A computational framework of routine test data for the cost-effective chronic disease prediction.

Chronic diseases, because of insidious onset and long latent period, have become the major global disease burden. However, the current chronic disease diagnosis methods based on genetic markers or imaging analysis are challenging to promote completely due to high costs and cannot reach universality and popularization. This study analyzed massive data from routine blood and biochemical test of 32 448 patients and developed a novel framework for cost-effective chronic disease prediction with high accuracy (AUC 87.32%). Based on the best-performing XGBoost algorithm, 20 classification models were further constructed for 17 types of chronic diseases, including 9 types of cancers, 5 types of cardiovascular diseases and 3 types of mental illness. The highest accuracy of the model was 90.13% for cardia cancer, and the lowest was 76.38% for rectal cancer. The model interpretation with the SHAP algorithm showed that CREA, R-CV, GLU and NEUT% might be important indices to identify the most chronic diseases. PDW and R-CV are also discovered to be crucial indices in classifying the three types of chronic diseases (cardiovascular disease, cancer and mental illness). In addition, R-CV has a higher specificity for cancer, ALP for cardiovascular disease and GLU for mental illness. The association between chronic diseases was further revealed. At last, we build a user-friendly explainable machine-learning-based clinical decision support system (DisPioneer: http://bioinfor.imu.edu.cn/dispioneer) to assist in predicting, classifying and treating chronic diseases. This cost-effective work with simple blood tests will benefit more people and motivate clinical implementation and further investigation of chronic diseases prevention and surveillance program.

Deep self-supervised machine learning algorithms with a novel feature elimination and selection approaches for blood test-based multi-dimensional health risks classification.

BACKGROUND: Blood test is extensively performed for screening, diagnoses and surveillance purposes. Although it is possible to automatically evaluate the raw blood test data with the advanced deep self-supervised machine learning approaches, it has not been profoundly investigated and implemented yet. RESULTS: This paper proposes deep machine learning algorithms with multi-dimensional adaptive feature elimination, self-feature weighting and novel feature selection approaches. To classify the health risks based on the processed data with the deep layers, four machine learning algorithms having various properties from being utterly model free to gradient driven are modified. CONCLUSIONS: The results show that the proposed deep machine learning algorithms can remove the unnecessary features, assign self-importance weights, selects their most informative ones and classify the health risks automatically from the worst-case low to worst-case high values.

Profiling of circulating glial cells for accurate blood-based diagnosis of glial malignancies.

Here, we describe a blood test for the detection of glial malignancies (GLI-M) based on the identification of circulating glial cells (CGCs). The test is highly specific for GLI-M and can detect multiple grades (II-IV) and subtypes including gliomas, astrocytomas, oligodendrogliomas, oligoastrocytomas and glioblastomas, irrespective of gender and age. Analytical validation of the test was performed as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Real-world performance characteristics of the test were evaluated in four clinical (observational) studies. The test has high analytical sensitivity (95%), specificity (100%) and precision (coefficient of variation [CV] = 13.7% for repeatability and CV = 23.5% for within laboratory precision, both at the detection threshold) and is not prone to interference from common drugs and serum factors. The ability of the test to detect and differentiate GLI-M from non-malignant brain tumours (NBT), brain metastases from primary epithelial malignancies (EPI-M) and healthy individual donors (HD) was evaluated in four clinical cohorts. Across these clinical studies, the test showed 99.35% sensitivity (95% confidence interval [CI]: 96.44%-99.98%) and 100% specificity (95% CI: 99.37%-100%). The performance characteristics of this test support its clinical utility for diagnostic triaging of individuals presenting with intracranial space-occupying lesions (ICSOL).

Longitudinal adherence to annual colorectal cancer screening among Black persons living in the United States enrolled in a community-based randomized trial.

BACKGROUND: This study examined repeat colorectal cancer screening rates at 12 and 24 months as part of a randomized intervention trial among Black persons living in the United States and factors associated with screening adherence. METHODS: Participants completed a survey assessing demographics and Preventive Health Model (PHM) factors (e.g., self efficacy, susceptibility) and received either a culturally targeted photonovella plus free fecal immunochemical test (FIT) kits (intervention group) or a standard educational brochure plus free FIT kits (comparison group). FIT return was assessed at 6, 12, and 24 months. Descriptive statistics summarized patterns of repeat screening. Logistic regression models assessed FIT uptake overtime, and demographic and PHM factors associated with screening adherence. RESULTS: Participants (N = 330) were U.S.-born (93%), non-Hispanic (97%), and male (52%). Initial FIT uptake within 6 months of enrollment was 86.6%, and subsequently dropped to 54.5% at 12 months and 36.6% at 24 months. Higher FIT return rates were observed for the brochure group at 24 months (51.5% vs 33.3% photonovella, p = .023). Multiple patterns of FIT kit return were observed: 37% completed FIT at all three time points (full adherence), 22% completed two of three (partial adherence), 29% completed one of three (partial adherence), and 12% did not return any FIT kits (complete nonadherence). Predictors of full adherence were higher levels of education and self-efficacy. CONCLUSIONS: Full adherence to repeat screening was suboptimal. Most participants had partial adherence (one or two of three) to annual FIT screening. Future studies should focus on strategies to support repeat FIT screening.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Fluorescent Phenotyping of Blood Cells Using a Differential Sensing Strategy: Differentiating Physiological Aging Stages and Neuro-Degenerative Disease Drugs.

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs.

Predictive values of an immunological fecal occult blood test for the diagnosis of colorectal cancer compared using colonoscopy in symptomatic patients in Yaounde (Cameroon).

INTRODUCTION: The predictive value of immunological fecal occult blood (iFOB) testing for the screening of colorectal cancer has been well described in the Western world. However, its relevance in Sub-Saharan Africa (SSA) is not well evaluated. It could be altered by the other causes of lower gastrointestinal bleeding such as parasitic infections. The aim of this study was to highlight the performance of an iFOB test for the prediction of colorectal cancer (CRC) during colonoscopy in SSA. METHODOLOGY: We conducted an analytical cross-sectional study in two digestive endoscopic centers of Yaoundé (Cameroon) from the 1st July to the 31 November 2022. Patients presenting with an indication for colonoscopy without any overt gastrointestinal bleeding were included. Sociodemographic and clinical data were collected. All consenting patients underwent a qualitative immunologic occult test through the iFOB test before colonoscopy. Data were analyzed using SPSS version 23.0 software. The performance of the iFOB test for the diagnosis of CRC during colonoscopy was evaluated in terms of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). RESULTS: We included 103 patients during the study period with a male predominance and a sex ratio of 1.7. The median age [IQR] was 52 [38-65] years (range 1 - 84 years). The most common colonoscopic lesions were polyps in 23 patients (22.3%), CRC in 17 patients (16.5%) and hemorrhoids in 15 patients (14.6%). Patients testing positive for iFOB test accounted for 43.7% (45 patients). Among these patients, 31.1% (14 patients) had a CRC. The Se of the occult blood test for CRC detection was calculated to be 82.3% (95%CI: 56.7-96.2); the Sp was 63.9% (95% CI: 53-74); the PPV was 31.1% (95% CI: 24-39) and the NPV was 94.8% (95% CI: 86.6-98.1). CONCLUSION: The iFOB test has a good NPV, but a poor PPV for the diagnosis of CRC in our study.

Exploring ethnic differences in the distribution of blood test results in healthy adult populations to inform earlier cancer detection: a systematic review.

BACKGROUND: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes. OBJECTIVE: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis. METHODS: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible. RESULTS: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women. CONCLUSIONS: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580.

A Canadian survey of perceptions and practices related to ordering of blood tests in the intensive care unit.

PURPOSE: The ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients. METHODS: We conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate. RESULTS: Over seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from Ontario. Respondents had a mean (SD) clinical experience of 12 (9) years, and 61% worked in academic centres. When asked about their perceptions of how frequently unnecessary blood tests are ordered, 61% responded "sometimes" and 23% responded "almost always." Fifty-seven percent favoured ordering complete blood counts one day in advance. Only 24% of respondents believed that advanced blood test ordering frequently led to changes in management. The most common factors perceived to influence blood test ordering in the ICU were physician preferences, institutional patterns, and order sets. CONCLUSION: Most respondents to this survey perceived that unnecessary blood testing occurs in the ICU. The survey identified possible strategies to decrease the number of blood tests.

RéSUMé: OBJECTIF: La prescription à l'avance de tests sanguins de routine est courante dans les unités de soins intensifs (USI), avec une prise en compte limitée de la probabilité de découverte d'anomalies avant le test. Cette pratique contribue à l'anémie, aux résultats faussement positifs et aux coûts des soins de santé. Nous avons cherché à comprendre les pratiques et les attitudes des intensivistes pour adultes au Canada en ce qui concerne la prescription d'analyses sanguines chez la patientèle gravement malade. MéTHODE: Nous avons mené un sondage transversal à l'échelle nationale au Canada en posant 15 questions évaluant trois domaines (perceptions globales, commande de tests, pratique quotidienne), ainsi que 11 questions démographiques. L'échantillon cible était composé d'un·e intensiviste par unité de soins intensifs pour adultes au Canada. Nous avons résumé les réponses à l'aide de statistiques descriptives et présenté les données sous forme de moyennes avec écarts type (ET) ou de dénombrements avec pourcentages, selon le cas. RéSULTATS: Sur une période de sept mois, 80 médecins sur 131 (61%) ont répondu dans 77 unités de soins intensifs, dont 50% en Ontario. Les répondant·es avaient une expérience clinique moyenne (ET) de 12 (9) ans, et 61% travaillaient dans des centres universitaires. Lorsqu'on leur a demandé ce qu'ils ou elles pensaient de la fréquence à laquelle des tests sanguins inutiles étaient prescrits, 61% ont répondu « parfois ¼ et 23% ont répondu « presque toujours ¼. Cinquante-sept pour cent étaient en faveur de la réalisation d'une formule sanguine complète un jour à l'avance. Seulement 24% des personnes interrogées estimaient que la prescription de tests sanguins à l'avance entraînait fréquemment des changements dans la prise en charge. Les facteurs les plus souvent perçus comme influençant la prescription d'analyses sanguines à l'unité de soins intensifs étaient les préférences des médecins, les habitudes institutionnelles et les ensembles d'ordonnances. CONCLUSION: La plupart des répondant·es à ce sondage ont l'impression que des tests sanguins inutiles sont prescrits aux soins intensifs. L'enquête a permis d'identifier des stratégies possibles pour réduire le nombre de tests sanguins.

Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.

There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients <40 y old, we observed that nonphosphorylated CRMP2 was higher than in controls, while phosphorylated CRMP2 remained unchanged from control. In the brain, these changes were associated with dendritic structural abnormalities. The abundance of active CRMP2 with insufficient opposing inactive p-CRMP2 yielded a unique lowering of the p-CRMP2:CRMP2 ratio in SCZ patients, implying a disruption in the normal equilibrium between active and inactive CRMP2. These clinical data suggest that measuring CRMP2 and p-CRMP2 in peripheral blood might reflect intracerebral processes and suggest a rapid, minimally invasive, sensitive, and specific adjunctive diagnostic aid for early SCZ: increased CRMP2 or a decreased p-CRMP2:CRMP2 ratio may help cinch the diagnosis in a newly presenting young patient suspected of SCZ (versus such mimics as mania in bipolar disorder, where the ratio is high).

Lack of social support, gender and colorectal cancer screening participation across Europe: How do screening programmes mitigate the effect of social support for men and women?

This study investigates how a lack of social support differentially affects men and women's colorectal cancer (CRC) screening participation, considering different screening strategies implemented across European countries. Although health sociology has stressed gender differences in social support and its effects on health behaviours, this was overlooked by cancer screening research. Using a data set of 65,961 women and 55,602 men in 31 European countries, we analysed the effect of social support variables on CRC screening uptake. We found that living alone and lower perceived social support were associated with lower screening uptake for both men and women. These effects were, however, stronger among men. Population-based screening programmes mitigated these effects, particularly for women, but not for men living alone. In countries with opportunistic screening programmes, social support variables remained associated with screening uptake. We conclude that cancer screening interventions should pay attention to social support and its gender-differentiated effects.

Point-of-care blood tests using a smartphone-based colorimetric analyzer for health check-up.

A microscale colorimetric assay was designed and implemented for the simultaneous determination of clinical chemistry tests measuring six parameters, including glucose (GLU), total protein (TP), human serum albumin (HSA), uric acid (UA), total cholesterol (TC), and triglycerides (TGs) in plasma samples. The test kit was fabricated using chromogenic reagents, comprising specific enzymes and binding dyes. Multiple colors that appeared on the reaction well when it was exposed to each analyte were captured by a smartphone and processed by the homemade Check6 application, which was designed as a colorimetric analyzer and simultaneously generated a report that assessed test results against gender-dependent reference ranges. Six blood checkup parameters for four plasma samples were conducted within 12 min on one capture picture. The assay achieved wide working concentration ranges of 10.45-600 mg dL-1 GLU, 1.39-10.0 g dL-1 TP, 1.85-8.0 g dL-1 HSA, 0.86-40.0 mg dL-1 UA, 11.28-600 mg dL-1 TC, and 11.93-400 mg dL-1 TGs. The smartphone-based assay was accurate with recoveries of 93-108% GLU, 93-107% TP, 92-107% HSA, 93-107% UA, 92-107% TC, and 99-113% TGs. The coefficient of variation for intra-assay and inter-assay precision ranged from 3.2-5.2% GLU, 4.6-5.3% TP, 4.3-5.3% HSA, 2.8-6.6% UA, 2.7-6.5% TC, and 1.1-3.9% TGs. This assay demonstrated remarkable accuracy in quantifying the concentration-dependent color intensity of the plasma, even in the presence of other suspected interferences commonly present in serum. The results of the proposed method correlated well with results determined by the microplate spectrophotometer (R2 > 0.95). Measurement of these six clinical chemistry parameters in plasma using a microscale colorimetric test kit coupled with the Check6 smartphone application showed potential for real-time point-of-care analysis, providing cost-effective and rapid assays for health checkup testing.

Dietary nutrient intake and nutritional status in maintenance hemodialysis patients: a multicenter cross-sectional survey.

PURPOSE: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators. METHODS: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy. RESULTS: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females. CONCLUSIONS: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.

Endoscopic findings and predictors of gastrointestinal lesions in children with iron deficiency anemia.

Iron deficiency anemia (IDA) can be caused by occult gastrointestinal (GI) blood loss; however, the endoscopic findings in children with anemia are unclear. The study aimed to determine the frequency and factors related to lesions in children with IDA undergoing endoscopy. We retrospectively analyzed the clinical and endoscopic findings of children with a laboratory-based diagnosis of IDA. Of 58 patients, 36 (62.1%) had upper GI tract lesions, with erosive gastritis being the most common lesion. Further, 26 patients underwent concomitant colonoscopy, and 12 (46.2%) had lower GI tract lesions. Overall, 44 (75.9%) patients had lesions in either the upper or lower GI tract. Helicobacter pylori infection was detected in 13 patients (22.4%). Patients with lesions found by endoscopy had significantly lower hemoglobin level (8.9 vs. 10.0 g/dL, p = 0.047) and mean corpuscular volume (75.5 vs. 80.9 fL, p = 0.038). The proportion of patients with previous treatment for IDA was also higher in those with lesions on endoscopy. In multivariate analysis, age of ≥10 years (odds ratio [OR], 6.00; 95% confidence Interval [CI], 0.56-10.75) and positive fecal occult blood test (FOBT) findings (OR, 2.25; 95% CI, 0.14-4.52) were factors related to GI lesions. The presence of GI symptoms was not associated with GI lesions. A high proportion of GI lesions were found by endoscopy in children with IDA in this study. Endoscopy should be considered in children with IDA even without GI symptoms, especially in older children, and those with positive FOBT results.

Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice.

INTRODUCTION: We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P-)tau181, amyloid-beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS: We measured the plasma biomarkers with Simoa (n = 1199), applied LASSO regression for biomarker selection and receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. We validated our findings in two independent cohorts and constructed a visualization approach. RESULTS: P-tau181, GFAP, and NfL were selected. This combination had area under the curve (AUC) = 83% to identify amyloid positivity in pre-dementia stages, AUC = 87%-89% to differentiate Alzheimer's or controls from frontotemporal dementia, AUC = 74%-76% to differentiate Alzheimer's or controls from dementia with Lewy bodies. Highly reproducible AUCs were obtained in independent cohorts. The resulting visualization tool includes UpSet plots to visualize the stand-alone biomarker results and density plots to visualize the biomarker results combined. DISCUSSION: Our multimarker blood test interpretation tool is ready for testing in real-world clinical dementia settings. HIGHLIGHTS: We developed a multimarker blood test interpretation tool for clinical dementia practice. Our interpretation tool includes plasma biomarkers P-tau, GFAP, and NfL. Our tool is particularly useful for Alzheimer's and frontotemporal dementia diagnosis.

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Objective: To explore the relationship between baseline clinical characteristics and hematological parameters of patients undergoing radical resection for pancreatic ductal adenocarcinoma (PDAC) and their prognosis, and to provide references for stratifying the patients' clinical risks. Methods: We retrospectively collected clinical data from 445 patients who underwent radical surgical treatment for PDAC at West China Hospital, Sichuan University between January 2010 and February 2019. Then, we conducted retrospective clinical analysis with the collected data. Data on patients' basic clinical characteristics, routine blood test results, and tumor indicators were collected to explore their effects on the postoperative overall survival (OS) of PDAC patients. Cox proportional hazards regression was used to identify factors affecting OS. Statistical analysis was performed using the SPSS 23.0 software package. Results: The postoperative median overall survival (mOS) was 17.0 months (95% CI: 15.0-19.0). The 1, 2, 3, 4, and 5-year survival rates of the patients included in the study were 60.6%, 33.4%, 19.1%, 12.7%, and 9.6%, respectively. The multivariate Cox proportional hazards model analysis demonstrated that a number of factors independently affect postoperative survival in PDAC patients. These factors include tumor location (hazards ratio [HR]=1.574, 95% CI: 1.233-2.011), degree of tumor cell differentiation (HR=0.687, 95% CI: 0.542-0.870), presence of neural invasion (HR=0.686, 95% CI: 0.538-0.876), TNM staging (HR=1.572, 95% CI: 1.252-1.974), postoperative adjuvant therapy (HR=1.799, 95% CI: 1.390-2.328), preoperative drinking history (HR=0.744, 95% CI: 0.588-0.943), and high serum CA199 levels prior to the surgery (HR=0.742, 95% CI: 0.563-0.977). Conclusion: In PDAC patients, having tumors located in the head of the pancreas, moderate and high degrees of differentiated, being free from local neurovascular invasion, being in TNM stage Ⅰ, undergoing postoperative adjuvant therapy, no history of alcohol consumption prior to the surgery, and preoperative serum CA199 being less than or equal to 37 U/mL are significantly associated with a better prognosis.

Validation of the Blood Test MACK-3 for the Noninvasive Diagnosis of Fibrotic Nonalcoholic Steatohepatitis: An International Study With 1924 Patients.

BACKGROUND & AIMS: Drug development in nonalcoholic steatohepatitis (NASH) is hampered by a high screening failure rate that reaches 60% to 80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including 3 biomarkers (aspartate aminotransferase, homeostasis model assessment, and cytokeratin 18), recently was developed for the noninvasive diagnosis of fibrotic NASH. We aimed to validate the diagnostic accuracy of this noninvasive test in an international multicenter study. METHODS: A total of 1924 patients with biopsy-proven nonalcoholic fatty liver disease from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all patients. FibroScan-aspartate aminotransferase score (FAST), an elastography-based test for fibrotic NASH, also was available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with a Nonalcoholic Fatty Liver Disease Activity Score of 4 or higher and fibrosis stage of F2 or higher according to the NASH Clinical Research Network scoring system. RESULTS: The area under the receiver operating characteristic of MACK-3 for fibrotic NASH was 0.791 (95% CI 0.768-0.814). Sensitivity at the previously published MACK-3 threshold of less than 0.135 was 91% and specificity at a greater than 0.549 threshold was 85%. The MACK-3 area under the receiver operating characteristic was not affected by age, sex, diabetes, or body mass index. MACK-3 and FAST results were well correlated (Spearman correlation coefficient, 0.781; P < .001). Except for an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate). CONCLUSIONS: The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials.

Implementation of a home-based colorectal cancer screening intervention in Malaysia (CRC-SIM).

INTRODUCTION: The Colorectal Cancer Screening Intervention for Malaysia (CRC-SIM) was a CRC study of home-based testing designed to improve low screening uptake using the immunochemical fecal occult blood test (iFOBT) in Malaysia. METHODS: This quasi-experimental study was informed by the Implementation Research Logic Model and evaluated with the RE-AIM framework. Trained data collectors recruited by phone, randomly selected, asymptomatic adults aged 50-75 years from Segamat District, who previously completed a health census form for the South East Asia Community Observatory (SEACO). Participants were posted an iFOBT kit and asked to return a photo of the completed test for screening by health care professionals. A regression analysis of evaluation data was conducted to identify which variables were associated with the outcome indicators of 'study participation' and 'iFOBT completion' and the CRC-SIM was evaluated in terms of its appropriateness, feasibility and acceptability. RESULTS: Seven hundred forty-seven eligible adults (52%) agreed to participate in this study and received an iFOBT kit. Participation was significantly lower amongst Chinese Malaysians (adjusted OR 0.45, 95% CI 0.35 - 0.59, p<0.001) compared to Malays and amongst participants from the rural sub-district (Gemereh) (adjusted OR 0.71, 95% CI 0.54 - 0.92, p=0.011) compared to the urban sub-district (Sungai Segamat). Less than half of participants (42%, n=311/747) completed the iFOBT. Test-kit completion was significantly higher amongst Chinese Malaysians (adjusted OR 3.15, 95% CI 2.11 - 4.69, p<0.001) and lower amongst participants with a monthly household income ≥RM 4,850 (adjusted OR 0.58, 95% CI 0.39 - 0.87, p=0.009) compared to participants with a lower household income. The main reported reason for non-participation was 'not interested' (58.6%) and main implementation challenges related to invalid photographs from participants and engaging iFOBT positive participants in further clinic consultations and procedures. CONCLUSION: Home-testing for CRC (test completion) appeared to be acceptable to only around one-fifth of the target population in Malaysia. However, mindful of the challenging circumstances surrounding the pandemic, the CRC-SIM merits consideration by public health planners as a method of increasing screening in Malaysia, and other low- and middle-income countries.

The potential of high-order features of routine blood test in predicting the prognosis of non-small cell lung cancer.

BACKGROUND: Numerous studies have demonstrated that the high-order features (HOFs) of blood test data can be used to predict the prognosis of patients with different types of cancer. Although the majority of blood HOFs can be divided into inflammatory or nutritional markers, there are still numerous that have not been classified correctly, with the same feature being named differently. It is an urgent need to reclassify the blood HOFs and comprehensively assess their potential for cancer prognosis. METHODS: Initially, a review of existing literature was conducted to identify the high-order features (HOFs) and classify them based on their calculation method. Subsequently, a cohort of patients diagnosed with non-small cell lung cancer (NSCLC) was established, and their clinical information prior to treatment was collected, including low-order features (LOFs) obtained from routine blood tests. The HOFs were then computed and their associations with clinical features were examined. Using the LOF and HOF data sets, a deep learning algorithm called DeepSurv was utilized to predict the prognostic risk values. The effectiveness of each data set's prediction was evaluated using the decision curve analysis (DCA). Finally, a prognostic model in the form of a nomogram was developed, and its accuracy was assessed using the calibration curve. RESULTS: From 1210 documents, over 160 blood HOFs were obtained, arranged into 110, and divided into three distinct categories: 76 proportional features, 6 composition features, and 28 scoring features. Correlation analysis did not reveal a strong association between blood features and clinical features; however, the risk value predicted by the DeepSurv LOF- and HOF-models is significantly linked to the stage. Results from DCA showed that the HOF model was superior to the LOF model in terms of prediction, and that the risk value predicted by the blood data model could be employed as a complementary factor to enhance the prognosis of patients. A nomograph was created with a C-index value of 0.74, which is capable of providing a reasonably accurate prediction of 1-year and 3-year overall survival for patients. CONCLUSIONS: This research initially explored the categorization and nomenclature of blood HOF, and proved its potential in lung cancer prognosis.

Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D.

BACKGROUND: Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis. METHODS: We performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated. RESULTS: Profilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study. CONCLUSION: PFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.