A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts.

OBJECTIVES: Malignant tumor is a top-ranking cause of pediatric (>1-year) mortality in America and Europe. Among pediatric tumors, germ cell tumors (GCT) and gonadal tumors rank fourth (6%) by the Surveillance, Epidemiology, and End Results (SEER) program (seer.cancer.gov). Continuous research on tumor markers harnesses their full potential in tumor detection and management. We evaluated the effectiveness of beta-human chorionic gonadotropin (ß-hCG) and Alpha-fetoprotein (AFP) in Romanian children with (para)gonadal tumors and cysts, determining their accuracy in detecting malignancy, tumor-type, stage, complications, prognosis, and treatment response. METHODS: A 10-year retrospective study of AFP and ß-hCG in 134 children with cysts and (para)gonadal tumors aged one month to 17 years was performed. RESULTS: AFP/ß-hCG was unelevated in patients with cysts and nonmalignant tumors. Forty-eight/86 patients (43 GCT and 5 non-GCT) with malignant tumors had elevated AFP/ß-hCG, 3/48 patients had recurrences, and 25/48 had mixed-GCT (68% had elevated AFP + ß-hCG). All 30 patients with Yolk sac tumors (YST) or their components had elevated AFP. Area under the curve, sensitivity and specificity for GCT were: AFP + ß-hCG- 0.828, 67.2%, 100%; AFP- 0.813, 64.1%, 100%; and ß-hCG- 0.664, 32.8%, 100%. Two patients whose AFP/ß-hCG levels remained elevated died. Common mixed-GCT components were YST-80% and embryonal carcinoma-72%. Thirty of 34 metastasis cases were GCT, with 26/34 patients having elevated AFP/ß-hCG. CONCLUSIONS: AFP/ß-hCG detects malignant GCT and can determine tumor-type. GCT patients with markedly elevated AFP + ß-hCG had poor prognosis, especially if recurrence or metastasis was present. Recurrence is unrelated to elevated AFP/ß-hCG. The tumor components and quantity present determine AFP/ß-hCG values in mixed-GCT.

Assessment of Platelet Mitochondrial Respiration in a Pediatric Population: A Pilot Study in Healthy Children and Children with Acute Lymphoblastic Leukemia.

Characterization of mitochondrial respiration in peripheral blood cells has recently emerged as a potential biomarker for the assessment of the severity of hematological malignancies (HM) in adults. Whether changes in platelet respiratory function occur in children with or without HM it is unknown. The present pilot study was double-aimed: (i) to investigate whether platelet respiration is age-dependent in non-HM children and (ii) to assess the platelet mitochondrial respiration in children with newly diagnosed acute lymphoblastic leukemia (ALL). Blood samples obtained from age-grouped children (10-11, 13-14 and 16-17 years) with non-HM and children with ALL (10-11 years) were used to isolate platelets via differential centrifugation. High-resolution respirometry studies of isolated platelets were performed according to a protocol adapted to evaluate complex I and II-supported respiration. An age-related decrease in respiration was observed in the non-HM pediatric population and had comparable values for the 13-14 and 16-17 years. groups. In children with ALL, a significant increase in C I-supported active respiration and decrease in maximal noncoupled respiration were found at the disease onset. In conclusion, in a pediatric population, platelet mitochondrial respiration is age-dependent. Platelet respiratory dysfunction occurs in children with newly-diagnosed ALL, an observation that warrants further investigation of this change as a disease biomarker.

Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden.

Monoamine oxidases (MAO) with 2 isoforms, A and B, located at the outer mitochondrial membrane are flavoenzyme membranes with a major role in the metabolism of monoaminergic neurotransmitters and biogenic amines in the central nervous system and peripheral tissues, respectively. In the process of oxidative deamination, aldehydes, hydrogen peroxide, and ammonia are constantly generated as potential deleterious by-products. While being systematically studied for decades as sources of reactive oxygen species in brain diseases, compelling evidence nowadays supports the role of MAO-related oxidative stress in cardiovascular and metabolic pathologies. Indeed, oxidative stress and chronic inflammation are the most common pathomechanisms of the main noncommunicable diseases of our century. MAO inhibition with the new generation of reversible and selective drugs has recently emerged as a pharmacological strategy aimed at mitigating both processes. The aim of this minireview is to summarize available information regarding the contribution of MAO to the vascular oxidative stress and endothelial dysfunction in hypertension, metabolic disorders, and chronic kidney disease, all conditions associated with increased inflammatory burden.

Monoamine oxidase is a source of oxidative stress in obese patients with chronic inflammation 1.

Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms. Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study was conducted to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production, quantitative real-time PCR, and immunohistology studies. The human visceral adipose tissue and mesenteric artery branches contain mainly the MAO-A isoform, as shown by the quantitative real-time PCR and immunohistology experiments. A significant upregulation of MAO-A, the impairment in vascular reactivity, and increase in ROS production were found in obese vs. non-obese patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominant isoform in human abdominal adipose and vascular tissues, is overexpressed in the setting of inflammation, and contributes to the endothelial dysfunction.

New Approach to Rare Pediatric Multicystic Mesenteric Lymphangioma; Would It Guide the Development of Targeted Therapy?

In children, lymphangiomas are extremely rare pathologic entities that are characterized by unusual locations. The mesenteric localization is extremely rare in children, and the clinical signs usually mimic an acute abdominal syndrome. For most of the cases, their diagnosis is established by the radiologist, and the main therapeutic option is represented by surgery for lesion removal. We hereby describe the case of a 4 year old girl admitted to the pediatric emergency department for continuous abdominal pain, more intense in the orthostatic position, associated with abdominal distension, nausea, and vomiting. These symptoms raised the clinical suspicion of acute abdominal syndrome. The patient had no previous clinically significant events. Radiologic examination suggested a mesenteric multicystic lymphangioma certified by surgical and histopathological evaluation. No specific targeted therapy is currently available; moreover, no specific criteria for recurrences have been stated. A new approach of infantile lymphangiomas following surgery, regarding the use of specific lymphatic markers panel including D2-40, Prox-1, VEGFR-3, PDGFs, and Ki67 may improve the characterization of such lesions regarding their prognosis, recurrence rate and targeted therapy implementation especially for those with a more aggressive or recurrent behavior.

New Molecular and Epigenetic Expressions as Novel Biomarkers in Critically Ill Polytrauma Patients with Acute Kidney Injury (AKI).

BACKGROUND: A high percentage of the critically ill polytrauma patients develop acute kidney injury (AKI) secondary to trauma and are therefore prone to high morbidity and mortality rates. One of the main objectives in these cases is the fast detection of the condition and continuous rigorous monitoring of the patients. Currently the panel of biomarkers available for monitoring and for the prognosis of AKI is limited. Numerous studies have proven the importance of microRNAs in this field. In this actualization paper we wish to summarize the most relevant microRNAs that can be used as biomarkers for patients with AKI. METHODS: For this paper, we looked into the studies available in scientific databases such as PubMed and Scopus. For the analysis we used the following key words: "miRNAs biomarker", "acute kidney injury AKI", "genetic expression in AKI", and "epigenetic microRNAs biomarkers in AKI". RESULTS: Numerous studies have shown high specificity for certain microRNA species in the case of patients with AKI. Moreover, they have reported a series of microRNAs that present high specificity and that have a strong expression in fluids that can be sampled through non-invasive methods, such as urine and saliva. CONCLUSIONS: The expression of microRNAs can be successfully used in the future as a non-invasive method for the evaluation and monitoring of AKI patients.