Pancreatic cancer survival prediction via inflammatory serum markers

Background For prognostic evaluation of pancreatic ductal adenocarcinoma (PDAC), the only well-established serum marker is carbohydrate antigen CA19-9. To improve the accuracy of survival prediction, we tested the efficacy of inflammatory serum markers. Methods A preoperative serum panel comprising 48 cytokines plus high-sensitivity CRP (hs-CRP) was analyzed in 173 stage I–III PDAC patients. Analysis of the effect of serum markers on survival utilized the Cox regression model, with the most promising cytokines chosen with the aid of the lasso method. We formed a reference model comprising age, gender, tumor stage, adjuvant chemotherapy status, and CA19-9 level. Our prognostic study model incorporated these data plus hs-CRP and the cytokines. We constructed time-dependent ROC curves and calculated an integrated time-averaged area under the curve (iAUC) for both models from 1 to 10 years after surgery. Results Hs-CRP and the cytokines CTACK, MIF, IL-1β, IL-3, GRO-α, M-CSF, and SCF, were our choices for the prognostic study model, in which the iAUC was 0.837 (95% CI 0.796–0.902), compared to the reference model’s 0.759 (95% CI 0.691–0.836, NS). These models divided the patients into two groups based on the maximum value of Youden’s index at 7.5 years. In our study model, 60th percentile survival times were 4.5 (95% CI 3.7–NA) years (predicted high-survival group, n = 34) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 128), log rank p < 0.001. By the reference model, the 60th percentile survival times were 2.8 (95% CI 2.1–4.4) years (predicted high-survival group, n = 44) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 118), log rank p < 0.001. Conclusion Hs-CRP and the seven cytokines added to the reference model including CA19-9 are potential prognostic factors for improved survival prediction for PDAC patients.

Preliminary Clinical Validation of a Filtration-Based CTC Assay for Tumor Burden and HER2 Status Monitoring in Metastatic Breast Cancer

<b><i>Background:</i></b> Bearing multidimensional tumor-relevant information ranging from genomic alterations to proteomic makeup, circulating tumor cells (CTCs) constitute a promising material for liquid biopsy. The clinical validity of CTCs has been most extensively studied in metastatic breast cancer (MBC). The Cellsearch assay is currently the most widely used, while alternative strategies are pursued. A filtration-based microfluidic device has been described for CTC enrichment, but its clinical relevance remains unknown. <b><i>Methods:</i></b> In this preliminary study, we prospectively enrolled 47 MBC patients and evaluated the performance of the abovementioned CTC assay for tumor burden monitoring and human epidermal growth factor receptor 2 (HER2) status determination. <b><i>Results:</i></b> At baseline, 51.1% patients (24/47) were CTC positive. CTC count and positivity were also significantly higher in samples that accompanied poorer radiographic response evaluations. Serial blood draws suggested that CTC count enabled more accurate monitoring of tumor burden than serum markers carcinoembryonic antigen and cancer antigen 15-3. Also, in contrast to previous reports, CTC-HER2 status was moderately consistent with tumor-HER2 status. CTC-HER2 status assessment was further supported by <i>HER2</i> copy number measurements in select samples. <b><i>Conclusion:</i></b> The preliminary results from this study suggest promise for the interrogated CDC assay in several aspects, including sensitive CTC detection, accurate disease status reflection, and HER2 status determination. More studies are warranted to validate these findings and further characterize the value of CTC assay.

Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes

Background Systemic inflammatory processes plausibly contribute to the development of cardiovascular complications, causing increased morbidity and mortality in type 2 diabetes. Circulating inflammatory markers, i.e., interleukin (IL)-6 and tumour necrosis factor-α, are associated with neurocardiac measures. We examined a broad panel of various inflammatory and inflammation-related serum markers to obtain more detailed insight into the possible neuro-immune interaction between cardiovascular regulation and systemic level of inflammation. Methods Serum samples from 100 participants with type 2 diabetes were analysed. Heart rate variability, cardiovascular autonomic reflex tests, and cardiac vagal tone tests were performed based on electrocardiographic readings. Data regarding covariates (demographic-, diabetes-, and cardiovascular risk factors) were registered. Results Increased serum levels of IL-12/IL-23p40 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.007) were associated with diminished heart rate variability measures. After all adjustments, the associations between IL-12/23p40, SDANN and VLF persisted (p = 0.001). Additionally, serum levels of vascular endothelial growth factor (VEGF)-C were associated with response to standing (p = 0.005). Discussion The few but robust associations between neurocardiac regulation and serum markers found in this study suggest systemic changes in proinflammatory, endothelial, and lymphatic function, which collectively impacts the systemic cardiovascular function. Our results warrant further exploration of IL-12/IL-23p40, ICAM-1, and VEGF-C as possible cardiovascular biomarkers in T2D that may support future decisions regarding treatment strategies for improved patient care.

Regulatory T cells control Effector T cell Inflammation in Human Prediabetes

A disparate array of plasma/serum markers provide evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and meta-flammation. These remain largely non-actionable, and contrast with our rich understanding of inflammation in human type 2 diabetes. New data show that<b> </b>inflammatory profiles produced by CD4⁺ T cells define human prediabetes as a unique inflammatory state. Regulatory T cells (Tregs) control mitochondrial function and cytokine production by CD4⁺ effector T cells (Teff) in prediabetes and type 2 diabetes by supporting Th17 or Th1 cytokine production, respectively. These data suggest that Treg control of Teff metabolism controls inflammation differentially in prediabetes compared to type 2 diabetes. Queries of genes that impact mitochondrial function and/or pathways leading to transcription of lipid metabolism genes identified the fatty acid importer CD36 as highly expressed in Tregs but not Teff from prediabetes subjects. Pharmacological blockade of CD36 in Tregs from prediabetes subjects decreased Teff production of the Th17 cytokines that differentiate overall prediabetes inflammation. We conclude Tregs control CD4⁺ T cell cytokine profiles through mechanisms determined, at least in part, by host metabolic status. Furthermore, Treg CD36 uniquely promotes Th17 cytokine production by Teff in prediabetes.

Wellens Syndrome: A Review Article

Wellens syndrome is a pre-infarct stage of coronary syndrome and a clinical condition associated with left descending proximal anterior artery stenosis. Diagnostic criteria for Wellens syndrome include clinical history, ECG changes, and laboratory results. The pathognomonic ECG of Wellens syndrome is anterior inverted T-wave in precordial leads, which can be seen during pain-free period, accompanied by isoelectric or minimally elevated ST segment (<1 mm), no precordial Q waves, and normal or slightly elevated cardiac serum markers. Early diagnosis leads to early management and a better prognosis. Early management of Wellens syndrome involves maintaining an airway, breathing, circulation, monitoring vital signs, and medical management. Still, the only definitive management is urgent cardiac angiography to prevent further myocardial ischemia. The combination of early diagnostic and appropriate management will reduce complications and mortality rates. Keywords: Wellens Syndrome, Acute Coronary Syndromes, pre-Infarct MI.

VEGF and IL-6 correlation in POEMS: a potential upcoming marker of active disease and early autologous BMT response.

Introduction: VEGF function may be responsible for most POEMS manifestations, and it is considered a reliable marker of disease. COVID-19 era arose increasing interest for other inflammatory cytokines, with particular focus on Interleukin-6; VEGF production is stimulated by IL-6 and IL1β, whose concentrations appear to be elevated in clonal plasma cells. Objectives: This study aims to simultaneously evaluate VEGF and IL-6 values in patients (pts) with POEMS at different stages of the disease to find a correlation between them. Methods: We performed a monocentric study, measuring serum levels of VEGF and IL-6 in 8 POEMS pts at different time points of the disease. Results: We observed elevated serum levels of both VEGF and IL-6 in three pts before transplant, while the day after the infusion of autologous stem cells, we observed a steep decrease of both serum markers. Among the four-pts tested only after transplant, two presented with a consensual level of VEGF and IL-6, while the others did not correlate. One patient observed at POEMS diagnosis, during active disease, presented with strikingly high levels of both serum markers. Conclusions: So far, to the best of our knowledge, IL-6 could be considered as a marker of active disease and reliable up to the very first months after BMT, after which its accuracy appears to be lost due to unknown factors, still to be investigated.

Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

Purpose: Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness.Methods: We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency.Results: A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required.Conclusions: The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

Serum and Salivary Levels of Glucose and Urea in Pregnant and Non-pregnant Women: A Comparative Study

Background: Pregnancy is one of the most critical periods in the life of most women. Since it is necessary to be aware of the health of the mother and fetus, serum markers (i.e., glucose and urea) need to be monitored during pregnancy. A routine strategy in this area is venipuncture which is applied to measure the level of these markers. It is also a stressful procedure for pregnant women. The purpose of this study was to determine the salivary level of these markers as a stress-free method in pregnant women. Materials and Methods: The samples were collected from 30 pregnant and 30 non-pregnant fasting women. Then, the serum and salivary levels of glucose and urea were measured, analyzed, and compared by photometry. Results: Results indicated that the mean salivary glucose level was 10.2±1.4 mg/dL and 6.4±0.9 mg/ dL in non-pregnant and pregnant women, respectively. In addition, the mean serum glucose level was 106.5±5.3 mg/dL and 82.9±4.5 mg/dL in non-pregnant and pregnant women, respectively. Further, the mean salivary urea level was 37.1±3.3 mg/dL in non-pregnant women and 27.1±1.9 mg/dL in pregnant women. Moreover, the mean serum urea level was 26.9±1.9 mg/dL and 19.5±2.3 mg/dL in non-pregnant and pregnant women, respectively. Conclusion: Serum and salivary levels of glucose and urea in pregnant women were lower than those in non-pregnant women, and there was a positive correlation between serum and salivary levels. Therefore, it seems that saliva can be a substitute for serum regarding the measurement of glucose and urea levels.

Significance of Early Acidosis in Predicting Early Mortality Among Flame Burned Patients in a Kenyan National Hospital

Background: Burn pathophysiology, fluid therapy and mortality have been assessed by various laboratory parameters including lactate and base deficit serum markers. This study targeted flame injured cohort with an objective to determine the significance of early acidosis, through measurement of three acid base indices at admission in predicting 5-day (early) mortality among the flame burned patients.Methodology: A cohort study. Eighty flame injured patients presenting within 24 hours of incident were assessed for arterial blood pH, lactate and base deficit (BD). Mortality was recorded until day 28. Receiver operating characteristics curves were drawn; area under curve, cut offs, sensitivities and specificities for BD, lactate and pH were determined for 5-day mortality. The cut offs were used to derive contingency tables for calculation of predictive values. Odds ratios were calculated at 95% confidence interval. 28 day survival curve was generated. Level of significance was <0.05.Results: 28-day mortality was 39%. Five-day mortality was 24%. The latter was predicted by a lactate level of 2.36 mmol/L, BD of -10.05 mmol/L and pH of 7.344 with 75%,74% and 95% sensitivities respectively. Odds of patients dying at these levels or worse were 6.3, 11.4 and 36.9 respectively all with significant p-values.Conclusion: Arterial pH, base deficit and lactate are good predictors of 5-day mortality among fire victims in the Kenyan context.