Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer.

The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4-6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.

Ovarian Cancer-Insights into Platinum Resistance and Overcoming It.

Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells' resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients' poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.

Cardiac Troponin Biosensor Designs: Current Developments and Remaining Challenges.

Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.

Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.

Implementation of paediatric vision screening in urban and rural areas in Cluj County, Romania.

BACKGROUND: In 2018 and 2019, paediatric vision screening was implemented in Cluj County, Romania, where universal paediatric vision screening does not yet exist. We report on the preparation and the first year of implementation. METHODS: Objectives, target population and screening protocol were defined. In cities, children were screened by kindergarten nurses. In rural areas, kindergartens have no nurses and children were screened by family doctors' nurses, initially at the doctors' offices, later also in rural kindergartens. CME-accredited training courses and treatment pathways were organised. Implementation was assessed through on-site observations, interviews, questionnaires and analysis of screening results of referred children. RESULTS: Out of 12,795 eligible four- and five-year-old children, 7,876 were screened in 2018. In the cities, kindergarten nurses screened most children without difficulties. In Cluj-Napoca 1.62x the average annual birth rate was screened and in the small cities 1.64x. In the rural areas, however, nurses of family doctors screened only 0.49x the birth rate. In 51 out of 75 rural communes, no screening took place in the first year. Of 118 rural family doctors' nurses, 51 had followed the course and 26 screened children. They screened only 41 children per nurse, on average, as compared to 80 in the small cities and 100 in Cluj-Napoca. Screening at rural kindergartens met with limited success. These are attended by few children because of low population density, parents working abroad or children being kept at home in case of bad weather and road conditions. CONCLUSIONS: Three times fewer children were screened in rural areas as compared to urban areas. Kindergartens in rural areas are too small to employ nurses and family doctors' nurses do not have easy access to many children and have competing healthcare priorities: there are 1.5x as many family doctors in urban areas as compared to rural areas. For nationwide scaling-up of vision screening, nurses should be enabled to screen a sufficient number of children in rural areas.

Continuous Intravenous Administration of Granulocyte-Colony-Stimulating Factors-A Breakthrough in the Treatment of Cancer Patients with Febrile Neutropenia.

(1) Background: Febrile neutropenia (FN) remains one of the most challenging problems in medical oncology and is a very severe side effect of chemotherapy. Its late consequences, when it is recurrent or of a severe grade, are dose reduction and therapy delays. Current guidelines allow the administration of granulocyte-colony-stimulating factors (G-CSF) for profound FN (except for the case when a pegylated form of G-CSF is administrated with prophylactic intention) in addition to antibiotics and supportive care. (2) Methods: This is a prospective study that included 96 patients with confirmed malignancy, treated with chemotherapy, who developed FN during their oncological therapy, and were hospitalized. They received standard treatment plus a dose of G-CSF of 16 µg/Kg/day IV continuous infusion. (3) Results: The gender distribution was almost symmetrical: Male patients made up 48.96% and 51.04% were female patients, with no significance on recovery from FN (p = 1.00). The patients who received prophylactic G-CSF made up 20.21%, but this was not a predictive or prognostic factor for the recovery time from aplasia (p = 0.34). The median chemotherapy line where patients with FN were included was two and the number of previous chemotherapy cycles before FN was three. The median serological number of neutrophils (PMN) was 450/mm3 and leucocytes (WBC) 1875/mm3 at the time of FN. Ten patients possess PMN less than 100/mm3. The median time to recovery was 25.5 h for 96 included patients, with one failure in which the patient possessed grade 5 FN. Predictive factors for shorter recovery time were lower levels of C reactive protein (p < 0.001) and procalcitonin (p = 0.002) upon hospital admission and higher WBC (p = 0.006) and PMN (p < 0.001) at the time of the provoking cycle of chemotherapy for FN. The best chance for a shorter duration of FN was a short history of chemotherapy regarding the number of cycles) (p < 0.0001). (4) Conclusions: Continuous IV administration of G-CSF could be an alternative salvage treatment for patients with profound febrile neutropenia, with a very fast recovery time for neutrophiles.

Novel Mutation in GALT Gene in Galactosemia Patient with Group B Streptococcus Meningitis and Acute Liver Failure.

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) involved in galactose metabolism. Bacterial infections are a known cause of early morbidity and mortality in children with classic galactosemia. The most common agent is Escherichia coli, but in rare situations, other bacteria are incriminated. We report a case of a three-week-old female patient with galactosemia, who presented with Group B Streptococcus (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia.

The role of biomarkers and echocardiography in the evaluation of cardiotoxicity risk in children treated for leukemia.

PURPOSE: To describe the high-risk profile group, susceptible to develop anthracycline-induced cardiomyopathy in children with acute leukemia. METHODS: The study involved 35 pediatric patients diagnosed with acute lymphoblastic (ALL) or acute myeloblastic leukemia (AML), from March 2014 to December 2016. Serologic markers used for the analysis of cardiac dysfunction were troponin T, NT-proBNP and PCRhs. Also, the patients have had echocardiographic evaluation at the beginning of treatment to determine LVEF, SF and A, E, E' Doppler waves. RESULTS: Positive linear correlation was shown between NT-proBNP and leukocyte values, NT-proBNP and blast cells value, and NT-proBNP and LDH. Significant linear negative correlations between LVEF with leukocyte values, blast cells values, LDH, SF and leukocyte values, LVEF and NT-proBNP values and LVEF and troponin T values were also identified. A weak negative correlation between E/E' ratio and blast cells values has been observed. All of these correlations were statistically significant (p<0.05). CONCLUSIONS: Leukocyte value, as well as the other serological markers assessed (NT-proBNP, Troponin T), are useful tools to evaluate the risk of anthracycline-induced cardiotoxicity. The variation of the biological markers at the beginning of the cytotoxic treatment confirms the presence of an early myocardial dysfunction, emphasizing the importance of systematic evaluation of this particular group of patients.

Platinum derivatives: a multidisciplinary approach.

Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds. However, adverse reactions and allergic reactions are a major impediment in therapy with platinum derivatives. This paper summarizes data about platinum derivatives through a multidisciplinary approach, starting from a chemical point of view and on to their mechanism of action, mechanism of cellular resistance, predictive factors for the outcome of chemotherapy such as micro RNAs (miRNAs), tumor suppressor protein p53, and the excision repair cross-complementing 1 protein (ERCC1).

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. METHODS: Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. RESULTS: In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. CONCLUSION: The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Ivemark syndrome-a rare entity with specific anatomical features.

Ivemark syndrome (IS) is a rare embryological disorder which results from failure of development of the left-right asymmetry of organs. It is often associated with cardiac and other organ abnormalities, which are the usual causes of death in early neonatal life. We report a 3 months old girl with IS with dextrocardia, transposition of the great vessels, atrio-ventricular connection, total anomalous pulmonary venous drainage, a right atrial and right pulmonary isomerism, a midline liver, a midline gallbladder, asplenia, intestinal malrotation and vena cava anomalies. To our knowledge, complete right heterotaxia syndrome has been rarely described in literature. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development are considered as defects of the primary developmental field. Therefore, additional malformations in IS can be synchronic defects in the primary developmental field rather than causally independent malformations.

Hypersensitivity reactions to platinum derivatives: findings of new predictive markers.

PURPOSE: Platinum derivatives play a very important role in cancer therapy. Despite their outstanding results in the treatment of tumors with different locations, the occurrence of hypersensitivity reactions raises issues when it comes to therapy decision, because the changing of chemotherapy line could influence the tumor's evolution. Over the years the scientific community has paid particular attention to the mechanism by which this occurs and to identification of predictive factors. The purpose of this case-control, retrospective study was to find new predictive markers for the occurrence of allergic reactions to platinum derivatives. METHODS: We identified 59 cases of allergic reactions to platinum derivatives in the Oncology Institute "Prof. Dr. Ion Chiricuta" from Cluj-Napoca city in 2013. Blood tests data were analyzed before the administration of the cycle on which the allergic reaction occurred, along with the mandatory analyses for the patients and we focused on the values of neutrophils, lymphocytes, monocytes, eosinophils and basophils. RESULTS: When these values were compared with the values of the control group (,which was made at a ratio of 1:2 or 1:3, matched for age, tumor location and chemotherapy cycle) we found that each increase of lymphocytes or doses of platinum and each drop in monocytes number increased the risk for allergic reactions to occur. CONCLUSION: These findings are of a great value for the physicians and represent a starting point for more detailed studies.

The activity of 8-iso-prostaglandin F2alpha as an oxidative stress marker in vivo in paediatric patients with type 1 diabetes mellitus and associated autoimmunities.

BACKGROUND: Oxidative stress and inflammatory reactions are known to hold an important role in the etiopathogeny and persistence of acute or chronic clinical entities. Isoprostanes--a group of prostaglandin-like compounds, active products of arachidonic acid--have proved to be representative biomarkers of lipid peroxidation. The aim of this study was to determine the activity of serum 8-iso-prostaglandin F2alpha, (8iPGF2alpha), as an in vivo oxidative stress marker, in paediatric patients with diabetes mellitus type 1 (DM1) and in a control group. The main goals of this study were the following: establishing a possible correlation between the activity of 8iPGF2alpha and the presence of an autoimmune disease associated with DM1 and identifying a possible correlation between 8iPGF2alpha, the value of glycosylated hemoglobin (HbA1c) and the pancreatic autoimmune markers GAD65, IA2, IA in the group of patients with DM1 and other associated autoimmune diseases. METHODS: Fifty-one children and adolescents (31 males) aged 11.65 +/- 4.1 years with DM1 were enrolled in the study. Twenty-seven healthy children, age- and gender-matched, were enrolled as controls. Patients and controls underwent the 8iPGFzalpha assessment through an ELISA serum method. RESULTS: The mean 8iPGF2alpha value was 2090.6 +/- 3536.5 in the DM1 patient group and 509.9 +/- 493.5 in controls (p = 0.03). The mean 8iPGF2alpha value was 2178.19 +/- 4017.05 in patients with DM1 who did not suffer from other associated autoimmune diseases (n = 38) vs. 1834.95 +/- 1504.73 in patients with DM1 and other associated autoimmune diseases (n = 13) (p = 0.76). The correlation between the 8iPGF2alpha and the HbA1c values was determined by obtaining a correlation coefficient r = 0.38 and p = 0.0057. No correlation was observed between GAD65 and 8iPGF2alpha (r = 0.3; p = 0.29), IA2 and 8iPGF2alpha (r = -0.02; p = 0.92), IAA and 8iPGF2alpha (r = 0.4; p = 0.12). CONCLUSIONS: Oxidative stress reactions are more intense in patients with diabetes mellitus type 1 than in healthy patients. Similar results were obtained in patients associating other autoimmune diseases. 8iPGF2alpha can be an ideal marker for determining oxidative reactions in vivo.

Portable microfluidic plasmonic chip for fast real-time cardiac troponin I biomarker thermoplasmonic detection.

Acute myocardial infarction is one of the most serious cardiovascular pathologies, impacting patients' long-term outcomes and health systems worldwide. Significant effort is directed toward the development of biosensing technologies, which are able to efficiently and accurately detect an early rise of cardiac troponin levels, the gold standard in detecting myocardial injury. In this context, this work aims to develop a microfluidic plasmonic chip for the fast and accurate real-time detection of the cardiac troponin I biomarker (cTnI) via three complementary detection techniques using portable equipment. Furthermore, the study focuses on providing a better understanding of the thermoplasmonic biosensing mechanism taking advantage of the intrinsic photothermal properties of gold nanoparticles. Specifically, a plasmonic nanoplatform based on immobilized gold nanobipyramids was fabricated, exhibiting optical and thermoplasmonic properties that promote, based on a sandwich-like immunoassay, the "proof-of-concept" multimodal detection of cTnI via localized surface plasmon resonance, surface enhanced Raman spectroscopy and thermoplasmonic effects under simulated conditions. Furthermore, after the integration of the plasmonic nanoplatform in a microfluidic channel, the determination of cTnI in 16 real plasma samples was successfully realized via thermoplasmonic detection. The results are compared with a conventional high-sensitivity enzyme-linked immunosorbent clinical assay (ELISA), showing high sensitivity (75%) and specificity (100%) as well as fast response features (5 minutes). Thus, the proposed portable and miniaturized microfluidic plasmonic chip is successfully validated for clinical applications and transferred to clinical settings for the early diagnosis of cardiac diseases, leading towards the progress of personalized medicine.

Wolf-Parkinson-White Syndrome: Diagnosis, Risk Assessment, and Therapy-An Update.

Wolf-Parkinson-White (WPW) syndrome is a disorder characterized by the presence of at least one accessory pathway (AP) that can predispose people to atrial/ventricular tachyarrhythmias and even sudden cardiac death. It is the second most common cause of paroxysmal supraventricular tachycardia in most parts of the world, affecting about 0.1-0.3% of the general population. Most patients with WPW syndrome have normal anatomy, but it may be associated with concomitant congenital heart disease or systemic diseases. Although many individuals are asymptomatic, during supraventricular arrhythmia episodes, they may experience severe symptoms, including syncope or even sudden cardiac death (mainly due to pre-excited atrial fibrillation over rapidly conducting AP). In addition to arrhythmia-related symptoms, for some specific locations of the APs with overt anterograde conduction, there might be a reduction in exercise capacity mediated by a reduction in LV systolic performance due to anomalous LV depolarization. Although it is typically diagnosed through electrocardiography (ECG), additional tests are necessary for risk assessment. Management of WPW syndrome may be quite challenging and can vary from only acknowledging the presence of the accessory pathway to pharmacological treatment or radiofrequency ablation. Early diagnosis, risk assessment, and appropriate treatment are critical steps in the management of WPW syndrome, aiming to improve the quality of life and reduce the risk of life-threatening arrhythmias.

Investigating Potential Correlations between Calcium Metabolism Biomarkers and Periprocedural Clinical Events in Major Cardiovascular Surgeries: An Exploratory Study.

Background: There is emerging but conflicting evidence regarding the association between calcium biomarkers, more specifically ionized calcium and the prognosis of intensive care unit (ICU) postoperative cardiac patients. Methods: Our study investigated the relationship between ionized calcium, vitamin D, and periprocedural clinical events such as cardiac, neurologic and renal complications, major bleeding, vasoactive-inotropic score (VIS), and length of ICU and hospitalization. Results: Our study included 83 consecutive subjects undergoing elective major cardiac surgery requiring cardiopulmonary bypass. The mean age of the participants was 64.9 ± 8.5 years. The majority of procedures comprised isolated CABG (N = 26, 31.3%), aortic valve procedures (N = 26, 31.3%), and mitral valve procedures (N = 12, 14.5%). A difference in calcium levels across all time points (p < 0.001) was observed, with preoperative calcium being directly associated with intraoperative VIS (r = 0.26, p = 0.016). On day 1, calcium levels were inversely associated with the duration of mechanical ventilation (r = -0.30, p = 0.007) and the length of hospital stay (r = -0.22, p = 0.049). At discharge, calcium was inversely associated with length of hospital stay (r = -0.22, p = 0.044). All calcium levels tended to be lower in those who died during the 1-year follow-up (p = 0.054). Preoperative vitamin D levels were significantly higher in those who experienced AKI during hospitalization (median 17.5, IQR 14.5-17.7, versus median 15.3, IQR 15.6-20.5, p = 0.048) Conclusion: Fluctuations in calcium levels and vitamin D may be associated with the clinical course of patients undergoing cardiac surgery. In our study, hypocalcemic patients exhibited a greater severity of illness, as evidenced by elevated VIS scores, and experienced prolonged mechanical ventilation time and hospital stays. Additional larger-scale studies are required to gain a deeper understanding of their impact on cardiac performance and the process of weaning from cardiopulmonary bypass, as well as to distinguish between causal and associative relationships.

Innovative, Flexible, and Miniaturized Microfluidic Paper-Based Plasmonic Chip for Efficient Near-Infrared Metal Enhanced Fluorescence Biosensing and Imaging.

The implementation of metal enhanced fluorescence (MEF) as an efficient detection tool, especially in the near-infrared region of the electromagnetic spectrum, is a rather new direction for diagnostic analytical technologies. In this context, we propose a novel microfluidic plasmonic design based on paper for efficient MEF detection of the "proof-of-concept" biotin-streptavidin recognition interaction. Our design made use of the benefits of gold nanobipyramids (AuBPs), considering the strong enhanced electromagnetic field present at their sharp tips, and filter paper to operate as a natural microfluidic channel due to excellent wicking abilities. The calligraphed plasmonic paper, obtained using a commercial pen filled with AuBPs, was integrated in a robust sandwich optically transparent polydimethylsiloxane chip, exhibiting portability and flexibility while preserving the chip's properties. To place the Alexa 680 fluorophore at an optimal distance from the nanobipyramid substrate, the human IgG-anti-IgG-conjugated biotin sandwich reaction was employed. Thus, upon the capture of Alexa 680-conjugated streptavidin by the biotinylated system, a 1.3-fold average enhancement of the fluorophore's emission was determined by bulk fluorescence measurements. However, the local enhancement factor was considerably higher with values spanning from 5 to 6.3, as proven by mapping the fluorescence emission under both re-scan microscopy and fluorescence lifetime imaging, endorsing the proposed chip's feasibility for bulk MEF biosensing as well as high-resolution MEF bioimaging. Finally, the versatility of our chip was demonstrated by adapting the biosensing protocol for cardiac troponin I biomarker detection, validated using 10 plasma samples collected from pediatric patients and corroborated with a conventional ELISA assay.

Wolcott-Rallison Syndrome, a Rare Cause of Permanent Diabetes Mellitus in Infants-Case Report.

Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient's need for comfort and lack of distress with the clinicians' need for adequate information regarding the patient's glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.

Anthracycline's Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs-Pilot Study.

Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m2). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters' ratio also displayed a significant difference (p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity.

Therapeutic Plasma Exchange in Catastrophic Antiphospholipid Syndrome (CAPS): A Rare Case Report and Literature Review.

BACKGROUND/AIM: Catastrophic antiphospholipid syndrome (CAPS) may be the first manifestation ("de novo") of antiphospholipid syndrome (APS) or a complication in the clinical course of patients known to have this syndrome. Approximately 40% of patients had an associated autoimmune disease, mainly, systemic lupus erythematosus (SLE). The trigger can be one of the following: infections, surgical interventions, neoplasms, pregnancy, discontinuation of anticoagulant treatment, and others. CAPS is a medical emergency in which early identification and prompt initiation of aggressive therapy is extremely important. According to the Guidelines for the use of Therapeutic Apheresis in Clinical Practice developed by the American Society for Apheresis (ASFA), last updated in April 2023, in CAPS, the indication for therapeutic plasma exchange (TPE) is category I, grade 2C. CASE REPORT: We present a case of probable CAPS secondary to systemic lupus erythematosus (SLE) in an elderly patient in whom clinical and biological improvement was achieved through a multidisciplinary approach and prompt initiation of TPE. Because TPE is considered first-line therapy in CAPS, we initiated the procedure as soon as the attending rheumatologist raised this suspicion. Four plasmapheresis sessions were performed in the Intensive Care Unit. We used TPE by membrane filtration. Following the therapeutic intervention with TPE, corticotherapy (Solumedrol in puls-therapy), cyclophosphamide and anticoagulant treatment, the evolution was favourable, with clinical and biological improvement. CONCLUSION: The prompt initiation of TPE, because of the suspicion of CAPS, increases the chances of a favourable evolution.