE algorithm performed well in this cohort, with overall sensitivity 53%, specificity 99%, positive predictive value 97%, negative predictive value 74%, and AUC 76%. Among patients with RA duration <2 years, sensitivity and AUC were only 9% and 54%, respectively, but increased to 71% and 85% among patients with RA duration >10 years. Longer EHR lookback also improved model performance up to a threshold of 10 years, in which sensitivity reached 52% and AUC 75%. However, optimal EHR lookback varied by RA duration; an EHR lookback of 3 years was best able to identify recently diagnosed RA cases. Conclusions eMERGE algorithm performance improves with longer RA duration as well as EHR duration up to 10 years, though shorter EHR lookback can improve identification of recently diagnosed RA cases.

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Isolated demyelinating syndromes: comparison of CSF oligoclonal bands and different MR imaging criteria to predict conversion to CDMS

Multiple Sclerosis Journal ◽

10.1177/135245850100700603 ◽

2001 ◽

Vol 7 (6) ◽

pp. 359-363 ◽

Cited By ~ 62

Author(s):

M Tintoré ◽

A Rovira ◽

L Brieva ◽

E Grivé ◽

R Jardí ◽

...

Keyword(s):

Mr Imaging ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Predictive Value ◽

High Sensitivity ◽

Oligoclonal Bands ◽

High Negative Predictive Value ◽

Csf Oligoclonal Bands ◽

Sensitivity Specificity

Aim of the study: To evaluate and compare the capacity of oligoclonal bands (OB) and three sets of MR imaging criteria to predict the conversion of clinically isolated syndromes (CIS) to clinically definite multiple sclerosis (CDMS). Patients and methods: One hundred and twelve patients with CIS were prospectively studied with MR imaging and determination of OB. Based on the clinical follow-up (conversion or not conversion to CDMS), we calculated the sensitivity, specificity accuracy, positive and negative predictive value of the OB, and MR imaging criteria proposed by Paty et al, Fazekas et al and Barkhof et al. Results: CDMS developed in 26 (23.2%) patients after a mean follow-up of 31 months (range 12-62). OB were positive in 70 (62.5%) patients and were associated with a higher risk of developing CDMS. OB showed a sensitivity of 81%, specificity of 43%, accuracy of 52%, positive predictive value (PPV) of 30% and negative predictive value (NPV) of 88%. Paty and Fazekas criteria showed the same results with a sensitivity of 77%, specificity of 51%, accuracy of 57%, positive predictive value of 32% and negative predictive value of 88%. Barkhof criteria showed a sensitivity of 65%, specificity of 70%, accuracy of 69%, PPV of 40% and NPV of 87%. The greatest accuracy was achieved when patients with positive OB and three or four Barkhof's criteria were selected. Conclusions: We observed a high prevalence of OB in CIS. OB and MR imaging (Paty's and Fazekas' criteria) have high sensitivity. Barkhof's criteria have a higher specificity. Both OB and MR imaging criteria have a high negative predictive value.

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Correlation of cord blood albumin values with neonatal jaundice in health new-borns: a prospective observational study

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20190702 ◽

2019 ◽

Vol 6 (2) ◽

pp. 634

Author(s):

Jehangir Allam Bhat ◽

Roshan Ara

Keyword(s):

Cord Blood ◽

Negative Predictive Value ◽

Predictive Value ◽

Mode Of Delivery ◽

Subsequent Development ◽

High Sensitivity ◽

High Specificity ◽

Observation Study ◽

Blood Albumin ◽

Group B

Background: The objective of the present study was to investigate the predictability of pathological jaundice on cord blood albumin values.Methods: It was a prospective observation study conducted in Kurji holy family hospital on 289 healthy new-borns. Babies were divided into two groups. Group A who developed physiological jaundice and group B who developed pathological jaundice. Cord blood albumin was estimated in all new-born who were then followed up-to 5th day of life. Babies who developed jaundice requiring treatment were admitted in NICU for phototherapy. Rest where checked regularly up-to 5th day of life and value recorded on 5th day by estimation of serum albumin.Results: Incidence of pathological hyperalbuminemia in present study was 11.2%. There was statistically significant correlation between cord blood albumin and development of pathological jaundice. Gender, age, mode of delivery and birth weight has no correlation with cord albumin and the subsequent development of jaundice. Cord blood albumin <3.5mg/dl when compared with subsequent development of jaundice has high specificity (83.92%) and negative predictive value (87.35%). Cord blood value of >2.5mg/dl has high sensitivity (97.06%), specificity (99.22%), Positive predictive value (94.29%) and negative predictive value (99.61%) in predicting future development of pathological jaundice.Conclusions: The 87.35% negative predictive value in the present study suggests that in healthy term babies (Cord blood albumin ≤3.5mg/dl) cord serum albumin can help to identify those new-borns who are unlikely to require further evaluation and intervention. These new-borns can be discharged with assurance to parents. Babies with CBA level <2.5mg/dl should be followed more frequently. Thus, this study concludes that cord blood total albumin levels reliably predict the occurrence of pathological hyperalbuminemia.

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Development of the Brief Bedside Dysphagia Screening Test – Revised: a Cross-Sectional Czech Study

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2015.93 ◽

2015 ◽

Vol 58 (2) ◽

pp. 49-55 ◽

Cited By ~ 7

Author(s):

Petra Mandysová ◽

Edvard Ehler ◽

Jana Škvrňáková ◽

Michal Černý ◽

Iva Bártová ◽

...

Keyword(s):

Negative Predictive Value ◽

Predictive Value ◽

Gold Standard ◽

Screening Test ◽

High Sensitivity ◽

Endoscopic Examination ◽

Swallowing Function ◽

Cross Sectional ◽

Neurological Conditions ◽

Nose And Throat

Aim: The purpose of this study was to develop a revised version of the Brief Bedside Dysphagia Screening Test for determining penetration/aspiration risk in patients prone to dysphagia. The priority was to achieve high sensitivity and negative predictive value. Methods: The study screeners conducted bedside assessment of the swallowing function in 157 patients with a neurological (mainly stroke) or an ear, nose, and throat diagnosis (mainly head and neck cancer). The results were compared with a gold standard, flexible endoscopic examination of swallowing. Results: For the neurological subgroup (N = 106), eight statistically significant bedside assessment items were combined into the Brief Bedside Dysphagia Screening Test-Revised (BBDST-R). Cut-off score 1 produced the highest sensitivity (95.5%; 95% confidence interval CI [CI]: 84.9–98.7%) and negative predictive value (88.9%; 95% CI 67.2–96.9%). Conclusion: The BBDST-R is suitable for dysphagia screening in departments caring for patients with neurological conditions.

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High Sensitivity of PD-L1 analysis from pleural effusion in non-small cell lung cancer

ERJ Open Research ◽

10.1183/23120541.00787-2020 ◽

2020 ◽

pp. 00787-2020

Author(s):

Lars Hagmeyer ◽

Stephan Schäfer ◽

Marianne Engels ◽

Anja Pietzke-Calcagnile ◽

Marcel Treml ◽

...

Keyword(s):

Lung Cancer ◽

Pleural Effusion ◽

Small Cell Lung Cancer ◽

Negative Predictive Value ◽

Cell Lung Cancer ◽

Predictive Value ◽

High Sensitivity ◽

Small Cell ◽

Small Cell Lung ◽

Sensitivity Specificity

BackgroundPD-1/PD-L1 immune checkpoint inhibitors have been approved for monotherapy of metastatic non-small cell lung cancer (mNSCLC) depending on tumor cells' PD-L1 expression. Pleural effusion (PE) is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from PE samples is unclear.Aim of the studyTo analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of PE in NSCLC as compared to immunohistochemistry of pleural biopsies.Patients and Methods50 consecutive subjects (17 female, median age 72.5, 7 never-smokers) were enrolled in this prospective controlled two-center study. Inclusion criteria were PE, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, positive (PPV) and negative predictive value (NPV) was performed for PD-L1 detection from PE.Results50 subjects underwent pleural puncture and thoracoscopy. Pathologic diagnoses were lung cancer (48), lymphoma (1), mesothelioma (1). Sensitivity, specificity, positive-predictive-value and negative-predictive-value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% confidence interval 46–100%), 63%(36–84%), 45%(18–75%), 100%(66–100%), and with expression ≥1% defined as positive 86%(56–97%), 43%(12–80%), 75%(47–92%), 60%(17–93%).ConclusionPD-L1 analysis in tumor-positive PE samples shows a very high sensitivity and negative-predictive-value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negatve-predictive-value, making other invasive procedures necessary. (NCT02855281)

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Lung ultrasound in ruling out COVID-19 pneumonia in the ED: a multicentre prospective sensitivity study

Emergency Medicine Journal ◽

10.1136/emermed-2020-210973 ◽

2021 ◽

pp. emermed-2020-210973

Author(s):

Carmine Cristiano Di Gioia ◽

Nicola Artusi ◽

Giovanni Xotta ◽

Marco Bonsano ◽

Ugo Giulio Sisto ◽

...

Keyword(s):

Negative Predictive Value ◽

Likelihood Ratio ◽

Predictive Value ◽

Lung Ultrasound ◽

High Sensitivity ◽

Index Test ◽

Blood Gas ◽

Reference Standard ◽

Arterial Blood ◽

Rule Out

PurposeEarly diagnosis of COVID-19 has a crucial role in confining the spread among the population. Lung ultrasound (LUS) was included in the diagnostic pathway for its high sensitivity, low costs, non-invasiveness and safety. We aimed to test the sensitivity of LUS to rule out COVID-19 pneumonia (COVIDp) in a population of patients with suggestive symptoms.MethodsMulticentre prospective observational study in three EDs in Northeastern Italy during the first COVID-19 outbreak. A convenience sample of 235 patients admitted to the ED for symptoms suggestive COVIDp (fever, cough or shortness of breath) from 17 March 2020 to 26 April 2020 was enrolled. All patients underwent a sequential assessment involving: clinical examination, LUS, CXR and arterial blood gas. The index test under investigation was a standardised protocol of LUS compared with a pragmatic composite reference standard constituted by: clinical gestalt, real-time PCR test, radiological and blood gas results. Of the 235 enrolled patients, 90 were diagnosed with COVIDp according to the reference standard.ResultsAmong the patients with suspected COVIDp, the prevalence of SARS-CoV-2 was 38.3%. The sensitivity of LUS for diagnosing COVIDp was 85.6% (95% CI 76.6% to 92.1%); the specificity was 91.7% (95% CI 86.0% to 95.7%). The positive predictive value and the negative predictive value were 86.5% (95%CI 78.8% to 91.7%) and 91.1% (95% CI 86.1% to 94.4%) respectively. The diagnostic accuracy of LUS for COVIDp was 89.4% (95% CI 84.7% to 93.0%). The positive likelihood ratio was 10.3 (95% CI 6.0 to 17.9), and the negative likelihood ratio was 0.16 (95% CI 0.1 to 0.3).ConclusionIn a population with high SARS-CoV-2 prevalence, LUS has a high sensitivity (and negative predictive value) enough to rule out COVIDp in patients with suggestive symptoms. The role of LUS in diagnosing patients with COVIDp is perhaps even more promising. Nevertheless, further research with adequately powered studies is needed.Trial registration numberNCT04370275.

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The Value of MicroRNA-375 Detection for Triaging Primary Human Papillomavirus Positive Women: A Cross-Sectional Study in a General Population

Frontiers in Oncology ◽

10.3389/fonc.2021.771053 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiongyan Wu ◽

Lingfang Wang ◽

Xiumin Zhao ◽

Qifang Tian ◽

Fenfen Wang ◽

...

Keyword(s):

Human Papillomavirus ◽

General Population ◽

Predictive Value ◽

Intraepithelial Neoplasia ◽

Population Based ◽

Cross Sectional Study ◽

Cross Sectional ◽

Exfoliated Cells ◽

Lower Specificity ◽

Mirna Detection

PurposeThis study aims to validate the value of microRNA (miRNA) detection for triaging human papillomavirus (HPV)-positive women in the general population.Patients and MethodsmiR-375 detection in cervical exfoliated cells has been demonstrated to have the superior value to cytology in triaging primary HPV-positive women in the hospital population. In this study, residual samples of cervical exfoliated cells from 10,951 women in a general population were used to detect miRNA. The performance efficiency of miRNA detection in identifying high-grade cervical intraepithelial neoplasia (CIN) was evaluated. Pearson chi-square test and McNemar pairing test were used to compare miRNA detection and cytology.ResultsIn valid 9,972 women aged 25–65, miR-375 expression showed a downward trend along with an increase in cervical lesion severity. The expression level of miR-375 ≤1.0 × 10-3 was identified as positive. In the HPV-positive and 12 HPV genotypes other than 16/18 (HR12)-positive women, miR-375 detection showed equivalent sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to that of cytology (≥ASC-US) and higher or similar sensitivity and NPV but lower specificity and PPV than that of cytology (≥ASC-H) in identifying CIN3+ and CIN2+. In HPV 16-positive women, miR-375 positivity had higher sensitivity and NPV but lower specificity and PPV than that of cytology (≥ASC-H and HSIL) in identifying CIN3+ and CIN2+. The immediate CIN3+ risk of miR-375 positivity was 19.8% (61/308) in HPV-positive, 10.8% (22/204) in HR12-positive, and 43.5% (37/85) in HPV16-positive women, respectively.ConclusionThe detection of miR-375 in cervical exfoliated cells may be an optional method for triaging primary HPV-positive women in population-based cervical cancer screening.

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