Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

Cancer predisposition syndromes (CPS) result from germline pathogenic variants, and they are increasingly recognized in the etiology of many pediatric cancers. Herein, we report the genetic/genomic analysis of 40 pediatric patients enrolled from 2016 to 2018. Our diagnostic workflow was successful in 50% of screened cases. Overall, the proportion of CPS in our case series is 10.9% (20/184) of enrolled patients. Interestingly, 12.5% of patients achieved a conclusive diagnosis through the analysis of chromosomal imbalance. Indeed, we observed germline microdeletions/duplications of regions encompassing cancer-related genes in 50% of patients undergoing array-CGH: EIF3H duplication in a patient with infantile desmoplastic astrocytoma and low-grade Glioma; SLFN11 deletion, SOX4 duplication, and PARK2 partial deletion in three neuroblastoma patients; a PTPRD partial deletion in a child diagnosed with glioblastoma multiforme. Finally, we identified two cases due to DICER1 germline mutations.     

Review of the new second-generation cephalosporins: cefonicid, ceforanide, and cefuroxime

The new second-generation cephalosporins, cefonicid, ceforanide, and cefuroxime, have recently become available. These agents are generally less active against gram-positive cocci than first-generation cephalosporins and, at best, equal to cefoxitin and cefamandole against many gram-negative bacteria. Cefuroxime, however, is the most active cephalosporin for beta-lactamase-producing Haemophilus influenzae. These newer agents have superior pharmacokinetic characteristics over cefoxitin and cefamandole. Smaller doses, longer dosing intervals and, potentially, a reduction in total drug cost may be the real advantage of these agents. Open trials and a limited number of comparative studies have documented the effectiveness of cefonicid, ceforanide, and cefuroxime in the treatment of most mild-to-serious infectious diseases, although failures with cefonicid in the treatment of staphylococcal infections have been reported. Notably, cefuroxime has received approval for the treatment of common pediatric bacterial meningitis infections. Replacement of cefamandole or cefoxitin with one of these "longer-acting" agents may be cost-beneficial; however, clinicians must be on alert for the development of bacterial resistance or decreased efficacy.     

Concomitant post-traumatic craniocervical junction epidural hematoma and pontomedullary junction infarction: clinical, neurophysiologic, and neuroradiologic features

STUDY DESIGN: A case report. OBJECTIVES: To report and discuss a case of post-traumatic epidural hematoma of the craniocervical junction with concomitant brain stem infarction. SUMMARY OF BACKGROUND DATA: Post-traumatic epidural hematoma of the cervical spine and brain stem post-traumatic infarction are very rare disorders. Post-traumatic epidural hematoma is usually located dorsally in the epidural space. METHODS: The clinical, neuroradiologic, and neurophysiologic findings in one patient with post-traumatic epidural hematoma located ventrally at the cervicomedullary junction and associated with medial infarction at the pontomedullary junction are reported. RESULTS: The main clinical finding in this patient was bilateral corticospinal and corticobulbar tract involvement. A magnetic resonance image showed displacement and flattening of the medulla oblongata and of the most cranial portion of cervical cord, which were caused by the epidural hematoma associated with an ischemic lesion of the pontomedullary junction. Results of central motor conduction studies indicated that the abnormality of the central motor pathways was localized at brain stem level, and that there was normal conduction from the cervicomedullary junction to spinal cord. CONCLUSION: This is the first reported case of spinal epidural hematoma located ventrally in the cervical spine at the cervicomedullary junction level and concomitant infarction at the pontomedullary junction resulting from whiplash injury.     

Adaptive response to hydrogen peroxide in yeast: Induction,time course,and relationship to dose–response models

The assay for trp5 gene conversion and ilv1‐92 reversion in Saccharomyces cerevisiae strain D7 was used to characterize the induction of an adaptive response by hydrogen peroxide (H₂O₂). Effects of a small priming dose on the genotoxic effects of a larger challenge dose were measured in exponential cultures and in early stationary phase. An adaptive response, indicated by smaller convertant and revertant frequencies after the priming dose, occurred at lower priming and challenge doses in young, well‐aerated cultures. Closely spaced priming doses from 0.000975 to 2 mM, followed by a 1 mM challenge, showed that the induction of the adaptive response is biphasic. In exponential cultures it was maximal with a priming dose of 0.125–0.25 mM. Very small priming doses were insufficient to induce the adaptive response, whereas higher doses contributed to damage. A significant adaptive response was detected when the challenge dose was administered 10–20 min after the priming exposure. It was fully expressed within 45 min, and the yeast began to return to the nonadapted state after 4–6 hr. Because of the similarity of the biphasic induction to hormetic curves and the proposal that adaptive responses are a manifestation of hormesis, we evaluated whether the low doses of H₂O₂ that induce the adaptive response show a clear hormetic response without a subsequent challenge dose. Hormesis was not evident, but there was an apparent threshold for genotoxicity at or slightly below 0.125 mM. The results are discussed with respect to linear, threshold, and hormesis dose–response models. Environ. Mol. Mutagen. 54:384–396, 2013. © 2013 Wiley Periodicals, Inc.     

Hereditary stomatocytosis: An underdiagnosed condition

Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in inappropriate shrinkage or swelling of the erythrocytes, and water lost or gained osmotically. The last few years have been crucial for new acquisitions in this field in terms of identifying new causative genes and of studying their pathogenetic mechanisms. This review summarizes the main features of erythrocyte membrane transport diseases, dividing them into forms with either isolated erythroid phenotype (nonsyndromic) or extra‐hematological manifestations (syndromic), and focusing particularly on the most recent advances regarding dehydrated forms of hereditary stomatocytosis and familial pseudohyperkalemia.     

A gravity-assisted approach to the management of urinary diversion: 99mTc-MAG3 diuresis renography with F + 10(sp) method

Annals of Nuclear Medicine - Radical cystectomy with permanent urinary diversion is the gold standard treatment for invasive muscle bladder cancer. Hydronephrosis is common in these patients, but...