NGR Tumor-Homing Peptides : Structural Requirements for Effective APN (CD13) Targeting

Acknowledgements We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P.Peer reviewedPublisher PD

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 6410% at 3 months, 641% at 6 months, 640.1% at 12 months, 640.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

Selecting for BRCA1 testing using a combination of homogeneous selection criteria and immunohistochemical characteristics of breast cancers

<p>Abstract</p> <p>Background</p> <p>BRCA1 gene-related tumours are more frequently estrogen receptor (ER) and progesterone receptor (PR) negative with a lower prevalence of human epidermal growth factor receptor 2 (HER2) overexpression or amplification. We evaluated the effectiveness of a combination of homogeneously selected criteria and immunohistochemical (IHC) characteristics of Familial Breast Cancers (FBCs) in detecting BRCA1 mutation carriers.</p> <p>Methods</p> <p>Primary breast tumours from 93 FBC patients defined by specific eligibility criteria, based on personal and familial tumour history, were evaluated by Allred's method. The BRCA1 molecular analysis, including Multiplex Ligation-dependent Probe Amplification (MLPA), was considered as the gold standard assay.</p> <p>Results</p> <p>A total of 10 BRCA1 pathogenetic mutations was found. With the exclusion of the tumours characterized by double positive receptorial status and/or strong HER2 positivity (3+), we identified 22 patients, 10 of whom resulted as BRCA1 mutation carriers. The sensitivity, specificity, positive and negative predictive values were 100%, 83.3%, 45.4% and 100% respectively.</p> <p>Conclusion</p> <p>Our findings suggest that the IHC analysis by Allred's method improves our ability to select patients for BRCA1 testing.</p

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Feeding habits of the Atlantic bluefin tuna, Thunnus thynnus (L. 1758), in the central Mediterranean Sea (Strait of Messina)

The study of feeding habits of the Atlantic bluefin tuna was carried out in 123 specimens, ranging from 115 to 222 cm fork length (FL) and collected during spring seasons of 2010 and 2011 in the central Mediterranean Sea (Strait of Messina). The analysis of stomach contents allowed us to identify 91 taxa of prey items, mainly belonging to Teleostea (54), Cephalopoda (20) and Crustacea (13). The percentage of index of relative abundance (IRI) shows the highest values for the myctophid Hygophum benoiti (%IRI = 22.854) and the stomiid Chauliodus sloani (%IRI = 15.124), followed by the oegopsid squid Illex coindetii (%IRI = 14.316). The broad spectrum of prey items could suggest a generalist behavior of this predator, with several species that occasionally occurs in its diet. However, if prey are grouped into food categories, the importance of mesopelagic and benthopelagic fishes can be appreciated (54.41 % of %IRI). The assessment of the hypothetical foraging rhythm of the Atlantic bluefin tuna highlighted that its feeding activity is concentrated on diel migrating fauna during night and on larger preys upon daylight. The predation on the high-energetic food as mesopelagic and bathypelagic fishes during the pre-spawning and the spawning period may bring an energetic advantage in tuna metabolism and gonadal maturation

Point-of-care lung ultrasound in infants with bronchiolitis in the pediatric emergency department: a prospective study

Bronchiolitis is the most common cause of hospitalization of children in the first year of life. The lung ultrasound is a new diagnostic tool which is inexpensive, non-invasive, rapid, and easily repeatable. Our prospective study was conducted in the emergency department and all patients underwent a routine clinical evaluation and lung ultrasound by the pediatricians who defined the clinical and the ultrasound score. We enrolled 76 infants (median age 90 days [IQR 62-183], 53.9% males). In nasopharyngeal aspirates, the respiratory syncytial virus was isolated in 33 patients. Considering the clinical score, children with higher score had a higher probability of requiring respiratory support (p 0.001). At the ultrasound evaluation, there was a significant difference on ultrasound score between those who will need respiratory support or not (p 0.003). Infants who needed ventilation with helmet continuous positive airway pressure had a more severe ultrasound score (p 0.028) and clinical score (p 0.004), if compared with those who did not need it.Conclusion: Our study shows that lung ultrasound in the bronchiolitis may be a useful method to be integrated with the clinical evaluation to better define the prognosis of the individual patient. Multicenter studies on larger populations are necessary to confirm our data. What is Known: \u2022 Bronchiolitis is the main cause of lower respiratory tract infection in children younger than 24 months. \u2022 Ultrasound can evaluate the lung parenchyma without ionizing radiations. What is New: \u2022 Lung ultrasound may be a useful diagnostic tool to define the prognosis of the infants affected by bronchiolitis if performed at the first assessment in the emergency department. \u2022 The score obtained at the ultrasound evaluation is higher in those who will need oxygen therapy during admission for more time and in those who will need respiratory support with helmet continuous positive airway pressure