Rapid intraoperative insulin assay: a novel method to differentiate insulinoma from nesidioblastosis in the pediatric patient

Introduction: Hyperinsulinism is the most common cause of recurrent and persistent hypoglycemia in infancy and childhood. Causes can include nesidioblastosis, pancreatic islet cell tumors such as insulinoma, and associations with multiple endocrine neoplasia syndromes. Although new, improved imaging techniques have allowed for more precise preoperative localization of insulinomas, the differentiation of nesidioblastosis and insulinoma, particularly in children, can be challenging. To improve intraoperative localization and confirmation of successful resection of insulinoma, a novel hormonal assay, the rapid intraoperative insulin assay, is reported for the first time in a pediatric patient. This intraoperative radioimmunoassay for insulin yields results within several minutes and confirms complete resection of insulinoma. Case description: We present a case of pancreatic insulinoma in a child with symptoms of severe hypoglycemia, causing seizures. The insulinoma was enucleated laparoscopically, and rapid intra-operative insulin assay used to determine the success of the procedure. Discussion and evaluation: This rapid intra-operative test provides a valuable adjunct for determining complete excision in complicated cases of recurrent or questionable insulinoma. Although not a common problem, for pediatric patients in whom the diagnosis is not clear, this test may provide a novel approach to confirming disease. Conclusion: We propose the use of this assay in facilitating intra-operative resection and confirmation of complete excision in pediatric patients. This population may especially benefit from this novel assay to confirm complete resection and to differentiate multiple etiologies of hyperinsulinism

Mechanisms of Mycotoxin-Induced Neurotoxicity through Oxidative Stress-Associated Pathways

Among many mycotoxins, T-2 toxin, macrocyclic trichothecenes, fumonisin B1 (FB1) and ochratochin A (OTA) are known to have the potential to induce neurotoxicity in rodent models. T-2 toxin induces neuronal cell apoptosis in the fetal and adult brain. Macrocyclic trichothecenes bring about neuronal cell apoptosis and inflammation in the olfactory epithelium and olfactory bulb. FB1 induces neuronal degeneration in the cerebral cortex, concurrent with disruption of de novo ceramide synthesis. OTA causes acute depletion of striatal dopamine and its metabolites, accompanying evidence of neuronal cell apoptosis in the substantia nigra, striatum and hippocampus. This paper reviews the mechanisms of neurotoxicity induced by these mycotoxins especially from the viewpoint of oxidative stress-associated pathways

Differential Diagnosis between Ulcerative Colitis and Clostridium Difficile-Associated Disease in a Patient with Autoimmune Polyglandular Syndrome Type 1

Aim: to demonstrate the clinical picture and the tactics of differential diagnosis between ulcerative colitis and Clostridium difficile-associated disease in a patient with APS-1, as well as to describe the tactics of managing such patients.Key findings. A 25-year-old patient with autoimmune polyglandular syndrome type 1 (APS-1) complained of loose stools up to 10 times a day with blood admixture, rapidly growing weakness and a weight loss of 5 kg per week. When examined on the day of admission, surgical pathology was excluded. Further differential diagnostics between Clostridium difficile-associated disease and ulcerative colitis was carried out, with the possibility of combining these diseases being not excluded. The examination confirmed Clostridium difficile-associated disease, while the diagnosis of ulcerative colitis needed further verification. APS-1 is often combined with other diseases and is likely to be pathogenetically related with them; however, the mechanisms of such interrelations still remain unknown. Previous research has reported the relationship between APS-1 and clostridial infection. The combination of ulcerative colitis with APS-1 has not thus far been described.Conclusion. A specific feature of the described clinical case consists in the development of severe Clostridium difficile-associated disease against the background of autoimmune polyglandular syndrome type 1. The management of patients with APS-1 should take into account the possibility of developing a clostridial infection, since these diseases can co-occur. When treating a patient with APS-1 in non-endocrine hospital units, consultation with an endocrinologist is necessary

Differential Diagnosis between Ulcerative Colitis and Clostridium Difficile-Associated Disease in a Patient with Autoimmune Polyglandular Syndrome Type 1

Aim: to demonstrate the clinical picture and the tactics of differential diagnosis between ulcerative colitis and Clostridium difficile-associated disease in a patient with APS-1, as well as to describe the tactics of managing such patients.Key findings. A 25-year-old patient with autoimmune polyglandular syndrome type 1 (APS-1) complained of loose stools up to 10 times a day with blood admixture, rapidly growing weakness and a weight loss of 5 kg per week. When examined on the day of admission, surgical pathology was excluded. Further differential diagnostics between Clostridium difficile-associated disease and ulcerative colitis was carried out, with the possibility of combining these diseases being not excluded. The examination confirmed Clostridium difficile-associated disease, while the diagnosis of ulcerative colitis needed further verification. APS-1 is often combined with other diseases and is likely to be pathogenetically related with them; however, the mechanisms of such interrelations still remain unknown. Previous research has reported the relationship between APS-1 and clostridial infection. The combination of ulcerative colitis with APS-1 has not thus far been described.Conclusion. A specific feature of the described clinical case consists in the development of severe Clostridium difficile-associated disease against the background of autoimmune polyglandular syndrome type 1. The management of patients with APS-1 should take into account the possibility of developing a clostridial infection, since these diseases can co-occur. When treating a patient with APS-1 in non-endocrine hospital units, consultation with an endocrinologist is necessary

Predictive model for preoperative risk calculation of cerebrospinal fluid leak after resection of midline craniofacial mass lesions

Background: Complex anterior skull base defects produced by resection of mass lesions vary in size and configuration and may be extensive. We analyzed the largest single-center series of midline craniofacial lesions extending intra- and extracranially. The study aims at the development of a predictive model for preoperative measurement of the risk of the postoperative cerebrospinal fluid (CSF) leak based on patients' characteristics and surgical plans. Methods: 166 male and 149 female patients with mean age 40,5 years (1 year and – 81 years) operated for benign and tumor-like midline craniofacial mass lesions were retrospectively analyzed using logistic regression method (Ridge regression algorithm was selected). The overall CSF leak rate was 9.6%. The ROSE algorithm and ‘glmnet’ software suite in R were used to overcome the cohort's disbalance and avoid overtraining the model. Results: The most influential modifiable negative predictor of the postoperative CSF leak was the use of extracranial and combined approaches. Use of transbasal approaches, gross total resection, utilization of one or two vascularized flaps for skull base reconstruction were the foremost modifiable predictors of a good outcome. Criterium of elevated risk was established at 50% with a specificity of the model as high as 0.83. Conclusions: The performed study has allowed for identifying the most significant predictors of postoperative CSF leak and developing an effective formula to estimate the risk of this complication using data known for each patient. We believe that the suggested web-based online calculator can be helpful for decision making support in off-pattern clinical situations

Pilot study of p62 DNA vaccine in dogs with mammary tumors

Our previous data demonstrated profound anti-tumor and anti-metastatic effects of p62 (sqstm1) DNA vaccine in rodents with various types of transplantable tumors. Testing anti-cancer medicine in dogs as an intermediary step of translational research program provides two major benefits. First, clinical data collected in target animals is required for FDA/USDA approval as a veterinary anti-cancer drug or vaccine. It is noteworthy that the veterinary community is in need of novel medicine for the prevention and treatment of canine and feline cancers. The second more important benefit of testing anti-cancer vaccines in dogs is that spontaneous tumors in dogs may provide invaluable information for human trials. Here, we evaluated the effect(s) of p62 DNA vaccine on mammary tumors of dogs. We found that p62DNA vaccine administered i.m. decreased or stabilized growth of locally advanced lesions in absence of its overall toxic effects. The observed antitumor activity was associated with lymphocyte infiltration and tumor encapsulation via fibrotic reaction. This data justifies both human clinical trials and veterinary application of p62 DNA

Dimerization and Ubiquitin Mediated Recruitment of A20, a Complex Deubiquitinating Enzyme

A20 is an anti-inflammatory protein linked to multiple human autoimmune diseases and lymphomas. A20 possesses a deubiquitinating motif and a zinc finger, ZF4, that binds ubiquitin and supports its E3 ubiquitin ligase activity. To understand how these activities mediate A20's physiological functions, we generated two lines of gene-targeted mice, abrogating either A20's deubiquitinating activity (Tnfaip3(OTU) mice) or A20's ZF4 (Tnfaip3(ZF4) mice). Both Tnfaip3(OTU) and Tnfaip3(ZF4) mice exhibited increased responses to TNF and sensitivity to colitis. A20's C103 deubiquitinating motif restricted both K48- and K63-linked ubiquitination of receptor interacting protein 1 (RIP1). A20's ZF4 was required for recruiting A20 to ubiquitinated RIP1. A20(OTU) proteins and A20(ZF4) proteins complemented each other to regulate RIP1 ubiquitination and NFκB signaling normally in compound mutant Tnfaip3(OTU/ZF4) cells. This complementation involved homodimerization of A20 proteins, and we have defined an extensive dimerization interface in A20. These studies reveal how A20 proteins collaborate to restrict TNF signaling