Biomarkers In Adult Patients Research Articles

CD64 Expression on Neutrophils (nCD64) as a Biomarker in Adult Patients With Sepsis: A Cross-Sectional Study.

Introduction Neutrophils that are at rest exhibit very low expression of CD64, the high-affinity immunoglobulin fragment crystallizable γ receptor I, which is also found in monocytes. Neutrophils that have been exposed to endotoxins or are infected express more CD64. Objectives The aim of this study was to assess the CD64 biomarker expression on neutrophils using the flow cytometry method and its comparison with total leukocyte count, C-reactive protein (CRP) level, and blood culture sensitivity test in the diagnosis of sepsis in adults. Materials and methods Using the quick Sequential Organ Failure Assessment (qSOFA) scoring criteria, 94 blood samples from individuals with clinical indications of sepsis were included in this investigation. Samples were collected in K2 EDTA (ethylenediaminetetraacetic acid) vacutainers and analyzed for neutrophil CD64 (nCD64) levels using BD FACSLyricTM flow cytometer (BD, Franklin Lakes, NJ) within 24 hours of collection. Total leukocyte count, CRP levels, and blood culture sensitivity tests were also assessed simultaneously. Results Majority of the patients, i.e., 29 (30.9%), belonged to the age group of 19 to 35 years, with a female preponderance. The mean total leukocyte count was 19.49 ± 8.12 x 103/µL, mean CRP level was 81.19 ± 56.33 mg/dL, and the mean nCD64 expression - median fluorescence intensity was 197.26 ± 79.56. A positive blood culture was found in 59 (62.8%) cases. Neutrophils showed bright expression of nCD64 in 39 (41.5%) patients, dim expression in 35 (37.2%) patients, and moderate expression in 20 (21.3%) patients in the present study. The correlation between nCD64 expression with CRP, total leukocyte count, and blood culture sensitivity test was statistically significant (p=0.001). nCD64 expression showed a sensitivity of 93.2% and specificity of 91.4% for diagnosing sepsis, with an area under the curve (AUC) of 0.973. This proves nCD64 to be a highly effective biomarker compared to conventional methods. Conclusion nCD64 has a higher sensitivity and specificity as compared to total leukocyte count, CRP levels, and blood culture sensitivity test in the diagnosis of sepsis. It is an effective and rapid test that can enhance sepsis diagnostic accuracy, when combined with other biomarkers. Multicentric research needs to be conducted to validate these findings.

Inflammatory biomarkers in depression: scoping review.

Inflammation is increasingly recognised as a fundamental component of the pathophysiology of major depressive disorder (MDD), with a variety of inflammatory biomarkers playing pivotal roles. These markers are closely linked to both the severity of symptoms and the responsiveness to treatments in MDD. This scoping review aims to explore the scientific literature investigating the complex relationships between inflammatory biomarkers and depression, by identifying new studies and critical issues in current research. Following the PRISMA Extension for Scoping Reviews guidelines, we systematically searched databases including PubMed, Scopus, PsycINFO, Open Grey and Cochrane Library. Our search focused on articles published from 1 January 2020 to 1 May 2024. We included studies evaluating inflammatory biomarkers in adult patients with MDD, utilising observational and randomised controlled trial designs, and review studies. Our analysis examined 44 studies on the complex interplay between inflammation and its multiple effects on MDD. Significant associations between specific inflammatory biomarkers and depression severity were found, requiring cautious interpretation. We also highlight several methodological limitations in the current studies, which warrant caution in directly applying these findings to clinical practice. However, identified methodologies show potential for using these biomarkers as diagnostic tools or therapeutic targets, including anti-inflammatory interventions. The findings emphasise the need for sophisticated, integrative research to understand inflammation's role in MDD. Future studies should identify specific biomarker panels for diagnosing depression and bridging peripheral biomarker measurements with central neuroinflammatory processes, leading to better diagnostic and treatment strategies.

Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Patients with cancer have an increased risk of venous thromboembolism (VTE). Currently, several VTE risk prediction tools have been developed to identify candidates for primary VTE thromboprophylaxis. However, the availability of reliable and highly discriminatory prediction models for VTE risk assessment in cancer patients is limited, warranting further improvement of VTE risk stratification strategies. The implementation of biomarkers in risk assessment models might lead to refined VTE risk prediction, but it remains to be more comprehensively investigated. In this systematic review and meta-analysis, we aimed to evaluate and summarize all candidate biomarkers and their association with cancer-associated VTE. We conducted an electronic search in Medline, EMBASE and Cochrane central databases for studies that evaluated biomarkers in adult patients with cancer from inception to September 26 th 2022. We included observational and interventional studies reporting on subsequent VTE occurring after a cancer diagnosis. The baseline or index event of the biomarker measurements had to be definitively and uniformly applied to all enrolled patients. Two reviewers independently screened titles, abstracts and full-text articles for inclusion. Median differences (for continuous measures) and Odds Ratios (OR) (for dichotomous cut-off measures) with 95% confidence intervals (95% CI) were estimated and pooled using random-effects models. We assessed each studies risk of bias using the Quality in Prognostic Studies (QUIPS) risk of bias tool. Our search identified 4274 studies that were screened for inclusion (Figure 1). Following the screening, 109 studies (with 520 biomarker measurements) met the inclusion criteria and were included in the systematic review. Of these, 51 studies (with 174 biomarker measurements) were included in the meta-analysis. The majority of the studies were cohort studies (n=47; 32 prospective and 15 retrospective), while the other 4 studies were nested case-control studies. Eighteen studies had a study population of mixed cancer types and the remaining studies had a study population of specific cancer types, including: lung (n=6), gynecologic (n=5), breast (n=3), stomach (n=3), lymphoma (n=2), myeloma (n=2), ovarian (n=2), pancreas (n=2), brain (n=1), colorectal (n=1), gastrointestinal (n=1), genitourinary (n=1), gynecologic or breast (n=1), head and neck (n=1), liver (n=1), and prostate (n=1). We calculated the median difference and 95% CI for 23 different biomarkers. Cancer patients who experienced subsequent VTE events had significantly higher pre-treatment factor VIII activity, peak thrombin, platelet count and prothrombin fragment F1+2 levels compared to patients who did not experience VTE events (Table 1). Pre-treatment d-dimer levels were also higher in cancer patients who developed VTE, however, considerable heterogeneity was observed (Table 1). Contrastingly, pre-treatment hemoglobin, lag time - thrombin generation, prothrombin time and time to peak thrombin levels were significantly lower in those experiencing VTE events compared to patients who did not experience any events (Table 1). D-dimer levels on day-1 after cancer surgery were reported in two studies which, when pooled, revealed that cancer patients with subsequent VTE had higher d-dimer levels post-operatively compared to those with no events (Table 1). Moreover, pre-treatment hemoglobin levels 100 g/L was significantly associated with future VTE risk [OR: 1.42 (95%CI: 1.03-1.97), I 2=0%, n=11] while neutrophil lymphocyte ratio 3 was associated, yet insignificant [OR: 1.60 (95%CI: 0.99-2.60), I 2=43%, n=4]. Pre-treatment platelet count 350 x 10 9/L and white blood count levels 11 x 10 9/L were not significantly associated with future VTE risk [OR: 0.84 (95%CI: 0.66-1.06), I 2=0%, n=9 and 1.32 (0.86-2.03), I 2=56%, n=8, respectively]. From the 51 studies included in the meta-analyses, 27 studies had a low risk of bias, 19 studies had a moderate risk of bias and 5 studies had a high risk of bias. In conclusion, nine blood biomarkers were found to be significantly associated with VTE in cancer patients. Their utility as predictors of VTE in thrombotic risk assessment models may help in optimising VTE prediction and should be further explored in future studies.

Stress biomarkers in adult patients with drug-resistant epilepsy on a modified Atkins diet: A prospective study.

Ketogenic diets like the modified Atkins diet (MAD) are increasingly used in patients with refractory epilepsy. For epilepsy patients, stress is a well-known seizure-precipitating factor. New possibilities for measuring biomarkers of stress are now available. The purpose of this study was to investigate the impact of MAD on endocrine stress biomarkers. Forty-nine patients with drug-resistant epilepsy were investigated at baseline and after 12 weeks on MAD. Cortisol and cortisol-binding globulin (CBG) were measured and free cortisol index (FCI) calculated. We also measured metanephrine, normetanephrine, and methoxytyramine, all markers of epinephrine, norepinephrine, and dopamine, respectively. Changes were analyzed according to sex and antiseizure medications. The different markers at baseline and after 12 weeks of MAD treatment were correlated with seizure frequency and weight loss, respectively. The change in total cortisol was modest after 12 weeks on the diet (from 432.9 nmol/L (403.1-462.7)) to 422.6 nmol/L (384.6-461.0), P = 0.6). FCI was reduced (from 0.39 (0.36-0.42) to 0.34 (0.31-0.36), P = 0.001). CBG increased during the study (from 1126.4 nmol/L (1074.5-1178.3) to 1272.5 nmol/L (1206.3-1338.7), P < 0.001). There were no changes in the metanephrines after 12 weeks on the diet. The decrease in FCI was significant only in women, and only observed in patients using nonenzyme-inducing ASMs. We did not find any correlation between cortisol, CBG, or FCI levels and seizure frequency. After being on MAD for 12 weeks, FCI decreased significantly. The reduction in FCI may reflect reduced stress, but it may also be an effect of increased CBG. The reasons behind these alterations are unknown. Possibly, the changes may be a result of a reduction in insulin resistance and thyroid hormone levels. Treatment with MAD does not seem to influence "fight or flight" hormones.

Plasma Biomarker Profile and Clinical Correlations in Adult Patients With Tuberous Sclerosis Complex.

Different pathophysiologic mechanisms, especially involving astrocytes, could contribute to tuberous sclerosis complex (TSC). We assessed neurodegeneration and astrocytopathy plasma biomarkers in adult patients with TSC to define TSC biomarker profile and investigate clinical-radiologic correlations. Patients with TSC aged 15 years or older followed at Policlinico "Umberto I" of Rome were consecutively enrolled (July 2021-June 2022). The plasma levels of the following biomarkers were compared between patients and age/sex-matched healthy controls (HCs): tTau, pTau181, Abeta40, Abeta42, neurofilament light chain, and glial fibrillary acid protein (GFAP). Thirty-one patients (20 females/11 males; median age 30 years, interquartile range 24-47) and 38 HCs were enrolled. Only GFAP was significantly higher in the whole TSC population than in HCs (132.71 [86.14-231.06] vs 44.80 [32.87-66.76] pg/mL, p < 0.001), regardless of genotype. GFAP correlated with the disease clinical (ρ = 0.498, p = 0.005) and radiologic severity (ρ = 0.417, p = 0.001). It was significantly higher in patients with epileptic spasms (254.50 [137.54-432.96] vs 86.92 [47.09-112.76] pg/mL, p < 0.0001), moderate-severe intellectual disability (200.80 [78.40-427.6] vs 105.08 [46.80-152.58] pg/mL, p = 0.040), and autism spectrum disorder (306.26 [159.07-584.47] vs 109.34 [72.56-152.08] pg/mL, p = 0.021). Our exploratory study documented a significant increase of GFAP plasma concentration in adult patients with TSC, correlated with their neurologic severity, supporting the central role of astrocytopathy in TSC pathophysiology.

E24 Does juvenile onset impact the serum levels of bone-forming biomarkers in adult patients with Spondyloarthritis?

Abstract Introduction The Wnt signalling pathway regulates bone metabolism. Dickkopf1 (DKK-1) and Sclerostin are potent inhibitors of this pathway, and their dysfunction would be responsible for bone formation phenomena in patients with spondyloarthritis (SpA). Osteoprotegerin (OPG), a potent inhibitor of osteoclasts, regulated by the Wnt pathway, has also been implicated in this bone ossification phenomenon. We aimed to assess the impact of juvenile-onset on the serum levels of DKK-1, sclerostin, and OPG in adult with spondyloarthritis. Methods It was a cross-sectional case control study including patients with SpA (meeting ASAS criteria). Data collected included sociodemographic and disease characteristics. Biomarker assays were performed using an ELISA technique. Results Among one hundred and nine included patients, seven patients had a juvenile onset of the disease (six males, one female). The mean age of disease onset was 12.8 ± 4.3 [5–16] years. The mean duration of SpA at inclusion was 15 ± 6 years [4 – 21]. Two (28.6%) patients had an axial form, and five (71.4%) had an axial and peripheral form. Three patients (42.9%) had entheseal involvement. The means of serum levels of DKK-1 and sclerostin in patients with juvenile-onset SpA and healthy controls were (132 ± 81 vs 122 ± 113; P = 0.439) and (27 ± 15 vs 39 ± 49; P = 0.985) respectively. The analysis did not show significant differences in serum levels of DKK-1 (P = 0.293), sclerostin (P = 0.428), and OPG (P = 0.504) between patients with SpA with juvenile onset and adult SpA. Conclusion In our study the juvenile onset of the disease did not correlate with the inhibitors of the Wnt signalling pathway and OPG in patients with SpA.

Preoperative Systemic Immune-Inflammation Index is a Potential Biomarker in Adult Patients with High-Grade Gliomas Undergoing Radical Resection.

Increasing evidence has highlighted that systemic immune-inflammation index (SII), a recently developed prognostic biomarker that utilizes peripheral platelet, lymphocyte and neutrophil counts, is associated with unfavorable prognosis in various tumors. Nevertheless, the prognostic significance of SII in high-grade gliomas patients undergoing radical resection remains unclear. Therefore, the present study aimed to assess the potential of SII as a prognostic biomarker in this patient population. A total of 111 adult patients with high-grade gliomas who underwent radical resection were consecutively enrolled in this investigation. The study involved the categorization of patients into high and low SII groups using predetermined cut-off values. Subsequently, forward stepwise logistic regression was employed to identify autonomous predictors for early gliomas recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was performed between high and low SII patients. Finally, the Kaplan-Meier approach was utilized to compare the progression-free survival (PFS) and overall survival (OS) of the two groups. The study involved the categorization of patients into two groups based on their SII levels, namely high SII (> 604.8) and low SII (≤ 604.8) groups. Forward stepwise logistic regression revealed that high SII (p < 0.001) and tumor size ≥ 50 mm (p < 0.001) were significantly related to early recurrence of gliomas. Furthermore, the results indicate that PFS and OS were significantly shorter in the high SII group compared to the low SII group, both before and after PSM (p < 0.05). Preoperative biomarker SII can serve as a prognostic biomarker for early recurrence and prognosis in patients with high-grade gliomas undergoing radical resection. Furthermore, the combination of tumor size and SII demonstrates a robust predictive capacity for early recurrence and prognosis in this patient population.

Inflammatory biomarkers behavior profile among patients following elective degenerative spine surgery and their differences with those coursing with a postoperative spinal infection: Protocol for a Systematic Review.

The incidence of postoperative spinal infection (PSI) ranges from 0% to 10%, devastatingly affecting the patient prognosis and increasing costs to the healthcare system because of higher morbidity. Postoperative spinal infections require a high level of suspicion as they are difficult to diagnose, especially in the early postoperative state, because of many confounding factors such as clinical symptoms, serum biomarkers rise or confusing imaging studies. Current research has focused on serum biomarkers at the early stages of disease, nevertheless, most rely on retrospective cohorts with serum biomarkers studied individually and at different time points. To determine the Inflammatory biomarkers behavior profile among patients following elective degenerative spine surgery and their differences with those coursing with postoperative spinal infection. The proposed systematic review will follow the PRISMA statement. This protocol was registered at PROSPERO on January 19th, 2022, obtaining the following register CRD42022304645 on February 19th, 2022. We will include studies related to biomarkers in adult patients operated on because of degenerative spinal diseases, and those developing a postoperative spinal infection. The following information will be extracted: (1)study title; (2)Study Author (3)year; (4)evidence-level; (5)Research-type; (6)diagnosis group (elective postoperative degenerative disease / PSI); (7a)region (Cervical, Thoracic, Lumbosacral, Coccigeal); (7b)Type of infection by anatomical or radiological site, (8)Surgery-Type (including instrumentation or not); (9)number of cases; (10)mean age or individual age; and (11) individual serum biomarker values from the preoperative state up to 90 days postop for both groups including: (10a)interleukine-6, (10b)Presepsine, (10c)Erythrocyte Sedimentation Rate, (10d)Leukocyte Count, (10e)Neutrophil Count, (10f)C-Reactive Protein, (10g)Serum Amyloid, (10h)White Cell Count, (10i)Albumin, (10j)Prealbumin, (10k)Procalcitonin, (10L)Retinol associated protein, (10M)Dickopf-1, (11)postoperative days at symptoms or diagnosis, (12)Type of organism, (13)day of starting antibiotics, (14)duration of treatment and (15)any biases (including comorbidities, especially those affecting immunological status). All biomarkers' data will be presented graphically over time. Figure 1 contains the flow diagram of the methodology. No ethical approval will be required, as this review is based on published data and does not involve interaction with human participants. The search for this systematic review commenced in February 2021, and we expect to publish the findings in middle 2023. The present study will provide the biomarkers' behavior profile for PSI and patients following elective surgery for degenerative spinal diseases from the preoperative period up to 90 days postoperative providing cut-off values at the day of diagnosis. It will provide clinicians with a better background to diagnose based on highly trustable information based on cut-off values from this systematic review. Finally we expect this review to provide a basis for future research on biomarkers to establish more accurate and timely diagnosis in the early stages of illness ultimately impacting the patient's physical and mental health, reducing the disease burden. PROSPERO register ID: CRD42022304645.

Urine neutrophil gelatinase-associated lipocalin as a biomarker of adult pyelonephritis

BackgroundPyelonephritis is a common infection at any age. Urine neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute renal failure, is related to pyelonephritis in pediatric patients, although the significance of this urine biomarker in adult patients are not clear. We investigated the relationship between urine NGAL of pyelonephritis and non-pyelonephritis. Patients and methodsWe prospectively enrolled adult patients who were hospitalized due to pyelonephritis or non-pyelonephritis. Pyelonephritis was diagnosed in patients with fever and bacteriuria, with no any other infection focuses. Non-pyelonephritis was diagnosed in patients who had fever and another infection focus without bacteriuria. Urine samples were collected on days 0, 3 and 7. Urine NGAL levels were measured by ELISA. ResultsThere were 35 patients in the pyelonephritis group and 19 patients in the non-pyelonephritis group. Urine NGAL level were significantly higher in the pyelonephritis group than the non-pyelonephritis group on day 0 (median 302 ng/mL vs 25 ng/mL, p = 0.006). The area under the receiver operating characteristic curve of NGAL was 0.78 (p = 0.006). Urine NGAL level had a specificity of 66.7% and sensitivity of 87.0% at the cut-off level of 250 ng/mL for diagnosing pyelonephritis. ConclusionsUrine NGAL level at the diagnosis of infection are elevated in adult patients with pyelonephritis, but not in those with non-pyelonephritis. Urine NGAL might be a supportive biomarker for the diagnosis of pyelonephritis.

Assessment of the Diagnostic Value of Novel Biomarkers in Adult Patients With Acute Appendicitis: A Cross-Sectional Study.

Background Acute appendicitis (AA) is one of the most frequent causes of abdominal pain requiring emergency intervention in adults. Approximately one-third of cases present with atypical clinical symptoms. This study aims to compare the monocyte-to-lymphocyte ratio (MLR), red cell distribution width (RDW) to lymphocyte ratio (RLR), and systemic immune inflammation index (SII) with other biomarkers in distinguishing patients with and without AA. Methodology A total of 347 patients (AA 125, nonspecific abdominal pain 90, and control group 132) were enrolled in the study according to the cross-sectional study design. Receiver operating characteristic (ROC) analysis was used to determine the cutoff in diagnostic value measurements. Statistical significance was determined by the statistics of sensitivity, specificity, positive predictive value, and negative predictive value. Comparison of ROC curves of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), MLR, and SII was evaluated with the pairwise comparison of ROC curves and 95% confidence interval. Results In detecting AA, CRP, WBC, NEU, NLR, MLR, and SII have excellent diagnostic power (area under the curve [AUC] 0.80-0.88), while RDW, lymphocyte count, monocyte (MON) count, and RLR had acceptable diagnostic power (AUC 0.70-0.77). When the power in the diagnosis of AA was compared, a significant difference was found between CRP and NEU, CRP and SII, WBC and NEU, and WBC and SII. Conclusions The diagnosis of AA remains dependent on many factors. Inflammatory biomarkers assist this process. MLR and SII may be recommended to use in diagnosing AA in adults, along with other clinical findings. RLR is adequate but not superior.

PD34 Neuron-specific Biomarkers Associated With Neurological Manifestations In COVID-19: An Evidence Mapping Systematic Review

IntroductionWe aimed to map and synthesize the available evidence on neuron-specific biomarkers related to COVID-19.MethodsA systematic review and qualitative evidence mapping synthesis was performed (PROSPERO-CRD42021266995). Searches were conducted in PubMed and Scopus, and complemented by manual search (July 2021). We included observational studies of any design assessing neurological biomarkers in adult patients (&gt;18 years; with or without neurological comorbidities) diagnosed with COVID-19. Methodological quality of nonrandomized studies (case-control, cohorts) was assessed using the Newcastle-Ottawa Scale.ResultsOverall, 14 studies (n=485 patients) conducted in Sweden (n=4 articles, 28.5%), Germany (n=3; 21.4%), USA (n=3; 21.4%), Canada, France, Italy and Norway (n=1 study each) were included. The most reported neurological symptoms (n=13 studies, 92.8%) were headache, confusion, general weakness, loss of smell/taste, cognitive impairments and behavioral changes. Prevalent neurological conditions included encephalopathies, neuropathies, myopathies, and delirium; most critical cases presented cerebrovascular events (n=4 studies, 28.5%). Hypertension, diabetes, obesity, dyslipidemia, and chronic lung disease were the most reported comorbidities. Eight different neuron-specific biomarkers were found in primary studies: neurofilament-light chain – NfL (n=10 studies; 71.4%), glial fibrillary acidic-protein – GFAp (n=5; 35.7%), tau protein (n=5; 35.7%), neurofilament-heavy chain – NfH, S100B protein, ubiquitin C-terminal hydrolase L1 - UCH-L1, neuron-specific enolase and beta protein-amyloid – Aβ (n=1 study each). These biomarkers were found both in cerebrospinal fluid and blood/plasma samples even without an evident cytokine storm. In patients with COVID-19, NfL and GFAp can act as sensitive indicators of neuroaxonal and astrocytic damages, respectively. Increased levels of NfL were significantly associated with severe COVID-19, unconsciousness and longer stay in the intensive care unit (p&lt;0.05). Studies had an overall poor to moderate methodological quality.ConclusionsWe identified eight neuron-specific biomarkers that should be further studied as prognostic factors of COVID-19. These findings can also guide the development of targeted therapies against SARS-CoV-2. Additional well-designed clinical trials are needed to strengthen this evidence and help understand the mechanisms of neurological symptoms and sequelae after COVID-19 infection.

СЕРДЕЧНЫЕ БИОМАРКЕРЫ У НОВОРОЖДЕННЫХ И ДЕТЕЙ РАННЕГО ВОЗРАСТА С ВРОЖДЕННЫМИ ПОРОКАМИ СЕРДЦА

Congenital heart defects (CHDs) have specific hemodynamics due to volume and pressure overloads of the heart chambers. Such hemodynamic disorders contribute to the development of hypertrophy and myocardial fibrosis, heart failure, damage and death of cardiomyocytes. Measurement of biomarker levels helps predict the development of these pathological conditions and provides information on the severity of the lesion. Information on the use of cardiac biomarkers in pediatric practice is limited, compared to the extensive data on the practical use of cardiac biomarkers in adult patients, primarily with coronary artery disease. We reviewed the current publications on the use of cardiac biomarkers in pediatric patients with CHDs, focusing on troponin as a biomarker of myocardial injury and B-type natriuretic peptide (BNP) as a biomarker of heart failure.

The Effects of Exercise Training on Cardiopulmonary Exercise Testing and Cardiac Biomarkers in Adult Patients with Hypoplastic Left Heart Syndrome and Fontan Circulation.

Background: Several studies have shown that adult patients with Hypoplastic Left Heart Syndrome (HLHS) and Fontan circulation have a reduced exercise tolerance that affects daily life. Recent studies have investigated the effects of aerobic exercise training in patients with univentricular heart; however, this research topic is still poorly studied. The aim of this study was to evaluate the effects of an aerobic exercise training program on cardiopulmonary exercise testing parameters and cardiac biomarkers in patients with HLHS. Methods: We enrolled 12 patients with a mean age of 24 ± 2.5 years (range 22–27 years), 50% male, with HLHS at Bambino Gesù Children’s Hospital IRCCS. All patients underwent a cardiopulmonary test and blood sampling before (T0) and after (T1) a 4-week aerobic exercise program. Cardiac biomarkers hs-cTnT, NT-proBNP, ST2, GDF-15 were studied. Results: Data analysis demonstrated an increase in cardiorespiratory performance after 4 weeks of aerobic exercise training activity. In particular, the data showed a significant improvement in test duration (p < 0.05), heart rate at rest (p < 0.05), heart rate recovery 1 min (p < 0.05), VO2 max (p < 0.01) and oxygen uptake efficiency slope (p < 0.05). At the same time, the data showed a significant reduction in NT-proBNP and ST2 values (p < 0.01 and p < 0.05, respectively) and a significant increase in GDF-15 (p < 0.01). No significant changes were found between the hs-cTnT values. Conclusions: Our study demonstrated the 4-week efficacy of an aerobic training program in improving cardiorespiratory performance and cardiac biomarker values in adult patients with HLHS and Fontan circulation. More studies with larger numbers of patients will be needed to confirm these data.

Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess the effects of vitamin E supplementation on endothelial dysfunction, inflammation, and oxidative stress biomarkers in adult patients receiving hemodialysis. We searched the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases and identified randomized controlled trials of adult patients receiving hemodialysis until 30 August 2021. A total of 11 trials with 491 randomized patients were included. The pooled data indicated that vitamin E supplementation significantly decreased intercellular adhesion molecule-1 [standardized mean difference (SMD): −1.35; 95% confidence interval (CI): −2.57, −0.13; p = 0.03, I2 = 89%], vascular cell adhesion molecule-1 (SMD: −1.08; 95% CI: −2.05, −0.11; p = 0.03, I2 = 81%), C-reactive protein (SMD: −0.41; 95% CI: −0.75, −0.07; p = 0.02, I2 = 64%), and malondialdehyde (SMD: −0.76; 95% CI: −1.26, −0.25; p = 0.003, I2 = 77%) levels, but not interleukin-6 levels compared to those in the control group. Our results suggest that vitamin E supplementation may help alleviate oxidative stress and both vascular and systemic inflammation in patients receiving hemodialysis.

PTGDR2 Expression in Peripheral Blood as a Potential Biomarker in Adult Patients with Asthma.

Background: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Methods: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. Results: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients’ peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.

Evaluation of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome

PurposeTo evaluate the performance of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome (CS). MethodsThis was a prospective, multicenter, nonrandomized, noninterventional study of a cortisol activity biomarker in adult patients (≥18 years) with documented ACTH-dependent, endogenous CS. The impact of surgery on FKBP5 mRNA expression levels in these patients and the difference in expression levels between these patients and healthy controls were evaluated. Cortisol and biomarker samples were collected before and immediately after surgery. A custom NanoString assay was used to quantify FKBP5 mRNA expression levels. The same method was used to analyze healthy volunteer samples collected from a different study. ResultsSurgery was considered successful in 14/24 patients (58.3%) and changes from baseline in serum cortisol were −92.6% (P = 0.0005) and −43.8% (not significant) in patients with successful and unsuccessful surgeries, respectively. A strong positive correlation between FKBP5 and cortisol levels was observed (before surgery: r = 0.72, P = 0.0002; after surgery: r = 0.85, P < 0.0001). After successful surgery, FKBP5 expression levels were similar to those of healthy subjects. In patients without surgical success, FKBP5 levels remained unchanged from baseline and distinct from healthy subjects (P = 0.0025). ConclusionsOur findings confirm that FKBP5 levels are higher in the presence of excess cortisol exposure in patients with CS and decrease to normal baseline levels after successful surgery. These findings suggest that FKBP5 can serve as a measure of biological cortisol activity and set the stage for the development of an FKBP5 mRNA expression assay as a biomarker of cortisol activity.

YKL-40 as a clinical biomarker in adult patients with CF: Implications of a CHI3L1 single nucleotide polymorphism in disease severity

BackgroundYKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease. MethodsA prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters. ResultsWe found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic. ConclusionOur study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile.

The effect of vitamin e supplementation in liver enzymes, histology and metabolic biomarkers in adult patients with non-alcoholic fatty liver disease (NAFLD). a systematic review and meta-analysis

Rationale: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolicsyndrome and is expected to be one of the leading causes of cirrhosis. Since currentpharmacotherapy recommendations do not exist, a meta-analysis was conductedinvestigating possible beneficial effects of vitamin E supplementation in NAFLD.

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients.

Colorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH+ and CD44+/CD326+ colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients’ samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted.

Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients: First clinical and biomarker results from the BioDay registry.

Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. To study the effect of 16-week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate-severe AD in daily practice. Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen-week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI-50 (Eczema Area and Severity Index) or EASI-75, as well as patient-reported outcomes measures (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty-one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16weeks). In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult-to-treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI-50 and EASI-75 were achieved by 114 (86%) and 82 (62%) patients after 16weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity-related serum biomarkers (TARC, PARC, periostin, and IL-22), eotaxin-1, and eotaxin-3 significantly decreased. Treatment with dupilumab significantly improved disease severity and decreased severity-related serum biomarkers in patients with very difficult-to-treat AD in a daily practice setting.