Primary Screening Test Research Articles

Explainable Vision Transformers and Radiomics for COVID-19 Detection in Chest X-rays.

The rapid spread of COVID-19 across the globe since its emergence has pushed many countries’ healthcare systems to the verge of collapse. To restrict the spread of the disease and lessen the ongoing cost on the healthcare system, it is critical to appropriately identify COVID-19-positive individuals and isolate them as soon as possible. The primary COVID-19 screening test, RT-PCR, although accurate and reliable, has a long turn-around time. More recently, various researchers have demonstrated the use of deep learning approaches on chest X-ray (CXR) for COVID-19 detection. However, existing Deep Convolutional Neural Network (CNN) methods fail to capture the global context due to their inherent image-specific inductive bias. In this article, we investigated the use of vision transformers (ViT) for detecting COVID-19 in Chest X-ray (CXR) images. Several ViT models were fine-tuned for the multiclass classification problem (COVID-19, Pneumonia and Normal cases). A dataset consisting of 7598 COVID-19 CXR images, 8552 CXR for healthy patients and 5674 for Pneumonia CXR were used. The obtained results achieved high performance with an Area Under Curve (AUC) of 0.99 for multi-class classification (COVID-19 vs. Other Pneumonia vs. normal). The sensitivity of the COVID-19 class achieved 0.99. We demonstrated that the obtained results outperformed comparable state-of-the-art models for detecting COVID-19 on CXR images using CNN architectures. The attention map for the proposed model showed that our model is able to efficiently identify the signs of COVID-19.

HIGH RESOLUTION COMPUTED TOMOGRAPHY VS RT-PCR CORRELATION FOR DIAGNOSIS OF COVID-19

To restrain the spread of this pandemic of COVID-19 we need an accurate and quick diagnostic tool. The diagnostic tool should be cost effective and sensitive as well. Real time RTPCR has been widely accepted throughout the world and is being done as a primary screening test, while HRCT is done to analyze lung involvement. It has been found that a signicant number of patients with negative RTPCR test have featured on HRCT suggestive of COVID-19. This study entails comparison of RTPCR and HRCT in terms of efcacy, cost and rapidness for diagnosis of COVID-19 infection.

Online Education Improves Clinicians’ Knowledge and Competence Related to Advances in Cervical Cancer Screening [A44

INTRODUCTION: Women who test positive on primary screening tests for human papillomavirus (HPV) infection are triaged with Pap to determine whether a colposcopy is needed. The diagnostic variability of Paps may lead to missed diagnosis. Clinicians would benefit from education that will provide expert guidance on best-practice triage strategies for women who test HPV-positive. METHODS: The educational initiative consisted of an online video-based continuing medical education (CME) discussion among three experts, with synchronized slides. Intervention included pre/post study assessment, and McNemar tests (P< .05 level) determined statistical significance. Learners who improved (answered ≥1 questions correctly pre-education than post) were identified. Data are reported from 1/11/2021-10/17/2021. RESULTS: The analysis set consisted of obstetrician-gynecologists (ob-gyns) (n=1,086) and primary care providers (PCPs) (n=296). Pre- vs. post-education decisions demonstrated significant improvement (P<.001) in knowledge and competence related to the following for HPV positive women (pre% vs. post%): Knowledge regarding the limitations of traditional cytology methods: 20% of ob-gyns improved (36% pre, 48% post, P<.001); 21% of PCPs improved (28% pre, 41% post, P<.001). Knowledge regarding newer methodologies to triage women with abnormal screening results: 41% of ob-gyns improved (31% pre, 67% post, P<.001); 33% of PCPs improved (24% pre, 49%,P<.001). Competence related to follow-up care: 21% of ob-gyns (16% pre, 30% post, P<.001); 11% of PCPs improved (18% pre, 24% post; P<.05). CONCLUSION: The intervention demonstrates improvements and highlights the role of online video-based CME discussion in improving knowledge and competence related to clinicians’ ability to triage women who are HPV positive or have an abnormal Pap test. Additional gaps were identified for future education.

Evaluation of the AFIAS-1 thyroid-stimulating hormone point of care test and comparison with laboratory-based devices.

Thyroid-stimulating hormone (TSH) is the routine primary screening test to assess thyroid function and rapid measurement of TSH levels is highly desirable especially in emergency situations. In the present study, we compared the analytical performance of a commercially available point-of-care test (AFIAS-1) and five laboratory-based systems. Left over material of 60 patient plasma samples was collected from patient care and used in the respective assay. For statistical analysis of the produced data Bland-Altman and Passing-Bablok regression analysis were applied. Good correlation (r=0.982 or higher) was found between all devices. Slopes from regression analysis ranged from 0.972 (95% CI: 0.927-1.013) to 1.276 (95% CI: 1.210-1.315). Among the compared devices, imprecision was high in terms of coefficient of variation (CV=10.3%) for low TSH concentrations and lower (CV=7.3%) for high TSH concentrations. Independent of the method used, we demonstrated a poor standardization of TSH assays, which might impact clinical diagnosis e.g. of hyperthyreosis. This study shows that the point-of-care (POC) test AFIAS-1 can serve as an alternative to laboratory-based assays. In addition the data imply that better standardization of TSH measurements is needed.

Efficacy of Visual inspection with acetic acid (VIA) and PAP smear as a screening method for diagnosis of premalignant lesions of cervix in high-risk patient

Background: Carcinoma Cervix is one of the common malignant pathology causing considerable morbidity and mortality in women. One of the important aspects of management of carcinoma cervix is its early detection and appropriate management since delay in the diagnosis can have catastrophic consequences. Unfortunately in developing countries in many cases, diagnosis is delayed due to non-availability of facilities at rural areas. To overcome this screening methods such as Visual Inspection with Acetic Acid (VIA) and PAP smear can be done in high-risk patients and in selected cases cervical biopsy can be done. Aims and Objectives: (1) To compare VIA and PAP smear in relation to colposcopy as a screening method for premalignant lesions of cervix. (2) To study the efficacy of VIA as a primary screening test for detection of premalignant lesions of cervical cancer. Materials and Methods: This was a prospective analytical study in which 100 women with unhealthy cervix attending obstetrics and gynecology out patient department who were willing to participate and gave written informed consent were enrolled in the study on the basis of a predefined inclusion and exclusion criteria. VIA was done. Pap smear was taken and slides were stained with modified Papanicolaou staining method and examined under light microscope. we compared the efficacy of VIA and PAP smear as a screening method for diagnosis of premalignant lesions of cervix in high-risk patient, and the results were confirmed with the help of colposcopy examination and its histopathological correlation with guided biopsy. Results: Mean age of the study population was found to be 40.94 years. When VIA, PAP Smear, and colposcopy were compared highest sensitivity was seen in VIA whereas colposcopy showed highest accuracy (82%). PAP was found to have a higher specificity (84.62%) as compared to VIA or colposcopy. Highest positive predictive value and negative predictive value was seen in PAP smear (78.95%) and colposcopy (86.96%). Conclusion: VIA is an easy to perform and highly sensitive test for diagnosis of carcinoma cervix however it has got a poor specificity. Colposcopy was found to be a better diagnostic test as it was both more sensitive as well as specific to diagnose premalignant lesions.

Modified multiple marker aneuploidy screening as a primary screening test for preeclampsia

BackgroundAbnormal levels of maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE). The secondary aim was to assess this combination in identifying pregnancies at risk for gestational hypertension and preterm birth.MethodsThis case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE who delivered at < 37 and < 34 weeks of gestation, respectively.ResultsThere were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p < 0.0001), PlGF (0.76 vs 1.01, p < 0.0001) and free-β hCG (0.81 vs. 0.98, p < 0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p < 0.01) and PlGF (0.75 vs 1.02, p < 0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free β-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester. The corresponding DR was 58% for gestational hypertension and 36% for preterm birth cases.ConclusionsMaternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy. This combination was less accurate in predicting women who have gestational hypertension or preterm birth.

HPV test kao primarni test skrininga u prevenciji cervikalnog karcinoma u Republici Hrvatskoj

The knowledge that persistent infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer has led to changes in strategies for the prevention and early detection of this cancer, with aim to eradicate it. Primary prevention through the use of vaccines that prevent HPV infection has been implemented since 2006, while secondary prevention of cervical cancer has been significantly improved by the introduction of the HPV test, either as the only method of primary screening or in combination with the Pap test. Screening based on the Pap smear has been unquestionably successful in reducing incidence and mortality in the last century. More recently, there have been gradual changes in the use of the HPV test, from its use as a reflex test after the detection of mild cytological abnormalities, through co-testing, to the use of the HPV test as the only test in primary screening thanks to the evidence gathered from the use of large, randomized research and meta-analysis. The advantages of using the HPV test over the Pap test include a higher sensitivity in detecting premalignant lesions, a higher negative predictive value of the test, and a safe extension of the time interval between screenings. However, the introduction of the HPV test as a primary screening test is not so simple and requires strict testing quality control and elaborate guidelines to ensure an optimal strategy and prevent additional burden on the healthcare system. This review presents the national cervical cancer screening program in the Republic of Croatia, the problems that prevented the start of a pilot project in one Croatian county selected for the introduction of the HPV test as a primary screening test in the prevention of cervical carcinoma, and the tasks ahead in the next period which would ensure the smooth implementation of the pilot project and implement the HPV test as the primary screening test in Croatia. Based on the results of the pilot project, it is necessary to precisely define: the age at which primary HPV testing should start and stop in the cervical cancer screening program, the examination interval after a negative primary HPV test, further procedures with women with a positive primary HPV test, the procedures for conducting reflex cytological testing and further treatment of the patient in accordance with the findings, the possibilities and justification of introducing self-sampling as part of the cervical cancer screening program based on the HPV test as the primary screening test, and finally the type of HPV test that is most suitable for the primary screening in Croatia.

Comparative performance of the human papillomavirus test and cytology for primary screening for high-grade cervical intraepithelial neoplasia at the population level.

The World Health Organization recommends high-risk human papillomavirus (hrHPV)-based screening for women 39 to 49 years, based on the greater accuracy of hrHPV-based screening for cervical cancer detection. Many cervical cancer screening programs have incorporated hrHPV testing and multiple early cervical cancer detection strategies have been evaluated, mostly under controlled conditions. However, there are few evaluations of combined hrHPV and cytology strategies post-implementation at the population level. Our study sought to estimate the relative yield of hrHPV testing compared to cervical cytology, as a primary screening test for cervical intraepithelial neoplasia grade 2+ (CIN2+), used at the population level. We analyzed screening data from Mexico's public cervical cancer prevention program from 2010 to 2015 in women 35 to 64 years. The study population consisted of two cohorts: one from a total of 2 881 962 cytology-based screening tests and another from a total of 2 004 497 hrHPV-based screening tests, which are concurrent in time. We performed a relative yield analysis using Poisson regression models to compare the effectiveness of hrHPV testing for CIN2+ with cervical cytology. A total of 4 886 459 records were analyzed, including 23 999 biopsies; 0.12% (n=6166) had a CIN2+ histologic diagnosis. hrHPV testing with cytological triage detects twice as many CIN2+ cases as screening using cytology alone.

Prenatal pre-eclampsia screening using maternal characteristics, maternal serum PAPP-A and PlGF in the first trimester

To assess the effectiveness of a combination of maternal characteristics, maternal serum pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF) as a primary screening test for pre-eclampsia.

XViTCOS: Explainable Vision Transformer Based COVID-19 Screening Using Radiography.

Objective: Since its outbreak, the rapid spread of COrona VIrus Disease 2019 (COVID-19) across the globe has pushed the health care system in many countries to the verge of collapse. Therefore, it is imperative to correctly identify COVID-19 positive patients and isolate them as soon as possible to contain the spread of the disease and reduce the ongoing burden on the healthcare system. The primary COVID-19 screening test, RT-PCR although accurate and reliable, has a long turn-around time. In the recent past, several researchers have demonstrated the use of Deep Learning (DL) methods on chest radiography (such as X-ray and CT) for COVID-19 detection. However, existing CNN based DL methods fail to capture the global context due to their inherent image-specific inductive bias. Methods: Motivated by this, in this work, we propose the use of vision transformers (instead of convolutional networks) for COVID-19 screening using the X-ray and CT images. We employ a multi-stage transfer learning technique to address the issue of data scarcity. Furthermore, we show that the features learned by our transformer networks are explainable. Results: We demonstrate that our method not only quantitatively outperforms the recent benchmarks but also focuses on meaningful regions in the images for detection (as confirmed by Radiologists), aiding not only in accurate diagnosis of COVID-19 but also in localization of the infected area. The code for our implementation can be found here - https://github.com/arnabkmondal/xViTCOS. Conclusion: The proposed method will help in timely identification of COVID-19 and efficient utilization of limited resources.

The Pap Smear Test Experience of Iranian Women: A Qualitative Study

Aims: The Pap smear test as the primary screening test for cervical cancer has a low application rate among Iranian women. This study aimed to explore Iranian women’s Pap smear test experiences at healthcare centers. Participants & Methods: This qualitative study was carried out in Varamin City, in 2018. To this end, 15 women admitted to healthcare centers were selected using purposive sampling. Inclusion criteria consisted of married women aged 20-50 years with a history of Pap smear, willingness to participate in the study, Iranian nationality, and ability to speak. To explore the women’s views and experiences, semi-structured interviews were conducted, recorded, transcribed, and analyzed using content analysis. Four criteria, namely credibility, confirmability, dependability, and transferability were used to verify the accuracy and consistency of the data. Findings: The data analysis yielded five main categories, including "intention to perform the test","policies and the administrative system", "social factors helping to perform the test", "barriers to perform the test", and "motivational factors to perform the test". From the participants’ perspective, risk concepts, and supportive policies were critical in enhancing test performance. Conclusions: The results showed that the women’s Pap smear test performance depended on some factors including convenient and friendly interactions with healthcare providers, family support, encouraging policies and laws, and awareness. The cooperation of other organizations to perform a Pap smear test is also emphasized.

Cervical Visual Inspection with Acetic Acid (VIA) and Oncogenic Human Papillomavirus Screening in Rural Indigenous Guatemalan Women: Time to Rethink VIA.

Single-visit “screen-and-treat” strategies using visual inspection with acetic acid (VIA) and cryotherapy (liquid nitrous oxide ablation) in low-resource settings are commonly used to detect and treat precancerous lesions for cervical cancer prevention. This study compared VIA sensitivity and specificity in rural indigenous Guatemalan communities, to that of oncogenic human papillomavirus (HPV) testing for detection of precancerous changes, using cytology as the reference standard. Between 3–8 September 2017, trained nurses examined 222 women aged 23–58 years with VIA. Specimens for liquid-based cytology and HPV testing were obtained prior to VIA with a cytobrush and transported in PreservCyt to a US clinical laboratory. VIA and HPV test sensitivities were assessed as proportions of women with abnormal cytology that had abnormal VIA or HPV results, respectively, and specificities, as proportions with normal cytology with normal VIA or negative HPV tests. Of 222 women, 18 (8.1%) had abnormal cytology (1 carcinoma in a participant who received VIA-based cryotherapy in 2015, 4 high- and 5 low-grade squamous intraepithelial lesions, and 8 atypical squamous cells of undetermined significance (ASCUS)). Excluding ASCUS, sensitivities of VIA and HPV were 20.0% and 100%, respectively. VIA-based screening may not be acceptable for detecting precancerous lesions, and field cryotherapy for preventing malignancy. The World Health Organization recommended in 2021 “…using HPV DNA detection as the primary screening test rather than VIA or cytology”.

Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss.

A 31-year-old healthy White man experienced painless sequential vision loss. Brain imaging and laboratory investigations for infectious, inflammatory, and nutritional conditions, in addition to targeted genetic testing for Leber hereditary optic neuropathy (LHON), were all normal or negative. Despite systemic corticosteroid therapy and plasma exchange, vision continued to worsen. Eventually, mitochondrial whole-genome sequencing was performed, which demonstrated a mutation at the 13513G>A position confirming the diagnosis of LHON. The three primary mutations (11778G>A, 14484T>C, and 3460G>A) account for 90% of LHON cases; therefore, it is important to consider whole-genome mitochondrial sequencing in cases with a high index of clinical suspicion and negative primary mutation screening testing.

Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study.

BackgroundHigh-risk human papillomavirus (hrHPV) testing on self-collected samples has potential as a primary screening tool in cervical screening, but real-world evidence on its accuracy in hrHPV-based screening programmes is lacking.MethodsIn the Netherlands, women aged 30–60 years invited for cervical screening can choose between sampling at the clinician's office (Cervex Brush) or self-sampling at home (Evalyn Brush). HrHPV testing is performed using Roche Cobas 4800. We collected screening test results between January 2017 and March 2018 and histological follow-up until August 2019. The main outcome measures were mean cycle threshold (Ct) value, cervical intraepithelial neoplasia (CIN) grade 3 or cancer (CIN3+) and CIN grade 2 or worse (CIN2+).Findings30,808 women had a self-collected and 456,207 had a clinician-collected sample. In hrHPV-positive women with adequate cytology, Ct values were higher for self-collection than clinician-collection with a mean Ct difference of 1·25 (95% CI 0·98–1·52) in women without CIN2+, 2·73 (1·75–3·72) in CIN2 and 3·59 (3·03–4·15) in CIN3+. The relative sensitivity for detecting CIN3+ was 0·94 (0·90–0·97) for self-collection versus clinician-collection and the relative specificity was 1·02 (1·02–1·02).InterpretationThe clinical accuracy of hrHPV testing on a self-collected sample for detection of CIN3+ is high and supports its use as a primary screening test for all invited women. Because of the slightly lower sensitivity of hrHPV testing on a self-collected compared to a clinician-collected sample, an evaluation of the workflow procedure to optimise clinical performance seems warranted.FundingNational Institute for Public Health and the Environment (the Netherlands) and the European Commission.

Detection and Identification of Plant Growth Promoting Bacteria from Sorghum (Sorghum bicolor L. Moench) Rhizosphere Soil in Northern Ethiopia

Plant growth promoting rhizobacteria are the bacteria which subsist inside and outside of the plant tissue and promote plant growth through direct or indirect mechanisms. To increase sorghum production and productivity we utilize herbicides and chemical fertilizers to overcome sorghum production constraints, but those chemicals have negative side effects. The current study was conducted with the objective of isolation of PGPR from sorghum rhizosphere and screening for primary growth related trait, evaluation of potential PGPR at greenhouse for sorghum growth performance and identify through biochemical characterization. So that, in this study a total of 117 plant growth promoting rhizobacteria were isolated from the rhizosphere of 12 sorghum (Sorghum bicolor L. Moench) genotype by cultivating using 3 collected soil samples from the northern part of Ethiopia (Amhara and Tigray regional states) in greenhouse. Isolated bacteria were screened for primary growth promoting traits such as phosphate solubilization test, IAA production test at different concentration of L-tryptophan and ammonia production test. From the isolated bacteria 28% solubilized Phosphorous, 78% produced IAA at different concentration of tryptophan. The greatest IAA production was scored at 100 mg/L of tryptophan and the lowest production of IAA was scored at 150 mg/L of tryptophan, 69% of isolated bacteria produced ammonia. Hence, 15% of isolated bacteria fulfilled the above primary screening test and used for further greenhouse evaluation. Accordingly, eighteen bacteria were tested for greenhouse experiment using completely randomized design and all 18 isolates were significantly increased all the agronomic parameter as compared to the control such as plant shoot height, plant shoot fresh and dry weight, root length, root fresh and dry weight at p &lt; 0.01 and P ≤ 0.001. Two isolates G6E29 and G4E19 had significantly increased all the parameter but two isolates (G12E19 and G3E40) were statistically non-significant for root fresh weight compared to the control. These 18 potential isolates were characterized morphologically and biochemically. Eight isolates were grouped at Pseudomonas genera. Six isolates were grouped at Azotobacter and the rest four isolates were grouped at Bacillus genera. Thus, the use of plant growth promoting rhizosphere bacteria could be useful to improve sorghum production and productivity. However, further molecular identification and evaluation of the isolates exhibiting multiple plant growths promoting traits on plant-microbe interaction for economic crop of Ethiopia is needed to uncover their efficacy as effective plant growth promoting rhizosphere bacteria.

Serologic and Molecular Detection of Mycoplasma gallisepticum in Layer Flocks in South Marmara Region of Turkey

Background: Due to the economic impacts of Mycoplasma gallisepticum (MG) infection in poultry, it is essential to have a fast, reliable and accurate diagnostic test to diagnose the infection.&#x0D; Aims: It was aimed to examine the presence of MG in the South Marmara Region of Turkey where extensive commercial layer flocks exist by RPA, ELISA and real-time PCR.&#x0D; Materials and Methods: In the study, 981 sera and 160 tracheal swab samples (20 swabs per each flock) obtained from eight layer flocks were examined for the presence of MG-antibody by RPA, ELISA, and the presence of MG by real-time PCR, respectively.&#x0D; Results: MG-seropositive flock rate was determined to be 100% by RPA. Twenty-three of the RPA positive sera in each flock LA, LB, LC, LD, LF, LG, and 17 RPA positive sera in flock LE (due to 17 positive RPA sera obtained) were examined for the presence of MG antibody by ELISA, and MG-seropositive flock rate was determined to be 87.5%. As a result of the examination of a total of 32 tracheal swab samples (20 swabs perflock/5 swabs=4 pooled samples, 8 flocksX4 pooled samples= 32 samples) for the presence of MG, real-time PCR positive flock rate was found to be 75%.&#x0D; Conclusion: To decide the flock whether it is infected or not and the initiate effective preventive measures against MG infection as soon as possible; serology should be applied simultaneously with bacteriology and/or PCR to prevent time loss due to shortcomings of serological tests used as primary screening test such as cross reactions, sensitivity and specificity problems.

Screening Tests for Early Diagnosis of Multiple Myeloma and Related Plasma Cell Disorders

Monoclonal gammopathy (MG) encompasses a diverse group of disorders characterized by the secretion of monoclonal immunoglobulins or their light-chain components. The incidence of multiple myeloma (MM) in South Korea is rapidly increasing, and it is important to be aware of its initial clinical presentations and the most efficient laboratory algorithms for early detection. Serum protein electrophoresis (SPE) and urine protein electrophoresis (UPE) are the primary screening tests for patients with clinically suspected MM or amyloid light-chain amyloidosis; these tests are reimbursed in South Korea. We reviewed clinical studies that applied national and international guidelines to evaluate test panels for early detection of MGs, including MM. The serum free light chain (sFLC) with SPE panel is recommended for the initial work up for diagnosis of MGs. In the case of a normal SPE, sFLC should be measured subsequently, so as not to miss the presence of M-protein. Use of this screening panel avoids medical expenses related to delayed diagnosis. Guidelines and recommendations suggest that no single method (SPE, serum immunofixation electrophoresis, sFLC, or UPE) should be used to exclude a diagnosis of MM. We believe that a screening test panel comprising SPE plus sFLC will increase the rate of early and accurate diagnosis of MM and related disorders.

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors.

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

HPV Screening Test for the Detection of Precancerous Cervical Lesions and Cervical Cancer in Israeli Women

Objectives: This work is aimed to summarize the first year of the high-risk human papillomavirus (hrHPV) screening test and compare it to the cytology screening test, regarding positivity rates and premalignant lesions diagnosed in the Israeli population. A specific consideration is for the age group 25–30 that is not considered mandatory for the HPV primary screening testing. Methods: A retrospective study was performed in women who were screened for prevention of cervical cancer in Maccabi HealthCare HMO from March 2017 to March 2019. Screening methods included hrHPV typing for types 16, 18, and the other 12 hrHPV types and the PAP LBC test. Results: A total of 115,807 cervical samples were tested for HPV presence and 91% (105,225) were found negative for hrHPV. The other 9% (10,582) were positive for one or more of the 14 hrHPV types tested, and 37% (3,916) of them showed abnormal PAP LBC results. In the age group of 25–30, 3,104 (17.5%) women were found positive for hr­HPV (825 had hrHPV types 16 and/or 18), of which 42% (1,293) of them showed abnormal PAP LBC results. During the hrHPV versus PAP LBC screening era, 258 more women were diagnosed with precancerous cervical lesions (CIN2/3), 70% increased detection versus cytology screening. Conclusions: The hrHPV screening test is currently the best method for the detection of precancerous cervical lesions and cervical cancer, and it is better started at age 25.

Evaluating the Performance of Hybrid Capture 2 Test as a Primary Screening Test from Studies Conducted in Low and Middle-Income Country Settings- Special Focus India.

Among the screening tests for cervical cancer, advantages of screening with second generation molecular Hybrid Capture 2 (HC2) test is the high sensitivity and negative predictive value that makes it easy to implement as a cervical cancer screening policy necessitating less screening rounds. High income countries are now implementing HC2 test in their national cervical cancer screening program. Since the acceptance of any screening test depends on the sensitivity of the test, the current study was carried out to evaluate the sensitivity of HC2 test reported from Low- and Middle-income countries (LMIC) which share major burden of cervical cancer globally and to establish if HC2 test could be used as a primary screening test in India. Materials and methods:The population based cross sectional studies from LMICs which evaluated HC2 test as a primary screening modality to diagnose Cervical intraepithelial neoplasm grade 2 and above (CIN2+) lesions were included. Results:A total of 18 studies from LMIC involving 1,13,086 women were reviewed for sensitivity of HC2 as a primary screening test. The overall average sensitivity and specificity to diagnose CIN2+ lesions were 79.84% (95% CI-71.01,86.73) and 85.63% (95% CI- 84.37,86.92) respectively. India demonstrated an average sensitivity and specificity of 65% (95% CI 57,77) and 93% (95% CI- 92,94) respectively. Conclusion:Results from LMIC demonstrate a comparably low sensitivity of HC2 test to diagnose CIN2+ lesions as compared to that reported from High income countries. Sensitivity of HC2 was substantially low for India. The current study discusses issues of HC2 assay and the role of untreated Reproductive tract infections as probable causes for low sensitivity of the test. This needs further research in an attempt to improve the sensitivity of the test in an era of self-sampling and low-cost HPV test on horizon to improve the coverage for cervical cancer.