Biomarkers Of Necrosis Research Articles

Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia–reperfusion injury

Background and aimHepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors. Materials and methodsThis study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. ResultsSerum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential. ConclusionsElevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Gadolinium Enhanced T2 FLAIR is an Imaging Biomarker of Radiation Necrosis and Tumor Progression in Patients with Brain Metastases.

Differentiating radiation necrosis (RN) from tumor progression (TP) after radiotherapy for brain metastases is an important clinical problem requiring advanced imaging techniques which may not be widely available and are challenging to perform at multiple time points. The ability to leverage conventional MRI for this problem, could have meaningful clinical impact. The purpose of this study was to explore contrast enhanced T2 FLAIR (T2FLAIRc) as a new imaging biomarker of RN and TP. This single-institution retrospective study included patients with treated brain metastases undergoing DSC-MRI between January 2021 and June 2023. Reference standard assessment was based on histopathology or serial follow-up including results of DSC-MRI for a minimum of 6 months from the first DSC-MRI. The index test was implemented as part of the institutional brain tumor MRI protocol and preceded the first DSC-MRI. T2FLAIRc and gadolinium enhanced T1 MPRAGE (T1c) signal were normalized against normal brain parenchyma and expressed as z-score. Mean signal intensity of enhancing disease for RN and TP groups were compared using unpaired t-test. Receiver operator characteristic (ROC) curves and area under the ROC curve (AUC) were derived by bootstrapping. DeLong test was used to compare AUC. 56 participants (mean age, 62 years +/-12.7 [SD]; 39 females); 28 RN, 28 TP were evaluated. The index MRI was performed on average 73 days +/-34 [SD] before the first DSC-MRI. Significantly higher z-scores were found for RN using T2FLAIRc (8.3 versus 5.8, p<0.001) and T1c (4.1 versus 3.5, p=0.02). AUC for T2FLAIRc (0.83, 95% CI, 0.72-0.92) was greater than T1c (0.70, 95% CI, 0.560.83) (p = 0.04). The AUC of DSC derived rCBV (0.82, 95% CI, 0.70-0.93) was not significantly different from T2FLAIRc (p = 0.9). A higher normalized T1c and T2FLAIRc signal intensity was found for RN. In a univariable test, mean T2FLAIRc signal intensity of enhancing voxels showed good discrimination performance for distinguishing RN from TP. The results of this work demonstrate the potential of T2FLAIRc as an imaging biomarker in the work-up of RN in patients with brain metastases. AUC = area under the receiver operating characteristic curve; RN = radiation necrosis; ROC = receiver operating characteristic; SRS = stereotactic radiosurgery; T1c = contrast enhanced T1; T2FLAIRc = contrast enhanced T2 FLAIR; TP = tumor progression.

Peak Serum Creatinine as a Biomarker of Pancreatic Necrosis in Acute Pancreatitis: A Cross-Sectional Study

Pancreatitis is the inflammation of the pancreas. Pancreatitis can result in pancreatic necrosis which may lead to significant morbidity and mortality. It is possible to predict pancreatic necrosis and organ dysfunction using many biochemical indicators and markers. Peak serum creatinine has been identified as one of such useful markers to predict pancreatic necrosis. Objective: To find the diagnostic accuracy of elevated peak serum creatinine as a predictor of pancreatic necrosis in patients with acute pancreatitis taking the contrast-enhanced computed tomogram scan (CECT) as the gold standard and to establish the degree of agreement between the two clinical tests. Methods: A cross-sectional, analytical study that was carried out at the Department of Surgery, Benazir Bhutto Hospital, Rawalpindi from January 2020 to January 2023. 150 patients diagnosed as having pancreatitis were enrolled in the study. Peak serum creatinine at 48 hours &gt; 1.8 mg/dl was labeled as a predictor of pancreatic necrosis. Contrast-enhanced computed tomogram scan was done within 96 hours of admission. The pancreatic necrosis suggested by raised serum creatinine was confirmed by CECT. The diagnostic accuracy of peak serum creatinine and the degree of agreement between the two modalities was calculated. The Kappa coefficient was used to calculate the strength of agreement. Results: The results show that Peak serum creatinine has a sensitivity of 45.5%, specificity of 97.35%, PPV of 85.0 %, NPV of 93.8 %, and accuracy of 84.6%. This study found that the degree of agreement between raised peak serum creatinine levels and CECT to predict pancreatic necrosis was 84.7% with a “Kappa coefficient” of 0.51. Consequently, the null hypothesis was rejected in light of these findings. Conclusions: It was concluded that elevated serum creatinine (SCr &gt;1.8 mg/dl) at 48 h of admission can be used as a predictor of pancreatic necrosis in patients with acute pancreatitis.

Pilot study: Significance of I-FABP2 in the diagnosis of acute abdominal episodes in children

BackgroundPediatric abdominal conditions, including necrotizing gastrointestinal diseases, pose significant diagnostic challenges due to clinic symptoms and limited diagnostic tools. Intestinal fatty acid binding protein 2 (I-FABP2) has emerged as a potential biomarker for intestinal damage, but its efficacy in diagnosing pediatric intestinal necrosis remains under explored. MethodsA prospective study was conducted on 55 pediatric patients presenting with abdominal pain and suspected intestinal necrosis or intestinal perforation. Clinical, laboratory, and radiological data were collected, and intraoperative assessment of bowel necrosis was performed. Gene expression of I-FABP2 in peripheral blood was measured using Real-Time RT-PCR, and correlations with surgery and laboratory parameters were analyzed. ResultsIntraoperative assessment revealed a moderate sensitivity (61.1%) and specificity (73.7%) of I-FABP2 in identifying bowel necrosis. Positive predictive value (PPV) was high (81.5%), indicating a high likelihood of the condition when I-FABP2 is positive. However, the negative predictive value (NPV) was limited (50%), suggesting challenges in confidently excluding necrosis based on negative I-FABP2 results. Correlations were observed between I-FABP2 expression and elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC), indicating its association with inflammatory processes. ConclusionsWhile I-FABP2 shows promise as a biomarker for pediatric intestinal necrosis, its diagnostic utility may be enhanced when considered alongside other clinical parameters. Further research and validation studies are warranted to refine its clinical application and improve diagnostic accuracy in pediatric gastrointestinal conditions.

Evaluation of Urinary Interleukin-18 Changes in Patients Treated with Vancomycin

Background: Vancomycin, used to treat severe gram-positive infections, can induce acute kidney injury. Some evidence introduced Interleukin-18 (IL-18) as an inflammatory mediator of ischemic damage to many organs and urinary IL-18 as a diagnostic biomarker of acute tubular necrosis. Objective: The current study aimed to evaluate the urinary level of IL-18 after vancomycin therapy. Methods: This cross-sectional study was conducted on patients under treatment with vancomycin selected from those referred to Dr. Sheikh Hospital, Mashhad, Iran, from 2018-2019. Urinary IL-18 was measured based on nanograms per milliliter using a human IL-18 enzyme-linked immunosorbent assay kit about this cytokine before vancomycin administration and then two days later. All the analyses were performed in SPSS software (version 25), and a P-value less than 0.05 was considered statistically significant. Results: A total of 36 patients with a mean age of 40.06±36.67 months were included in the study. The mean scores of IL-18 before and after taking vancomycin were 1453.00±555.01 and 1713.00±660.98, respectively. The IL-18 was significantly lower before vancomycin consumption than the level reported after 48 h (P&lt;0.05). Conclusions: The present study highlighted a higher level of urinary IL-18 after vancomycin treatment, which may indicate kidney injuries. Therefore, it may be considered a potential biomarker of acute tubular necrosis in patients under vancomycin therapy.

Contemporary Prediction of Myocardial Infarction by Proximity of Cardiac Protein Analysis

Cardiovascular infection influences about all racial and ethnic bunches around the world. The World Health Organization gauges that cardiovascular illness is dependable for 323 million passings around the world. A heart assault happens when the heart muscle does not get sufficient blood stream. Decreased blood stream is as a rule caused by a blockage in one or more of the heart's courses, in spite of the fact that there are incalculable elective conceivable outcomes. Disappointment to reestablish blood stream after a heart assault can result in irreversible heart harm or indeed death. Using symptomatic strategies based on immunological tests, myocardial localized necrosis can be anticipated. When looking for biomarkers for myocardial localized necrosis (MI), immunoassay strategies experience impedances issues that can lead to wrong comes about and distortion by doctors. This approach employments antibodies particular for MI biomarkers. Contrasts in counter acting agent specificity may influence the precision of myocardial localized necrosis discovery and thus the reliability of the strategy. Troponin could be a complex chemical found in certain sorts of muscles. It is display in muscle cells and circulates in little sums within the circulation system. The standard convention for troponin testing employments a assortment of analytical methods, including the immunoassay strategy. The immunoassay cannot distinguish little sums of cardiac troponin within the blood within the to begin with hours after an intense myocardial infarction. To overcome this impediment, the troponin substance within the blood is decided utilizing fluorescence spectroscopy. The blood test is assessed utilizing fluorescence spectroscopy and after that compared with the ECG flag. Troponin is as it were show when the LV is changing and cherry fluorescence is obvious; something else lost. Reperfusion treatment, moreover called topical or thrombolytic treatment, may be a fast intercession that, in the event that analyzed early and accurately, can reestablish blood stream to the harmed heart muscle and minimize harm.

Neutrophil CD64 index as a new early predictive biomarker for infected pancreatic necrosis in acute pancreatitis

ObjectiveInfectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitisMethodsThis study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed.ResultsWe observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p < 0.001). In the training cohort, a higher occurrence rate of IPN was observed in the high nCD64 index group compared to the moderate and low nCD64 index group (p < 0.001). Further analysis showed that nCD64 index was significant positive correlated with the incidence rate of IPN (p < 0.001, correlation coefficient = 0.972). Furthermore, logistic regression analysis showed that high expression of the nCD64 index on admission was a risk factor for the occurrence of IPN (OR = 2.971, p = 0.038). We further found that the nCD64 index of IPN patients was significantly higher than the Non-IPN patients on the days 1, 3, and 5 after admission, and the nCD64 index of IPN patients before and after the onset (p < 0.05). At the same time, this study revealed that the nCD64 index on admission showed good predictive efficacy for IPN (AUC = 0.859, sensitivity = 80.8%, specificity = 87.5%), which was comparable to APACHE II score. And this finding was further validated in an independent cohort of 100 participants (AUC = 0.919, Sensitivity = 100.0%, Specificity = 76.6%).ConclusionThis study demonstrated the clinical value of nCD64 index in patients with IPN patients for the first time through two independent cohort studies. The nCD64 index can be used as an early prediction and risk assessment tool for the occurrence of IPN, contributing to the improvement of patient outcomes and efficiency of medical resource allocation.

Exploring D-Lactate as a Biomarker for Acute Intestinal Necrosis in 2958 Patients: A Prospective Cross-Sectional Study

BackgroundTimely diagnosis of acute intestinal necrosis (AIN) is lifesaving, but challenging due to unclear clinical presentation. D-lactate has been proposed as an AIN biomarker. ObjectivesWe aimed to test the diagnostic performance in a clinical setting. MethodsWe performed a cross-sectional prospective study, including all adult patients with acute referral to a single tertiary gastrointestinal surgical department during 2015–2016 and supplemented by enrollment of high-risk in-hospital patients suspected of having AIN during 2016–2019. AIN was verified intraoperatively, and D-lactate was analyzed using an automatic spectrophotometric set-up. A D-lactate cut-off for AIN was estimated using the receiver operating characteristic curve. The performance according to patient subgroups was estimated using the area under the receiver operating characteristic curve (AUC). Given the exploratory nature of this study, a formal power calculation was not feasible. ResultsForty-four AIN patients and 2914 controls were enrolled. The D-lactate cut-off was found to be 0.0925 mM. Due to lipemic interference, D-lactate could not be quantified in half of the patients, leaving 23 AIN patients and 1456 controls for analysis. The AUC for the diagnosis of AIN by D-lactate was 0.588 (95% confidence interval 0.475–0.712), with a sensitivity of 0.261 and specificity of 0.892. Analysis of high-risk patients showed similar results (AUC 0.579; 95% confidence interval 0.422–0.736). ConclusionD-lactate showed low sensitivity for AIN in both average-risk and high-risk patients. Moreover, lipemic interference precluded valid spectrophotometric assessment of D-lactate in half of the patients, further disqualifying the clinical utility of D-lactate as a diagnostic marker for AIN.

TAKOTSUBO SYNDROME

Takotsubo syndrome, also known as Takotsubo cardiomyopathy, stress-induced cardiomyopathy, transient apical ballooning and broken heart syndrome, is a disease characterized by transient regional left ventricular systolic dysfunction. It is usually determined by emotional or physical stress. Even though it was thought to be a self-limiting condition, Takotsubo syndrome is now known to be associated with important short and long-term morbidity and mortality. Takotsubo syndrome affects 2-3% of all patients and 5-6% of female patients presenting with acute coronary syndrome (frequently women in the sixth decade). The Takotsubo syndrome cases are mostly preceded by acute emotional or physical triggers such as: family death, financial loss, anxiety, excessive work, domestic abuse, anxiety, fear for medical procedures, severe pain, sepsis, post surgeries, and cancer. Diagnosis of Takotsubo syndrome can sometimes be difficult due to clinical manifestations similar to acute myocardial infarction. Myocardial necrosis biomarkers (Troponin I, Troponin T and Creatinin kinase) are elevated, with values comparable to those in patients with acute myocardial infarction. Transthoracic echocardiography usually shows akinetic or dyskinetic apical and mid-ventricular segments of the left ventricle compared to the hyperkinetic basal segments (“apical ballooning” aspect) and left ventricle systolic dysfunction. The positive diagnosis of Takotsubo syndrome is made on coronary angiography, normal or non-obstructive coronary artery disease

Myocardial oxidative stress is increased in early reperfusion, but systemic antioxidative therapy does not prevent ischemia-reperfusion arrhythmias in pigs.

Arrhythmias in the early phase of reperfusion after myocardial infarction (MI) are common, and can lead to hemodynamic instability or even cardiac arrest. Reactive oxygen species (ROS) are thought to play a key role in the underlying mechanisms, but evidence from large animal models is scarce, and effects of systemic antioxidative treatment remain contentious. MI was induced in 7 male and 7 female pigs (Norwegian landrace, 35-40 kg) by clamping of the left anterior descending artery (LAD) during open thorax surgery. Ischemia was maintained for 90 min, before observation for 1 h after reperfusion. Pigs were randomized 1:1 in an operator-blinded fashion to receive either i.v. N-acetylcysteine (NAC) from 70 min of ischemia and onwards, or 0.9% NaCl as a control. Blood samples and tissue biopsies were collected at baseline, 60 min of ischemia, and 5 and 60 min of reperfusion. ECG and invasive blood pressure were monitored throughout. The protocol was completed in 11 pigs. Oxidative stress, as indicated by immunoblotting for Malondialdehyde in myocardial biopsies, was increased at 5 min of reperfusion compared to baseline, but not at 60 min of reperfusion, and not reduced with NAC. We found no significant differences in circulating biomarkers of myocardial necrosis, nor in the incidence of idioventricular rhythm (IVR), non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT) or ventricular fibrillation (VF) between NAC-treated and control pigs during reperfusion. Myocardial oxidation was increased early after reperfusion in a porcine model of MI, but systemic antioxidative treatment did not protect against reperfusion arrhythmias.

Predictivity of aspartate aminotransferase to alanine aminotransferase (De Ritis) ratio for detecting bowel necrosis in incarcerated inguinal hernia patients.

Early diagnosis of necrotic bowel segment resulting from incarcerated inguinal hernia (IIH) is crucial for reducing morbidity and mortality. The aim of this study was to investigate the efficacy of the De Ritis ratio (DRR), also known as the ratio of aspartate aminotransferase to alanine aminotransferase, as a biomarker for intestinal necrosis. This retrospective study included 132 patients who underwent emergency surgery for IIH. Patients were divided into two groups: those who underwent bowel resection for necrosis (Group 1) and those who did not (Group 2). Patients' demographic and clinical data were recorded. Using laboratory test results, DRR, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and lymphocyte-to-CRP ratio (LCR) were calculated. The morbidity and mortality rates and the length of stay for Group 1 were statistically significantly different (p < 0.0001). The DRR, NLR, PLR, LMR, and LCR values of the same group were also significantly different (p < 0.05). DRR can be used as a biomarker for early diagnosis of bowel necrosis in patients with IIH.

Difficulties in electrocardiographic diagnosis of hyperkalemia and acute coronary syndrome: clinical case

BACKGROUND: Clinical practice testifies to the difficulties in diagnosing hyperkalemia according to electrocardiographic (ECG) criteria during the primary contact between the doctor and the patient. This leads to the establishment of alternative diagnoses, particularly acute coronary syndrome, a delay in the implementation of measures aimed at lowering the blood potassium levels and a possible adverse outcome.&#x0D; CLINICAL CASE DESCRIPTION: The article presents the clinical observation of a patient with severe hyperkalemia in the background of acute renal injury caused by mesenteric thrombosis, with ECG changes in the form of high-amplitude T wave in leads V2V6 and induced non-sustained ventricular tachycardia. Considering the patients history of coronary heart disease, ECG data (high-amplitude T wave in leads V2V6) were regarded as acute coronary syndrome with ST segment elevation. According to emergency indications, the patient underwent coronary angiography and endoprosthetics of the left circumflex artery (stenosis 99%). Upon further examination, levels of biomarkers of myocardial necrosis were slightly increased, which confirmed the established preliminary diagnosis and hyperkalemia. However, 6 h after hospitalization, the patient died. A subsequent autopsy revealed a contradiction between the clinical path and anatomical diagnosis.&#x0D; CONCLUSION: This case reveals the complexity of the differential diagnosis of changes in the T wave and ST segment. Failure to promptly determine the underlying cause of these ECG changes in the presented case led to an inaccurate management strategy that negatively affects the prognosis.

Ventricular tachycardia and myocardial infarction during antiarrhythmic therapy: a case report

The article analyzes the case of the development of ventricular tachycardia and type 2 myocardial infarction (MI) in an 80-year-old patient with a history of coronary artery disease, MI and chronic heart failure. In 2020, the patient was diagnosed with ventricular extrasystole and started antiarrhythmic therapy with diethylamino propionylethoxycarbonylaminophenothiazine 150 mg per day and sotalol 160 mg per day. In 2022, the patient had an episode of clinical death due to ventricular tachycardia with successful resuscitation. A diagnosis of non-ST-elevation acute coronary syndrome was made, coronary angiography was performed, which did not reveal significant coronary stenosis. Upon further examination, the dynamics of biomarkers of myocardial necrosis confirmed the diagnosis of acute MI. In the analyzed case, the development of ventricular tachycardia and MI is most likely associated with the intake of diethylaminopropionylethoxycarbonylaminophenothiazine in combination with sotalol, prescribed in the presence of contraindications to their use.

Abnormal release of cardiac biomarkers in the presence of myocardial oedema evaluated by cardiac magnetic resonance after uncomplicated revascularization procedures.

To analyse the association of myocardial oedema (ME), observed as high T2 signal intensity (HT2) in cardiac magnetic resonance imaging, with the release of cardiac biomarkers, ventricular ejection, and clinical outcomes after revascularization. Patients with stable coronary artery disease with the indication for revascularization were included. Biomarker levels [troponin I (cTnI) and creatine kinase MB (CK-MB)] and T2-weighted and late gadolinium enhancement (LGE) images were obtained before and after the percutaneous or surgical revascularization procedures. The association of HT2 with the levels of biomarkers, with and without LGE, evolution of left ventricular ejection fraction (LVEF), and 5-year clinical outcomes were assessed. A total of 196 patients were divided into 2 groups: Group 1 (HT2, 40) and Group 2 (no HT2, 156). Both peak cTnI (8.9 and 1.6 ng/mL) and peak CK-MB values (44.7 and 12.1 ng/mL) were significantly higher in Group 1. Based on the presence of new LGE, patients were stratified into Groups A (no HT2/LGE, 149), B (HT2, 9), C (LGE, 7), and D (both HT2/LGE, 31). The peak cTnI and CK-MB values were 1.5 and 12.0, 5.4 and 44.7, 5.0 and 18.3, and 9.8 and 42.8 ng/mL in Groups A, B, C, and D, respectively, and were significantly different. The average LVEF decreased by 4.4% in Group 1 and increased by 2.2% in Group 2 (P = 0.057). ME after revascularization procedures was associated with increased release of cardiac necrosis biomarkers, and a trend towards a difference in LVEF, indicating a role of ME in cardiac injury after interventions.

Kynurenine pathway alteration in acute pancreatitis and its role as a biomarker of infected necrosis

IntroductionInfected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN. MethodsPatients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1β, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data. ResultsWe recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5–97.4) in discriminating IPN. ConclusionHLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN.

Exploring I-FABP, endothelin-1 and L-lactate as biomarkers of acute intestinal necrosis: a case-control study

Objective Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase patient survival. We aimed to assess intestinal fatty acid binding protein (I-FABP) and endothelin-1 as diagnostic biomarkers for AIN. To our knowledge, this is the first study exploring endothelin-1 in AIN patients from a general surgical population. Design We conducted a single-centre nested case–control study comparing acutely admitted AIN patients to age- and sex-matched non-AIN patients during 2015–2016. I-FABP and endothelin-1 were analysed using an enzyme-linked immunosorbent assay. L-lactate levels were also measured in all patients. Cut-offs were estimated using receiver operator characteristic curves, and the diagnostic performance was estimated using the area under the receiver operator characteristic curve (AUC). Results We identified 43 AIN patients and included 225 matched control patients. Median levels of I-FABP, endothelin-1 and L-lactate were 3550 (IQR: 1746–9235) pg/ml, 3.91 (IQR: 3.33–5.19) pg/ml and 0.92 (IQR: 0.74–1.45) mM in AIN patients and 1731 (IQR: 1124–2848) pg/ml, 2.94 (IQR: 2.32–3.82) pg/ml and 0.85 (IQR: 0.64-1.21) mM in control patients, respectively. The diagnostic performances of endothelin-1 and of I-FABP + endothelin-1 combined were moderate. Endothelin-1 alone revealed an AUC of 0.74 (0.67; 0.82). The sensitivity and specificity of endothelin-1 were 0.81 and 0.64, respectively. Conclusion I-FABP and endothelin-1 are promising biomarkers for AIN, with moderate diagnostic performance compared with the commonly used biomarker L-lactate. Preregistration ClinicalTrials.gov: NCT05665946.

Sodium Selenite Modulates Global Activation of Proinflammatory M1-like Macrophages, Necroinflammation and M1-like/M2-like Dichotomy at the Onset of Human Type 1 Diabetes.

The study aims to show that sodium selenite (Ss) would have an immunomodulatory effect on the functional activity of proinflammatory macrophages (Mφs) during their extended extracellular activation at the onset of human type 1 diabetes (T1D). Exacerbated activation of proinflammatory "M1" macrophages (Mφs) can promote chronic local pancreatic islet inflammation and T1D development. We investigated the ex vivo effects of Ss on the immune modulation of global/extended activation of human proinflammatory M1-like Mφs. Experiments were carried out on primary monocytes-derived Mφs (MDMs). The levels of IL-1β, TNF-α, H2O2 and intracellular free calcium ions (ifCa2+), and the ratios of IL-1β-to-IL-10 and TNF-α-to-IL-10 were markedly increased in T1D Mφs than in healthy control Mφs. Conversely, both IL-10 production and arginase 1 (ARG1) activity were downregulated in T1D Mφs. Additionally, Ss treatment induced a marked downregulation of respiratory burst, ifCa2+ levels, M1-like Mφ-associated inducible nitric oxide (NO) synthase (iNOS) activity, cell necrosis and related necroinflammation biomarkers, including IL-1β and TNF-α, CD14 expression, and the ratios of iNOS-to-ARG1, IL-1β-to-IL-10, and TNF-α-to-IL-10. Moreover, Ss upregulated anti-inflammatory "M2-like" Mφ activity as demonstrated by ARG1 activity and IL-10 production, as well as phagocytosis capacity. Ss exerts a potent immunomodulatory role on functional activities of human proinflammatory T1D M1-like Mφs subjected to extended activation, as well as on the M1-like/M2-like dichotomy. Additionally, the current study provides a novel therapeutic approach using Ss to promote the anti-inflammatory function of Mφs at the onset of T1D.

Dural Tail Sign and Middle Meningeal Artery Hypertrophy in Glioblastoma: A Rarity?

Dural tail sign and increased caliber of branches of the external carotid artery (ECA) are common findings in meningioma and they have been rarely reported in intra-axial lesions. Anyway, some cases of glioblastoma (GBM) are reported in the literature, mostly superficially localized, characterized by these 2 findings and therefore, misdiagnosed with meningioma. The aim of this study is to verify the prevalence of dural tail sign and hypertrophy of middle meningeal artery (MMA) in a large cohort of GBMs. 180 GBM patients were retrospectively evaluated. Deep or superficial localization of GBM was established and the presence of dural tail sign and hypertrophy of the ipsilateral MMA were assessed. The rate of tumor necrosis and the incidence of dural metastases during the radiological follow-up were also evaluated. Inter-rater reliability was calculated using Cohen's K-test. Dural tail sign and enlarged MMA were evident in 30% and 19% of 96 superficial GBM, respectively. Deep GBM did not present those signs. Only one patient developed dural metastasis at follow-up and no differences in terms of tumor necrosis and hypoxic biomarkers expression were evident among GBMs with and without dural and vessel signs. Dural tail sign and hypertrophy of the MMA in superficial GBM are more common than expected. They probably represent reactive rather than a neoplastic infiltration. Knowing these radiological signs may be important in terms of neurosurgery planning and avoiding excessive bleeding. Anyway, this hypothesis should be confirmed by a prospective neurosurgery studio.

Clinical findings using echocardiography and plasma cardiac troponin I and pathological findings in dogs with hypertrophic cardiomyopathy: A retrospective study.

Hypertrophic cardiomyopathy (HCM) is considered rare in dogs, and there is a lack of clinical data. Cardiac troponin I (cTnI) is a biomarker of cardiomyocyte damage and necrosis and can be used to diagnose cat and human HCM. We investigated whether the presence of cTnI in clinical data can be used in conjunction with echocardiography to diagnose canine HCM. This study comprised client-owned dogs with clinical evidence of concentric hypertrophy on echocardiographic images, serum total thyroxine levels of ≤5 µg/dl, systolic blood pressure of ≤180 mmHg, and absence of aortic stenosis. All cases were necropsied. Cardiomyocyte hypertrophy (mean diameter, 18.3 ± 1.8 µm), myocardial fiber disarray (70%), interstitial fibrosis (80%), and small vessel disease (100%) were assessed. In dogs with HCM, the left ventricles were concentric, almost symmetrical, and hypertrophied above the aortic diameter. The end-diastolic interventricular septum normalized to body weight [intraventricular septal thickness in diastole (IVSDN)] was 0.788 [interquartile range (IQR), 0.7-0.92], which exceeded the normal range (5%-95%, IQR: 0.33-0.52). In total, 70% of the dogs with HCM had syncope and dyspnea, and all dogs had high cTnI levels (median, 3.94 ng/ml), exceeding the upper limit of normal (0.11 ng/ml) and indicating cardiomyocyte damage. IVSDN and serum cTnI levels were correlated (ρ = 0.839, p = 0.01). Ventricular wall thickening and high serum cTnI levels can provide a presumptive diagnosis of HCM and prompt the initiation of treatment or additional diagnostic investigations.

Interpreting Myocardial Enzymatic Biomarkers in the Setting of Acute Myocardial Infraction AMI

The rates of morbidity and mortality for acute myocardial infarction (AMI) have been rising quickly in the last few years. In the systemic circulatory loop, the heart normally pumps blood to the body's extremities. Cardiovascular disease, however, results from any heart function problem. The most fatal diseases in the world are known to be those involving the cardiovascular system. Over the past decade, biochemical marker testing are an important step in the diagnosis, and management of heart failure and in lowering one's risk of developing cardiovascular disease. Early diagnosis is paramount to choosing a clear and effective treatment strategy. Cardiac biomarkers are another effective method for classifying myocardial injury. The myocardial enzymatic biomarkers, also known as myocardial necrosis biomarkers, were among the various biomarkers that were initially studied. This review aims to allow for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.