Screening Of Asymptomatic Individuals Research Articles

Mapping local evidence on early recognition and management of people with potential cancer symptoms: a narrative review

Aim Early cancer detection has potential to improve outcomes. However, many patients in South Africa present when the disease is at an advanced stage. The World Health Organization recommends two approaches to early cancer detection: screening asymptomatic individuals, and early recognition and management of symptomatic individuals. This paper focuses on the latter. For people with potential cancer symptoms, the journey to diagnosis is complex and influenced by multiple factors. Most symptomatic people will self-present to primary health care clinics, where primary health care providers are pivotal in triage. Methods This article presents local insights into cancer awareness measurement tools: community-level cancer symptom awareness, lay beliefs, and symptom appraisal; factors influencing the journey from symptom discovery to diagnosis; primary health care provider challenges in assessing symptomatic individuals, and interventions to support symptom assessment and help-seeking. It draws on findings from the African Women Awareness of CANcer (AWACAN) project and a narrative review of relevant published articles on journeys to cancer diagnosis in SA (2013-2023). Findings Very few cancer awareness measurement tools have been locally validated, hampering comparison and limiting opportunities for intervention development and evaluation. The AWACAN study developed and validated a local cancer awareness measurement tool for breast and cervical cancer. Studies show that most people in SA need information on cancer risk, symptoms, and pathways to care. Barriers to accessing health care include financial, infrastructural, safety, stigma, and previous health facility experiences. Primary health care providers require support for symptom assessment and referral systems. There is limited local work on developing and evaluating interventions to improve timely cancer diagnosis. Conclusions This paper underscores the importance of prioritising early recognition and management of people with symptomatic cancer as part of a comprehensive cancer control plan, providing insights for improving the journey to diagnosis.

557P Three-year update of real-world evaluation of ColonAiQ for colorectal cancer screening in asymptomatic individuals

557P Three-year update of real-world evaluation of ColonAiQ for colorectal cancer screening in asymptomatic individuals

Observations Regarding the Detection of Abnormal Findings Following a Cancer Screening Whole-Body MRI in Asymptomatic Subjects: The Psychological Consequences and the Role of Personality Traits Over Time.

The use of whole-body MRI (WB-MRI) in oncology has uncovered frequent unexpected abnormal findings (AFs). However, the impact of AFs on the patients' mental well-being is still poorly examined. To investigate the long-term psychological consequences of AF detection following WB-MRI for cancer screening in asymptomatic individuals. Prospective, longitudinal. 121 consecutive subjects of the general population (mean age = 52.61 ± 11.39 years; 63% males) scheduled for cancer screening by WB-MRI. 1.5-T and 3-T; protocol complied with Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) guidelines. Participants completed the first psychological investigation (T0) immediately after the WB-MRI. Subsequently, it was repeated after 1-year (T1), and 4-years (T2, subgroup of 61 participants) without an MRI exam, assessing personality traits, tumor risk perception, quality of life, depressive, and anxious symptoms. Radiologists directly reported WB-MRI findings to the participants, explaining the clinical implications and the location of the AFs. The number and severity of AFs were assessed. Pearson's correlations and analysis of variance with repeated measures assessed the psychological health variables' relationship and their changes over time. A P-value <0.05 was considered statistically significant. All participants presented AFs, with 101 individuals categorized as ONCO-RADS 2 and 19 as ONCO-RADS 3. The AFs were most prevalent in bones (31.5%). The overall participants showed only a slight increase in depressive symptoms at T1 [F(1,112) = 7.54]. The severity and the number of AFs were not significantly related to psychological changes [ranging from P = 0.503 to P = 0.997]. Depressive and anxious symptoms over time were significantly affected by the traits of conscientiousness [T1: F(1,112) = 7.87; T2: F(1.708,90.544) = 3.40] and openness [T1: F(1,112) = 4.41]. Disclosing AFs by WB-MRI exams for cancer screening may not lead to long-term psychosocial consequences. Certain personality traits may, however, influence the psychological distress experienced by individuals with AFs after WB-MRI exams. Stage 5.

Attitudes to multi-cancer early detection (MCED) blood tests for population-based screening: A qualitative study in Great Britain

BackgroundTrials are underway to test the clinical utility of multi-cancer early detection (MCED) blood tests for screening asymptomatic individuals. We sought to understand the acceptability of MCED blood test screening and potential barriers and facilitators to participation among the general public. MethodsWe conducted eleven semi-structured online focus groups with 50-77-year-olds (n = 53) in April–November 2022. Participants were purposefully sampled to include a mix of socio-economic and ethnic backgrounds as well as people who would not want ‘a blood test for cancer’. Participants were shown information about MCED blood tests. Transcripts were analysed using reflexive thematic analysis. ResultsParticipants showed enthusiasm for MCED screening. Perceived benefits included procedural familiarity and the potential to screen for many cancers. Enthusiasm was driven by beliefs that cancer is a real and increasing risk (both at population level and personally with age) and that early detection reduces treatment burden and cancer mortality. Some felt they would not want to know if they had cancer. The potential for MCED tests to raise anxiety was a concern, especially in a false-positive scenario. Participants wanted to avoid unpleasant and unnecessary procedures. The initial blood test was deemed “less invasive” than current screening tests, but potential follow-up procedures were a concern. Views on MCED screening were influenced by wider factors including dislike of uncertainty, desire for choice and control over one's health, and existing relationships with the NHS. ConclusionThe introduction of MCED screening is likely to be appealing due to the simplicity and familiarity of the primary test procedure. Test accuracy needs to be high to facilitate acceptability and should be communicated from the outset. Some people would rather not know if they have cancer, and MCEDs will not appeal to all.

Whole-Body Positron Emission Tomography with 18F-Fluorodeoxyglucose/Magnetic Resonance Imaging as a Screening Tool for the Detection of Malignant Transformation in Individuals with Neurofibromatosis Type 1

Malignant peripheral nerve sheath tumors (MPNST) are the leading cause of death in Neurofibromatosis type 1 (NF1). They can result from premalignant neurofibromas (NF) including NF with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP). Some phenotypic characteristics have been described as associated with their development. The aim was to outline our use of whole-body 18F-FDG-PET/MRI in adults with NF1, especially in the screening of asymptomatic individuals with a higher risk of developing a MPNST, and to study its impact on NF classification (malignant vs premalignant) and MPNST staging over time. Individuals with NF1 who underwent a 18F-FDG-PET/MRI between 2017 to 2021 were included, analyzing separately the screened population. Maximum standard uptake value and diffusion-weighed imaging were assessed. Biopsy/surgery confirmed the diagnosis. In all, 345 18F-FDG-PET/MRI were performed in 241 patients including 149 asymptomatic (62%), but at risk. Eight MPNST in 8 screened individuals (5%), 6 NF with atypia in 4 (3%) and 29 ANNUBP in 23 (15%) were diagnosed. Over time, the proportion of grade 3 MPNST and the malignant/premalignant ratio in screened individuals significantly decreased (p=0.03 and p<0.001, respectively). This study emphasizes the diagnostic and screening performances of whole-body 18F-FDG-PET/MRI in adults with NF1.

Development of a triage algorithm for mild cognitive impairment using electronic health record data

AbstractBackgroundTimely detection and diagnosis of early‐stage Alzheimer’s disease (AD) become increasingly relevant with the introduction of new therapies. Electronic health records (EHR) data present an opportunity to identify cases with elevated risk of undiagnosed cognitive impairment and triage them for further evaluation. Such triage tools are critically important because population‐based screening of asymptomatic individuals is currently not recommended, but spontaneous detection rates are low. We previously developed a risk prediction algorithm to identify likely cases aged ≥50 years based on claims data.MethodWe will build on this work and develop an algorithm based on three data sources: claims, EHR data and the National Alzheimer’s Coordinating Centers (NACC) data. The claims database study, already completed, included newly‐diagnosed mild cognitive impairment (MCI) individuals and non‐MCI individual matched on age, gender and geographic region. Using data 2 years prior to diagnosis, medical conditions associated with MCI were used to build a predictive model. The EHR study will aim to augment the model with clinical data such as body mass index, smoking status, vital signs and laboratory results. The NACC study, including ∼5,400 MCI and ∼15,800 cognitively normal (CN) individuals, will be used to validate the algorithm.ResultThe claims database study identified 25 medical conditions that predict MCI risk (area under the curve, AUC = 0.78). The top five predictors for MCI were depression, stroke/transient ischemic attack, obstructive sleep apnea, hyperlipidemia, and hypertension. The predictive performance was better in the 50‐64 year than in the older age groups. Analyses of the EHR and NACC data are ongoing.ConclusionData routinely collected in claims and EHR may be accurate enough to triage individuals with potential MCI for cognitive assessment in primary care.

Large-scale pancreatic cancer detection via non-contrast CT and deep learning

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986–0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening.

Comparison of Manual versus Automated SARS-CoV-2 Rapid Antigen Testing in Asymptomatic Individuals.

The SARS-CoV-2 pandemic has infected more than 770 M people and killed more than 6.9 M persons worldwide. In the USA, as of August 2023, it has infected more than 103 M people while causing more than 1.1 M deaths. During a pandemic, it is necessary to rapidly identify those individuals infected with the virus so that disease transmission can be stopped. We examined the sensitivity of the Quidel Rapid Antigen test on the manual Sofia 2 platform and the Beckman-Coulter antigen test on the automated DxI-800 system for use in screening asymptomatic individuals at the University of Arizona from March through May 2021. A total of 378 asymptomatic subjects along with 176 validation sets of samples in 23 independent experiments were assessed in side-by-side antigen testing using both assays. Nasal swabs and saliva were used as viral sources. Manual testing (Quidel) was compared with automated testing (Beckman) methods for cost and efficiency. Limit dilution of viral antigen spiked samples was performed to determine sensitivity to antigen load by the tests. The results between the two tests were found to be concordant. Both tests were comparable in terms of detecting low numbers of positive subjects in the asymptomatic population. A concordance of 98% was observed between the two tests. Experiments also demonstrated that saliva specimens were an acceptable viral source and produced comparable results for each test. Overall, the two methods were interchangeable.

Utility of RT-PCR versus electronic track and trace system for pre-procedural COVID-19 screening- a retrospective cohort study

Background and aimsCOVID-19 has disrupted the patient workflow in all healthcare settings. Procedures such as bronchoscopy and spirometry require additional pre-procedure screening for SARS-CoV-2. However, there is uncertainty regarding the utility of this universal pre-procedure screening. The State of Qatar has a robust contact tracing system in place in the form of the mobile application ‘Ehteraz.’ This study assesses the utility of various pre-procedural screening measures in asymptomatic patients and generate recommendations for any potential improvement in the workflow. MethodsThis is a cross-sectional study of asymptomatic patients who had SARS-CoV-2 RT-PCR screening performed before bronchoscopy or lung function testing scheduled on an elective basis. Descriptive statistics were used to summarize and determine the sample characteristics. The rate of the positive PCR test result was subsequently calculated. ResultsTwo patients (0.34%) tested positive for COVID-19 on their pre-procedural screen. Four patients (0.68%) had an inconclusive result. ConclusionThe positivity rate of SARS-CoV-2 RT-PCR is extremely low in asymptomatic individuals screened before bronchoscopy and spirometry. The authors recommend pre-procedural symptom and electronic application-based contact screening instead of universal pre-procedural SARS-CoV-2 RT-PCR for screening asymptomatic individuals.

Abstract IA001: Innovation and equity in cancer prevention and screening

Abstract This presentation will highlight some of the opportunities for improving cancer prevention and screening of asymptomatic individuals, which includes increasing the uptake of current standard of care and research for new interventions that can become standard of care. It is important to strive to address cancer disparities in the US and globally, as the greatest population-wide benefit for current and new interventions will be derived from equitable access to them. To increase the likelihood that uptake of new interventions will be equitable, this parameter should be considered throughout the development and evaluation of the candidate interventions, rather than waiting until after they have been approved. The main goals of prevention and screening are to enable people to live longer healthier lives, and approved interventions should ultimately be held to this standard, although initial approval, especially for primary prevention, may be based on surrogate endpoints. For example, initial HPV vaccine approval, in 2006, was based on its reduction in cervical dysplasia rates. Reduced cancer risk was not observed until more than a decade after that, and the vaccine has still not been formally shown to reduce mortality rates from HPV-associated cancer. The global equitable uptake of the HPV vaccine lags considerably, although the vast majority of HPV-associated cancers occur in low- and middle-income countries. We and others are conducting research to address this important gap. For cancer screening, a much shorter interval is usually needed to determine if the intervention does reduce cancer-specific mortality rates. This parameter is highly relevant for multicancer detection tests, which have considerable potential. While these tests can detect asymptomatic cancer earlier than if one waited for symptoms to develop, it remains to be demonstrated whether cancer detected by this approach will reduce cancer-specific mortality rates. It is also critical to develop equitable approaches for cancer diagnosis and treatment triggered by a positive test. Citation Format: Douglas R. Lowy. Innovation and equity in cancer prevention and screening. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA001.

Low incidence of HIV infection and decreasing incidence of sexually transmitted infections among PrEP users in 2020 in Germany

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019–12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32–45), 98.6% men who have sex with men (MSM). The median duration of PrEP exposure was 451 days (IQR 357–488), totaling 5132 py. Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029–0.208). For two, suboptimal adherence was reported and in the third case, suboptimal adherence and resistance to emtricitabine were observed. One infection was likely acquired before PrEP start. Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the COVID-19 pandemic period.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Phenotypic Features of Cystic Lung Disease in Proteus Syndrome: A Clinical Trial.

Rationale: Limited information is available regarding cystic lung disease in Proteus syndrome, a rare overgrowth disorder caused by a somatic activating variant in AKT1. Objectives: To define the phenotype of cystic lung disease in Proteus syndrome. Methods: Medical records, pulmonary function tests, and chest computed tomography of 39 individuals with Proteus syndrome evaluated at a single center were retrospectively reviewed. Lung histopathology from five affected individuals was examined. Results: Cystic lung disease affected 26 (67%) of 39 individuals. The mean age of affected individuals was 17.1 years. The lung cysts varied in size and location. Focal regions of heterogeneous lung parenchyma resembling emphysema were found in 81% of affected individuals. Mass effect was seen in 12% of affected individuals; pneumothorax occurred in one. Dyspnea and respiratory infections were reported by 38% and 35% of affected individuals, respectively. Abnormal pulmonary function and scoliosis were found in 96% of affected individuals. Lung disease progressed in seven of 10 affected individuals, and all five affected individuals younger than 20 years of age had progressive cystic lung disease. Three affected individuals had symptomatic improvement after lung resection. Histopathology showed cystic air space enlargement of varying severity. Conclusions: Cystic lung disease is common in Proteus syndrome and is likely to progress in affected individuals younger than 20 years of age. Screening asymptomatic individuals with Proteus syndrome for cystic lung disease is indicated. Surgical lung resection is a therapeutic option for affected individuals with severe disease. Clinical trial registered with www.clinicaltrials.gov (NCT00001403).

Performance of an electronic health record-based predictive model to identify patients with atrial fibrillation across countries.

BackgroundAtrial fibrillation (AF) burden on patients and healthcare systems warrants innovative strategies for screening asymptomatic individuals.ObjectiveWe sought to externally validate a predictive model originally developed in a German population to detect unidentified incident AF utilising real-world primary healthcare databases from countries in Europe and Australia.MethodsThis retrospective cohort study used anonymized, longitudinal patient data from 5 country-level primary care databases, including Australia, Belgium, France, Germany, and the UK. The study eligibility included adult patients (≥45 years) with either an AF diagnosis (cases) or no diagnosis (controls) who had continuous enrolment in the respective database prior to the study period. Logistic regression was fitted to a binary response (yes/no) for AF diagnosis using pre-determined risk factors.ResultsAF patients were from Germany (n = 63,562), the UK (n = 42,652), France (n = 7,213), Australia (n = 2,753), and Belgium (n = 1,371). Cases were more likely to have hypertension or other cardiac conditions than controls in all validation datasets compared to the model development data. The area under the receiver operating characteristic (ROC) curve in the validation datasets ranged from 0.79 (Belgium) to 0.84 (Germany), comparable to the German study model, which had an area under the curve of 0.83. Most validation sets reported similar specificity at approximately 80% sensitivity, ranging from 67% (France) to 71% (United Kingdom). The positive predictive value (PPV) ranged from 2% (Belgium) to 16% (Germany), and the number needed to be screened was 50 in Belgium and 6 in Germany. The prevalence of AF varied widely between these datasets, which may be related to different coding practices. Low prevalence affected PPV, but not sensitivity, specificity, and ROC curves.ConclusionsAF risk prediction algorithms offer targeted ways to identify patients using electronic health records, which could improve screening number and the cost-effectiveness of AF screening if implemented in clinical practice.

Correlation of Biochemical Abnormalities with the Severity of Hospitalized Covid-19 Patients

Background: Coronavirus Disease-19 (COVID-19) has a global impact. The laboratory assessments in Covid-19 illness help in better understanding the disease pathophysiology useful in screening asymptomatic individuals to diagnosis, prognosis and monitoring the affected patients. The aim of the study:To observe the association between biochemical and inflammatory parameters among the hospitalised COVID-19 patients of different clinical severity. Materials and methods: This was a retrospective study carried out with the approval of the Institutional Ethics Committee. The study included patients over 18 years, hospitalised with COVID-19 infection, grouped into three severity groups, admitted to ward, high dependency unit or intensive care unit between May to September 2020. Data collection was carried out by manual perusal of inpatient case sheets, computerised patient data system and transcription database for discharge summaries. The biochemical and inflammatory markers like plasma glucose, renal function tests, serum electrolytes, liver function tests, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), d-dimer, ferritin, Lactate dehydrogenase (LDH) at the time of admission were collected. Data was expressed as mean and standard deviation or median and range. ANOVA test followed by post hoc (Tukey) test, Pearson correlation and Receiver Operating Characteristics (ROC) Curve analysis were performed. Results: Significant correlations were observed between the mild and moderate-severe illness groups with respect to fasting plasma glucose, blood urea nitrogen, creatinine, direct bilirubin, total protein, albumin, ferritin and LDH. The AUC was the highest for LDH at 0.64 followed by blood urea nitrogen to creatinine ratio at 0.62. Conclusion: High levels of renal function parameters were potential predictors of acute kidney injury among patients with COVID-19. Fasting plasma glucose, serum albumin, LDH, Blood urea nitrogen (BUN) and BUN-creatinine ratio are better indicators of the severity of the disease with multiorgan dysfunction.

Mycoplasma genitalium screening in a specialized French unit: A retrospective study

ObjectiveMycoplasma genitalium (MG) infection accounts for 10–35% of non-gonococcal non-chlamydial (NGNC) urethritis. However, given that most people infected with MG do not develop symptoms and that antimicrobial resistance is increasing worldwide, there is no evidence of any benefits of screening asymptomatic individuals. We conducted this study to describe MG screening practices and outcomes at a French Sexually Transmitted Infections (STI) center in which MG testing was performed selectively and multiplex assays were not carried out [i.e., simultaneous screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and MG]. MethodsA retrospective, observational, single-center study was conducted at the STI unit of Saint-Louis Hospital in Paris. The records of all patients undergoing MG testing from January 1st, 2017, to December 31st, 2018, were reviewed. The primary aim of the study was to describe and evaluate the proportion of MG-positive (MG+) patients among those tested. Secondary objectives were determination of the prevalence of MG+ status among symptomatic patients, risk factors associated with MG infection, and therapeutic modalities and efficacy. ResultsTwo hundred and forty-nine patients underwent MG testing, 28 (11%) of whom were positive (MG+). The prevalence of MG+ status among symptomatic NGNC patients was 12%. HIV-positive (HIV+) status was significantly associated with MG+ status in univariate and multivariate analyses (Odds Ratio=7.3, 95% Confidence Interval 1.3-41.7; P=0.02). Twenty-three patients (85%) received antibiotics. Eighteen (67%) received azithromycin for 5 days, but 7 had clinical resistance. No quinolone resistance was reported. ConclusionDespite unavailability of multiplex testing at our facility, which led to targeted-only screening for MG, its relatively high local prevalence is in keeping with what is generally observed at similar facilities across the world, where use of multiplex tests enables systematic screening for MG alongside NG and CT. This reinforces the current recommendations in Europe, France and the US against systematic MG testing or treatment in asymptomatic patients.

Development of a highly sensitive multicancer, targeted, cell-free DNA epigenomic assay for integrated screening of lung and colorectal cancer.

3542 Background: Cancer screening in asymptomatic individuals who meet guideline criteria has yielded reductions in cancer death rates. However, adherence to screening guidelines remains below targets set forth by leading health-care organizations. A blood-based multi-cancer screening assay with clinically meaningful sensitivity and specificity, in cancer types where early detection and intervention can save lives, that is integrated with existing clinical pathways may increase access to and adherence with guideline recommendations, ensuring more individuals benefit from these proven interventions. We evaluated the performance of a blood-based multi-cancer screening assay that interrogates cell-free DNA (cfDNA) methylation signatures for cancer detection and tissue of origin prediction in a set of tumor types where cancer screening can save lives. Methods: Whole blood from 1,607 individuals with and 3,298 individuals without cancer was obtained from multiple unique cohorts. Plasma-derived cfDNA was profiled using a custom assay that enriches fragments with dense CpG methylation and further depletes uninformative background molecules containing unmethylated CpGs. We utilized a broad genomic panel (16 Mb) targeting regions with low rates of methylation in individuals without cancer. The panel captures tumor-associated molecules and allows for high sensitivity of detection at low sequencing costs. A cross-validated analysis was used to estimate the performance of the predictive model upon the sample set. Classification thresholds corresponding to 90%, 95%, and 98% specificities were established using samples from individuals without a cancer diagnosis. Results: At 90% specificity, overall sensitivity for lung cancer detection was 92.1% (95% CI: 80-100%; 90.2% in Stage I/II disease (N = 82) and 93.1% in Stage III/IV disease (N = 159)) and 93.1% (CI: 88-98%) for CRC detection (92% in Stage I/II disease (N = 743) and 94.5% in Stage III/IV disease (N = 623)). Tissue of origin prediction evaluated at 98% specificity yielded accurate identification in 99% of CRC and 98% of lung cancers. Lung cancer histology was known for approximately 74% of the cohort. Across Stage I – IV cancers, at 90% specificity, sensitivity was 97.3% in lung squamous cancer (N = 73) and 86.8% in lung adenocarcinoma (N = 106). At 95% and 98% specificity thresholds, overall sensitivity was 86.3% (CI: 75-98%) and 66.4% (CI: 56-77%) for lung cancer and 85.7% (CI:81-91%) and 71.6% (CI: 67-76%) for CRC, respectively. Conclusions: This blood-based multi-cancer screening assay yields clinically meaningful sensitivity and specificity for early-stage cancers. This assay is undergoing further development to expand detection capabilities to additional cancer types where screening can save lives. Clinical evaluation in registrational screening trials is ongoing (SHIELD; NCT05117840).

Prevalence and Factors Associated with Mycoplasma genitalium Infection in At-risk Adolescent Females

Background: Mycoplasma genitalium is a sexually transmitted infection (STI) that has been associated with poor reproductive health outcomes in women. The prevalence of M.genitalium is unknown as screening of asymptomatic individuals is not recommended, and until 2019 the available tests lacked sensitivity. We aimed to use the Aptima/Hologic transcription mediated amplification assay (MG-TMA), with a sensitivity and specificity of 80% or higher for urine and endocervical samples, to diagnose M.genitalium infection in a clinical sample of sexually active adolescent females and to describe associated symptoms and risk factors.

Carotid artery screening in asymptomatic individuals of different ethnic origins

Kontext a cíle: Některá chronická onemocnění jako hypertenze, diabetes mellitus (DM), hypercholesterolemie a kuřáctví jsou již delší dobu považována za rizikové faktory vzniku stenóz karotických tepen. Zatím však nebyl publikován žádný rozsáhlejší výzkum zaměřený na otázku zúžení karotických tepen u různých etnických skupin. Cílem této studie je zhodnotit tento jev u pacientů různých etnik. Metody: Do naší prospektivní studie, která se prováděla v Istanbulu v době mezi březnem a zářím 2018, bylo zařazeno 246 (61,2 %) rodilých Turků a 153 (39,8 %) syrských imigrantů. Všech 399 účastníků studie bylo ve věku od 50 do 65 let a byl u nich diagnostikován alespoň jeden rizikový faktor v podobě hypertenze, hyperlipidemie, DM, obezity, tíživé socioekonomické situace a kuřáctví. Pacienti absolvovali vyšetření celého karotického povodí dopplerovským ultrazvukem. Výsledky: Průměrný věk pacientů byl 54,2 &#177; 7,2 roku; žen bylo ve studii 50,4 %. Nejčastějším rizikovým faktorem v obou skupinách byla hypertenze (41,1 % vs. 47,7 %; p = 0,596). Více kuřáků bylo mezi rodilými Turky (p = 0,022). Přítomnost hyperlipidemie, DM i stresu z tíživé socioekonomické situace byla podobná v obou skupinách (p &gt; 0,05). I výskyt nadváhy a obezity mezi rodilými Turky a syrskými imigranty byl podobný (p = 0,071 a p = 0,279). Lehká (&lt; 50 %), středně těžká (50-70 %) a významná stenóza karotických tepen (&gt; 70 %) byla zjištěna u 332 (83,2 %), resp. 33 (8,3 %) a 34 (8,6 %) pacientů. Žádný statisticky významný rozdíl v závažnosti stenózy karotid mezi oběma etniky nebyl zjištěn (p &gt; 0,05). Závěr: Výskyt středně těžkých a významných stenóz karotid u syrských imigrantů a rodilých Turků je podobný, což lze vysvětlit etnickou podobností a sdílením podobného rizikového faktoru.

Detection of SARS-CoV-2 infection by exhaled breath spectral analysis: Introducing a ready-to-use point-of-care mass screening method.

SummaryBackgroundThe current SARS-CoV-2 pandemic created an urgent need for rapid, infection screening applied to large numbers of asymptomatic individuals. To date, nasal/throat swab polymerase chain reaction (PCR) is considered the “gold standard”. However, this is inconducive to mass, point-of-care (POC) testing due to person discomfort during sampling and a prolonged result turnaround. Breath testing for disease specific organic compounds potentially offers a practical, rapid, non-invasive, POC solution. The study compares the Breath of Health, Ltd. (BOH) breath analysis system to PCR's ability to screen asymptomatic individuals for SARS-CoV-2 infection. The BOH system is mobile and combines Fourier-transform infrared (FTIR) spectroscopy with artificial intelligence (AI) to generate results within 2 min and 15 s. In contrast to prior SARS-CoV-2 breath analysis research, this study focuses on diagnosing SARS-CoV-2 via disease specific spectrometric profiles rather than through identifying the disease specific molecules.MethodsAsymptomatic emergency room patients with suspected SARS-CoV-2 exposure in two leading Israeli hospitals were selected between February through April 2021. All were tested via nasal/throat-swab PCR and BOH breath analysis. In total, 297 patients were sampled (mean age 57·08 SD 18·86, 156 males, 139 females, 2 unknowns). Of these, 96 were PCR-positive (44 males, 50 females, 2 unknowns), 201 were PCR-negative (112 males, 89 females). One hundred samples were used for AI identification of SARS-CoV-2 distinguishing spectroscopic wave-number patterns and diagnostic algorithm creation. Algorithm validation was tested in 100 proof-of-concept samples (34 PCR-positive, 66 PCR-negative) by comparing PCR with AI algorithm-based breath-test results determined by a blinded medical expert. One hundred additional samples (12 true PCR-positive, 85 true PCR-negative, 3 confounder false PCR-positive [not included in the 297 total samples]) were evaluated by two blinded medical experts for further algorithm validation and inter-expert correlation.FindingsThe BOH system identified three distinguishing wave numbers for SARS-CoV-2 infection. In the first phase, the single expert identified the first 100 samples correctly, yielding a 1:1 FTIR/AI:PCR correlation. The two-expert second-phase also yielded 1:1 FTIR/AI:PCR correlation for 97 non-confounders and null correlation for the 3 confounders. Inter-expert correlation was 1:1 for all results. In total, the FTIR/AI algorithm demonstrated 100% sensitivity and specificity for SARS-CoV-2 detection when compared with PCR.InterpretationThe SARS-CoV-2 method of breath analysis via FTIR with AI-based algorithm demonstrated high PCR correlation in screening for asymptomatic individuals. This is the first practical, rapid, POC breath analysis solution with such high PCR correlation in asymptomatic individuals. Further validation is required with a larger sample size.FundingBreath of Health Ltd, Rehovot, Israel provided study funding.

Incidence, demographic, biochemical, and clinicopathological profile of primary IgAN in a tertiary care center from Northern India

BackgroundPrimary IgA nephropathy (IgAN) has variable distribution and clinicopathological spectrum throughout the world. We report the incidence, demographic, and clinicopathological profile of primary IgAN from a tertiary care center in Northern India.MethodsThis is a single-center, prospective, observational study conducted at Sheri- Kashmir Institute of Medical Sciences, J&K, India, from January 2015 to December 2018. The study was approved by the hospital ethical committee.ResultsA total of 106 patients were included in this study, accounting for 19% (106/558) of all native kidney biopsies done during the period from January 2015 till December 2018. Males and females accounted for 60.4% (64/106) and 39.6% (42/106), respectively, with a ratio of 1.5:1. The mean age was 31.37±11.60 years. Edema and hypertension were the most common presenting symptoms and signs, seen in 69 (65.1%) and 72 (67.9%) patients, respectively. The baseline 24-h urine protein excretion was 2.32 ±1.34 g, Nephrotic range proteinuria (≥3.5g/day) was seen in 23/106 (21.7%). Average serum creatinine was 1.6±0.80 mg/dl and estimated glomerular filtration rate using CKD-EPI was <60 ml/min/1.73 m2 in 48.1% of patients (51/106). In patients with < 1 g proteinuria, 36.8% had E1, 78.9% had S1, 36.8% had T1, and 42.1% had T2 lesions.ConclusionsIgAN is common in North India and has a more severe histopathological presentation, characterized by extensive sclerosis and tubulointerstitial fibrosis. Renal dysfunction and nephrotic range proteinuria are common. Hypertension, low eGFR, and proteinuria correlate with the presence of segmental scarring, endocapillary hypercellularity, and IFTA. Screening of asymptomatic individuals might help in early diagnosis and long-term preservation of renal function.