Simple Blood Test Research Articles

Predictive markers of early endothelial dysregulation in type-1 diabetes: a meta-analysis.

This study identifies a new set of salient risk factors that may trigger danger signals of vascular dysregulation in T1D. Vascular abnormalities and impairment of CVD is a major adverse effect of T1D, particularly affecting children, adolescents and young adults. The patients of T1D were compared with the healthy control (HC) for the risk factors of vascular dysregulation in published studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, relevant to clinical subjects. A random effects model was followed and analysed by RevMan 5.4 and GraphPad Prism software. 80 relevant case-control studies having 7492 T1D patients and 5293 HC were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of < 40 years were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-c, AI%, sICAM-1, and FMD% which could be evaluated with a simple blood test or non-invasive techniques. These may serve dual purposes as biomarkers of rapid diagnosis that could offer prospective tailor-made therapeutics for T1D. (Protocol registered at https://www.crd.york.ac.uk/prospero/CRD42022384636 ).

Combined analysis of a serum mRNA/miRNA marker signature and CA 19-9 for timely and accurate diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma: A prospective multicenter cohort study.

Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples. In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data. The best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures. TaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.

Huge and Multiple Xanthomas Misdiagnosed as Rheumatoid Nodules and Mistreated with Multiple Surgical Excisions over 4 Years, A Case Report

Background: Xanthoma is the iceberg of familial hypercholesterolemia; it’s resemblance to other cutaneous lesions such as rheumatoid nodules might lead to misdiagnosis. We emphasize in this case report the importance of comprehensive clinical and investigatory approach to cutaneous lesions as they could be the only manifestation of systemic diseases, and this helps to avoid delayed management and unnecessary interventions. Aim: Xanthomas as a possible diagnosis for multiple skin nodules, as it can be easily supported by performing simple noninvasive blood tests; the lipid panel. Case report: Female patient, presented with multiple skin lesions and a strong family history of premature coronary artery disease. She was firstly managed with multiple surgical resections as having benign masses, and later was misdiagnosed as having rheumatoid nodules and referred to rheumatology clinic for evaluation, wherein a clinical suspicion of xanthomas originated, and was supported by the severely elevated serum LDL level and a tissue diagnosis of xanthoma. She has been started on statins with regular clinic. Conclusion: The purpose of this case study is to explain the importance of including xanthomas within the differential diagnosis of recurrent skin lesions. Whereas the tissue diagnosis is the gold-slandered investigation, simple noninvasive blood test, serum lipid measurement can be the clue for diagnosis of the hidden fatal but easily controllable disease; familial hypercholesterolemia.

Understanding Hypothyroidism: Causes, Symptoms, Diagnosis, and Treatment Options for Optimal Thyroid Health

Hypothyroidism is a condition where your thyroid gland doesn’t produce enough thyroid hormone leading to symptoms like fatigue, weight gain, and feeling cold. Globally, the lack of iodine in the environment is the leading cause of hypothyroidism. However, in regions where there is enough iodine, Hashimoto’s thyroiditis, an autoimmune disorder is the most common cause. Risk factors include having a family history of thyroid disease, being over 6o years and being female. Diagnosis done with a simple blood test that measures the levels of serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH). High TSH and FT4 levels usually indicate Hypothyroidism. Even daily medication with synthetic thyroid hormone (levothyroxine), regular follow up with your doctor is important to monitor your TSH level and adjust the dosage of medication as needed.

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.

Physiological and behavioural implications of the portosystemic shunt in C57Bl/6J mice.

A significant fraction of the popular inbred C57Bl/6J mice show structural and biochemical features of the congenital portosystemic shunt (PSS). How this hepatic abnormality affects physiological and behavioural parameters has not been explored in detail. Here, we confirmed the frequent occurrence of the PSS in C57Bl/6J mice by three different methods. We screened a cohort of 119 C57Bl/6J mice for total bile acids (TBA) in plasma, identified 11 animals (9.2%) with high TBA (>11µm; 171.1 ± 76.8µm), and confirmed PSS presence in that subset by magnetic resonance angiography and 1H-magnetic resonance spectroscopy of brain metabolites in the hippocampal area. In addition to the high glutamine and low myo-inositol levels, we detected lower levels of several neurotransmitters and metabolites in the hippocampus, higher brain weight and volume, as well as enhanced brain glucose utilisation in the PSS mice. We also observed differences in peripheral organ weights, haematological cell counts and clinical chemistry parameters in C57Bl/6J mice with and without PSS. Animals with PSS were slightly hyperlocomotive, had better balance on the rotarod, showed altered gait properties, and displayed attenuated fear memory in the fear conditioning test. Furthermore, we revealed a significant alteration of the pharmacokinetic profile of diazepam in C57Bl/6J mice with PSS. Our data support previous reports of hepatic disturbances and demonstrate an altered neurobiological phenotype in C57Bl/6J mice with PSS. Such congenital differences between inbred C57Bl/6J littermates may significantly distort experimental outcomes of pharmacological, behavioural and genetic studies. KEY POINTS: A significant proportion of C57Bl/6J mice, an inbred strain popular in preclinical research, have congenital portosystemic shunts (PSS) that allow venous blood to enter systemic circulation bypassing the liver. In this study, we extended existing knowledge of PSS consequences, particularly with respect to the effects on brain structure and function. We demonstrated that C57Bl/6J mice with PSS differ from their normal counterparts in brain size and contents of several neuroactive substances, as well as in peripheral organ weights, rate of glucose utilisation, blood cell counts and blood clinical chemistry parameters. C57Bl/6J mice with PSS showed altered locomotor behaviour, performed worse in a memory test and had abnormal blood pharmacokinetics of a benzodiazepine drug after a single administration. PSS presence may significantly complicate the interpretation of experiments in C57Bl/6J mice; therefore, we propose that before their use in biomedical studies, these mice should be screened with a simple blood test.

A Novel Index Including Age, Sex, hTERT, and Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

Introduction: As the incidence of gastric cancer (GC) is increasing in East Asia including Japan, a simple blood test for early GC is needed as an alternative to upper gastrointestinal (UGI) endoscopy. We performed this study to address this issue. Methods: We collected serum samples from 319 participants comprising 225 healthy subjects without GC (control group) and 94 patients with early GC (early GC group). After evaluating copy numbers of serum hTERT and methylated RUNX3 (m-RUNX3) using the Combined Restriction Digital PCR (CORD) assay, which we developed, we assessed the diagnostic performance of hTERT and m-RUNX3 for early GC. Results: Serum levels of hTERT and m-RUNX3 were significantly higher in the early GC group than in the control group. The area under the curve (AUC) was 0.89 for hTERT and 0.78 for m-RUNX3. Multivariate logistic regression analysis revealed age, sex, hTERT copy number, and m-RUNX3 copy number to be independent factors for early GC. We then established a prediction formula and named it the ASTEm-R3 (age, sex, hTERT, and m-RUNX3) index. The AUC of the ASTEm-R3 index was 0.93 with a sensitivity of 79.7% and specificity of 91.1%. Conclusion: We demonstrated excellent performance of the ASTEm-R3 index using the CORD assay to detect early GC. This index might be a promising alternative to UGI endoscopy.

387. VALIDATION OF PROMARKERESO, A DIAGNOSTIC BLOOD TEST TO IDENTIFY ESOPHAGEAL ADENOCARCINOMA

Abstract Background Esophageal adenocarcinoma (EAC) has become the predominant type of esophageal cancer in Western countries. Early diagnosis and intervention of EAC significantly reduces the disease mortality. A previous study identified a panel of novel serum glycoprotein biomarkers that were associated with EAC, enabling the development of a prototype diagnostic blood test, PromarkerEso. The current study aimed to validate PromarkerEso in an independent cohort of patients with EAC. Methods Blood samples from an independent cohort of 165 participants (n=99 negative controls, n=66 diagnosed with EAC) were analyzed. Five candidate biomarkers were measured after lectin pulldown using a targeted mass spectrometry assay. Model performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC) with sensitivity and specificity determined. Results After adjusting for clinical variables, diagnostic models showed good discrimination to distinguish participants with EAC from negative control participants. Conclusions This study validates a panel of serum glycoprotein biomarkers for the diagnosis of EAC. These biomarkers have potential utility as a simple blood test, PromarkerEso, that could be used for screening EAC in a large population.

Comparison of Monocyte to Lymphocyte and Platelet to Lymphocyte Ratio between Patients with Depression according to Severity of Disease

Background: Depression is one of the most common psychiatric disorders with global public health concern that is linked to systemic inflammation. The monocyte to lymphocyte (MLR) and platelet to lymphocyte ratio (PLR) are partially new markers which may be evaluated with simple blood test and which are shown to be highly informative in showing chronic low grade inflammation associated with pathophysiology of depressive disorder. Objective: To evaluate the relation of MLR and PLR between patients with depression according to severity of disease. Methods: This observational study was conducted in the Department of Psychiatry of Jahurul Islam Medical College Hospital (JIMCH), Bajitpur, Kishoregonj between November 2012 and April 2013. Subjects between the age group of 25 and 55 were included in the study that involved 253 subjects with diagnosed depressive disorder according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Revised Text (DSM IV-TR) who received no pharmacological therapy of depression within the past 01 month. A sociodemographic information form and the Hamilton Rating Scale for depression (HAM-D) were administered. Patients were classified into four groups according to their HAM-D score such as mild, moderate, severe, and very severe depression. Blood sample were taken for biochemical analysis and complete blood parameters were evaluated in the hematology laboratory of JIMCH. All data were expressed as mean±SD. For statistical analysis, Chi-square test (χ2) was used to compare categorical variables, frequencies, and ratios. An independent sample ‘t’ test was used to compare normally distributed variables between two groups. Results: In the present study, it was found significant differences in the MLR, PLR, monocyte, leukocyte values of the patient group with depression according to severity of disease. Severe and very severe depression had significantly higher MLR levels compared to patients with mild and moderate depression. On the other hand, mild and moderate depression. On the other hand, mild and moderate depression had significantly higher PLR levels compared to patients with severe and very severe depression. Conclusion: In summary, the findings of the study reveal that higher HAM-D scores are associated with higher MLR and lower PLR levels in patients with depressive illness compared to patients with lower HAM-D scores. Moreover, a high MLR values supports the view that inflammation is a critical factor in the etiology of depression. JAFMC Bangladesh, Vol 19, No 2 (December) 2023:12-15.

A Predictive Noninvasive Single-Nucleotide Variation-Based Biomarker Signature for Resectable Pancreatic Cancer: Protocol for a Prospective Validation Study.

Single-nucleotide variations (SNVs; formerly SNPs) are inherited genetic variants that can be easily determined in routine clinical practice using a simple blood or saliva test. SNVs have potential to serve as noninvasive biomarkers for predicting cancer-specific patient outcomes after resection of pancreatic ductal adenocarcinoma (PDAC). Two recent analyses led to the identification and validation of three SNVs in the CD44 and CHI3L2 genes (rs187115, rs353630, and rs684559), which can be used as predictive biomarkers to help select patients most likely to benefit from pancreatic resection. These variants were associated with an over 2-fold increased risk for tumor-related death in three independent PDAC study cohorts from Europe and the United States, including The Cancer Genome Atlas cohorts (reaching a P value of 1×10-8). However, these analyses were limited by the inherent biases of a retrospective study design, such as selection and publication biases, thereby limiting the clinical use of these promising biomarkers in guiding PDAC therapy. To overcome the limitations of previous retrospectively designed studies and translate the findings into clinical practice, we aim to validate the association of the identified SNVs with survival in a controlled setting using a prospective cohort of patients with PDAC following pancreatic resection. All patients with PDAC who will undergo pancreatic resection at three participating hospitals in Switzerland and fulfill the inclusion criteria will be included in the study consecutively. The SNV genotypes will be determined using standard genotyping techniques from patient blood samples. For each genotyped locus, log-rank and Cox multivariate regression tests will be performed, accounting for the relevant covariates American Joint Committee on Cancer stage and resection status. Clinical follow-up data will be collected for at least 3 years. Sample size calculation resulted in a required sample of 150 patients to sufficiently power the analysis. The follow-up data collection started in August 2019 and the estimated end of data collection will be in May 2027. The study is still recruiting participants and 142 patients have been recruited as of November 2023. The DNA extraction and genotyping of the SNVs will be performed after inclusion of the last patient. Since no SNV genotypes have been determined, no data analysis has been performed to date. The results are expected to be published in 2027. This is the first prospective study of the CD44 and CHI3L2 SNV-based biomarker signature in PDAC. A prospective validation of this signature would enable its clinical use as a noninvasive predictive biomarker of survival after pancreatic resection that is readily available at the time of diagnosis and can assist in guiding PDAC therapy. The results of this study may help to individualize treatment decisions and potentially improve patient outcomes. DERR1-10.2196/54042.

The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure

Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF.

COVID-19: The Development and Validation of a New Mortality Risk Score.

Background: The coronavirus disease 2019 (COVID-19) pandemic has found the whole world unprepared for its correct management. Italy was the first European country to experience the spread of the SARS-CoV-2 virus at the end of February 2020. As a result of hospital overcrowding, the quality of care delivered was not always optimal. A substantial number of patients admitted to non-ICU units could have been treated at home. It would have been extremely useful to have a score that, based on personal and clinical characteristics and simple blood tests, could have predicted with sufficient reliability the probability that a patient had or did not have a disease that could have led to their death. This study aims to develop a scoring system to identify which patients with COVID-19 are at high mortality risk upon hospital admission, to expedite and enhance clinical decision making. Methods: A retrospective analysis was performed to develop a multivariable prognostic prediction model. Results: Derivation and external validation cohorts were obtained from two Italian University Hospital databases, including 388 (10.31% deceased) and 1357 (7.68% deceased) patients with confirmed COVID-19, respectively. A multivariable logistic model was used to select seven variables associated with in-hospital death (age, baseline oxygen saturation, hemoglobin value, white blood cell count, percentage of neutrophils, platelet count, and creatinine value). Calibration and discrimination were satisfactory with a cumulative AUC for prediction mortality of 0.924 (95% CI: 0.893-0.944) in derivation cohorts and 0.808 (95% CI: 0.886-0.828) in external validation cohorts. The risk score obtained was compared with the ISARIC 4C Mortality Score, and with all the other most important scores considered so far, to evaluate the risk of death of patients with COVID-19. It performed better than all the above scores to evaluate the predictability of dying. Its sensitivity, specificity, and AUC were higher than the other COVID-19 scoring systems when the latter were calculated for the 388 patients in our derivation cohort. Conclusions: In conclusion, the CZ-COVID-19 Score may help all physicians by identifying those COVID-19 patients who require more attention to provide better therapeutic regimens or, on the contrary, by identifying those patients for whom hospitalization is not necessary and who could therefore be sent home without overcrowding healthcare facilities. We developed and validated a new risk score based on seven variables for upon-hospital admission of COVID-19 patients. It is very simple to calculate and performs better than all the other similar scores to evaluate the predictability of dying.

Simple blood tests to diagnose compensated advanced chronic liver disease and stratify the risk of clinically significant portal hypertension.

Compensated advanced chronic liver disease (cACLD) identifies patients at risk for clinically significant portal hypertension (CSPH), and thus, for liver-related complications. The limited availability of liver stiffness measurements (LSM) impedes the identification of patients at risk for cACLD/CSPH outside of specialized clinics. We aimed to develop a blood-based algorithm to identify cACLD by fibrosis-4 (FIB-4) and CSPH by von Willebrand factor/platelet count ratio (VITRO). Patients with (suspected) compensated chronic liver disease undergoing FIB-4+LSM were included in the LSM/FIB-4 cohorts from Vienna and Salzburg. The HVPG/VITRO cohorts included patients undergoing HVPG-measurement + VITRO from Vienna and Bern.LSM/FIB-4-derivation-cohort: We included 6143 patients, of whom 211 (3.4%) developed hepatic decompensation. In all, 1724 (28.1%) had LSM ≥ 10 kPa, which corresponded to FIB-4 ≥ 1.75. Importantly, both LSM (AUROC:0.897 [95% CI:0.865-0.929]) and FIB-4 (AUROC:0.914 [95% CI:0.885-0.944]) were similarly accurate in predicting hepatic decompensation within 3 years. FIB-4 ≥ 1.75 identified patients at risk for first hepatic decompensation (5 y-cumulative incidence:7.6%), while in those <1.75, the risk was negligible (0.3%).HVPG/VITRO-derivation cohort: 247 patients of whom 202 had cACLD/FIB-4 ≥ 1.75 were included. VITRO exhibited an excellent diagnostic performance for CSPH (AUROC:0.889 [95% CI:0.844-0.934]), similar to LSM (AUROC:0.856 [95% CI:0.801-0.910], p = 0.351) and the ANTICIPATE model (AUROC:0.910 [95% CI:0.869-0.952], p = 0.498). VITRO < 1.0/ ≥ 2.5 ruled-out (sensitivity:100.0%)/ruled-in (specificity:92.4%) CSPH. The diagnostic performance was comparable to the Baveno-VII criteria.LSM/FIB-4-derivation cohort findings were externally validated in n = 1560 patients, while HVPG/VITRO-derivation-cohort findings were internally (n = 133) and externally (n = 55) validated. Simple, broadly available laboratory tests (FIB-4/VITRO) facilitate cACLD detection and CSPH risk stratification in patients with (suspected) liver disease. This blood-based approach is applicable outside of specialized clinics and may promote early intervention.

Correlation between neutrophil to lymphocyte ratio and disease activity in patients with rheumatoid arthritis.

Objective: To figure out correlation between neutrophils to lymphocyte ratio in rheumatoid arthritis and its relationship with the disease severity. Study Design: Prospective study. Setting: Department of Rheumatology Fauji Foundation Hospital, Rawalpindi, Pakistan. Period: July 1st to December 31st, 2021. Material &amp; Methods: Study population included rheumatoid arthritis patients fulfilling American college for rheumatology criteria. On the basis of disease activity score-28 (DAS-28), the subjects were categorised into active and remission groups. The control group consisted of healthy age and gender matched subjects. Relationship between neutrophils to lymphocytes ratio with disease activity was analyzed. Data was analysed using SPSS 21. Results: 140 patients with RA were evaluated along with 70 healthy control subjects. NLR was higher in active RA (1.99±0.84) as compared to RA with remission (1.76±0.41) and controls (1.77±0.79). p value&lt;0.05 was obtained which was statistically significant. NLR is significantly correlated with CDAI and SDAI (r=0.24, p=0.04 each). CRP and ESR were also significantly higher in active RA patients compared to those in remission (p&lt;0.005 and p&lt;0.00 respectively) and control group. Conclusion: The neutrophil to lymphocyte ratio is a measure derived from a simple blood test. An elevated NLR is often considered an indicator of systemic inflammation. High NLR values may suggest increased inflammation and immune system activation, which are key features of RA. NLR may serve as a less expensive and easily accessible marker to detect inflammation in RA. It can be utilized in future as disease assessment tool.

Monitoring gene expression in the brain with synthetic serum markers

Blood tests are among the most common clinical tools due to their low cost, simplicity, and ability to observe many markers at once. However, currently, blood tests can only monitor a fraction of physiological processes that happen to have a serum marker. Here, we will present our work on the development of synthetic serum markers that can track gene expression in intact brain cells with a simple blood test. The synthetic marker approach has several advantages. First, detection of existing markers may be challenging due to their low levels in blood. With a synthetic marker, one can design a reporter that is easy to detect allowing for superior sensitivity. Second, there are large numbers of genes in each cell, but available brain imaging techniques can at most represent only a few signals (e.g., a few colors of fluorescent proteins, or types of MRI contrast). Synthetic serum markers use biochemical detection and can be designed to be massively multiplexed similarly to how thousands of proteins can be detected in blood simultaneously with mass spectrometry. Third, synthetic serum markers can surveil large brain regions, unlike invasive locally implanted devices. Finally, these markers have the potential for inexpensive and simple readout. We show applications of this concept with markers that can cross through an intact blood–brain barrier to report on gene expression and markers whose release from the brain relies on sonobiopsy to provide spatial selectivity.

Circulating Tumor Cells: How Far Have We Come with Mining These Seeds of Metastasis?

Circulating tumor cells (CTCs) are cancer cells that slough off from the tumor and circulate in the peripheral blood and lymphatic system as micro metastases that eventually results in macro metastases. Through a simple blood draw, sensitive CTC detection from clinical samples has proven to be a useful tool for determining the prognosis of cancer. Recent technological developments now make it possible to detect CTCs reliably and repeatedly from a simple and straightforward blood test. Multicenter trials to assess the clinical value of CTCs have demonstrated the prognostic value of these cancer cells. Studies on CTCs have filled huge knowledge gap in understanding the process of metastasis since their identification in the late 19th century. However, these rare cancer cells have not been regularly used to tailor precision medicine and or identify novel druggable targets. In this review, we have attempted to summarize the milestones of CTC-based research from the time of identification to molecular characterization. Additionally, the need for a paradigm shift in dissecting these seeds of metastasis and the possible future avenues to improve CTC-based discoveries are also discussed.

Prognostic nutritional index instead of serum Vitamin D levels as a determinant of the presence of osteoporosis in adult male patients with neurological impairment

Background: Complications of non-traumatic fractures and osteoporosis, which reduce mobility and quality of life, should not be ignored in patients with neurological impairment (NI). Aim: To diagnose osteoporosis in adult patients with NI, a readily available and easily obtained index, instead of serum Vitamin D level or bone mineral density (BMD), was explored. Methods: This was a single-center retrospective study. The participants were inpatients with NI admitted between August 2020 and June 2022. Patient data regarding (1) patient information, (2) blood data, including the prognostic nutrition index (PNI), which predicts outcomes of various diseases, (3) body composition, (4) T-score by BMD, (5) nutritional measures, and (6) outcome measures were collected. Enrolled patients were divided into two groups, with or without osteoporosis, according to their T-score. The data were analyzed by three methods: (1) comparison of all collected data between the two groups to analyze the factors influencing osteoporosis; (2) multiple logistic regression analysis; and (3) receiving operating characteristic curve analysis. Results: Patients with osteoporosis had a significantly lower PNI (45 vs. 49, P = 0.045), and higher Vitamin D insufficiency (71% vs. 31%, P = 0.031). PNI was the strongest influencing factor, and its cutoff value for osteoporosis was 50. Conclusion: The PNI is the strongest determinant of osteoporosis in patients with NI. Therefore, PNI can potentially be used as a surrogate for BMD instead of serum Vitamin D levels in institutionalized and homebound patients who do not have BMD measurement devices. Relevance for Patients: Prognostic nutrition index, which is a simple blood test, outperforms serum vitamin D concentration as a good indicator for early detection of osteoporosis.

Diagnostic Ability of Simple Noninvasive Blood Tests to Predict Increased Liver Stiffness in People Living With HIV and Steatotic Liver Disease.

Steatotic liver disease is common in people with HIV (PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with AF assessed by liver stiffness measurement (LSM). We prospectively collected data on adults participating in 2 National Institute of Health-sponsored HIV NAFLD networks. All had HIV on antiretroviral therapy (ART) ≥6 months with HIV RNA <200 copies/mL. Those with viral hepatitis, other liver disease, excessive alcohol use, or hepatic decompensation were excluded. Vibration-controlled transient elastrography for LSM was performed, and AF defined as ≥11 kPa was compared with FIB-4 and NFS at predefined thresholds (<1.3 and >2.67 for FIB-4 and <-1.455 and >0.675 for NFS). A total of 1,065 participants were analyzed: mean age 51.6 years, 74% male, 28% White, 46% Black, 22% Hispanic, with 34% overweight (body mass index 25-29 kg/m 2 ) and 43% obese (body mass index ≥30 kg/m 2 ). Features of the metabolic syndrome were common: hyperlipidemia 35%, type 2 diabetes 17%, and hypertension 48%. The median CD4 + T-cell count was 666 cells/mm 3 , 74% had undetectable HIV RNA, and duration of HIV-1 was 17 years with most taking a nucleoside reverse transcriptase inhibitor (92%) and an integrase inhibitor (83%). The mean LSM was 6.3 kPa, and 6.3% had AF. The area under the receiver characteristic curve for FIB-4 and NFS to identify AF were 0.70 and 0.75, respectively. While both had high negative predictive values (97%-98%), the sensitivity at low thresholds and specificity at high thresholds were 64% and 97% for FIB-4 and 80% and 96% for NFS, respectively. Neither FIB-4 nor NFS at either threshold had good positive predictive value to detect AF. FIB-4 and NFS have excellent specificity and negative predictive value for detecting AF, and thus can be used as screening tools in PWH to exclude those with AF who do not need further testing (LSM) or referral to hepatologist.

Association between preablation and postablation neutrophil-lymphocyte ratio and atrial fibrillation recurrence: A meta-analysis.

Atrial fibrillation (AF) recurrence has become common in patients who have undergone catheter ablation. High neutrophil lymphocyte ratios (NLR) have been linked to an increased risk of recurrent AF. The research is, however, not conclusive. This meta-analysis addressed the value of easily accessible and affordable pre- and postablation NLR levels as indicators of AF recurrence in patients who had undergone ablation. We searched PubMed, SCOPUS, and Google Scholar for pertinent studies through May 2023. Using random effects models, the aggregated odds ratio (OR) of pre- and post-NLR and AF recurrence was estimated. Inter-study heterogeneity was described using I 2 statistics and leave-one-out sensitivity analysis. A p-value < .05 was considered statistically significant. The literature search yielded 270 studies, seven of which were included in this meta-analysis of 1923 patients who experienced AF recurrence after undergoing ablation. There are five retrospective and two prospective studies with a mean follow-up of 20.5 months. The unadjusted odds ratio (OR) of AF recurrence for preablation NLR was 1.33 (95% CI: 1.04-1.71, p < .01, I 2 = 95.49%), while the adjusted OR was 1.45 (95% CI: 0.87-2.43, p < .01, I 2 = 95.1%). The unadjusted odds ratio (OR) for postablation NLR was 1.21 (95% CI: 1.09-1.36, p < .01, I 2 = 85.9%), and the adjusted odds ratio (OR) was 1.28 (95% CI: 0.93-1.76), demonstrating significant heterogeneity (I 2 = 95.32%) with a p-value < .01. NLR was significantly associated with AF recurrence prediction. To detect AF recurrence, we recommend that clinicians add a simple NLR blood test to their diagnostic modalities.

CRP Albumin Ratio: A novel noninvasive and cost-effective method for assessing the severity of acute pancreatitis.

Acute pancreatitis is a significant and potentially life-threatening gastrointestinal disorder that requires prompt and accurate diagnosis for effective treatment. Current diagnostic methods often involve expensive and inaccessible imaging studies, such as CT scans, limiting their utility in emergency settings and underserved areas. This correspondence discusses an innovative and cost-effective approach to assessing the severity of acute pancreatitis, focusing on the C-Reactive Protein-Albumin Ratio (CAR). We searched relevant articles and studies from 2015 till date on PubMed, Web of Science, and Google Scholar using these keywords: "C-Reactive Protein", "Albumin Ratio", "Acute pancreatitis", "Cost-effective", "Non-invasive", and "Severity". The CAR diagnostic method involves a simple blood test that measures the levels of C-Reactive Protein (CRP) and albumin, both commonly used markers for assessing inflammation. Elevated CRP and decreased albumin levels are indicative of inflammation, and the CAR has shown a strong positive correlation with the severity of acute pancreatitis. This method offers a non-invasive, time-efficient, and cost-friendly alternative to traditional diagnostic techniques. The potential of CAR as an assessment tool for the severity of acute pancreatitis is highlighted, especially in resource-limited settings. This innovation holds promise for improving the timely and accurate diagnosis of acute pancreatitis, ultimately enhancing patient outcomes and reducing mortality rates.