Search

The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA. ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported. The primary analysis, adjusted for age, body mass, socioeconomic status, and ethnicity, was to determine any differences in biomarkers between those with/without combat injury, rOA and pain. Secondary analyses were performed to compare post-traumatic/idiopathic OA, painful/painfree rOA and injury patterns. A total of 1145 male participants were recruited, aged 34.1 ± 5.4, 8.9 ± 2.2 years post-injury (n = 579 trauma-exposed, of which, traumatic-amputation n = 161) or deployment (n = 566 matched). Cartilage oligomeric matrix protein (COMP) was significantly higher in the combat-injured group compared to uninjured (p = 0.01). Notably, COMP was significantly lower in the traumatic-amputation group compared to non-amputees (p < 0.001), decreasing relative to number of amputations (p < 0.001). Leptin was higher (p = 0.005) and adiponectin lower (p = 0.017) in those with v without knee pain, associated with an increased risk of 22% and 17% for pain, and 46% and 34% for painful rOA, respectively. There were no significant differences between trauma-exposed and unexposed participants with rOA. The most notable findings of this large, unique study are the similarities between those with rOA regardless of trauma-exposure, the injury-pattern and traumatic-amputation-associated differences in COMP, and the relationship between adipokines and pain. [ABSTRACT FROM AUTHOR]

Brain injury is a multifaceted condition arising from nonspecific damage to nervous tissue. The resulting cognitive developmental impairments reverberate through patients' lives, affecting their families, and even the broader economic landscape. The significance of early brain injury detection lies in its potential to stave off severe consequences and enhance the effectiveness of tailored therapeutic interventions. While established methods like neuroimaging and neurophysiology serve as valuable diagnostic tools, their demanding nature restricts their accessibility, particularly in scenarios such as small hospitals, nocturnal or weekend shifts, and cases involving unstable patients. Hence, there is a pressing need for more accessible and efficient diagnostic avenues. Among the spectrum of brain injuries, hypoxic-ischemic encephalopathy stands out as a predominant affliction in the pediatric population. Diagnosing brain injuries in newborns presents challenges due to the subjective nature of assessments like Apgar scores and the inherent uncertainty in neurological examinations. In this context, methods like magnetic resonance and ultrasound hold recommendations for more accurate diagnosis. Recognizing the potential of serum biomarkers derived from blood samples, this paper underscores their promise as a more expedient and resource-efficient means of assessing brain injuries. The review compiles current insights into serum biomarkers, drawing from experiments conducted on animal models as well as human brain pathologies. The authors aim to elucidate specific characteristics, temporal profiles, and the available corpus of experimental and clinical data for serum biomarkers specific to brain injuries. These include neuronspecific enolase (NSE), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and high-mobility-group-proteinbox-1 (HMGB1). This comprehensive endeavor contributes to advancing the understanding of brain injury diagnostics and potential avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Perioperative neurocognitive disorders (PND) are a common central nervous system complication that predominantly affects the elderly. PND after surgery includes postoperative delirium (POD), delayed neurocognitive recovery up to 30 days (DNR), and postoperative neurocognitive disorder up to 12 months. Diabetes is an important independent risk factor for PND. Over the years, few studies have assessed the incidence of PND and the difference in serum biomarkers between diabetic and non-diabetic patients. We sought to examine the difference in the incidence of PND between elderly diabetic and non-diabetic patients in China and identify the risk factors of PND in elderly diabetics. Methods: We conducted a secondary and exploratory data analysis from our prior studies, including patients aged 65 years or older who underwent non-cardiac elective surgery with general anesthesia. We used the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Montreal Cognitive Assessment (MoCA) to assess patient cognition. Results: A total of 236 patients were analyzed; the incidence of PND was significantly higher in diabetic than in non-diabetic patients within 30 days (59.2% vs. 36.8%) (P = 0.022). Multivariate logistic regression analysis showed that the preoperative MoCA was an independent risk factor for PND (odds ratio, 0.88 [0.8 to 0.97]; P = 0.014), and Hosmer–Lemeshow tests showed that it could predict PND in diabetic patients (P = 0.360). According to the maximum Youden index, the optimal cutoff for preoperative MoCA was 21.5 points, yielding a specificity and sensitivity of 88.0% and 55.2% for PND. The levels of glial fibrillary acidic protein (GFAP) and Tau in diabetic patients before and after surgery were significantly higher than in non-diabetic patients among cases of PND (P = 0.002 and 0.011, respectively). Conclusion: The incidence of PND is higher in diabetic than in non-diabetic patients in China, and preoperative MoCA is an independent risk factor for PND in diabetics. Meanwhile, the changes in GFAP and p-Tau in diabetic patients who experienced PND were significantly higher than in non-diabetic ones. [ABSTRACT FROM AUTHOR]

Diagnosis of bone and joint infections can be difficult. In recent years there has been great progress in defining how we diagnose fracture-related infection (FRI) and prosthetic joint infection (PJI). Definitions have been proposed based on the best evidence from the literature, including well-established tests performed before and during surgery. These allow surgeons to make better decisions for treatment and to counsel patients. This paper presents the elements of the International Consensus Definition of FRI and the European Bone & Joint Infection Society Definition of Prosthetic Joint Infection (PJI), together with the current knowledge on how these definitions can help in clinical practice. [ABSTRACT FROM AUTHOR]

Background Up to date, a well-defined microRNAs (miRNAs) profile involved in hepatocellular carcinoma (HCC) pathogenesis remains indecisive. Thus, employing miRNAs for HCC diagnosis is demanded for early therapeutic interventions. We aimed to evaluate the usage of miRNAs set related to the SuperPath: miRNAs involved in DNA damage response pathway as effective biomarkers for HCV-related HCC diagnosis. Results The study enrolled 97 patients with HCV-related HCC, 84 with hepatitis C virus (HCV), 97 with liver cirrhosis (LC), and 84 healthy individuals. Serum miRNA-23a, miRNA-203, miRNA-100-5p, and miRNA-16 were quantified using qRT-PCR experiments, AFP and routine LFTs were estimated via standard techniques. Pathway enrichment analysis along with the construction of miRNAs regulatory network were performed. With respect to healthy individuals, miRNA-203, miRNA-100-5p, and miRNA-16 were significantly downregulated in HCC, HCV, and LC groups, while miRNA-23a showed significant upregulation (p < 0.001). miRNAs exhibited significant correlations with AFP, ALT, AST, and albumin. Also, elevated levels of miRNA-23a were recognized in patients with multiple focal lesions and/or lesion size > 5 cm. Additionally, the diagnostic performance of miRNA-23a expression level at a selected cut-off value of 3.99 overtakes AFP, while expressions of miR-203, miRNA-100-5p, and miRNA-16 represent poor diagnostic outcomes. Conclusions Keeping in mind the individual variability and high level of heterogeneity in HCC, our data revealed the diagnostic value of miRNA-23a expression in HCV-related HCC patients. Further extra in silico HCC-specific microR- NAs sets are demanded in diagnosis. [ABSTRACT FROM AUTHOR]

To evaluate the ability of at-admission (Day 1) estimated serum levels of inflammatory biomarkers and clinical scorings for prediction of survival outcome of sepsis patients admitted to surgical ICU. One hundred and seventy-eight patients were clinically evaluated and gave blood samples for estimation of serum biomarkers' levels (Day 1 data) and re-evaluated on Days 2–3 for the National Early Warning-2 (NEWS-2) score and Day 3 for the Sequential organ failure assessment (SOFA) score and serum level of presepsin (PSP). During 28-day, patients were grouped according to survival outcome as Survivors and Non-survivors. Day1 clinical scorings and biomarkers' levels were significantly higher in non-survivors (n = 41) than survivors (n = 137). Day 3 SOFA scores of all patients were significantly higher than Day1 scores with significantly higher scores for non-survivors. Through Day1-3, the number of patients with high-grade risk on NEWS2 was significantly higher among non-survivors. Day-3 serum PSP levels were significantly decreased in survivors, while increased in non-survivors. The statistical analyses defined high NEWS2, SOFA, PSP, and procalcitonin serum levels as the significant predictors of mortality. Diagnostic performance characteristics of combined NEWS score and PSP showed high sensitivity, specificity, and accuracy rates with a 99% negative predictive value for survival outcomes. Sequential estimation of NEWS2 score and serum PSP can discriminate between high-risk patients and those prone to die. Coupling of NEWS-2 scoring and estimation of serum PSP allowed more accurate early identification of patients vulnerable to deterioration with high sensitivity and accuracy rates. [ABSTRACT FROM AUTHOR]

The exact mechanism by which aspirin prevents preeclampsia remains unclear. Its effects on serum placental biomarkers throughout pregnancy are also unknown. To investigate the effects of aspirin on serum pregnancy-associated plasma protein A and placental growth factor trajectories using repeated measures from women at increased risk of preterm preeclampsia. This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention trial using repeated measures of pregnancy-associated plasma protein A and placental growth factor. In the trial, 1620 women at increased risk of preterm preeclampsia were identified using the Fetal Medicine Foundation algorithm at 11 to 13+6 weeks of gestation, of whom 798 were randomly assigned to receive aspirin 150 mg and 822 to receive placebo daily from before 14 weeks to 36 weeks of gestation. Serum biomarkers were measured at baseline and follow-up visits at 19 to 24, 32 to 34, and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effect of aspirin on biomarker trajectories over time. Overall, there were 5507 pregnancy-associated plasma protein A and 5523 placental growth factor measurements. Raw pregnancy-associated plasma protein A values increased over time, and raw placental growth factor increased until 32 weeks of gestation followed by a decline. The multiple of the median mean values of the same biomarkers were consistently below 1.0 multiple of the median, reflecting the high-risk profile of the study population. Trajectories of mean pregnancy-associated plasma protein A and placental growth factor multiple of the median values did not differ significantly between the aspirin and placebo groups (aspirin treatment by gestational age interaction P values:.259 and.335, respectively). In women at increased risk of preterm preeclampsia, aspirin 150 mg daily had no significant effects on pregnancy-associated plasma protein A or placental growth factor trajectories when compared to placebo. [ABSTRACT FROM AUTHOR]

Objective: To assess biomarkers between symptomatic and asymptomatic patients, and to construct a classification and regression tree (CART) algorithm for their discrimination. Patients and Methods: 136 patients were enrolled. They were symptomatic (high risk) (N = 82, stenosis degree ≥ 50%, proven to be responsible for ischemic stroke the last six months) and asymptomatic (low risk) (N = 54, stenosis degree ≤ 50%). Levels of fibrinogen, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase- 1 (TIMP-1), soluble intercellular adhesion molecule (SiCAM), soluble vascular cell adhesion molecule (SvCAM), adiponectin and insulin were measured on a Luminex 3D platform and their differences were evaluated; subsequently, a CART model was created and evaluated. Results: All measured biomarkers, except adiponectin, had significantly higher levels in symptomatic patients. The constructed CART prognostic model had 97.6% discrimination accuracy on symptomatic patients and 79.6% on asymptomatic, while the overall accuracy was 90.4%. Moreover, the population was split into training and test sets for CART validation. Conclusion: Significant differences were found in the biomarkers between symptomatic and asymptomatic patients. The CART model proved to be a simple decision-making algorithm linked with risk probabilities and provided evidence to identify and, therefore, treat patients being at high risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction: Altered placental expression of high temperature requirement factor A1 (HtrA1) is implicated in abnormal trophoblastic invasion and endothelial dysfunction in pre-eclampsia (PE). Serum levels of HtrA1 have been proposed as a novel biomarker to improve the prediction of PE. This study assesses serum HtrA1 levels in prospectively collected samples of women who developed PE compared to normotensive pregnancies.Methods: This was a case-control study of serum HtrA1 levels in second and third trimester samples in women who later developed preterm or term PE compared to controls. Overall, 300 serum samples were drawn from a prospective observational study of adverse pregnancy outcomes in three different gestational age windows (19-24, 30-34 and 35-37 weeks) at the Fetal Medicine Research Institute, King's College Hospital, London. Serum HtrA1 levels were determined by enzyme-linked immunosorbent assay (ELISA) by a blinded laboratory professional. Median HtrA1 MoM values, adjusted for gestational age and maternal characteristics, were compared between cases and controls at each gestational age group.Results: Women who later developed PE, compared to controls, had significantly higher maternal weight and more frequently had chronic hypertension or a history of PE in a previous pregnancy. In normotensive pregnancies, serum HtrA1 increased with increasing gestational age, whereas, in PE pregnancies HtrA1 levels remained stable, but were not significantly different from control pregnancies at any gestational age.Discussion: Serum HtrA1 levels are not significantly different in women who develop PE compared to controls. [ABSTRACT FROM AUTHOR]

Background: Inflammation has been implicated in the initiation and perpetuation of non‐valvular atrial fibrillation (AF). However, there is a lack of similar data on AF in rheumatic heart disease (RHD). The objective of this study was to analyze the association of inflammation as measured by serum inflammatory biomarkers with AF in rheumatic mitral stenosis (Rh‐MS). Methods: A comparative cross‐sectional analytical study was conducted on 181 Rh‐MS patients in normal sinus rhythm (NSR; n = 69), subclinical transient AF (SCAF; detected by 24‐hours Holter monitoring; n = 30) and chronic AF (n = 82). Serum hs‐CRP, IL‐6, and sCD‐40L were assessed using ELISA immunoassay and compared in all groups of Rh‐MS with or without AF. Results: We found significantly higher serum hs‐CRP and sCD‐40L levels in the overall AF (Chronic AF + SCAF) group (hs‐CRP: 4.5 ± 3.4 vs 2.3 ± 2.9 mg/L, P <.01; sCD‐40L: 6.4 ± 4.8 vs 3.1 ± 3.4 ng/mL, P <.01) and chronic AF subgroup (hs‐CRP: 4.9 ± 3.4 vs 2.3 ± 2.9 mg/L, P <.01; sCD‐40L: 6.9 ± 5.1 vs 3.1 ± 3.4 ng/mL, P <.01) compared to patients with sinus rhythm. There was a statistically significant graded increase of serum IL‐6 level from the NSR to the SCAF (vs NSR: 6.8 ± 3.9 vs 4.0 ± 2.2 pg/mL, P =.03), and chronic AF subgroups (vs NSR: 9.3 ± 6.5 vs 4.0 ± 2.2 pg/mL, P <.01; vs SCAF: 9.3 ± 6.5 vs 6.8 ± 3.9, P =.05) of atrial fibrillation. Conclusions: Elevated levels of serum hs‐CRP, IL‐6, and sCD‐40L were strongly associated with overall AF and also with SCAF and chronic AF in Rh‐MS patients indicating a potential role of inflammation in the pathophysiology of rheumatic AF. [ABSTRACT FROM AUTHOR]

Metastasis development represents an important threat for melanoma patients, even when diagnosed at early stages and upon removal of the primary tumor. In this scenario, determination of prognostic biomarkers would be of great interest. Serum contains information about the general status of the organism and therefore represents a valuable source for biomarkers. Thus, we aimed to define serological biomarkers that could be used along with clinical and histopathological features of the disease to predict metastatic events on the early‐stage population of patients. We previously demonstrated that in stage II melanoma patients, serum levels of dermcidin (DCD) were associated with metastatic progression. Based on the relevance of the immune response on the cancer progression and the recent association of DCD with local and systemic immune response against cancer cells, serum DCD was analyzed in a new cohort of patients along with interleukin 4 (IL‐4), IL‐6, IL‐10, IL‐17A, interferon γ (IFN‐γ), transforming growth factor‐β (TGF‐ β), and granulocyte–macrophage colony‐stimulating factor (GM‐CSF). We initially recruited 448 melanoma patients, 323 of whom were diagnosed as stages I‐II according to AJCC. Levels of selected cytokines were determined by ELISA and Luminex, and obtained data were analyzed employing machine learning and Kaplan–Meier techniques to define an algorithm capable of accurately classifying early‐stage melanoma patients with a high and low risk of developing metastasis. The results show that in early‐stage melanoma patients, serum levels of the cytokines IL‐4, GM‐CSF, and DCD together with the Breslow thickness are those that best predict melanoma metastasis. Moreover, resulting algorithm represents a new tool to discriminate subjects with good prognosis from those with high risk for a future metastasis. [ABSTRACT FROM AUTHOR]

• Osteoarthritis (OA) is one of the leading causes of pain and disability worldwide, and a large percentage of patients with osteoarthritis are individuals with obesity. • Animals fed an obesity-inducing diet from adulthood had more knee joint damage when compared to both the control diet animals and animals fed a bad diet from a young age. • These findings indicate that dietary exposure time in young animals may induce less damage than exposure to bad diets during adulthood, indicating the importance of the onset of dietary challenge in studies that aim to assess the short-term influence of obesity-inducing diets on knee joint health. Osteoarthritis is one of the leading causes of pain and disability worldwide, and a large percentage of patients with osteoarthritis are individuals who are also obese. In recent years, a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage (both with and without the superimposition of trauma), which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators. Of note, there is a disparity between whether the dietary challenges commence at weaning, representing a weanling onset, or at skeletal maturity, representing an adult onset of obesity. We wished to evaluate the effect of the dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose (HFS) diet to determine whether these factors may result in disparate outcomes, as there is evidence suggesting that these factors result in differential metabolic disturbances. Based on dietary exposure time, we hypothesized that rats fed an HFS diet for 14 weeks from weaning (HFS Weanling) would demonstrate an increase in knee joint damage scores, whereas rats exposed to the HFS diet for 4 weeks, starting at 12 weeks of age (HFS Adult) and rats exposed to a standard chow diet (Chow) would not display an increase in knee joint damage scores. Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning (HFS Weanling) or an HFS diet for 4 weeks, starting at 12 weeks of age (HFS Adult). At sacrifice, joints were scored using the modified Mankin Criteria, and serum was analyzed for a defined subset of inflammatory markers (Interleukin-6, leptin, monocyte chemoattractant protein-1, and tumor necrosis factor α). When the HFS Weanling and HFS Adult groups were compared, both groups had a similar percent of body fat, although the HFS Weanling group had a significantly greater body mass than the HFS Adult group. The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group. Although knee joint damage scores were low in all 3 groups, we found, contrary to our hypothesis, that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups. Furthermore, we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group. These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group. Interestingly, when assessing various serum proinflammatory markers, no significant differences were detected between the HFS Adult and HFS Weanling groups. Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated, these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced. Moreover, increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet. Image, graphical abstract [ABSTRACT FROM AUTHOR]

• Many patients with ischemic stroke suffer from cognitive impairment which affects the quality of life. • No biomarkers have been widely recommended for identifying post-stoke cognitive impairment (PSCI) early. • The correlation between insulin resistance and PSCI remains unclear. • The triglyceride-glucose (TyG) index may be an easily available biomarker for identifying PSCI early. • This is the first study evaluating the predictive value of TyG for PSCI. Post-stroke cognitive impairment (PSCI) is a very common complication of ischemic stroke (IS). Triglyceride-glucose (TyG) index was an effective alternative marker of insulin resistance (IR). This prospective study was designed to explore the correlation between TyG index and PSCI. Between January 1 2021 to June 30 2022, consecutive patients with first onset IS were enrolled prospectively. Baseline information was collected at admission and fasting blood was drawn the next morning. Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function at three months after stroke. Multiple regression analysis was used to explore the correlation between PSCI and TyG. Receiver operating characteristic (ROC) was performed to evaluate the predictive ability. Ultimately, 313 patients were enrolled in this study. The TyG index was higher in patients with PSCI than those without PSCI (8.99 (8.55, 9.54) vs. 8.61(8.25, 8.87), P <0.001). The spearman correlation analysis indicated that TyG index was negatively correlated with MoCA score (r=-0.272, P< 0.001). The multivariate logistic regression analysis demonstrated that TyG index was correlated with PSCI independently (P< 0.001) regardless of whether the patients had diabetes or not. The area under curve (AUC) of the ROC was 0.684 (95%CI=0.635-0.768, P <0.001). The optimal cutoff value of TyG index for predicting PSCI was 8.81, with a sensitivity of 61.7% and a specificity of 73.6%. A higher TyG index level at admission was independently correlated with increased risk of PSCI three months later and could be used as a predictor. [ABSTRACT FROM AUTHOR]

Abstract Objective To identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB). Methods A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability. Results Microarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen-specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability. Conclusion Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB. [ABSTRACT FROM AUTHOR]

Introduction: Chronic histiocytic intervillositis (CHI) of the placenta although rare, has a high recurrence rate, is associated with serious adverse pregnancy outcomes and has no available treatment. This study aims to determine clinical, biochemical and radiological factors associated with CHI, to guide management of subsequent pregnancies.Methods: This retrospective observational study included consecutive cases with a histopathologic diagnosis of CHI after 18 weeks of gestation, between 2001 and 2014, and no controls. Clinical (maternal, fetal and delivery outcomes), biochemical (first- and second-trimester biomarkers for fetal aneuploidy and serum alkaline phosphatase) and radiological (second- and third-trimester fetal, placental and Doppler ultrasound) factors associated with a histopathological diagnosis of CHI were identified and results presented as percentages. Outcomes of subsequent pregnancies were described.Results: Of 231 identified cases of 'intervillositis', 33 were confirmed to have CHI, of which only 4/33 (12.1%) had prior uncomplicated term deliveries. During pregnancy, 10/18 (55.5%) had abnormal first-trimester screening, 4/16 (25%) had abnormal second-trimester screening, 6/19 (31.6%) had at least one elevated alkaline phosphatase level, and 15/20 (75%) had at least one abnormal feature on mid-trimester placental ultrasound. In subsequent pregnancies that were closely followed with a combination of biochemical and radiologic tests, there were no cases of fetal loss, and lower incidence of fetal growth restriction and preterm birth.Discussion: No clinical, biochemical or radiological finding is consistently associated with CHI and adverse outcomes thereof. Whether the incorporation of these tests in individualized care-plans could improve outcomes in subsequent pregnancies needs to be studied further. [ABSTRACT FROM AUTHOR]

Cirrhosis is the end result of chronic liver damage, associated with altered serum biomarkers and lipid profile. However, only few studies regarding serum biomarkers and plasma lipid profile in non-alcoholic liver cirrhosis subjects have been undertaken in Pakistan. This study aimed to evaluate the degree of alterations of tumor markers and lipid profile in liver cirrhosis patients and in normal healthy individuals. Levels of serological markers and plasma lipid pattern was measured in liver cirrhosis patients and in sex and age matched normal healthy individuals (n=46). Tumor marker alpha-fetoprotein (AFP) was measured by ELISA, whereas plasma lipid profile and biomarker alanine aminotransferase (ALT) was determined by colorimetric assays. In patients with cirrhosis significant increase was observed in serum AFP and ALT levels when compared with healthy individuals (p<0.05).The triglyceride levels were found to be significantly higher, while LDL-C was significantly lower (p<0.05) in liver cirrhosis patients. There was no significant difference in the plasma concentration of cholesterol, total lipids and HDL-C in liver cirrhosis patients as compared with normal individuals. AFP and ALT are useful markers in the diagnosis of cirrhosis and can be used for the detection of hepatocellular carcinoma (HCC) in cirrhosis patients. The assessment of plasma lipids and lipoprotein pattern is also important for prognostic evaluation of patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Background: The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats. Methods: Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A-F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days. Results: The exposure of rats to DOX led to a significant (p < 0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system. Conclusions: The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage. [ABSTRACT FROM AUTHOR]

The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining. HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up. Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P <.05). In HBeAg− participants, there were not significant declines in HBV RNA (P =.49) and HBcrAg (P =.63), despite modest reductions in hepatitis B surface antigen (P <.01) and HBV DNA (P =.03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P >.05). In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg− patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action. [ABSTRACT FROM AUTHOR]

Background and aim Vibration Controlled Transient Elastography (VCTE) is a non-invasive test for liver fibrosis and cirrhosis but may be inaccurate in some patients, especially in those with chronic hepatitis B. This study aims at improving the accuracy of VCTE in cirrhosis detection by combining ultrasound and routine blood parameters. Methods Hepatitis B patients with liver biopsies samples ≥20 mm underwent VCTE, ultrasound and blood tests, and were divided into training set ( n = 170) and validation set ( n = 75). Results An algorithm consisting of VCTE, international normalization ratio (INR), ultrasonic hepatic vessel and platelet count (CIR-4) and a VCTE-based cirrhosis six-index score (CIR-6) comprised VCTE, INR, platelet, albumin, ultrasonic hepatic vessel and liver parenchyma were derived. In training set, area under receiver operating characteristics curve of CIR-6 and CIR-4 to detect cirrhosis was 0.946 and 0.945, respectively, which was superior to that of VCTE 0.907. CIR-4 could save more liver biopsies. In validation set, CIR-6 detected cirrhosis with accuracy similar to that in training set. However, the sensitivity of CIR-4 and VCTE in validation set lowered to 0.538 and 0.846, respectively. Conclusions Combining routine markers improve the accuracy of VCTE for cirrhosis detection in hepatitis B patients. CIR-6 may be more valuable. [ABSTRACT FROM AUTHOR]

Summary Objectives Patients infected with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) are at greater risk of cirrhosis and hepatocellular carcinoma. The objective of this study was to identify virus-specific serum microRNA profiles associated with liver function and disease progression. Microarray analysis of serum microRNAs was performed using the Toray 3D array system in 22 healthy subjects, 42 HBV patients, and 30 HCV patients. Selected microRNAs were then validated by qRT-PCR in 186 HBV patients, 107 HCV patients, and 22 healthy subjects. Results Microarray analysis showed up-regulation of a number of microRNAs in serum of both HBV and HCV patients. In qRT-PCR analysis, miR-122, miR-99a, miR-125b, miR-720, miR-22, and miR-1275 were up-regulated both in HBV patients relative to healthy subjects, and all except miR-1275 were up-regulated in HBeAg-positive patients relative to HBeAg-negative patients. Specific microRNAs were independently associated with different aspects of HBV infection. MiR-122 was independently associated with HBV DNA level, whereas miR-125b was independently associated with levels of HBV DNA, HBsAg, and HBeAg. MiR-22 and miR-1275 were independently associated with serum γ-glutamyl transpeptidase levels. Conclusions Serum microRNA levels reflect differences in the etiology and stage of viral hepatitis. [ABSTRACT FROM AUTHOR]

Introduction. Patients with pulmonary and pulmonary plus extrapulmonary sarcoidosis differ in symptom severity and health status impairment. To date there is no information on differences in clinical and laboratory parameters between these phenotypes and limited information on extrapulmonary involvement in Czech sarcoidosis patients exists. Methods. We therefore compared clinical data (age, gender, organ involvement, lung function tests) and laboratory data (blood counts, bronchoalveolar fluid (BAL) cellular profile, serum levels of CRP, SACE, sIL-2R, neopterin) between patients with newly diagnosed pulmonary sarcoidosis (n=107) and those with pulmonary plus extrapulmonary sarcoidosis (n=54). Results. Extrapulmonary sarcoidosis was diagnosed in 33% of patients, mostly affecting lymph nodes and skin and having hypercalciuria. There was no difference in the prevalence of extrapulmonary sarcoidosis between genders. Patients with extrapulmonary sarcoidosis were older and mostly non-smokers when compared to those with limited pulmonary form. X-ray Stage I and erythema nodosum were less frequent in extrapulmonary disease. Serum levels of CRP, SACE, sIL-2R and neopterin and BAL cellular profile did not differ between both phenotypes. We observed lower platelets, FEV1, VC, and BAL CD19+ in females with extrapulmonary involvement than in those with pulmonary disease. Conclusion. Affected lymph nodes, skin and hypercalciuria were the most common in sarcoidosis patients with extrapulmonary involvement. Pulmonary sarcoidosis did not differ in clinical and routine laboratory parameters from pulmonary plus extrapulmonary sarcoidosis. Observation of low platelets, VC, FEV1 and BAL CD19+ in females with extrapulmonary sarcoidosis needs further verification in larger cohort. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The present study evaluated the cardioprotective property of the hydroethanol extract of Urtica parviflora leaf material (EEUP) against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was produced by doxorubicin administration (15 mg·kg−1 i.p. for 21 days). The rats received EEUP at 200 and 400 mg·kg−1 b.w. (i.p.) daily for 21 days. After 24 h, serum cardiac biomarkers, i.e. creatine phosphokinase (CPK) and lactate dehydrogenase (LDH); serum lipid profiles, like high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG); serum biochemical parameters, viz. aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP); myocardial antioxidant parameters, viz. malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were measured. Results: EEUP treatment significantly (P < 0.01) and dose dependently protected the myocardium by decreasing the elevated level of MDA; elevating the diminished levels of GSH, SOD, CAT and HDL, with a concomitant decrease in the elevated levels of HDL, LDL, and TG. EEUP also significantly (P < 0.01) reduced the increased activities of AST, ALT, ALP, CPK and LDH. The results revealed that EEUP demonstrated dose dependent cardioprotective efficacy by restoration of the serum biomarkers profile and antioxidant property. Conclusion: From the present study, U. parviflora leaf extract showed promising cardioprotective effect against doxorubicin-induced cardiotoxicity in Wistar rats. [Copyright &y& Elsevier]

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in adults and children. Predicting outcome after TBI is difficult, but it is important for acute management, counseling of family members, and provision of rehabilitation services. Serum biomarkers may be useful alone or in combination with clinical variables to predict outcome after TBI. This article reviews the potential uses of serum biomarkers for the clinician, current literature related to the use of serum biomarkers for outcome prediction after adult and pediatric TBI, limitations of the literature, and future direction for this field. [ABSTRACT FROM AUTHOR]

The article discusses findings of a study to determine the protective activity of the plant powder Tephrosia purpurea (TP) on arsenic induced toxicity in Wistar albino rats. It notes that the rats were given a daily oral dosage of the TP powder for 28 days and measured for total arsenic concentration in the tissues of the liver, kidney, heart, brain, and lungs. The research confirmed that oral administration of the herbal TP powder resulted in mild protection against arsenic toxicity.

Squalene epoxidase (SQLE) is the rate-limiting enzyme for cholesterol biosynthesis. We elucidated the functional significance, molecular mechanisms, and clinical impact of SQLE in nonalcoholic steatohepatitis (NASH). We performed studies with hepatocyte-specific Sqle overexpression transgenic (Sqle tg) mice and mice given high-fat high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diet to induce NASH. SQLE downstream target carbonic anhydrase III (CA3) was identified using co-immunoprecipitation and Western Blot. Some mice were given SQLE inhibitor (terbinafine) and CA3 inhibitor (acetazolamide) to study the therapeutic effects in NASH. Human samples (N = 217) including 65 steatoses, 80 NASH, and 72 healthy controls were analyzed for SQLE levels in liver tissue and in serum. SQLE is highly up-regulated in human NASH and mouse models of NASH. Sqle tg mice triggered spontaneous insulin resistance, hepatic steatosis, liver injury, and accelerated HFHC or MCD diet–induced NASH development. Mechanistically, SQLE tg mice caused hepatic cholesterol accumulation, thereby triggering proinflammatory nuclear factor-κB signaling and steatohepatitis. SQLE directly bound to CA3, which induced sterol regulatory element-binding protein 1C activation, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase1 expression and de novo hepatic lipogenesis. Combined targeting SQLE (terbinafine) and CA3 (acetazolamide) synergistically ameliorated NASH in mice with superior efficacy to either drug alone. Serum SQLE with CA3 could distinguish patients with NASH from steatosis and healthy controls (area under the receiver operating characteristic curve, 0.815; 95% confidence interval, 0.758–0.871). SQLE drives the initiation and progression of NASH through inducing cholesterol biosynthesis, and SQLE/CA3 axis-mediated lipogenesis. Combined targeting of SQLE and CA3 confers therapeutic benefit in NASH. Serum SQLE and CA3 are novel biomarkers for the noninvasive diagnosis of patients with NASH. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Recurrent hepatitis C after liver transplantation is a rapidly evolving condition in which fibrosis deposition is accelerated, with 30% of patients developing graft cirrhosis within the first 5 years after transplantation. Antiviral therapy after transplantation achieves sustained virological response (SVR) in approximately 30% of patients, and a milder fibrosis stage at treatment seems to increase the probabilities of response to treatment. Importantly, SVR to antiviral therapy in this setting has been shown to modify the natural history of the disease, given the excellent prognosis of patients who are able to clear the virus. In this regard, an early recognition of these patients can help to start antiviral therapy in less advanced stages of the recurrence, with higher probabilities of achieving SVR. Non-invasive methods, and especially Fibroscan™, have been shown to significantly correlate with fibrosis stage and, more importantly, to permit early identification of those patients at higher risk of presenting worse outcomes. In addition, they can also confidently distinguish those patients who will present a good outcome and in which a significant number of protocol liver biopsies may be avoided. [Copyright &y& Elsevier]

Abstract: Introduction: Serological biomarkers could reflect asymptomatic infrarenal aortic aneurysm (AAA) activity and guide patient management. Report: Serum concentrations of C-reactive protein (CRP), alpha 1-antitrypsin and lipoprotein(a) were measured in blood samples from 35 AAA patients and 35 controls and correlated with the aortic diameter and AAA growth in the previous 12 months. We found a positive correlation between CRP and AAA diameter (r =0.46; p =0.007) and alpha 1-antitrypsin and AAA growth (r =0.55; p =0.004). Conclusions: Alpha 1-antitrypsin may be a promising biomarker of AAA growth. [Copyright &y& Elsevier]

Tilapias are cultured globally and are rising in acceptance as the most important freshwater aquaculture species. Monitoring of serum biomarkers is a promising tool in aquaculture to screen the health status as they are virtuous indicators of extreme stress and organ dysfunction in fish. The present study examined the serum biomarkers of oxytetracycline (OTC)-dosed Nile tilapia Oreochromis niloticus at 0, 80 and 800 mg/kg biomass/day, i.e., 0X, 1X, and 10X the approved dose (X = 80 mg OTC/kg biomass/day) for 10 consecutive days. The fish biomass and levels of serum glucose, aspartate aminotransferase, alanine aminotransferase, creatinine and C-reactive protein (CRP) were determined at scheduled intervals. A significant dose-dependent reduction in fish biomass during the OTC-dosing (5.84%) and post-OTC dosing (8.16%) periods was observed. All the serum biomarkers of Nile tilapia increased significantly on day 10 OTC-dosing. Though their levels reduced significantly, normalcy was not achieved even after 42 days of cessation of OTC-dosing, except CRP. The CRP reached the normal level on day 25 post-OTC dosing in the 1X group. The results, thus, demonstrated that the oral OTC-dosing influences the physiological state of apparently healthy Nile tilapia in a dose-dependent manner. These changes were, however, reversible upon discontinuation of OTC-dosing. The set of data observed on growth reduction and elevated serum biomarker levels even after 42 days of cessation of OTC-dosing, thus, raises questions on the utility of oral OTC-dosing. • Effects of oral oxytetracycline (OTC)-dosing on the growth and serum biomarkers of Nile tilapia Oreochromis niloticus at the therapeutic dose and dosage was assessed. • Oral OTC-dosing influenced the physiological state of apparently healthy Nile tilapia in a dose-dependent manner. • Reduced growth and elevated serum biomarker levels were noted even on day 42 post-OTC-dosing. • The effects of OTC are reversible and inferred as an adaptive defence response of fish. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is estimated to afflict approximately 1 billion individuals worldwide. In a subset of NAFLD patients, who have the progressive form of NAFLD termed nonalcoholic steatohepatitis (NASH), it can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without peri-sinusoidal fibrosis. Thus, key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. Until now, liver biopsy has been the gold standard for identifying these 2 critical end points, but has well-known limitations, including invasiveness; rare but potentially life-threatening complications; poor acceptability; sampling variability; and cost. Furthermore, due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. Although much of the work remains to be done in establishing cost-effective strategies for screening for NASH, advanced fibrosis, and cirrhosis, in this review, we summarize the current state of the noninvasive assessment of liver disease in NAFLD, and we provide an expert synthesis of how these noninvasive tools could be utilized in clinical practice. Finally, we also list the key areas of research priorities in this area to move forward clinical practice. [ABSTRACT FROM AUTHOR]

The article discusses an attempt to validate a novel multiplex assay that uses a panel of six serum biomarkers and CA125 for early detection of ovarian cancer. Patients who participated were newly diagnosed with ovarian cancer. According to the article, results indicate that the assay has potential utility for early detection of ovarian cancer.

Background & Aims We aimed to identify new serum biomarkers of esophageal adenocarcinoma (EAC). Methods We performed metabolomic analyses of serum samples from 2 sets of case-control pairs in the discovery phase, each consisting of 30 patients with histologically confirmed EAC (cases) from the University of Texas MD Anderson Cancer Center and 30 matched subjects without EAC (controls). We identified metabolites whose levels differed significantly between cases and controls and validated those with the greatest difference in an analysis of 321 EAC cases and 331 controls. We generated a metabolite risk score (MRS) for the metabolites. Results The levels of 64 metabolites differed significantly between EAC cases and controls in the discovery phase. The metabolites with the greatest difference were amino acid L-proline (LP), ketone body 3-hydroxybutyrate (BHBA), and carbohydrate D-mannose (DM); these differences were confirmed in the validation set. Cases had lower mean levels of LP than controls (22.78 ± 6.79 μg/mL vs 28.24 ± 8.64 μg/mL; P < .001) and higher levels of BHBA (18.06 ± 17.84 μg/mL vs 7.73 ± 9.92 μg/mL; P < .001) and DM (9.87 ± 4.28 μg/mL vs 6.28 ± 3.61 μg/mL; P < .001). Levels of DM were significantly higher in patients with late-stage EAC than early-stage EAC (10.61 ± 4.79 μg/mL vs 8.97 ± 3.36 μg/mL; P = .005). Higher levels of LP were associated with significant decrease in risk of EAC (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.18−0.38). A significant increase in risk of EAC was associated with higher levels of BHBA (OR, 4.05; 95% CI, 2.84−5.78) and DM (OR, 7.04; 95% CI, 4.79−10.34). Levels of all 3 metabolites associated with EAC risk in a dose response manner; the level of risk conferred by the metabolites increased jointly with smoking status and body mass index. Individuals with high MRS had significant (7.76-fold) increase in risk of EAC vs those with low MRS. Smokers with high MRS had the greatest risk of EAC (OR, 23.40; 95% CI, 10.95−50.00), compared with never smokers with low MRS. Conclusions On the basis of a case vs control metabolic profile analysis, levels of LP, BHBA, and DM are associated with risk of EAC. These markers might be used as risk and prognostic factors for patients with EAC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the cardioprotective effect of aqueous, ethanol and aqueous ethanol extract of Aerva lanata (A. lanata) against doxorubicin induced cardiomyopathy in Wistar rats. Methods: In this study, cardioprotective effect of aqueous, ethanol and aqueous ethanol extract of A. lanata against doxorubicin induced cardiomyopathy rats at the dosage of 200 mg/kg body weight for 28 days and also compared with standard allopathic drug aspirin. At the end of 28 days, enzymatic antioxidants, non-enzymatic antioxidants, lipid peroxidation, membrane bound enzymes were estimated in tissue homogenate. Cardiac biomarkers such as LDH, AST, ALT and lipid profiles such as cholesterol, triglycerides, HDL, LDL and VLDL were estimated in serum. Histopathology of heart samples was also performed. Results: It was shown that all the three extracts of A. lanata has cardioprotective activity (P<0.05) similar to that of aspirin. There are no significant changes between groups VI, VII and VIII with group I. These results implied that A. lanata does not contain toxic substances. Conclusions: By all these findings A. lanata has showed significant cardioprotective activity, which provides scientific proof of these traditional values. [Copyright &y& Elsevier]