Simple Blood Test Research Articles

Systematic Review of Existing Stroke Guidelines: Case for a Change.

Methods We systematically searched for guideline recommendation on the day-to-day use of peripheral inflammatory markers such as NLR published in the English language between January 1, 2005, and October 2020. Any other evidence of system biology-based approach or recommendation was explored within the selected guidelines for this scoping review. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 4 authors to determine clinical scenarios explained/given, scientific evidence used, and recommendations presented in the context of system biology. Results The scoping review found 2,911 titles at the beginning of the search. Final review included with 15 guidelines. Stroke-related organizations wrote sixty-five percent of the guidelines while national ministries wrote a fewer number of guidelines. We were primarily interested in recommendations for acute management in AIS published in the English language. Fifteen eligible guidelines were identified from 15 different countries/regions. None of the guidelines recommended the routine use of peripheral markers of inflammation, such as NLR, among their acute assessment and management recommendations. None of the existing guidelines explored the system biology approach to one of the most complex diseases affecting the human brain, stroke. Conclusions This systematic review has identified a significant evidence-practice gap in all existing national stroke guidelines published in English medium as of October 2020. These guidelines included the only current “living stroke guidelines,” stroke guidelines from Australia with a real opportunity to modernize the living stroke guidelines with systems biology approach, and provide 2020 vision towards better stroke care globally. Investigation of complex disease such as stroke is best served through a systems biology approach. One of the easiest places to start is simple blood tests such as total white cell count and NLR. Systems biology approach point us towards simple tools such immune-inflammatory index (SII) and serial systemic immune inflammatory indices (SSIIi) which should pave the way for the stroke physician community address the challenges in systems biology approach in stroke care. These challenges include translating bench research to the bedside, managing big data (continuous pulse, blood pressure, sleep, oxygen saturation, progressive changes in NLR, SII, SSIIi, etc.). Working with an interdisciplinary team also provides a distinct advantage. Recent adoption of historic WHO-IGAP calls for immediate action. The 2022 World Brain Day campaign on Brain Health for All is the perfect opportunity to raise awareness and start the process.

Abstract 5931: Development and validation of a novel circulating cell-free microRNA diagnostic model with high accuracy for multi-cancer early detection

Abstract Introduction: Early detection is critical to reduce cancer deaths as treating early stage cancers is more likely to be successful. We aimed to develop and validate a noninvasive blood-based diagnostic model capable of detecting multiple cancers by assessing the expression levels of serum microRNAs (miRNAs). Patients and Methods: Four microarray datasets assessing expression profiles of 2588 serum miRNAs with a standardized platform were assembled from Gene Expression Omnibus (GEO) totaling 7536 participants including 3604 cancer patients across 13 cancer types and 3932 non-cancer controls. A diagnostic model was built in a training set of 416 participants, including 208 lung cancer patients and 208 non-cancer controls matched for age, sex, and smoking history. The model performance was assessed in the validation sets consisting of all the remaining 7120 participants. Results: A 4-miRNA diagnostic model was developed from the lung cancer training set. The model showed 99% sensitivity and specificity in the lung cancer validation set (n=3328, 1358 cancer & 1970 non-cancer participants); and the sensitivity remained to be >99% for patients with stage 1 disease. When applied to the additional dataset of 3792 participants including 2038 cancer patients across 12 cancer types and 1754 independent non-cancer controls, the model showed high sensitivities ranging from 83⋅2% to 100% for biliary tract, bladder, colorectal, esophageal, gastric, glioma, liver, pancreatic, and prostate cancers, and reasonable sensitivities of 68⋅2% and 72⋅0% for ovarian cancer and sarcoma, respectively, while maintaining 99⋅3% specificity (Table 1). Conclusion: The study provided a proof-of-concept demonstrating that the 4-miRNA model has the potential to be developed into a simple, inexpensive and noninvasive blood test for early detection of multiple cancers with high accuracy. Table 1. Sensitivities of the 4-miRNA diagnostic model in 12 cancer types. N Sensitivity Lung Cancer 1358 99.3% Biliary Tract Cancer 40 97.5% Bladder Cancer 392 98.2% Colorectal Cancer 155 85.8% Esophageal Cancer 124 84.7% Gastric Cancer 150 100% Glioma 40 87.5% Liver Cancer 348 84.2% Ovarian Cancer 333 68.2% Pancreatic Cancer 149 83.2% Prostate Cancer 40 92.5% Sarcoma 132 72.0% Citation Format: Andrew Zhang, Hai Hu. Development and validation of a novel circulating cell-free microRNA diagnostic model with high accuracy for multi-cancer early detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5931.

Predicting outcomes with circulating adrenergic neuroblastoma mRNAs in children with relapsed and refractory neuroblastoma: A BEACON-Neuroblastoma biomarker study.

10039 Background: Children with relapsed and refractory neuroblastoma (RR-NBL) have poor outcomes. Early identification of children at greatest risk of relapse could mean timelier modifications of treatment to improve outcomes. High levels of adrenergic neuroblastoma mRNAs in blood of children with stage M neuroblastoma receiving frontline treatment predict poor outcome (Viprey PMID: 24590653). Since these markers have not been thoroughly studied in the RR-NBL population, we have prospectively evaluated the prognostic potential of the adrenergic neuroblastoma mRNAs paired-like homeobox 2B (PHOX2B ) and tyrosine hydroxylase (TH) in blood from children with RR-NBL treated in the BEACON-Neuroblastoma trial (NCT02308527). Methods: Blood samples collected at baseline from 88 children were analysed by reverse transcriptase polymerase chain reaction (RTqPCR) for PHOX2B and TH mRNAs. The prognostic power of these mRNAs was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression. Progression-free (PFS) and overall survival (OS) were calculated from the date that the blood sample was taken at screening to the date of an event; progression, disease recurrence, death or censored alive at the last clinical evaluation. Results: Of the children in this cohort, 58 (66%) had relapsed and 30 (34%) had refractory disease. Twenty-three (26%) had MYC-N amplified tumours. TH and PHOX2B mRNAs were detected in 55% and 60% of blood samples respectively; the correlation coefficient between TH and PHOX2B was 0.75. Higher levels of TH, PHOX2B mRNAs or both combined were associated with reduced PFS and OS (Table). For TH, median PFS for children with TH levels below the median was 12 months (95%CI, 4.6–13 months) versus 5.5 months (95%CI, 1.8–9.4 months) for those children with TH levels above the median. For PHOX2B, median PFS for children with PHOX2B levels below the median was 11.5 months (95%CI, 7.6–34 months), compared to 5.7 months (95%CI, 1.8–10.5 months) where levels were above the median. Conclusions: TH and PHOX2B mRNAs in blood collected at baseline identify children with refractory or relapsed neuroblastoma at greatest risk of progression or death. In the RR-NBL setting, this simple blood test could be used to stratify treatment strategies. Clinical trial information: NCT02308527. [Table: see text]

The Role of Simple Blood Tests and a Modified Chest X-Ray Scoring System in Assessing the Severity Disease and Mortality Risk in COVID-19 Patients in a Secondary Hospital, Indonesia.

BackgroundCoronavirus disease 2019 (COVID-19) has resulted in millions of mortality cases and significant incremental costs to the healthcare system. Examination of CRP and D-dimer were considered to have higher costs, and the use of simple hematological parameters such as lymphocyte, neutrophil, and white blood cell (WBC) which have more affordable costs would be cost-saving. Radiological imaging complements clinical evaluation and laboratory parameters for managing COVID-19 patients. Therefore, categorizing patients into severe or non-severe becomes more defined, allowing for earlier interventions and decisions of hospital admission or being referred to a tertiary hospital.PurposeTo evaluate the variables correlated with poor outcomes in COVID-19 patients.Patients and MethodsThis was a retrospective study on COVID-19 patients in a secondary referral hospital in treating COVID-19 in Indonesia. Demographic, clinical data, laboratory parameters, CXR (analyzed using a modified scoring system), and prognosis were collected through electronic nursing and medical records.ResultsThis study included 476 hospitalized COVID-19 patients. Severe patients were commonly found with older age (median of 57 vs 40), dyspnea (percentage of 85.2% vs 20.5%), higher CXR score (median of 7 vs 5), higher levels of neutrophil (median of 79.9 vs 68.3), and lower lymphocyte levels (median of 13.4 vs 22.7), compared to non-severe patients. These variables were known to increase the odds of severe disease. Older age (median of 57 vs 48), SpO2 <94% room air (percentage of 87.4% vs 31.5%), higher CXR score (median of 8 vs 5), and higher respiratory rate (median of 25 vs 20) were found higher in death patients and were known to increase the odds of death outcome.ConclusionThe simple blood tests (neutrophil and lymphocyte) and modified CXR scoring system are useful in risk stratification for severe disease and mortality in COVID-19 patients to decide the earlier interventions and treatment.

Independent validation of a novel noninvasive 4-microRNA diagnostic model for multicancer early detection.

3065 Background: Cancer early detection is critical to reduce mortality as treating early stage cancers is more likely to have better outcomes. We previously developed a diagnostic model based on 4 serum cell-free microRNAs (miRNAs) capable of detecting 12 cancer types with high accuracy (AACR 2022, Poster 2890; Manuscript submitted). In the current study, we aimed to validate this diagnostic model using independent serum microRNA microarray datasets. Methods: Four microarray datasets assessing the expression of 2588 serum miRNAs in patients with esophageal squamous cell carcinoma, gastric cancer, prostate cancer and glioma, as well as non-cancer healthy controls with a standardized platform were identified from Gene Expression Omnibus (GEO). The datasets were combined, cases that were redundant among them or with the cases used in our previous study (correlation &gt; 0.99) were excluded. The 4-miRNA model was applied to the final combined dataset to calculate a diagnostic index and make prediction of cancer vs. no-cancer using previously determined algorithm and cut-point. The performance of the diagnostic model was assessed using Receiver Operating Characteristic (ROC) analysis, sensitivity and specificity. Results: After excluding redundant cases, the final combined dataset consisted of 3877 subjects, including 447 esophageal, 1267 gastric, 769 prostate and 196 glioma cancer patients, as well as 1198 healthy controls. The 4-miRNA model demonstrated an area under the curve (AUC) of 0.986, 0.995, 0.992 and 0.990 in the ROC analysis, with a sensitivity of 85.0%, 99.6%, 90.6% and 86.7% for esophageal, gastric, prostate and glioma cancers, respectively, while achieving a 99.1% specificity. These performance metrics were highly consistent to those reported in our previous study (Table). Conclusions: The study provided an independent validation of the previously developed 4-miRNA model, further demonstrating that the diagnostic model we developed has the potential to be developed into a simple, inexpensive and noninvasive blood test for multi-cancer early detection with high accuracy. [Table: see text]

Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood.

T cell immunity to natural SARS-CoV-2 infection may be more robust and longer lived than Ab responses. Accurate assessment of T cell responses is critical for understanding the magnitude and longevity of immunity across patient cohorts, and against emerging variants. By establishing a simple, accurate, and rapid whole blood test, natural and vaccine-induced SARS-CoV-2 immunity was determined. Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with previous PCR-confirmed infection, suspected infection, or with no exposure history (n = 128), as well as in donors before and after vaccination (n = 32). Longitudinal assessment of T cell responses following initial vaccination and booster vaccination was also conducted (n = 50 and n = 62, respectively). Cytokines were measured by ELISA and multiplex array. IL-2 and IFN-γ were highly elevated in PCR-confirmed donors compared with history-negative controls, with median levels ∼33-fold and ∼48-fold higher, respectively. Receiver operating curves showed IL-2 as the superior biomarker (area under the curve = 0.9950). Following vaccination, all donors demonstrated a positive IL-2 response. Median IL-2 levels increased ∼32-fold from prevaccination to postvaccination in uninfected individuals. Longitudinal assessment revealed that T cell responses were stable up to 6 mo postvaccination. No significant differences in cytokine production were observed between stimulations with Wuhan, Delta, or Omicron peptides. This rapid, whole blood-based test can be used to make comparable longitudinal assessments of vaccine-induced T cell immunity across multiple cohorts and against variants of concern, thus aiding decisions on public health policies.

Developing a simple and practical decision model to predict the risk of incident type 2 diabetes among the general population: The Di@bet.es Study

AimsTo develop a simple multivariate predictor model of incident type 2 diabetes in general population. MethodsParticipants were recruited from the Spanish Di@bet.es cohort study with 2570 subjects meeting all criteria to be included in the at-risk sample studied here. Information was collected using an interviewer-administered structured questionnaire, followed by physical and clinical examination. CHAID algorithm, which collects the information of individuals with and without type 2 diabetes, was used to develop a decision tree based type 2 diabetes prediction model. Results156 individuals were identified as having developed type 2 diabetes (6.5% incidence). Fasting plasma glucose (FPG) at the beginning of the study was the main predictive variable for incident type 2 diabetes: FPG ≤ 92 mg/dL (ref.), 92–106 mg/dL (OR = 3.76, 95%CI = 2.36–6.00), > 106 mg/dL (OR = 13.21; 8.26–21.12). More than 25% of subjects starting follow-up with FPG levels > 106 mg/dL developed type 2 diabetes. When FPG <106 mg/dL, other variables (fasting triglycerides (FTGs), BMI or age) were needed. For levels ≤ 92 mg/dL, higher FTGs levels increased risk of incident type 2 diabetes (FTGs > 180 mg/dL, OR = 14.57; 4.89–43.40) compared with the group of FTGs ≤ 97 mg/dL (FTGs = 97–180 mg/dL, OR = 3.12; 1.05–9.24). This model correctly classified 93.5% of individuals. ConclusionsThe type 2 diabetes prediction model is based on FTGs, FPG, age, gender, and BMI values. Utilizing commonly available clinical data and a simple blood test, a simple tree diagram helps identify subjects at risk of developing type 2 diabetes, even in apparently low risk subjects with normal FPG.

General practitioner perspectives and experiences when screening for primary aldosteronism in hypertensive patients.

Context: Primary aldosteronism (PA) is a common form of hypertension caused by excess production of the adrenal hormone aldosterone. Screening hypertensive patients with a simple blood test enables early detection and targeted treatment of PA, leading to fewer cardiovascular complications. Australian family physicians (FPs) rarely screen for PA, and screening rates are equally low among North American FPs. Limited awareness of PA is thought to explain the low screening rates in family practice. Objective: To understand the factors that influence an FP's decision to screen for PA in hypertensive patients. Study Design: Qualitative study using phenomenology to explore the experiences of FPs when screening for PA. Setting/Population: Set in South-East Melbourne, participating FPs had received an educational session on PA from an endocrinologist. We conducted semi-structured interviews with FPs who had screened at least one patient following the teaching session. Interviews were transcribed verbatim, entered into NVivo for coding, and analyzed for emerging themes. Results: The 16 participants varied by clinical experience (1-35 years), practice location (3 regional, 13 urban), and the number of patients screened for PA (1-44 patients). FPs overwhelmingly preferred screening newly diagnosed hypertensive patients over those already being managed with antihypertensive medications. Only a few FPs opted to screen all hypertensive patients, while the majority questioned the necessity of screening patients whom they thought fitted their clinical impression of essential hypertension. Many FPs found it challenging to both comply with testing requirements and interpret screening results within the existing organizational constraints of their practice. FPs that had diagnosed at least one patient with PA acknowledged the positive impact that targeted treatment had on patient wellbeing and this reinforced their role in assisting with the detection of PA. Knowledge and convenience of the screening process, the conceptualization of risk, and the perceived impacts of detecting PA were influencing factors that modified the FP screening experience. Conclusion: This study demonstrates that additional factors, other than limited awareness, influence a FP's decision to screen for PA. Our findings have the potential to inform future policy, practice, and training interventions to improve the detection of PA in family practice.

Clinical Features and Possible Prognostic Factors in Patients with Marginal Zone Lymphoma: Retrospective Analysis from Two Centers

Objective: Marginal zone lymphoma accounts 5%-17% of all non-Hodgkin lymphomas and has an indolent clinical course. The parameters that predict prognosis and the need for treatment are still unclear. The aim of the current study was to examine the impact of parameters on the course of disease and the need for treatment in marginal zone lymphoma. Patients and Methods: A retrospective study was conducted with marginal zone lymphoma patients in the hematology departments of two centres between 2010 and 2018. The demographic and disease characteristics, and also hematological and biochemical parameters at the time of diagnosis were examined. The effect of the parameters on overall survival and need for treatment were analyzed. Fourty patients were included in this study. Results: A total of 40 MZL patients, 25 (62.5%) women and 15 (37.5%) men, were evaluated. During the follow-up, 25 patients required treatment and 15 patiens were followed up without treatment. overall survival of all marginal zone lymphoma patients was 58.4 months. Overall survival was significantly higher in patients with nodal marginal zone lymphoma than in extranodal and splenic marginal zone lymphoma patients. The platelet count of untreated patients at the time of diagnosis were significantly higher than patients who received treatment (p= 0.04). Conclusion: We demonstrated platelet count at the time of diagnosis as a predictive factor for future treatment need. It is an objective and simple blood test that may be helpful to predict the course of the disease although further studies are warranted.

Donor-derived Cell-free DNA Shows High Sensitivity for the Diagnosis of Pancreas Graft Rejection in Simultaneous Pancreas-kidney Transplantation.

Background.Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management.Methods.Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient’s plasma (quantity; copies/mL).Results.In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward (median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P = 0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P = 0.006) and quantity (81.3 versus 35.3 cp/mL; P = 0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current biomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase).Conclusions.dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.

A Novel Blood-Based microRNA Diagnostic Model with High Accuracy for Multi-Cancer Early Detection.

Simple SummaryDevelopment of noninvasive diagnostic tests capable of detecting multiple cancer types early is urgently needed. Majority of the tests that are currently in development for multi-cancer early detection are based on next generation sequencing technology to evaluate methylation or fragmentation patterns of circulating tumor DNAs. Here, we developed a serum-based 4-microRNA diagnostic model, which when compared to the existing next generation sequencing-based tests, demonstrated superior performance in detecting 12 cancer types in the largest case-control validation cohort to date. The simplicity of our model also makes it feasible to develop an in vitro diagnostic (IVD) test capable of decentralized testing, supporting the wide adoption and compliance in the at-risk general population.Early detection is critical to reduce cancer deaths as treating early stage cancers is more likely to be successful. However, patients with early stage diseases are often asymptomatic and thus less likely to be diagnosed. Here, we utilized four microarray datasets with a standardized platform to investigate comprehensive microRNA expression profiles from 7536 serum samples. A 4-miRNA diagnostic model was developed from the lung cancer training set (n = 416, 208 lung cancer patients and 208 non-cancer participants). The model showed 99% sensitivity and specificity in the lung cancer validation set (n = 3328, 1358 cancer patients and 1970 non-cancer participants); and the sensitivity remained to be >99% for patients with stage 1 disease. When applied to the additional combined dataset of 3792 participants including 2038 cancer patients across 12 different cancer types and 1754 independent non-cancer controls, the model demonstrated high sensitivities ranging from 83.2 to 100% for biliary tract, bladder, colorectal, esophageal, gastric, glioma, liver, pancreatic, and prostate cancers, and showed reasonable sensitivities of 68.2 and 72.0% for ovarian cancer and sarcoma, respectively, while maintaining 99.3% specificity. Our study provided a proof-of-concept data in demonstrating that the 4-miRNA model has the potential to be developed into a simple, inexpensive and noninvasive blood test for early detection of multiple cancers with high accuracy.

Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system

ObjectiveTo determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system.MethodsUsing data obtained from a large epidemiological database...

Comparing Spot Urine Protein: Creatinine Ratio 24-Hour Urinary Protein Estimation in Type 2 Diabetes Mellitus Patients

Background &amp; Objective: A simple blood test (urea and creatinine) and a urine test may indicate renal function deterioration and presence of microalbuminuria, which is also the first clinical signs of renal dysfunction in patients with diabetes mellitus. This cost effective test easy to perform even in the absence of advance facilities in a hospital. That is why we planned to conducted this study to assess the comparison between of spot urine protein:creatinine ratio with 24-hour urinary protein in patients with type 2 diabetes mellitus.&#x0D; Materials and Methods: This prospective hospital based clinical study was conducted in the Department of General Medicine, Liaquat University of Medical &amp; Health Sciences, Jamshoro, over a period of six months from 10th May 2018 to 9th November 2019 through a consecutive sampling technique. All the patients having age more than 18 years of both gender, and type 2 diabetes mellitus were enrolled in this study. Three cc blood was taken to determine the serum creatinine levels and twenty-four hour 2ml urine sample was also collected to determine the urinary protein levels. The proteinuria ≥300mg/dl in 24-hour urine sample was considered as significant proteinuria. Kappa statistics was used to find agreement between spot urine protein and 24 hours urinary protein.&#x0D; Results: A total 95 patients were evaluated and their mean age was 41.91±14.29 years, with male predominance (n = 66, 69.4%). Average 24 hour urinary protein was 1216.99±949.51mg and spot-urine evaluation of protein was 1919.12±2129.25mg. The agreement between spot urinary protein creatinine ratio and 24 hour urinary protein was found in 82.1% of cases through Kappa statistics and the calculated agreement between the two procedures was 0.975 which provides sufficient agreement to use spot urine protein:creatinine ratio in routine diagnosis of proteinuria.&#x0D; Conclusion: The study have shown that the protein:creatinine ratio for a random urine sample might be used to rule out the presence of significant proteinuria as defined by a quantitative measure of the 24-hour urine protein excretion.

N-myristoyltransferase 2-based Blood Test for the Detection of Colorectal Adenomatous Polyps and Cancer.

Colorectal cancer is the second leading cause of cancer-related deaths. This study demonstrates the utility of a simple blood test with high sensitivity and specificity for colorectal adenomatous polyps and cancer. A simple blood test with high sensitivity and specificity for adenomas would help identify individuals for a follow-up colonoscopy during which any adenomatous polyps found could be removed, thus preventing colorectal cancer (CRC). We determined the H-score by using immunohistochemical analyses of N-myristoyltransferase 2 (NMT2) in peripheral blood mononuclear cells (PBMC) isolated from the blood. We determined the sensitivity and specificity of the NMT2-based blood test in identifying colorectal adenomatous polyps and cancer. All experimental procedures were performed by research personnel blinded to the colonoscopy status of the participants. In this cohort study, participants were recruited from those coming for an outpatient colonoscopy at a referral center. PBMC were collected from 74 subjects at the Health Sciences Centre, Winnipeg, Canada. Samples were collected from colonoscopy patients prior to colonoscopy. All 74 subjects were included in CRC vs. non-CRC analysis, whereas only 70 subjects were analyzed for colorectal adenomatous polyps and cancer versus individuals with no evidence of disease and non-adenomatous polyps. NMT2 expression was tested in samples by immunohistochemistry. The expression of NMT2 was significantly higher in PBMC of subjects with colorectal adenomatous polyps and cancer (n = 34) compared with individuals with non-adenomatous polyps or no evidence of disease (n = 36) (P < 0.0001). The test had an overall sensitivity of 91% (95% confidence intervals: 84.49-97.80) and specificity of 81% (95% confidence intervals: 71.28-89.83) in detecting colorectal adenomatous polyps and cancer (all stages). Our results suggest that the sensitivity of NMT2 in detecting adenomatous polyps is high (91%). A simple blood-based CRC screening test using NMT2 expression detects colorectal adenomatous polyps and cancer with high sensitivity and specificity has the potential of increasing the compliance for CRC screening as has been reported for other blood-based CRC screening tests.

Machine-Learning Approaches for Predicting the Need of Oxygen Therapy in Early-Stage COVID-19 in Japan: Multicenter Retrospective Observational Study.

BackgroundEarly prediction of oxygen therapy in patients with coronavirus disease 2019 (COVID-19) is vital for triage. Several machine-learning prognostic models for COVID-19 are currently available. However, external validation of these models has rarely been performed. Therefore, most reported predictive performance is optimistic and has a high risk of bias. This study aimed to develop and validate a model that predicts oxygen therapy needs in the early stages of COVID-19 using a sizable multicenter dataset.MethodsThis multicenter retrospective study included consecutive COVID-19 hospitalized patients confirmed by a reverse transcription chain reaction in 11 medical institutions in Fukui, Japan. We developed and validated seven machine-learning models (e.g., penalized logistic regression model) using routinely collected data (e.g., demographics, simple blood test). The primary outcome was the need for oxygen therapy (≥1 L/min or SpO2 ≤ 94%) during hospitalization. C-statistics, calibration slope, and association measures (e.g., sensitivity) evaluated the performance of the model using the test set (randomly selected 20% of data for internal validation). Among these seven models, the machine-learning model that showed the best performance was re-evaluated using an external dataset. We compared the model performances using the A-DROP criteria (modified version of CURB-65) as a conventional method.ResultsOf the 396 patients with COVID-19 for the model development, 102 patients (26%) required oxygen therapy during hospitalization. For internal validation, machine-learning models, except for the k-point nearest neighbor, had a higher discrimination ability than the A-DORP criteria (P < 0.01). The XGboost had the highest c-statistic in the internal validation (0.92 vs. 0.69 in A-DROP criteria; P < 0.001). For the external validation with 728 temporal independent datasets (106 patients [15%] required oxygen therapy), the XG boost model had a higher c-statistic (0.88 vs. 0.69 in A-DROP criteria; P < 0.001).ConclusionsMachine-learning models demonstrated a more significant performance in predicting the need for oxygen therapy in the early stages of COVID-19.

Circulating Tumor Cell Identification Based on Deep Learning.

As a major reason for tumor metastasis, circulating tumor cell (CTC) is one of the critical biomarkers for cancer diagnosis and prognosis. On the one hand, CTC count is closely related to the prognosis of tumor patients; on the other hand, as a simple blood test with the advantages of safety, low cost and repeatability, CTC test has an important reference value in determining clinical results and studying the mechanism of drug resistance. However, the determination of CTC usually requires a big effort from pathologist and is also error-prone due to inexperience and fatigue. In this study, we developed a novel convolutional neural network (CNN) method to automatically detect CTCs in patients’ peripheral blood based on immunofluorescence in situ hybridization (imFISH) images. We collected the peripheral blood of 776 patients from Chifeng Municipal Hospital in China, and then used Cyttel to delete leukocytes and enrich CTCs. CTCs were identified by imFISH with CD45+, DAPI+ immunofluorescence staining and chromosome 8 centromeric probe (CEP8+). The sensitivity and specificity based on traditional CNN prediction were 95.3% and 91.7% respectively, and the sensitivity and specificity based on transfer learning were 97.2% and 94.0% respectively. The traditional CNN model and transfer learning method introduced in this paper can detect CTCs with high sensitivity, which has a certain clinical reference value for judging prognosis and diagnosing metastasis.

Assessment of Hematological and Coagulation profile of patients diagnosed as Tuberculous lymphadenopathy on cytology: A cross sectional study in Industrial belt in Northern India

: Study of the hematological and coagulation parameters in cytologically diagnosed cases of tuberculous lymphadenopathy.: A cross sectional study of 60 newly diagnosed cases of tuberculosis on cytology was done. Venous blood samples were collected in EDTA and Citrate vacutainers. XN 1000 fully automated hematology analyzer and Vesmatic were used for hematology parameters and ESR respectively. Stago analyzer was used for coagulation studies. Hematological and coagulation parameters were studied and were analyzed using t test with significance level of 5%.: 60 cases presenting with tuberculous lymphadenopathy on cytology were analyzed which showed a M: F of 1.2 :1. Anemia was noted equally in both sexes. ESR and WBC count was raised in 92% and 45% of cases respectively. Prothrombin Time was raised in 87% of cases while Activated Partial Thromboplastin Time was raised in 45% of cases. Platelet count was normal in 88% of cases. Lymphocytosis was noted in 85% of cases while 52% cases revealed neutrophilia. Smoking and literacy rate had positive correlation. Paired t test shows positive correlation between age and WBC count (p&amp;#60;0.001) and age and Hemoglobin value (p&amp;#60;0.001). : Tuberculosis is a hypercoagulable state with alteration in the hematological profile. These simple blood tests with no additional cost can serve as guide to physicians in establishing the early diagnosis along with clinical findings and ancillary investigations. Such Pilot studies can be extended to larger populations and corporate setups to start early treatment and reduce the morbidity and mortality.

P202 Performance characteristics of serum FGF19 measurement compared with the Se-HCAT retention test in the diagnosis of bile acid diarrhoea in Crohn’s Disease

Abstract Background Bile acid diarrhoea (BAD) is common in patients with Crohn’s disease (CD), but its recognition is challenging since symptoms are similar to those of active inflammatory disease. The current clinical gold standard for diagnosing BAD is the Se-HCAT test, however, it is inconvenient to the patient and has limited availability. FGF19 is a hormone produced in the enterocytes of the ileum in response to absorbed BAs. Serum FGF19 levels are a direct marker of BA absorption, and they are reduced in BAD. The aim of this study was to evaluate the performance of FGF19 as a diagnostic tool for BAD in Crohn’s disease. Methods Fasting serum FGF19 levels and Se-HCAT retention were measured before bowel preparation in 63 consecutive Crohn’s disease patients referred for an ileocolonoscopy. Clinical, endoscopic and biologic data were prospectively recorded. BAD was defined as an abdominal retention &amp;lt;10% and severe BAD as &amp;lt;5% at day seven. Results BAD was present in 60% of non-resected CD (NR-CD) patients and in 93% of ileal-resected (IR-CD) patients. FGF19 levels were lower in IR-CD patients (median 23 pg/ml; IQR, 3–44) than in the NR-CD patients (61 pg/ml; IQR, 18–121) (p = 0.02). FGF19 levels were inversely related with ileal resection length in IR-CD patients (rs = -0.52, P = 0.01). FGF19 and Se-HCAT values were positively related (rs = 0.57, P &amp;lt; 0.0001), whereas FGF19 was inversely related with the number of bowel movements (rs = -0.31, P=0.01) and Bristol scale (rs = -0.27, P= 0.04). No significant relation was found between FGF19 and clinical (CDAI) nor endoscopic (SES-CD) scores. Area under the ROC curve for FGF19 to detect SeHCAT at &amp;lt;10% and &amp;lt;5% were 0.75 (95% CI 0.62–0.88) and 0.81 (95% CI 0.71–0.92) respectively. Conclusion Serum FGF19 can be used as a simple blood test to the diagnostic of BAD in CD. FGF19 measurement could be an adjunct in guiding treatments for diarrhoea in CD.

Pelatihan Skrining Penyakit Tidak Menular dan Pencegahannya Bagi Kader Kesehatan

Non-communicable disease (NCD) screening training aims to provide skills in determining a person's health condition based on body mass index (BMI) and simple blood tests. Health cadres who have been equipped with the skills to determine BMI and simple blood tests can then detect NCD in the community independently. Nutrition training aims to provide skills in calculating nutritional adequacy from a daily menu. Educational videos on simple blood tests were made to replace hands-on training due to limitations of the covid19 protocol. Before and after training, pre and posttest were carried out. The training was attended by 15 health cadres in Gamping Kidul Village, Ambarketawang, Gamping, Sleman, Yogyakarta. The average score before training was 67.14, increasing to 73.57 thereafter. Paired T-test analysis showed no significant difference in pre and posttest scores (p = 0.076). After receiving the training, it is hoped that health cadres can carry out screening independently around their respective homes, so that early detection of NCD in the community can take place, then prevention can be carried out so that it does not become a fatal complication. It was concluded that the training could improve health cadres' understanding of PTM screening, prevention and calculating a balanced nutritious diet but not significant.

Liquid biopsies to predict CDK4/6 inhibitor efficacy and resistance in breast cancer.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors combined with endocrine therapy have transformed the treatment of estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. However, some patients do not respond to this treatment, and patients inevitably develop resistance, such that novel biomarkers are needed to predict primary resistance, monitor treatment response for acquired resistance, and personalize treatment strategies. Circumventing the spatial and temporal limitations of tissue biopsy, newly developed liquid biopsy approaches have the potential to uncover biomarkers that can predict CDK4/6 inhibitor efficacy and resistance in breast cancer patients through a simple blood test. Studies on circulating tumor DNA (ctDNA)-based liquid biopsy biomarkers of CDK4/6 inhibitor resistance have focused primarily on genomic alterations and have failed thus far to identify clear and clinically validated predictive biomarkers, but emerging epigenetic ctDNA methodologies hold promise for further discovery. The present review outlines recent advances and future directions in ctDNA-based biomarkers of CDK4/6 inhibitor treatment response.