Hereditary breast cancer: beyond BRCA genetic analysis; PALB2 emerges

Abstract Despite the initial enthusiasm following the discovery of the association of BRCA germline mutations with hereditary breast and/or ovarian cancer, in many families affected by the syndrome no pathogenic mutations were detected in the two genes, although exhaustively searched. Many other genes have also been implicated due to their role in the same pathway of DNA repair where the BRCA1/2 genes are involved: homologous recombination (HR). Among them, PALB2 clearly emerges as the third breast cancer susceptibility gene. Its mutations have been detected in most populations investigated so far, albeit rarely: in 1%-4% of families negative for BRCA mutations, with either partial or complete penetrance. In some populations, PALB2 recurrent mutations have been identified and the estimated hazard risks are comparable to those of BRCA mutations. Since new effective targeted therapeutic options are becoming available ("synthetic lethality" with novel PARP inhibitors, etc.) that are applicable to all those patients with a defect in HR pathway, it is imperative to detect all these candidate patients. Data obtained from laboratory tests in the tumor (simple immunohistochemistry, gene expression analysis, etc.) can assist in the recognition of a specific pattern (BRCA1ness, HRless) so that even patients that look "sporadic" could benefit from these targeted therapies. Therefore, a genetic analysis algorithm is proposed, although with the advent of Next Generation Sequencing it is predicted that in the future most germline genetic alterations and also somatic or epigenetic events in the tumor of these genes will be detected.     

Three years of routine vitrification of human zygotes: is it still fair to advocate slow-rate freezing?

Cryopreservation of human oocytes and embryos is a necessary tool in assisted reproduction treatment that leads to an increased cumulative outcome while decreasing costs. Vitrification is a cryopreservation technique that leads to a glass-like solidification, with rapid cooling of cells or tissues. Nowadays vitrification is claimed to be the future of cryopreservation of human embryos due to improved survival rates and clinical outcomes. This study was conducted at a university clinic to assess the safety and efficiency of vitrification of human zygotes as a routine procedure. A total of 849 pronuclear-stage (PN) zygotes were vitrified between March 2004 and July 2006. During this period, 103 cycles of cryopreserved embryo transfer were completed. In total, 339 PN zygotes were thawed resulting in an 89% survival rate (302 PN zygotes). The mean number of embryos per transfer was 2.2. The pregnancy rate obtained was three times higher (36.9%) than that obtained with the slow-rate freezing method (10.2%) used previously in the same centre. In conclusion, vitrification of human zygotes at the pronuclear stage seems to be a successful and reliable method with favourable outcomes and can be recommended as a routine technique for cryopreservation of human embryos.     

Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid—an Experimental Study

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 μg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20?±?0.12 vs 1.17?±?0.78,p?=?0.29), while AV calcification progressed in the placebo group (1.22?±?0.15 vs 1.53?±?0.23,p?=?0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.     

Malignant carcinoid tumor of the cystic duct:a rare cause of bile duct obstruction

BACKGROUND:Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies,accounting for 0.2%-2%of all gastrointestinal carcinoid tumors,while carcinoids of the cystic duct are an uncommon entity and an extremely unusual cause of bile duct obstruction.METHODS:After an extensive literature review,we retrospectively analysed 61 cases of carcinoid tumor of the biliary tree as well as one additional case of a 60-yearold female with symptoms and laboratory/imaging examination findings compatib...     

Optic neuritis caused by varicella infection in an immunocompetent child

Chickenpox may lead to several neurologic complications, but optic neuritis has rarely been described. We report on a 6-year-old immunocompetent patient who presented with unilateral optic neuritis and severe visual loss because of varicella infection. A week after varicella eruption, the child experienced blurred vision. An examination revealed decreased visual acuity of his right eye, a right pupil poorly reactive to light, and almost no color vision in his right eye. A history of chickenpox, the fundus examination, and the measurement of visual-evoked potentials allowed us to make a diagnosis of optic neuritis caused by varicella infection. The patient received only symptomatic relief with antipyretics. Three months later, his visual acuity improved to 20/40 in the right eye.     

First urinary tract infection in neonates, infants and young children: a comparative study

In an attempt to evaluate first urinary tract infection (UTI) in neonates and infants, we estimated retrospectively in 296 patients (62 neonates and 234 infants) clinical and laboratory findings, occurrence of vesicoureteral reflux (VUR), urinary tract abnormalities and pyelonephritis. First UTI occurred more often in male than female neonates, whereas male and female infants/young children were affected at an equal rate. The pathogens isolated in urine cultures of neonates and infants did not statistically significantly differ (P>0.05); Escherichia coli predominated. Gram-negative bacteria other than E. coli affected boys more often than girls (P=0.0022). Fever was the most frequent symptom. Neonates had lower-grade fever of shorter duration than infants (P<0.05). The incidence of reflux and urinary tract abnormalities did not differ between neonates and infants, male and female neonates and infants (P>0.05). Pyelonephritis affected neonates and infants at an equal rate; it was more prevalent among female patients (P=0.038) and patients with VUR or urinary tract abnormalities other than VUR (P<0.0001). Neonates with reflux were more often affected by Gram-negative bacteria other than E. coli than were neonates without reflux (P=0.0008).