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Background of the study Acute kidney injury (AKI) is a common complication in critically ill burn patients and is associated with a number of serious adverse outcomes. The clinical decision-making process related to the management of AKI in burn patients is complex and has not been sufficiently standardized. The main aim of this study was to explore the diagnostic approach and clinician’s attitudes toward the management of AKI and RRT in burn patients around the world. Methods The questionnaire was widely distributed among the members of International Society for Burn Injury (ISBI), who were invited to complete the survey. Data collection and report was compliant with the the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) Web-survey guidelines. The survey form with multiple-choice questions was divided into 3 parts: a. physician and institutional demographics, b. AKI diagnostic information, c. technical aspects of RRT. Results A total of 44 respondents worldwide submitted valuable data in the 2-month period. Of all respondents, 43.2% were from Europe, 30% from North America, 7% from South-East Asia 2.3% from Africa and 18.2% from other regions. 93.1% of participants declare that they use specific definitions to detect AKI, while 11.4% declare the use of renal ultrasonography for AKI diagnosis. CRRT appeared to be the most preferred option by 43.2% of participants, followed by intermittent hemodialysis (25%), and prolonged intermittent RRT (6.8%). The expertise to deliver a modality and the availability of resources were considered important factors when selecting the optimal RRT modality by 20.5% and 29.6% of respondents. The use of specific serum biomarkers for AKI diagnosis are stated by 16% of respondents; 25% of specialists refer to the use of biomarkers of AKI as a criterium for discontinuing the RRT. Femoral vena and right jugular vena were the most frequently used location for RRT temporary catheter placement, 54.6% of respondents declared using ultrasound guidance for catheter placement. Conclusions The majority of burn specialists use specific consensus classifications to detect acute kidney injury. Continuous renal replacement therapy appeared to be the most preferred option, while the expertise to deliver a particular modality and resources availability play a significant role in modality selection. The use of ultrasound and specific biomarkers for AKI evaluation is infrequent in routine clinical practice.

Graphical abstract, Introduction Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. Methods COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. Results In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO

Cardiac involvement is the main cause of death in Becker muscular dystrophy (BMD). Identification of left ventricular (LV) function is crucial, but standard echocardiographic measurements such as LV ejection fraction (LVEF) might not be sensitive enough to detect early myocardial dysfunction. We explored the value of LV global longitudinal strain (GLS) as a more accurate echocardiographic parameter to detect and monitor LV dysfunction in BMD. Furthermore, we studied possible factors associated with LV dysfunction and progression. A total of 40 patients with BMD (age 39.0 +/- 13.2 years) and 21 matched controls were included. Clinical variables, pulmonary tests, serum biomarkers, and echocardiograms were collected at baseline and after 2 years. LV systolic function was assessed by LVEF and LV GLS; a significant progression in LV dysfunction was defined as an absolute LV GLS deterioration >= 15%. Responsiveness to cardiac disease progression was determined using standardized response means. Patients showed impaired LVEF and LV GLS compared with controls (p

Background Increasing evidence shows that pediatric atopic dermatitis (AD) differs from adult AD on a biologic level. Broad biomarker profiling across a wide range of ages of pediatric patients with AD is lacking. Objective Our aim was to identify serum biomarker profiles in children with AD aged 0 to 17 years and compare these profiles with those previously found in adults with AD. Methods Luminex multiplex immunoassays were used to measure 145 biomarkers in serum from 240 children with AD (aged 0-17 years). Principal components analysis followed by unsupervised k-means clustering were performed to identify patient clusters. Patients were stratified into age groups (0-4 years, 5-11 years, and 12-17 years) to assess association between age and cluster membership. Results Children aged 0 to 4 years had the highest levels of TH1 cell–skewing markers and lowest levels of TH17 cell–related markers. TH2 cell–related markers did not differ significantly between age groups. Similar to the pattern in adults, cluster analysis identified 4 distinct pediatric patient clusters (TH2 cell/retinol–dominant, skin-homing–dominant, TH1 cell/TH2 cell/TH17 cell/IL-1–dominant, and TH1 cell/IL-1/eosinophil–inferior clusters). Only the TH1 cell/TH2 cell/TH17 cell/IL-1–dominant cluster resembled 1 of the previously identified adult clusters. Although no association with age or age of onset seemed to be found, disease severity was significantly associated with the skin-homing–dominant cluster. Conclusion Four distinct patient clusters based on serum biomarker profiles could be identified in a large cohort of pediatric patients with AD, of which 1 was similar to previously identified adult clusters. The identification of endotypes driven by distinct underlying immunopathologic pathways might be useful to define pediatric patients with AD who are at risk of persistent disease and may necessitate different targeted treatment approaches.

OBJECTIVES: The objective of this study was to identify novel serum biomarkers specific to postoperative delirium following major cardiac surgery to provide insight into the pathological processes involved in delirium and its sequelae. DESIGN: Nested, case-control study. SETTING: Cardiac surgical intensive care unit in a single-site hospital setting. PARTICIPANTS: Twenty-four older adults (>60 years old) undergoing major cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a positive screen for delirium from postoperative day 1 through 3 based on criteria included in the long form of the Confusion Assessment Method. We applied a multiplexed proteomic approach using proximity extension assays to identify and quantify proteins found in serum collected on the day of surgery and postoperative day 1 in delirious and non-delirious patient cohorts. We identified an increase in serum fibroblast growth factor (FGF)-21 levels in the delirious cohort from a pre-surgery baseline of (mean ±stdev) 5.0 (±1.1) log2 abundance (95% confidence interval (CI) [4.3 to 5.7]) to 6.7 (±1.6) log2 abundance (95% CI [5.7 to 7.7], p=0.01) post-surgery. We identified a similar increase in FGF-23 from a pre-surgery baseline of 1.7 (±1.3) log2 abundance (95% CI [0.8 to 2.5]) to 3.4 (±2.2) log2 abundance (95% CI [2.0 to 4.8]), p=0.06) post-surgery. We also identified an increase in interleukin-6 serum levels in the delirious cohort from a pre-surgery baseline of 3.8 (±1.1) log2 abundance (95% CI [3.1 to 4.5]) to 8.7 (±1.9) log2 abundance (95% CI [7.5 to 9.9], p

Background Gastric cancer (GC) is one of the most lethal forms of cancer due to the absence of tools for its early detection. Here, we explored critical biomarkers for early diagnosis. Materials and methods Key biomarkers in serum from patients with early gastric cancer (EGC) and healthy controls (HCs) were identified via mass spectrometry and the expression of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) was evaluated using several methods. Furthermore, ITIH4 expression in sera and exosomes from patients with EGC, advanced GC (AGC), low grade intraepithelial neoplasia (LGN), chronic superficial gastritis with Helicobacter pylori infection (Hpi), other systemic malignant tumors (OSTs), and healthy controls was also evaluated. Results ITIH4 was identified as a key biomarker in patients with EGC. Its expression level in serum from the EGC group, which showed the highest specificity (94.44%), was significantly higher than those in sera from other GC groups as well as the control. Western blot analysis, immunohistochemical staining, and exosome analysis also confirmed ITIH4 expression in sera from patients with GC, but not in those from healthy individual. Conclusion ITIH4 is a key biomarker in serum from patients with EGC and has potential as a high value diagnostic marker for EGC.

BACKGROUND Perihematomal edema (PHE) following primary intracranial hemorrhages (ICHs) affects the patient outcome. Also, serum biomarkers such as S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) have been associated with ICHs outcome. We aimed to investigate the association between these biomarkers and PHE in ICH patients. METHODS In this cross-sectional study, patients with primary ICH between January 2020 and August 2020 were evaluated. All participants underwent spiral brain computed tomography scans upon admission, and 48 to 72 hours later and quantification of initial hematoma volume was performed. Serum level of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), GFAP, and S100B on admission were measured by enzyme-linked immunosorbent assays. Acute clinical outcome was assessed by the modified-Rankin scale, National Institute of Health Stroke Scale (NIHSS), and ICH score. RESULTS Thirty-seven ICH patients (21 patients with a favorable outcome and 16 unfavorable) were studied. Compared with survival patients, nonsurvivor patients showed a higher serum level of MMP-9, VEGF, GFAP, and S100B (P

Метою роботи було дослідити взаємозв’язок між рівнем Ser-Pro-Cys пептиду в сироватці крові хворих на розсіяний склероз (РС) та демографічними особливостями обстежених осіб, а також окремими властивостями перебігу цього захворювання. Матеріали та методи. У дослідженні брали участь 61 хворий на РС та 20 практично здорових осіб віком від 19 до 57 років. Методи дослідження: клінічні — аналіз скарг, анамнезу захворювання та життя, загальний та неврологічний огляди; лабораторні — білки сироватки крові послідовно осаджували трихлороцтовою (ТХО) кислотою. Утворену ТХО-розчинну фракцію піддали високоефективній рідинній хроматографії при довжині хвилі 280 нм. За допомогою двовимірної тонкошарової хроматографії та мас-спектрометрії було ідентифіковано Ser-Pro-Cys олігопептид. Результати. Виявлено вірогідну відмінність між середніми значеннями рівня Ser-Pro-Cys пептиду у сироватці крові хворих на РС різних вікових і гендерних груп порівняно з контрольною групою (p < 0,01). Натомість не встановлено вірогідних відмінностей у показниках рівня Ser-Pro-Cys пептиду між хворими на РС чоловіками і жінками. Незалежно від характеристики неврологічних проявів та віку дебюту захворювання в усіх групах хворих на РС концентрація Ser-Pro-Cys пептиду у сироватці крові була вищою порівняно з контрольною групою (p

Background: Whether blood biomarkers of neurovascular unit are associated with cortical amyloid deposition on positron emission tomography (PET) imaging remains unclear. Objective: To investigate the association between novel serum biomarkers of neurovascular unit, such as protein tyrosine phosphatase receptor type B (PTPRB), gap junction protein alpha-5 (GJA5), adenosine triphosphate-sensitive inward rectifier potassium channel-8 (KCNJ8), and von Willebrand factor (vWF), and cortical amyloid deposition. Methods: Between 2012 and 2018, 68 elderly individuals with amnestic mild cognitive impairment (32 men and 36 women; mean age 75.2 years) were enrolled. All participants underwent 11C-Pittsburgh compound-B (PiB)-PET, 18F-fluorodeoxyglucose-PET, and measurement of serum PTPRB, GJA5, KCNJ8, and vWF levels using commercially available human enzyme-linked immunosorbent assay kits. Based on the mean cortical standardized uptake value ratio, the participants were divided into two groups: PiB-negative group and PiB-positive group. Serum levels of PTPRB, GJA5, KCNJ8, and vWF were compared between the two groups. Multiple linear regression analysis was performed to investigate the relationship between serum PTPRB, GJA5, KCNJ8, and vWF levels and cortical amyloid deposition. Results: PTPRB and GJA5 levels were significantly lower and KCNJ8 and vWF levels were significantly higher in the PiB-positive group than in the PiB-negative group. PTPRB and GJA5 levels inversely correlated with mean PiB uptake, whereas KCNJ8 and vWF levels positively correlated with mean PiB uptake. Conclusion: Serum levels of PTPRB, GJA5, KCNJ8, and vWF correlate with cortical amyloid deposition. These novel blood biomarkers of neurovascular unit are useful for identifying elderly individuals at risk of developing Alzheimer’s disease.

To establish a risk prediction model and the clinical value of trisomy 21 using alpha-fetoprotein variants L2 (AFP-L2) combined with maternal serum biomarkers and nuchal translucency (NT) thickness in early pregnancy. A retrospective case–control study was conducted. The subjects were divided into the case group (n = 40) or the control group (n = 40). An enzyme-linked immunosorbent assay was used to measure the maternal serum AFP-L2 level in both groups. The AFP-L2 single-index or multi-index combined risk model was used to predict the efficiency of trisomy 21. The best cut-off value and area under the curve (AUC) were determined to evaluate the predictive efficacy of different risk models constructed by AFP-L2. The maternal serum AFP-L2 level in the case group was 1.59 (0.61–3.61) Multiple of medium (MoM), which was higher than 1.00 (0.39–2.12) MoM in the control group (P P P

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high associated morbidity and mortality. The therapeutic landscape has significantly changed in the last 20 years with two drugs currently approved that have demonstrated the ability to slow disease progression. Despite these developments, survival in IPF is limited, so there is a major interest in therapeutic targets which could serve to open up new therapeutic avenues. Areas covered We review the most recent information regarding drug targets and therapies currently being investigated in preclinical and early-stage clinical trials. Expert opinion The complex pathogenesis of IPF and variability in disease course and response to therapy highlights the importance of a precision approach to therapy. Novel technologies including transcriptomics and the use of serum biomarkers, will become essential tools to guide future drug development and therapeutic decision making particularly as it pertains to combination therapy.

This review summarizes the current state of non-invasive diagnosis of non-alcoholic fatty liver disease (NAFLD). This begins with a brief discussion of blood-based analysis (serum biomarkers) then progresses through various imaging modalities (imaging biomarkers) including magnetic resonance (MR), computed tomography (CT), and ultrasound-based imaging methods. The review concludes with comment on the advantages, disadvantages, and prospects of commercially available modalities and the impact they may have on diagnosis and management of patients with NAFLD.

Objective: Gastroenteropancreatic neuroendocrine carcinoma (GEPNEC) is a major research focus, but the application of biomarkers to guide its prognostication and management is unsatisfying. Clinical values of conventional serum biomarkers, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) warrant scrutiny. Methods: Patients diagnosed with GEPNEC with baseline NSE, CEA, and CA199 levels provided in Peking University Cancer Hospital were retrospectively studied. Relationships between biomarkers and prognosis were investigated by the χ2 test, Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses. Results: A total of 640 GEPNEC patients were enrolled. NSE, CEA, and CA199 were elevated in 59.5%, 28.5%, and 21.3% of the population, respectively. Higher NSE had worse median overall survival (OS) (17.0 months vs. not reached, hazard ratio = 2.77 [2.06, 3.73], p < 0.001), and so did patients with higher CEA and CA199. Multivariable analysis confirmed that NSE and CA199 correlated with OS independently. Baseline NSE level and NSE remission predicted OS and the response of patients with first-line etoposide plus cisplatin (EP) treatment. Furthermore, we combined NSE/CEA/CA199 to segregate GEPNEC into novel subgroups, namely, adenocarcinoma-like NEC (ALN), neuroendocrine-like NEC (NLN), and triple-normal NEC (TNN). The groups shared distinctive clinicopathologic features and prognosis (21.0 months vs. 17.1 months vs. not reached, p < 0.001). The EP regimen remained the priority treatment option in NLN/TNN, while ALN was predisposed to “adenocarcinoma-like chemotherapy.” Conclusions: Elevation of NSE, CEA, or CA199 was common and independently indicates poor prognosis in GEPNEC patients. Serum biomarker-based subtypes suggest meaningful clinical implications and appropriate therapeutic approaches, illuminating promising ways to characterize the prognosis of GEPNEC.

Background/aim We evaluated the predictive value of candidate serum biomarkers for recurrence in stage II and III colorectal cancer (CRC) after curative surgery. Patients and methods A total of 33 and 120 patients with CRC with or without recurrence at 5 years after curative surgery were included in the training set and the validation set, respectively. Possible serum biomarkers were examined for associations with CRC recurrence using receiver operating characteristics (ROC) curve analysis. Results In the training set, the expression levels of the 14 biomarkers were compared according to recurrence. Among them, five biomarkers that had significantly different expression levels were validated in 60 patients with recurrence at 5 years after curative surgery and 60 patients without. Multivariate analysis showed that natural log-transformed values of carcinoembryonic antigen (CEA), cyclin-dependent kinase regulatory subunit 2 (CKS2), 2'-5'-oligoadenylate synthetase 2 (OAS2), and autophagy-related gene 5 (ATG5) in preoperative serum were significantly related to recurrence. ROC analysis showed that these biomarkers were able to discriminate patients with recurrence from those without (area under the curve=0.828, 95% confidence interval=0.755-0.990). Conclusion Preoperative serum levels of CEA, CKS2, OAS2 and ATG5 were independent risk factors for recurrence. A combination of serum CEA, CKS2, OAS2 and ATG5 predicted tumor recurrence well in patients with stage II and III CRC.

Objective. The aim of this study was to evaluate the diagnostic and prognostic value of red blood cell distribution width (RDW) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods. We retrospectively reviewed 213 CTD-ILD patients and 97 CTD patients without ILD from February 2017 to February 2020. Hospital and office records were used as data sources. CTD-ILD patients were followed up. Results. Patients with CTD-ILD had significantly higher RDW than those with CTD without ILD ( p < 0.001 ). The area under the receiver operating characteristic curve (AUROC) of RDW for discriminating CTD-ILD from CTD without ILD was 0.64 (95% CI: 0.57-0.70, p < 0.001 ). The cutoff value of RDW for discriminating CTD-ILD from CTD without ILD was 13.95% with their corresponding specificity (55.9%) and sensitivity (70.1%). Correlation analyses showed that the increased RDW was significantly correlated with decreased DLCO%predicted ( r = − 0.211 , p = 0.002 ). Cox multiple regression analysis indicated that RDW ( HR = 1.495 , p < 0.001 ) was an independent factor in the survival of CTD-ILD. The best cutoff value of RDW to predict the survival of patients with CTD-ILD was 14.05% ( AUC = 0.78 , 95% CI: 0.72-0.84, p < 0.001 ). The log-rank test showed a significant difference in survival between the two groups ( RDW > 14.05 % and RDW < 14.05 % ). Conclusion. RDW was higher in CTD-ILD patients and had a negative correlation with DLCO%predicted. RDW may be an important serum biomarker for severity and prognosis of patients with CTD-ILD.

Various biomarkers of oxidative stress and redox status have been used in a number of clinical and epidemiological studies related to diseases and conditions that involve disturbances of the redox balance. However, a comprehensive study of diurnal variations of a set of biomarkers has not been conducted so far. Therefore, the aim of this study is to investigate circadian rhythm and time-of-day-effects of a set of frequently used biomarkers of oxidative stress, redox and antioxidant status in serum/plasma. These biomarkers include Reactive Oxygen Metabolites (ROM), Biological Antioxidant Potency (BAP), Total Thiols in Proteins (TTP), high-sensitive C-Reactive Protein (CRP) and Uric Acid (UA). During a 24-hr study, blood sampling was conducted 6 times at 4-hr intervals. The presence of circadian rhythm was analyzed with CircWave analysis, whereas the effect of time was analyzed with Repeated Measures ANOVA (RM-ANOVA). Thereby, the main focus was on the time points in working hours (8, 12 and 16 hr), which are used frequently in practice. Of all investigated biomarkers, only TTP in males demonstrated statistically significant circadian rhythm (p = 0.040). A statistically significant effect between all six time points with RM-ANOVA was observed for ROM, TTP and UA in both genders, and for BAP in females only. No statistically significant differences were observed between the time points 8 hr and 12 hr for any of the biomarkers that were assessed in our study. In conclusion, diurnal variations in some of the studied biomarkers that we demonstrate here should be taken into account when designing and conducting clinical and epidemiological studies. It is advised to standardize the time of sampling with a preference in the morning hours.

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI (“A1” class) from cases with other illnesses (“C” class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1β, IL-6 and TNF-α were observed in YEL-AEFI (“A1” and “C” classes) as compared to primary vaccines without YEL-AEFI [PV(day 3–28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1β, IL-15, IL-1Ra and G-CSF were found in “A1” as compared to “C” class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate “A1” from “C”. Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify “A1” followed by VEGF as branch nodes to discriminate Wild Type YFV infection (“C(WT-YFV)”) from cases with other illnesses (“C*”). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Background and Aim The Gut and Obesity in Asia Workgroup recently reported that a two‐step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non‐alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low‐risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry. Methods This cross‐sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis‐4 score [FIB‐4]) and LSM, alone or in combination. Results Of 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first‐step evaluation, only 21.4–38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB‐4 values followed by LSM in all subjects and using LSM after NFS or FIB‐4 determination only in subjects with indeterminate/high NFS or FIB‐4 values (two‐step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB‐4. Conclusion The two‐step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives., We validated “two step approach” using health checkup subjects with nonalcoholic fatty liver disease. In the first‐step evaluation, only 21.4–38.0% of subjects needed further testing. The percentage of misclassification based on NAFLD fibrosis score (NFS) or Fibrosis‐4 score (FIB‐4) values followed by liver stiffness measurement (LSM) in all subjects and using LSM after NFS or FIB‐4 determination only in subjects with indeterminate/high NFS or FIB‐4 values (two‐step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively.

Innumerable reasons have been reported that affect and infect the liver and cause liver diseases. The evaluation and follow-up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, it has become evident that this once defined as “gold-standard” is now not the best method as it involves many limitations. Attempts to reveal non-invasive diagnostic tools have generated serum biomarkers, multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and are less expensive than a liver biopsy. Biomarkers have various advantages like minimally invasive, easy to apply with great availability and easier reproducibility, useful for monitoring therapy and less expensive. But then, direct biomarkers involved in extracellular matrix turnover need further validation in different geographic population and indirect biomarkers may not predict early pathophysiological changes in liver parenchyma. The accuracy and diagnostic value of most, if not all, of these biomarkers remain controversial. Hence, there is a need for a biomarker that is specific for the liver and can identify the magnitude of the clinical outcome of the disease. : In this review, we discuss the clinical utility, limitations, and development of noninvasive biomarkers in their use as diagnostic and prognostic tests and analyze whether the present known serum biomarkers are laudable and accurate tools for the diagnosis of liver diseases.

Mild traumatic brain injury (mTBI) is the most prevalent neurological insult and leads to long-lasting cognitive impairment. Neuroimaging studies have discovered abnormalities in brain network connectivity following mTBI as the underlying neural basis of cognitive deficits. However, the pathophysiologic mechanisms involved in imaging alterations remain elusive. Proteins neuron-specific enolase (NSE) and ubiquitin C terminal hydrolase 1 are reliable markers for neuronal cell-body damage, both of which have been demonstrated to be increased in serum following mTBI. Therefore, we conducted a longitudinal study to examine relationships between abnormal brain network connectivity and serum neuronal biomarkers and their associations with cognitive recovery following mTBI. Sixty patients were followed-up at 1 week and 3 months post-injury and 41 controls were recruited. Resting-state functional magnetic resonance imaging was used to build a functional connectivity matrix within large-scale intrinsic networks, and their topological properties were analyzed using graph theory measures. We found that, compared with controls, mTBI patients showed significant decreases in a number of nodal characteristics in default mode network (DMN), salience network, and executive network (

Neonatal sepsis is a major cause of morbidity and mortality in neonates and is challenging to diagnose. Infants manifest nonspecific clinical signs in response to sepsis; these signs may be caused by noninfectious conditions. Time to antibiotics affects neonatal sepsis outcome, so clinicians need to identify and treat neonates with sepsis expeditiously. Clinicians use serum biomarkers to measure inflammation and infection and assess the infant's risk of sepsis. However, current biomarkers lack sufficient sensitivity or specificity to be consider useful diagnostic tools. Continued research to identify novel biomarkers as well as novel ways of measuring them is sorely needed.

Purpose - The present study aimed to identify differently expressed peptides involved in BC as potential biomarkers. Experimental Design - The serum proteomic profiling of 128 serum samples from 64 BC patients and 64 healthy controls (HC), using magnetic beads based immobilized metal ion affinity chromatography (MB-IMAC-Cu) separation followed by MALDI-TOF MS. ClinProTools software identified a number of distinct markers. Then, we performed liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to identify the candidate serum biomarker based on serum proteomics analysis. Finally, enzyme-linked immunosorbent assays (ELISAs) were used to verify the expression of the candidate serum biomarker in BC patients. Results - BC patients could be identified with sensitivity of 87.32% and specificity of 89.46%. Of 41 m/z peaks that differed between BC and HC, six peaks were significantly different between BC and HC (P0.01, fold change1.5), with peak 1 upregulated and peaks 2-6 downregulated in the BC group. The upregulated peak 1 (m/z: 6638.63) is identified as a region of apolipoprotein C1 (APOC1), and validation showed that APOC1 expression increased from healthy controls to those with FA as well as mastopathy, and finally BC patients. Conclusions and Clinical Relevance - The present study indicates that APOC1 could serve as a candidate serum diagnostic biomarker for BC.

Objectives: Preeclampsia (PE) is a multisystemic disorder portrayed by the new beginning of circulatory pressure more noteworthy than 140/90 mmHg and proteinuria with 0.3 g in a 24 h on dip stick emerging after 20 weeks of incubation. The hidden pathophysiology of PE includes endothelial brokenness and vasospasm beginning principally in the placenta. The unusual growth of blood vessels in placenta leads to poor perfusion. This relative hypoxic condition in placenta causes arrival of antiangiogenic factors into the maternal blood dissemination which prompts the modifications in maternal fundamental endothelial functions and causes hypertension. Soluble fms-like tyrosine kinase (sFlt) can form a heterodimer, binding with vascular endothelial growth Factor A and placental growth factor. In preeclamptic subjects, there will be an imbalance in anti-angiogenesis factors and there will be incomplete arterial transformation and cytotrophoblast cell division. Due to imbalance in sFlt levels in preeclamptic women it effects in the blood vessels by constriction and leads to endothelial dysfunction. This study aim is to compare the maternal serum concentration of sFlt levels in normotensive pregnant women to preeclamptic women in early and late gestational weeks. Material and Methods: Out of 300 participants in the case–control study, 150 were preeclamptic women as cases and 150 as normotensive pregnant women as controls participated in the present study. A 5 ml of maternal venous blood was collected; the serum was separated and stored at –800°C till the analysis. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits from Chongqing Biospes Co., Ltd., (suppliers: Infobio Company, New Delhi) was measured with ELISA microplate reader at 450 nm (Merilyzer Eiaquant Company). Results: Out of 300 participants in the study, 46 pregnant women were early gestational weeks and 254 were late gestational weeks. The complications due to severe PE such as intrauterine death are 15%, intrauterine fetal growth retardation 33%, and premature 15%. The statistical analyses were performed by Statistical Packages for the Social Sciences Software 22. The area under the receiver operating characteristic curve is 0.82, with 91% sensitivity, and 79% specificity. The significance in the maternal serum sFlt levels was calculated by the Mann–Whitney U-test. By comparing the cases and controls, it was found that maternal serum sFlt1 were significantly higher in preeclamptic women with Z = 2.96 and U = 9021 with P = 0.005 significance. Conclusion: This is the first South Indian study. If we compare the sFlt1 levels in early and late gestational weeks, in late gestational weeks in controls and PE the levels were highly significant than early gestational weeks of PE and controls. Maternal serum sFlt can be used as a preeclamptic diagnostic marker in South Eastern Kolar population.

Carotid atherosclerosis is responsible for a great proportion of ischemic strokes. Early identification of unstable or vulnerable carotid plaques, and therefore, of patients at high risk for stroke, is of significant medical and socioeconomical value. We reviewed the current literature and discussed the potential role of the most important serum biomarkers in identifying patients with carotid atherosclerosis who are at high risk for atheroembolic stroke.

Background Identifying patients at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) remains challenging. This study aimed to evaluate the concentration of serum biomarkers along with cerebral autoregulation impairment on DCI. Methods 55 patients suffering from aSAH were enrolled in the study. Serum S100 protein B (S100B) was tested both on the day of admission and over three consecutive days following the occurrence of aSAH. Cerebral autoregulation was assessed using a tissue oxygenation index (TOxa) based on near-infrared spectroscopy. Results Changes in serum S100B levels interacted with DCI status (presence vs. absence): F = 3.84, p = 0.016. Patients with DCI had higher S100B concentration level on day 3 than those without DCI (3.54 ± 0.50 ng/ml vs. 0.58 ± 0.43 ng/ml, p = 0.001). S100B concentration on day 3 following aSAH predicted DCI (AUC = 0.77, p = 0.006). Raised level of serum S100B on day 3 was related with higher TOxa, thus with impaired cerebral autoregulation (rS = 0.52, p = 0.031). Multivariate logistic regression analysis showed that impaired cerebral autoregulation and elevated S100B concentration on day 3 increase the likelihood of DCI. Conclusions Tracking changes in the serum biomarkers concentration along with monitoring of cerebral autoregulation, may play a role in early detection of patients at risk of DCI after aSAH. These results need to be validated in larger prospective cohorts.

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

One of the most probable markers of inflammatory response is serum protein. Recently, serum levels of these some proteins have been proven to be useful in clinical diagnosis. In this study, we comparatively investigated serum and saliva C - reactive protein (CRP), α-amylase and α-glucosidase activities in type II Diabetic and Normo-glycemic humans. Two hundred and thirteen (213) subjects of 173 Diabetics and 40 Non-diabetics (Control) were ethically recruited from the central hospital, warri, Delta State. For each participant, serum and saliva was collected and laboratorily analyzed for α-amylase, α-glucosidase and CRP levels, while comparing mean differences between groups with a student t-test and statistical measure of association (correlation). Result showed a statistically significant increase in CRP and α-amylase activity of diabetics than non-diabetic subjects, with a statistically significant increase in salivary and serum CRP, α-glucosidase and α-amylase levels across groups. This finding is suggestive that saliva and/or serum levels may be useful bioanalytes for non-invasive, alternative diagnosis of blood glucose levels. Similar studies that corroborate the efforts of this study is recommended. Further studies that assay other saliva and serum biomarkers may also be useful and thus recommended.

OBJECTIVE: Early identification of neonates at risk of neurological impairment is particularly important for the bedside clinician. Clinical value of S100b and neuron-specific enolase in neonates h...

Introduction. Serum concentrations of collagens I, III, IV types (K-I, K-III, K-IV) and hyaluronic acid (HA) are reported to be informative in terms of noninvasive diagnosis liver fibrosis stages. In pediatrics, there is not enough data on this. Purpose was to assess the diagnostic value of direct biomarkers in predicting the stage of fibrosis in children with chronic liver diseases (CLD). Materials and methods. A prospective single-center study included 80 children with CLD . All patients underwent marginal resection of liver tissue under laparoscopic control. The serum K-I, K-IV, and HA concentration were measured by enzyme immunoassay. The authors applied ROC curve analysis to assess quantitative signs’ diagnostic significance in predicting a specific outcome. Results.The optimal KI value for the diagnosis of cirrhosis was 144.24 ng/ml, with AUROC: 0.758 ± 0.101 with 95% CI: 0.560-0.957, sensitivity and specificity 65.2% and 77.8%, respectively. The optimal K-IV values for the diagnosis of moderate fibrosis and cirrhosis were 11.29 ng/ml and 27.40 ng/ml, respectively, with AUROC 0.807 ± 0.092 with 95% CI: 0.627-0.987, 0.685 ± 0.062 with 95% CI: 0.567-0.810, sensitivity 82.4% and 61.15%, specificity 66.7%, and 64.7%, respectively. The optimal BG values for the diagnosis of weak and moderate fibrosis were 34.9 ng/ml and 36.5 ng/ml, for cirrhosis 38.3 ng/ml, with AUROC 0.912 ± 0.050 with 95% CI: 0.815-1.00; 0.849 ± 0.064 with 95% CI: 0.723-0.974, and 0.825 ± 0.048 with 95% CI: 0.730-0.920, respectively. Sensitivity was 84.6% at all stages, specificity - 77.8%, 61.5% and 70.6%, respectively. Conclusions. LF biomarkers have diagnostic significance in the detection of the stages of liver fibrosis. LF biomarkers are informative, reproducible noninvasive indices in the diagnosis of liver fibrosis in children.

OBJECTIVE To establish predictive models for mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) using a combination of initial serum biomarker levels. METHODS The Multicenter Retrospective Cohort of Japanese Patients with Myositis-Associated ILD (JAMI) database of 497 incident cases of PM/DM-ILD was used as a derivation cohort, and 111 cases were additionally collected as a validation cohort. Risk factors predictive of all-cause mortality were identified by univariate and multivariable Cox regression analyses using candidate serum biomarkers as explanatory variables. The predictive models for mortality were generated in patients with and those without anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, using a combination of risk factors. Cumulative survival rates were assessed using Kaplan-Meier analysis, and were compared between subgroups using the Breslow test. RESULTS In the derivation cohort, C-reactive protein (CRP) and Krebs von den Lungen 6 (KL-6) levels were identified as independent risk factors for mortality in both anti-MDA-5-positive and anti-MDA-5-negative patients. We then developed a prediction model based on anti-MDA-5 antibody status, CRP level, and KL-6 level, termed the "MCK model," to identify patients at low (

China's HCC accounts for 90% of HBV related HCC. Early detection, diagnosis and treatment are the key to effective control of HCC. By measuring the levels of expression of AFP, DCP and GP73 in the serum of HBV-related HCC patients, the diagnostic value of single and combined detection of the above indicators in HBV-related HCC shall be discussed, and the mathematical model of differential diagnosis by SVM shall be established to provide reference for the diagnosis of HBV-related HCC. A total of 301 patients and healthy persons from March 2016 to January 2018 from Beijing Tongren Hospital affiliated to Capital Medical University have been selected. These lection includes 57 cases of HBV-related HCC, 61 cases of non- HBV-related HCC, 52 cases of HBV-related cirrhosis, 57 cases of chronic HBV, and 74 healthy persons in the same period. The levels of serum DCP, AFP and GP73 in each group were measured. Combined diagnosis of three indexes is better than single diagnosis, P

Objective: Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of 5 serum biomarkers (AFP, AFU, GGT-II, GPC3, and HGF) in the diagnosis of HCC. Methods: In this retrospective study, we measured the serum levels of each biomarker using ELISAs in 921 participants, including 298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controls from 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called “NBNC-HCC”) and patients positive for the above indices (called “HBV-HCC and HCV-HCC”) were enrolled. The selected diagnostic model was constructed using a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy. Results: The α-L-fucosidase (AFU)/α-fetoprotein (AFP) combination was best able to distinguish NBNC-HCC [area under the curve: 0.986 (95% confidence interval: 0.958–0.997), sensitivity: 92.6%, specificity: 98.9%] from healthy controls in the test cohort. For screening populations at risk of developing HCC (CH and LC), the AFP/AFU combination improved the diagnostic specificity for early-stage HCC [area under the curve: 0.776 (0.712–0.831), sensitivity: 52.5%, specificity: 91.6% in the test group]. In all-stage HBV-HCC and HCV-HCC, AFU was also the best candidate biomarker combined with AFP [area under the curve: 0.835 (0.784–0.877), sensitivity 69.1%, specificity: 87.4% in the test group]. All results were verified in the validation group. Conclusions: The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.

Background Despite impressive response rates, most patients with advanced melanoma ultimately progress following therapy with B-Raf proto-oncogene (BRAF) inhibitors (BRAFi). Therefore, frequent radiologic assessments are necessary, and reliable serum biomarkers would be beneficial for disease monitoring. Objective This study investigated the ability of lactate dehydrogenase (LDH) and S100 calcium-binding protein B (S100B) to detect response and disease progression during treatment with BRAFi. Patients and Methods Baseline levels of LDH and S100B and repeated measurements during therapy were recorded retrospectively in 191 patients with metastatic melanoma. LDH and S100B levels were compared between distinct time points (baseline, first follow-up visit [FV], best objective response [BR], and progressive disease [PD]). The prognostic ability of the serum biomarkers in relation to disease-specific survival (DSS) was assessed with univariable and multivariable Cox regression analysis. Results Elevated baseline LDH and S100B correlated with impaired DSS. In contrast with LDH (P = 0.12), S100B levels at FV correlated with response (P = 0.0030). Both markers significantly decreased during the first weeks of BRAFi treatment (LDH, P = 0.00034; S100B, P < 0.0001) and increased between BR and PD (LDH, P = 0.016; S100B, P < 0.0001). Patients with elevated S100B (P = 0.00062) but not with elevated LDH (P = 0.067) at the time point of radiologically confirmed PD showed significantly impaired DSS after PD. Interestingly, DSS after PD differed significantly according to S100B levels determined as early as 8 weeks (median) before PD (P = 0.0024). Conclusions LDH and S100B are suitable serum biomarkers during therapy with BRAFi. S100B shows stronger correlation with response and exhibits more accuracy in predicting PD. Close biomarker monitoring with S100B is recommended during treatment with BRAFi to detect PD early. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00792-8.

Background and aimsWe sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects.MethodsWe studied 1069 subjects (age 58.2±8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation.ResultsAt 14.5±2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p=0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p&nbsp

Given the known deleterious consequences of acute kidney injury (AKI), exciting recent research efforts have focused on developing strategies for the earlier recognition of AKI in the pediatric population. Recognizing the limitations of serum creatinine, investigators have focused on the study of novel biomarkers and practical bedside tools for identifying patients at risk for AKI prior to a rise in serum creatinine. In PubMed there are presently over 30 original research papers exploring the use of pediatric AKI risk prediction tools just in the last 2 years. The following review will highlight the most recent advances in the literature regarding opportunities to refine our ability to detect AKI early. Importantly, it will be discussed how prediction tools including novel urine and serum biomarkers, practical risk stratification tests, renal functional reserve and electronic medical record alerts may ultimately be applied to routine clinical practice.

The era of genetics and precision medicine has been reforming this world. How will plastic surgeons in the field of vascular anomalies conform to the trend? This article systematically reviews the identification of serum biomarkers, risk factors, specific mutations in the angiogenesis-related genes such as GNAQ, RASA1, TEK, and their impact on the diagnosis and treatment of vascular anomalies with preliminary results that have been previously reported and leading the tide. Moreover, a new disease classification for complex vascular malformations based on PIK3CA genetic evidence and various treatment breakthroughs is briefly summarized. With gene sequencing, bioinformatics, and big data, we confront the challenges of research in the vascular anomalies domain and explore possibilities of precision medicine development.

© Springer-Verlag GmbH, DE part of Springer Nature 2021, Recent advances in complementary diagnostic exams have helped to clarify stroke etiology, not only by helping to confirm established stroke causes but also by unveiling new possible stroke mechanisms. Etiological investigation for cardioembolic stroke has benefited in the last years from information provided by studies analysing serum biomarkers, heart rhythm monitoring and imaging methods like cardiovascular magnetic resonance (CMR) imaging. CMR has been particularly important for the characterization of possible new cardioembolic stroke mechanisms including atrial cardiomyopathy, silent myocardial infarction and cardiomyopathies.

Stiffening of large arteries, clinically manifesting as increased aortic pulse wave velocity (PWV), is an inevitable outcome of aging. Among other mechanisms, impaired glucose metabolism plays an important role, leading to the deposition of advanced glycation end products (AGEs). This process is counterbalanced by the circulating soluble receptor for AGEs (sRAGE). We investigated the association between arterial stiffness on one side and multiple circulating biomarkers and the degree of skin deposition of AGEs on the other. In a cross-sectional design, 867 participants based on a general population sample (Czech post-MONICA studies) were examined. PWV was measured by SphygmoCor device (AtCor Medical Ltd.), while skin AGEs were measured using a dedicated autofluorescence method (AGE Reader mu®). To quantify the circulating status of AGEs, carboxymethyl lysine (CML) and sRAGE concentrations were assessed by ELISA, along with conventional glucose metabolism indicators. When analyzing the whole sample using multiple linear or logistic regression models and after adjustment for potential covariates, a significant association with PWV was found for fasting glycemia, HbA1c, sRAGE, skin AGEs, and the skin AGE-to-sRAGE ratio. Among these parameters, stepwise models identified the strongest association for the skin AGEs and AGE-to-sRAGE ratio, and this was also true when diabetic subjects were excluded. In contrast, neither CML nor its ratio relative to sRAGE showed any association with arterial stiffness. In conclusion, skin AGEs along with their ratio relative to sRAGE were closely associated with arterial stiffness and is a better indicator of the current status of deposited AGEs than other relevant factors.

Gut microbiota are the candidate biomarkers for neurogenic bowel dysfunction (NBD) in patients with spinal cord injury (SCI). We aimed to identify the common features between patients with varying degree of thoracic SCI and healthy individuals and subpopulations of microbiota correlated with the serum biomarkers. Twenty-one patients with complete thoracic SCI (CTSCI), 24 with incomplete thoracic SCI (ITSCI), and 24 healthy individuals (HC) were enrolled in this study. Fresh stool samples and clinical data were collected from all participants, and their bowel functions with SCI were assessed. Microbial diversity and composition were analyzed by sequencing the 16S rRNA gene. The features of gut microbiota correlated with the serum biomarkers and their functions were investigated. The mean NBD score of patients with CTSCI was higher than that of patients with ITSCI. Diversity of the gut microbiota in SCI group was reduced, and with an increase in the degree of damage, alpha diversity had decreased gradually. The composition of gut microbiota in patients with SCI was distinct from that in healthy individuals, and CTSCI group exhibited further deviation than ITSCI group compared to healthy individuals. Four serum biomarkers were found to be correlated with most differential genera. Patients with thoracic SCI present gut dysbiosis, which is more pronounced in patients with CTSCI than in those with ITSCI. Therefore, the gut microbiota profile may serve as the signatures for bowel and motor functions in patients with thoracic SCI., GRAPHICAL ABSTRACT

Hepatocellular carcinoma (HCC) stands third among cancer-related deaths globally. Owing to its high incidence and linked mortality, early diagnosis is alarming for patient survival and the management of patients with developing HCC requires immediate attention. Advances in the knowledge of cancer biology and recognizing unique molecular candidates, including genomic and proteomic profiles, substantiate our understanding about several biological signatures connected with HCC. Precise identification and differential diagnosis of early HCC can remarkably improve patient survival. Currently, detection of HCC in clinical practice is performed by diagnostic imaging and noninvasive methods such as evaluation of serum biomarkers, growth factors, and the like. In this review, we discuss recent developments in targeting biomarkers for HCC.

To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells.Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome.128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest.ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE.

Background Atopic dermatitis (AD) is a highly heterogeneous disease, both clinically and biologically, whereas patients are still being treated according to a “one-size-fits-all” approach. Stratification of patients into biomarker-based endotypes is important for future development of personalized therapies. Objective Our aim was to confirm previously defined serum biomarker-based patient clusters in a new cohort of patients with AD. Methods A panel of 143 biomarkers was measured by using Luminex technology in serum samples from 146 patients with severe AD (median Eczema Area and Severity Index = 28.3; interquartile range = 25.2-35.3). Principal components analysis followed by unsupervised k-means cluster analysis of the biomarker data was used to identify patient clusters. A prediction model was built on the basis of a previous cohort to predict the 1 of the 4 previously identified clusters to which the patients of our new cohort would belong. Results Cluster analysis identified 4 serum biomarker–based clusters, 3 of which (clusters B, C, and D) were comparable to the previously identified clusters. Cluster A (33.6%) could be distinguished from the other clusters as being a “skin-homing chemokines/IL-1R1–dominant” cluster, whereas cluster B (18.5%) was a “TH1/TH2/TH17-dominant” cluster, cluster C (18.5%) was a “TH2/TH22/PARC-dominant” cluster, and cluster D (29.5%) was a “TH2/eosinophil-inferior” cluster. Additionally, by using a prediction model based on our previous cohort we accurately assigned the new cohort to the 4 previously identified clusters by including only 10 selected serum biomarkers. Conclusion We confirmed that AD is heterogeneous at the immunopathologic level and identified 4 distinct biomarker-based clusters, 3 of which were comparable with previously identified clusters. Cluster membership could be predicted with a model including 10 serum biomarkers.

BACKGROUND: Environmental enteric dysfunction (EED) is a chronic subclinical condition, contributed to limited sources and poor countries. EED pathology is concerned with small intestine structure and function, which affect the macronutrients and micronutrients absorption with consequent growth faltering. AIM: This study aimed to evaluate some serum biomarkers involved in EED and determine their association with stunting and faltering growth in children; zonulin, endotoxin core antibody (EndoCAb), high-sensitive C-reactive protein (hsCRP), alpha-1-acid glycoprotein (AGP), and tumor necrosis factor (TNF), serum iron, and Vitamins A and D. PATIENTS AND METHODS: This case–control study enrolled 105 children aged from 1 to 10 years old, having weight-for-age z-scores and height-for-age z-scores (WAZ or HAZ) ranging from −1.5 to −2. They were compared with control group consisted of 100 children having WAZ or HAZ > −1 of matched age and sex. Assessment of serum markers levels of enteric dysfunction (zonulin and EndoCAb), markers of systemic inflammation (Hs CRP and AGP), along with serum micronutrients (vitamin A, vitamin D and iron) in children with malnutrition in comparison to controls. RESULTS: There was a highly significant decrease as regarding the anthropometric measurements; weight, height, BMI, and arm circumference. Moreover, significant increase in serum zonulin, EndoCAb, HsCRP, and AGP and highly significant decrease of serum Vitamin D and iron in cases group as compared to control group. Height Z score showed negative correlation with zonulin, HsCRP, and AGP and positive correlation with Vitamin D. Weight Z score showed negative correlation with zonulin, HsCRP, and AGP and positive correlation with Vitamin D and Vitamin A. Regression analysis noted increase of zonulin and α1AGP as high associative markers with height Z score affection, however, increase of zonulin was high associative markers with weight Z score affection. CONCLUSION: Faltering growth is associated with elevated serum systemic markers of intestinal inflammation (HsCRP and α1AGP). EED may be a cause of faltering growth.

Objective: Printing workers experience a high rate of musculoskeletal disorders (MSDs). This study aims to determine the prevalence of MSDs, estimate serum biomarkers denoting musculoskeletal tissue changes, and determine some individual risk factors for MSDs among Egyptian printing workers. Methods: Eighty-five male printing workers and 90 male administrative employees (control group) were recruited from a printing press in Giza. A validated version of the standardized Nordic questionnaire was used. Serum biomarkers of inflammation (interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)), cell stress or injury (malondialdehyde (MDA) and creatine kinase skeletal muscle (CK-MM)), and collagen metabolism (collagen-I carboxy-terminal propeptide (PICP) and type-I collagen cross-linked C-telopeptide (CTx)) were measured for all participants. Results: This study showed a significant ( p < 0.001) prevalence of the musculoskeletal symptoms (76.5%) and significant ( p < 0.001) elevation in the levels of all measured biomarkers among the printing workers (means ± SD: IL-1α = 1.55 ± 0.9, IL-1β = 1.53 ± 0.87, IL-6 = 1.55 ± 0.85, TNF-α = 4.9 ± 2.25, CRP = 6.78 ± 3.07, MDA = 3.41 ± 1.29, CK-MM = 132.47 ± 69.01, PICP = 103.48 ± 36.44, and CTx = 0.47 ± 0.16) when compared with their controls (prevalence: 34.4%; means ± SD: IL-1α = 0.88 ± 0.61, IL-1β = 0.96 ± 0.72, IL-6 = 1.03 ± 0.75, TNF-α = 2.56 ± 1.99, CRP = 2.36 ± 1.1, MDA = 0.85 ± 0.21, CK-MM = 53.48 ± 33.05, PICP = 56.49 ± 9.05, and CTx = 0.31 ± 0.06). Also, significant ( p < 0.001) positive strong associations were observed between age, body mass index (BMI), and the duration of employment with all measured biomarkers, where all correlation coefficients were >0.7. Conclusion: Printing workers suffer a high prevalence of work-related MSDs that might be related to some individual factors (age, BMI, and duration of employment). Consequently, preventive ergonomic interventions should be applied. Further studies should be done to elucidate the link between tissue changes and detected biomarkers to follow the initiation and progression of MSDs and study the effectiveness of curative interventions.

Background The prognostic significance of serum biomarkers in patients with intracerebral hemorrhage (ICH) is not well investigated concerning inhospital mortality (IHM) and cardiopulmonary events within the first 24 hours of intensive care unit (ICU) treatment. The influence of troponin I (TNI) value and cortisol value (CV) on cardiopulmonary events within the first 24 hours of ICU treatment was reported in subarachnoid hemorrhage patients, but not in ICH patients up to now. The aim of this study was to investigate the role of early serum biomarkers on IHM and TNI value and CV on cardiopulmonary events within the first 24 hours of ICU treatment. Patients and Methods A total of 329 patients with spontaneous ICH were retrospectively analyzed. Blood samples were taken on admission to measure serum biomarkers. The TNI value and CV were defined as biomarkers for cardiopulmonary stress. Demographic data, cardiopulmonary parameters, including norepinephrine application rate (NAR) in microgram per kilogram per minute and inspiratory oxygen fraction (FiO2) within the first 24 hours, and treatment regime were analyzed concerning their impact on ICU treatment and in hospital outcome. Binary logistic analysis was used to identify independent prognostic factors for IHM. Results Patients with initially nonelevated CVs required higher NAR (p = 0.01) and FiO2 (p = 0.046) within the first 24 hours of ICU treatment. Lower cholinesterase level (p = 0.004), higher NAR (p = 0.002), advanced age (p Conclusion Higher levels of C-reactive protein, serum lactate, blood glucose, and lower cholinesterase level on admission were significantly associated with IHM. Patients with initially nonelevated CVs required higher NAR and FiO2 within the first 24 hours of ICU treatment. Furthermore, requiring an NAR > 0.5 µg/kg/min or an FiO2 > 0.21 were identified as additional independent predictors for IHM. These results could be helpful to improve ICU treatment in ICH patients.