Blood Test Screening Research Articles

Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is a genetic disease associated with renal, endocrine, neurological, skin and immune defects. SPLIS is caused by inactivating mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). SPL catalyzes the irreversible degradation of the bioactive sphingolipid sphingosine-1-phosphate (S1P), a key regulator of lymphocyte egress. The SPL reaction represents the only exit point of sphingolipid metabolism, and SPL insufficiency causes widespread sphingolipid derangements that could additionally contribute to immunodeficiency. Herein, we review SPLIS, the sphingolipid metabolic pathway, and various roles sphingolipids play in immunity. We then explore SPLIS-related immunodeficiency by analyzing data available in the published literature supplemented by medical record reviews in ten SPLIS children. We found 93% of evaluable SPLIS patients had documented evidence of immunodeficiency. Many of the remainder of cases were unevaluable due to lack of available immunological data. Most commonly, SPLIS patients exhibited lymphopenia and T cell-specific lymphopenia, consistent with the established role of the S1P/S1P1/SPL axis in lymphocyte egress. However, low B and NK cell counts, hypogammaglobulinemia, and opportunistic infections with bacterial, viral and fungal pathogens were observed. Diminished responses to childhood vaccinations were less frequently observed. Screening blood tests quantifying recent thymic emigrants identified some lymphopenic SPLIS patients in the newborn period. Lymphopenia has been reported to improve after cofactor supplementation in some SPLIS patients, indicating upregulation of SPL activity. A variety of treatments including immunoglobulin replacement, prophylactic antimicrobials and special preparation of blood products prior to transfusion have been employed in SPLIS. The diverse immune consequences in SPLIS patients suggest that aberrant S1P signaling may not fully explain the extent of immunodeficiency. Further study will be required to fully elucidate the complex mechanisms underlying SPLIS immunodeficiency and determine the most effective prophylaxis against infection.

Plasma and CSF neurofilament light chain distinguish neurodegenerative from primary psychiatric conditions in a clinical setting.

People with neurodegenerative disorders (ND) frequently face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (PPD), a common challenge in clinical settings. Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, and weight. A total of 337 participants were included: 136 ND, 77 PPD, and 124 Controls. Plasma NfL was 2.5-fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, [AUC]: 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2-fold elevated, AUC: 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40-<60 years). Additional findings were cutoffs optimized for sensitivity and specificity, and issues important for future clinical translation. This study adds important evidence for a simple blood-based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings. NfL levels were significantly higher in ND versus PPD. Plasma NfL showed strong diagnostic performance, comparable to CSF NfL, to distinguish ND from PPD. Diagnostic performance was higher in younger people, where diagnostic challenges are greater. Further research is needed on analytical and reference range factors, for clinical translation. These findings support a simple screening blood test for neurodegeneration.

7280 Pituitary Dysfunction Following Mild Traumatic Brain Injury in Female Athletes: Neuropsychological and Psychological Functioning

Abstract Disclosure: L.Ó. Eggertsdóttir Claessen: None. M.K. Jónsdóttir: None. H. Kristjánsdóttir: None. S.H. Lund: None. I. Unnsteinsdóttir Kristensen: None. H.Á. Sigurjónsdóttir: None. Background: Pituitary dysfunction (PD), as well as neuropsychological and psychological symptoms, have been reported following mild traumatic brain injury (mTBI). These symptoms may be due to the brain injury itself or PD as hypopituitarism (HP) can have neuropsychological and psychological effects. To the best of our knowledge, this study is the first to report neuropsychological and psychological outcomes in female athletes with PD following sport-related mTBI. Subjects: Female athletes aged 18 to 45 years currently active in or retired from soccer, team handball, basketball, ice hockey, and martial arts who answered an online questionnaire regarding mTBI history and mental health were included (n = 508). Of the 308 women who reported one or more mTBI, 166 (53.8%) accepted to participate in a further interview and neuropsychological tests. All 166 women were subsequently invited to participate in a medical interview. Of those 151 accepted (90.9%) and 131 (86.7%) of them participated in pituitary hormone screening blood tests (SBT). Methods: The online questionnaire included a post-concussion symptom scale, and mental health scales evaluating symptoms of anxiety, depression, stress, and quality of life. Sleep disturbances were evaluated, and neuropsychological tests were performed in the psychological interview. The Sustained Attention to Response Task (SART). Executive functioning, visual search, motor and processing speed, divided attention, working memory, and intellectual abilities were also measured. The SBT were taken at 8 a.m. and included S-IGF1 (age dependant reference range), S-cortisol (values &amp;lt; 350 nmol/L were considered abnormal), S-prolactin (reference range 4.79 - 23.3 μg/L), S-TSH (reference range 0.270 - 4.20 mIU/L), S-fT4 (reference range 12 - 22 pmol/L), S-FSH, S-oestrogen, and S-progesterone measurements. If SBT were repeatedly O-RV, detailed endocrinological tests were performed for each axis as indicated. Results: Following a detailed endocrinological evaluation, 16 women were diagnosed with PD (HP n = 6, hyperprolactinemia n = 10) following mTBI. Women with PD had a significantly higher mean SART error score than women with normal pituitary function (PF) (16.7 and 12.8 respectively; p = 0.04). No other significant differences in neuropsychological outcome were found between the two groups. Moreover, there was not a significant difference with regards to mTBI symptoms, anxiety, depression, stress, QOL or insomnia between women with PD and those with normal PF. Conclusions: Sustained attention or inhibitory performance may be affected in women with PD following mTBI as they had a higher mean SART error score than women with normal PF. No other significant difference in neuropsychological or psychological outcome was demonstrated. Presentation: 6/3/2024

Factors Affecting Colorectal Cancer Screening in Primary Care Physician Practices in Ukraine.

This study aims to identify the factors influencing colorectal cancer (CRC) screening practices, along with the barriers and facilitators from the perspective of primary care physicians (PCPs) in Ukraine. Considering health care system challenges, including those posed by the ongoing war, this research seeks to inform improvements in CRC screening and outcomes in Ukraine and other low- and middle-income countries (LMICs). A survey was designed and distributed electronically to Ukrainian PCPs, focusing on CRC screening practices, beliefs, and barriers. The survey incorporated questions adapted from established cancer screening surveys and frameworks. Complete responses were collected from 740 PCPs. Sample statistics were computed, and population-level perceptions and associations with CRC screening practices were estimated by standardizing responses to national PCP demographics. The majority of respondents were women (91%) and specialized in family medicine (84%). Respondents believed in the effectiveness of colonoscopy for reducing CRC mortality (80%), with 75% of PCPs referring patients for this screening modality. Major barriers identified include inadequate training of PCPs in screening and lack of resources. Respondents reported high utilization of fecal occult blood test and colonoscopy for screening when these tests were said to be available in their practices. Self-reported familiarity with CRC screening guidelines and participation in educational workshops were positively associated with screening referrals. The study highlights the role of access to CRC screening tests and awareness of screening guidelines in enhancing CRC screening practices among Ukrainian PCPs. Addressing training and resource barriers, alongside public health interventions targeting patient-related barriers, is essential. These findings offer valuable insights for LMICs facing similar challenges, emphasizing the need for tailored strategies to improve cancer screening in these health care settings.

Seroprevalence of Hepatitis B Virus among Blood Donors at National Blood Transfusion and Research Center-Taiz Branch, Yemen

Hepatitis B Virus (HBV) represents one of the most health problems. Almost more than 350 million infected persons were reported universally. Blood transfusion is commonly the most common route of transmission of HBV. Recently, Hospitals in Yemen are increasing demands for blood and blood products due to war injury, anemia, and malnutrition. The risk of transfusion transmission of infection relatively increases. This study aimed to determine hepatitis B virus prevalence among blood donors at the National Blood Transfusion Center -Taiz branch (NBTRC- TB). Data was collected from the National Blood Transfusion and Research Center (Taiz branch) from 1/4/2020 to 16/12/2020. A total of 3174 blood donors donated blood at the center. A descriptive cross-sectional study was conducted on them. Blood donor information was registered at the reception department, and all blood screening tests were performed. Data of HBsAg and total anti-HBc were analyzed statistically by using IBM SPSS version 26. Among 3174 blood donors, male blood donors were 3158 (99.5%) and female blood donors 16 (0.5%). Furthermore, 41 (1.3%) were positive for HBsAg (which all the positive results were for male donors and no positivity were for female donors) while 353 (11.1%) were positive for total anti- HBc Ab which is distributed at ratio of 11% (350) for males and 0.1% (3) for females. On the other hand, the result of HBsAg and total anti-HBc Ab together showed three levels of positivity as the (HBsAg positive / anti-HBc negative) were 12 (0.4%) in which was a low percentage and reversely, the (HBsAg negative/ HBcAb positive) were 316 (10.2%), While the HBsAg positive / anti-HBc positive were 27 (0.9%). So this study shed light on the result of HBsAg negative/ anti-HBc positive which the percentage (10.2%) of which statistically significant (p. value = 0.000) and was the highest result indicates donors with post HBV infection or have low HBV infection. This study showed the high prevalence of post-HBV infection among blood donors. Using both markers HBsAg and total anti-HBc Ab will improve the detection of HBV before blood transfusion.

A computer-aided detection system in the everyday setting of diagnostic, screening, and surveillance colonoscopy: an international, randomized trial.

Computer-aided detection (CADe) has been developed to improve detection during colonoscopy. After initial reports of high efficacy, there has been an increasing recognition of variability in the effectiveness of CADe systems. The aim of this study was to evaluate a CADe system in a varied colonoscopy population. A multicenter, randomized trial was conducted at seven hospitals (both university and non-university) in Europe and Canada. Participants referred for diagnostic, non-immunochemical fecal occult blood test (iFOBT) screening, or surveillance colonoscopy were randomized (1:1) to undergo CADe-assisted or conventional colonoscopy by experienced endoscopists. Participants with insufficient bowel preparation were excluded from the analysis. The primary outcome was adenoma detection rate (ADR). Secondary outcomes included adenomas per colonoscopy (APC) and sessile serrated lesions (SSLs) per colonoscopy. 581 participants were enrolled, of whom 497 were included in the final analysis: 250 in the CADe arm and 247 in the conventional colonoscopy arm. The indication was surveillance in 202/497 colonoscopies (40.6 %), diagnostic in 199/497 (40.0 %), and non-iFOBT screening in 96/497 (19.3 %). Overall, ADR (38.4 % vs. 37.7 %; P = 0.43) and APC (0.66 vs. 0.66; P = 0.97) were similar between CADe and conventional colonoscopy. SSLs per colonoscopy was increased (0.30 vs. 0.19; P = 0.049) in the CADe arm vs. the conventional colonoscopy arm. In this study conducted by experienced endoscopists, CADe did not result in a statistically significant increase in ADR. However, the ADR of our control group substantially surpassed our sample size assumptions, increasing the risk of an underpowered trial.

Characteristics of a cost-effective blood test for colorectal cancer screening.

Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy. We used the 3 Cancer Information and Surveillance Modeling Network-Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years. Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of $3811-$5384 per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of $5375-$7031 per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person. Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective.

A simple blood screening tests for predicting non-alcoholic fatty liver disease in obese patients

A simple blood screening tests for predicting non-alcoholic fatty liver disease in obese patients

Abstract 1074: Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer

Abstract The lack of reliable biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis due to advanced disease at diagnosis. Biopsies for pancreatic cancer are known to be particularly difficult to perform because of the location of the pancreas and low volume of primary tumors that metastasize aggressively. Currently, there is no blood test or other screening modality in use, for stratification of individuals with higher-than-average risk (5-8-fold) of developing PDAC in their lifetime. Given this existing void in the US and worldwide, an FDA-compliant, minimally invasive, quantitative biomarker test for the early detection of PDAC would be critical for screening subpopulations with, a) inherent genetic or familial predisposition; history of chronic pancreatitis; c) precursor lesions of pancreas; and d) older patients (&amp;gt;50 years) with new onset diabetes or sudden weight loss. Extracellular vesicles (EVs) are shed by normal and cancer cells and carry a rich molecular cargo that can be leveraged for biomarker discovery. Whereas molecular profiling of bio-fluids poses intrinsic limitations for detection of low abundant, disease-specific biomarkers due to matrix effects; EVs, on the other hand, offer promise as a robust and minimally invasive biomarker resource. Mass spectrometry data were developed in our laboratory, based on multi-omics (proteomics, lipidomics and metabolomics) analyses of plasma EVs derived from patients diagnosed with early-stage PC (N=60), pancreatitis (N=39), precursor lesions of pancreas (N=45) as well as normal controls (N=50). These clinically annotated samples were made available by the Georgetown University Medical Center (GUMC) repository. Feature selection using a training-validation design allowed the development of a multiplexed biomarker panel comprising of 12-analytes (5-lipids, 2-metabolites and 5-proteins) that can robustly stratify early-stage PC from normal controls with high accuracy (AUC&amp;gt;95%). Availability of a FDA compliant, multi-analyte-based classification algorithm that can stratify patients with precursor lesions of the pancreas that are at potential risk of progression to PC with &amp;gt; 90% specificity and sensitivity is a critical clinical need. Refinement of panel to improve positive predictive value as well as identification of markers predictive of progression of precursor lesions to malignant transformation is ongoing. Citation Format: Shivani Bansal, Shu Wang, Yaoxiang Li, Sunil Bansal, Jill Smith, John B. Tyburski, Keith Unger, Amrita Cheema. Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1074.

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.

Colorectal cancer screening; colonoscopy and biopsy results in people undergoing colonoscopy due to positive fecal occult blood test.

Screening programs are important for the early detection of colorectal cancer, which is one of the causes of high morbidity and mortality. In this study, we investigated the colonoscopy results, the incidence of adenoma and cancer, and the relationship between test results and cancer in individuals with a positive fecal occult blood test for colorectal cancer screening. Within the scope of the colorectal cancer screening program, colonoscopy was requested for individuals aged 50-70 years who applied to our outpatient clinic with a positive fecal occult blood test. The results were collected and analyzed. The results of the colonoscopy could be obtained in only 237 (56.43%) of the 420 patients who were referred for a colonoscopy because of a positive fecal occult blood test. Colonoscopy results were normal in 15 (6.33%), benign anal disease in 64 (27%), benign colonic disease in 12 (5.06%) and polyp + adenocarcinoma in 146 (61.61%). Pathology results were benign polyp in 37 (15.61%), adenomatous polyp in 86 (36.29%) and adenocarcinoma in 23 (9.71%). Quantitative test results were higher in the adenomatous polyp + adenocarcinoma group and statistically significant (p= 0.03). Individuals with positive fecal occult blood tests, especially those with high quantitative test results, should be encouraged to have a colonoscopy, and they should be warned about the high probability of adenomatous polyps and colorectal cancer.

A computer-aided polyp detection system in screening and surveillance colonoscopy: an international, multicentre, randomised, tandem trial

Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population. This multicentre, randomised, controlled trial was done in ten hospitals in Europe, the USA, and Israel by 31 endoscopists. Patients referred for non-immunochemical faecal occult blood test (iFOBT) screening or surveillance colonoscopy were included. Patients were randomomly assigned to CAD-assisted colonoscopy or conventional colonoscopy; a subset was further randomly assigned to undergo tandem colonoscopy: CAD followed by conventional colonoscopy or conventional colonoscopy followed by CAD. Primary objectives included adenoma per colonoscopy (APC) and adenoma per extraction (APE). Secondary objectives included adenoma miss rate (AMR) in the tandem colonoscopies. The study was registered at ClinicalTrials.gov, NCT04640792. A total of 916 patients were included in the modified intention-to-treat analysis: 449 in the CAD group and 467 in the conventional colonoscopy group. APC was higher with CAD compared with conventional colonoscopy (0·70 vs 0·51, p=0·015; 314 adenomas per 449 colonoscopies vs 238 adenomas per 467 colonoscopies; poisson effect ratio 1·372 [95% CI 1·068-1·769]), while showing non-inferiority of APE compared with conventional colonoscopy (0·59 vs 0·66; p<0·001 for non-inferiority; 314 of 536 extractions vs 238 of 360 extractions). AMR in the 127 (61 with CAD first, 66 with conventional colonoscopy first) patients completing tandem colonoscopy was 19% (11 of 59 detected during the second pass) in the CAD first group and 36% (16 of 45 detected during the second pass) in the conventional colonoscopy first group (p=0·024). CAD increased adenoma detection in non-iFOBT screening and surveillance colonoscopies and reduced adenoma miss rates compared with conventional colonoscopy, without an increase in the resection of non-adenomatous lesions. Magentiq Eye.

Exploring Feature Selection and Machine Learning Algorithms for Predicting Diabetes Disease

One of the most common diseases in the world is the chronic diabetes. Diabetes has a direct impact on the lives of millions of people worldwide. Diabetes can be controlled and improved with early diagnosis, but the majority of patients continue to live with it. There is a dispirit need to a system to anticipate and select the people who are most likely to be diabetes in the future. Diagnosing the future diseased person without taking any blood or glucose screening tests, is the main goal of this study. This paper proposed a deep-learning model for diabetes disease prediction. The proposed model consists of three main phases, data pre-processing, feature selection and finally different classifiers. Initially, during the data pre-processing stage, missing values are handled, and data normalization is applied to the data. Then, three techniques are used to select the most important features which are mutual information, chi-squared and Pearson correlation. After that, multiple machine learning classifiers are used. Four experiments are then conducted to test our models. Additionally, the effectiveness of the proposed model is evaluated against that of other well-known machine learning techniques. The accuracy, AUC, sensitivity, and F-measure of the linear regression classifier are higher than those of the other methods, according to experimental data, which show that it performs better. The suggested model worked better than traditional methods and had a high accuracy rate for predicting diabetic disease.

Multisite external validation of blood test for colorectal neoplasia screening in a majority average-risk screening cohort of 449 subjects.

66 Background: The FirstSight CRC screening blood test was previously shown to have sensitivities of 92.1% and 54.5% for CRC and AA at a specificity of 90.6% for 1,038 subjects from 18 clinical sites. In this report, we describe the independent external validation of the predefined FirstSight CRC screening blood test with new subjects from 16 sites dispersed across the US, 4 of which are new and did not participate in the previous study. Methods: The validation study included subjects from two sources: Average-risk, asymptomatic screening subjects from screening clinics supplemented with diseased-only subjects from surgical oncology centers. Blood was drawn before bowel prep for colonoscopy or treatment. External validation as well as Monte Carlo cross-validation (MCCV) methods were used to evaluate the performance of the pre-defined FirstSight assay, algorithm, and clinical thresholds in this independent external validation set. Results include sensitivity and specificity to detect CRC and AA and 95% confidence intervals. Results: The study cohort (55.2% female; mean age 56.9 yrs.) consisted of 449 subjects (White 61.7%; Black 14.5%; Hispanic 18%; AAPI and Middle Easterners 5.8%). The majority of them, 376 (84%), were asymptomatic, average-risk screening subjects (including 1 CRC, 53 AA, and all 322 negative subjects). An additional 73 (16%) diseased subjects (39 CRC and 34 AA) were enriched due to low disease prevalence. The FirstSight algorithm derives a test score from 0 to 100 as a quantitative measure of AA and CRC risk with a cutpoint to assign a binary low- or high-risk designation. The previously described cutpoint of 47.2 yielded a test specificity of 90.0%, and 90.0% and 52.9% sensitivity for the detection of CRC and AA, respectively. Here we report a higher cutpoint 50 with identical sensitivities but improved specificity to 90.7%. Point estimates of sensitivity and specificity, including CRC staging, and Clopper-Pearson exact 95% confidence intervals based on the external validation results are presented below. Conclusions: An external validation included 449 subjects from a multi-site, majority average-risk CRC screening study successfully validated the FirstSight Blood Test’s high performance as previously established with 1,038 subjects. The results bring forth confidence in the Test’s reproducibility in a large-scale clinical trial. Clinical trial information: NCT05127096 . [Table: see text]

Enhanced blood-based colorectal cancer screening with improved performance in detection of early stage disease.

68 Background: Blood based colorectal cancer (CRC) screening has been validated for use in average risk populations (ECLIPSE NCT#04136002; Guardant Health, USA). Here we present the performance of an enhanced version of a blood-based screening test developed to optimize detection of low shedding tumors by leveraging epigenomic features of cell-free DNA (cfDNA). Test performance was assessed across screen-relevant individuals from the intended use population, including a collection of screen-detected CRC and enriched cohort of individuals with endoscopy finding of CRC. Methods: We trained a regression model to classify whether aberrant cfDNA originated from individuals with CRC or non-ACN individuals and compared performance to an original model in a fixed set of screen-relevant samples sequenced to a median of 11M reads per sample across a panel approximately 1Mb in size. Model optimization focused on identifying training settings and samples to maximize detection of low shedding screen-relevant tumors and introduced noise reduction techniques to minimize technical variation. The final enhanced model was trained in over 4500 samples; the calling cut-off was set targeting 90% specificity in the average-risk population following US-Census age distribution. Analytical Limit of Detection (LoD) was estimated using ~5,000 in silico dilution samples generated from blood samples from 25 CRCs and ~1,650 non-ACNs. Results: This training approach yielded a 2X improvement in the analytical LoD95 (0.004% vs 0.008%) compared to the original model validated in the ECLIPSE trial. The model also yielded an increase in overall CRC clinical sensitivity from 84% to 91%, N=45, with notable sensitivity improvement from 76% to 88% in detecting early localized stage I/II CRC, N = 25, while maintaining specificity at 91%. Conclusions: This enhanced cfDNA-based CRC screening blood test shows improved performance in early stage CRC detection demonstrating the potential of continuous improvement in the performance of cfDNA-based screening tests powered by data and clinical insights.

Feasibility and Acceptability of Antenatal Hepatitis C Screening: A Pilot Study.

Hepatitis C virus (HCV) is not currently included in the United Kingdom routine antenatal screening program, but the latest guidelines from the Centers for Disease Control and Prevention, American Association for the Study of Liver Diseases, and Infectious Diseases Society of America recommend HCV screening for all pregnant women during each pregnancy. The aim of this study was to collect qualitative data on the feasibility and acceptability of antenatal HCV screening in pregnant women at the time of routine antenatal screening at 12 weeks, to estimate patient knowledge about HCV and identify the prevalence of HCV infection in antenatal women. This was a pilot study targeting a single hospital-based antenatal clinic in Birmingham, initially conducted for eight weeks with a further extension of the study period to enhance recruitment to meet the feasibility target of 500 patients. Data collected included demographic and epidemiological details. Pregnant women attending the antenatal unit were given information regarding HCV and antenatal screening for HCV prior to their initial antenatal visit. During the antenatal visit, research nurses provided further information about the study and HCV infection. Consent was obtained for taking part in the study and testing for HCV using blood samples taken at the same time as other routine antenatal screening blood tests. All women who agreed to participate in the study were asked to complete an acceptability and knowledge questionnaire. All women had HCV antibody testing as the primary screening assay. The test result was communicated in writing to the women and their general practitioner. Confirmatory positive antibody tests were followed up with quantitative HCV PCR and genotype analysis. The outcomes of testing were no evidence of HCV infection and evidence of past HCV infection or current HCV infection. Five hundred and forty-nine women were approached in the antenatal clinic; 30 women refused consent while 29 women were excluded from the study (blood tests not performed after consenting, age less than 18 years, and consent form lost). Four hundred and ninety women were included in the study. The median age of the study population was 29 years (range, 18-46). Knowledge about blood-borne viruses was limited; 75% of women had some understanding about antenatal hepatitis B (HBV) and human immunodeficiency virus (HIV) testing. Previous awareness about hepatitis C was reported by 55%. Ninety-one percent of women found the information they were given about hepatitis C helpful. Ninety-six percent of the women included in this study found the counselling they received about HCV useful and felt that the delivery of this information was carried out in an acceptable manner. Once given information about HCV, 99% felt that universal screening for HCV should be implemented. HCV antibody was negative in 489 women. One patient with a positive HCV antibody (prevalence: 0.2%) had a negative HCV PCR. Routine antenatal screening for HCV is not currently recommended in the UK. Our study suggests that antenatal HCV screening would be both feasible and acceptable to most pregnant women attending antenatal clinics. Though the awareness of HCV was low, with appropriate counselling and communication, 99% of pregnant women were in favor of antenatal screening for HCV. Antenatal screening would identify HCV-positive mothers and allow follow-up of their infants so that any infected mothers and infants could be offered effective curative therapy and prevent the progression of liver disease. The inclusion of HCV antenatal screening would complete the blood-borne virus profile and enhance the WHO target to eliminate HCV in the UK.

C-Reactive Protein and Erythrocyte Sedimentation Rates after Total and Unicompartmental Knee Arthroplasty-Less Implant Equals Quicker Normalization.

Postoperative follow up after total or unicondylar knee arthroplasty (UKA) includes C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to scan for and possibly diagnose a periprosthetic joint infection (PJI). The aim of this study was to describe the postoperative changes in CRP and ESR values after UKA and compare them with values obtained after TKA. Patients operated on between 2020 and 2022 were eligible for this retrospective study. Inclusion criteria were patients with at least 4 postoperative visits associated with blood test screening for PJI, aged > 45, with uneventful follow-up for the first 90 days. Exclusion criteria were a history of chronic inflammatory disease, revision for any reason, and readmission for any reason. Blood samples were collected on the 3rd, 15th, and 30th postoperative days and once between the 45th and the 90th day. The mean and peak values were compared between the two groups. The study included 277 patients (243 TKAs and 34 UKAs). Mean age was significantly lower in the UKA group (67.2 ± 7.5 vs. 60.0 ± 5.9). On the 3rd and the 15th postoperative day, the UKA patients had significantly lower ESR and CRP levels. The levels normalized after the first month. While the TKA patients showed higher values, the trend normalized after the 30th day. CRP and ESR values rose significantly after TKA and persisted up to the 15th day postoperatively. CRP and ESR values normalized faster in patients undergoing UKA. Patients > 65 had higher CRP and ESR values during their routine follow-ups.

Research of newborn screening of Glucose-6-phosphate dehydrogenase (G6PD) deficiency at Medlatec General Hospital

Objective: Survey some factors affecting Glucose-6-phosphate dehydrogenase (G6PD) enzyme activity from newborn heel blood samples and analyse screening results of some cases of G6PD enzyme deficiency. Research method: Retrospective and prospective cross-sectional description combined with case description. Results: Research on 3223 children who performed the newborn heel blood screening test from September 2022 to September 2023 showed that the high-risk rate of G6PD enzyme deficiency in boys is significantly higher than in girls. The difference is statistically significant when comparing the proportion of neonates with high-risk screening results in the Muong ethnic group and other ethnic minorities compared to the Kinh ethnic group (p&lt;0.01). Between different sampling age groups and different weight groups, the proportion of children with enzyme activity at the high-risk threshold for G6PD enzyme deficiency did not have a statistically significant difference (p&gt;0.05). The mutation encountered in the study was G6PD Union (c.1360C&gt;T) (p.Arg454Cys), the enzyme activity decreased by &lt;10% corresponding to the level of class II enzyme deficiency, showing mild hemolysis and no severe consequences in infancy. Conclusion: Children's gender and ethnicity are related to enzyme activity at risk thresholds for G6PD enzyme deficiency. Studying the correlation between genotype and phenotype is of great significance in genetic counselling, predicting prognosis and managing G6PD enzyme deficiency.

Pituitary dysfunction following mild traumatic brain injury in female athletes.

Pituitary dysfunction following mild traumatic brain injury can have serious physical and psychological consequences, making correct diagnosis and treatment essential. To the best of our knowledge, this study is the first to study the prevalence of pituitary dysfunction following mild traumatic brain injury in an all-female population following detailed endocrinological work-up after screening for pituitary dysfunction in female athletes. This is a retrospective cohort study. Hormone screening blood tests, including serum blood values for thyroid-stimulating hormone, free thyroxin, insulin-like growth factor 1, prolactin, cortisol, follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone, were taken in 133 female athletes. Results were repeatedly outside the reference value in 88 women necessitating further endocrinological evaluation. Two of those were lost to follow-up, and further endocrinological evaluation was performed in 86 participants. Six women (4.6%, n = 131) were diagnosed with hypopituitarism, four (3.1%) with central hypothyroidism and two with growth hormone deficiency (1.5%). Ten women (7.6%) had hyperprolactinemia, and four (3.1%) of them had prolactinoma. Medical treatment was initiated in 13 (9.9%) women. Significant prognostic factors were not found. As 12.2% of female athletes with a history of mild traumatic brain injury had pituitary dysfunction (hypopituitarism 4.6%, hyperprolactinemia 7.6%), we conclude that pituitary dysfunction is an important consideration in post-concussion care. Hyperprolactinemia in the absence of prolactinoma may represent pituitary or hypothalamic injury following mild traumatic brain injury. Mild traumatic brain injury (mTBI) has become a growing public health concern as 50 million people worldwide sustain a traumatic brain injury annually, with mTBI being the most common (70-90%). As studies on mTBI have focused on mostly male populations this study aims to explore pituitary dysfunction (PD) in female athletes following mTBI. To the best of our knowledge, it is the first all-female study on PD following mTBI. The study found that 12.2% of the participating women had PD after mTBI. Six (4.6%) had hypopituitarism and ten (7.6%) had hyperprolactinemia. These findings suggest that PD following mTBI is an important consideration that endocrinologists and other medical staff working with athletes need to be aware of.

Vitamin B12 deficiency in older people: a practical approach to recognition and management

AbstractVitamin B12 deficiency is common in older people and is linked to anaemia, cognitive decline, and dementia. Clinical presentation is variable, ranging from no symptoms or subtle, non‐specific symptoms, through to serious, irreversible neurological symptoms if left untreated. Although common, it is often under‐recognised, with diagnosis usually occurring on incidental blood test screening. Older people are at increased risk of vitamin B12 deficiency due to insufficient dietary intake, malabsorption associated with aged‐related changes in gastrointestinal function, higher incidence of pernicious anaemia, and chronic use of interfering medications such as metformin and proton‐pump inhibitors. Early detection and treatment in symptomatic deficiency are crucial to prevent irreversible damage. Vitamin B12 intramuscular injection bypasses potential absorption issues and is traditionally the first‐line treatment in older people. However, emerging evidence suggests that high‐dose oral replacement may be as effective. Older people often require lifelong therapy due to the irreversible nature of the underlying cause of deficiency. This review provides an overview of vitamin B12 deficiency and its management in older people.