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Growth hormone deficiency (GHD) describes the impairment of growth hormone (GH) secretion by the pituitary somatotroph cells. GHD may be congenital, with causes, including genetic alterations and structural brain malformations, or acquired, including midline tumours, cranial irradiation, traumatic brain injury, central nervous system infections and inflammatory conditions. GHD in children is characterised by short stature, delayed bone maturation and abnormalities in substrate metabolism, body composition, physical and psychosocial functioning, all of which improve with recombinant human GH (rhGH) therapy. The diagnosis of GHD is based on clinical signs and symptoms, biochemistry and imaging. Although GH stimulation tests are considered the mainstay of diagnostic investigations, the results must be interpreted with caution owing to the variability in cut-off values and reproducibility. Transition refers to the physical and psychosocial changes in adolescent patients during the mid-teens to late teens (usually 15–18 years of age) until about 6–7 years after achievement of adult height. During the transition age, only a small residual capacity of longitudinal growth is left, but body maturity is not yet complete. Discontinuation of rhGH treatment at the end of longitudinal growth in adolescents with permanent GHD is associated with decreased muscle strength and mass, increased body fat (mainly in the abdomen), the arrest or reversal of muscle mass and bone mass density (BMD) gain and lipid profile deterioration. For these reasons, patients whose GHD persists during the transition age need to continue rhGH treatment to obtain full somatic maturation and normalisation of body composition, BMD, quality of life (QoL) and lipid metabolism. There is some evidence that rhGH treatment during transition may result in improved growth and bone health, as well as a better prognosis for metabolic and cardiovascular risks in the long term. Since these patients need to continue treatment to complete their body development, a multidisciplinary approach is required to ensure continuity of care during the transfer from paediatric to adult endocrinology services. Guidelines for the diagnosis and treatment of young adults with GHD have been published by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), Endocrine Society, European Society of Paediatric Endocrinology (ESPE), Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society and Endocrine Society of Australia. However, clinical practice lacks uniformity in terms of diagnosis and treatment of transition-age patients, the impact of GH replacement during transition has not been adequately assessed in randomised clinical trials (RCTs), validated questionnaires to assess QoL in patients on rhGH treatment in the transition period are not available and there is still uncertainty about the multidisciplinary approach during transition [8]. Hence, a structured transition protocol is essential to establish the best practice for transitioning adolescents with GHD to adult care. A study in Italy in 2015 identified a low level of awareness of these issues in clinical practice and real-world gaps in the management of GHD patients during transition. To address these gaps and assist endocrinologists (adult and paediatric) in the diagnosis and treatment of GHD in transition-age patients, a Delphi consensus process was undertaken to develop clinically relevant recommendations. The current consensus statements address the diagnosis of GHD, benefits of treatment, monitoring and management of transition-age patients with GHD, along with treatment adherence and safety concerns.

Elisa De Carlo,1,* Monica Schiappacassi,2,* Martina Urbani,3 Roberto Doliana,2 Gustavo Baldassarre,2 Valentina Da Ros,1 Sandra Santarossa,1 Emanuela Chimienti,1 Eleonora Berto,1 Lucia Fratino,1 Alessandra Bearz1 1Clinical Oncology Department, IRCCS CRO Centro di Riferimento Oncologico Aviano, Aviano, Italy; 2Molecular Oncology Department, IRCCS CRO Centro di Riferimento Oncologico Aviano, Aviano, Italy; 3Radiology Department, IRCCS CRO Centro di Riferimento Oncologico Aviano, Aviano, Italy *These authors contributed equally to this work Background: The use of tyrosine kinase inhibitors (TKIs) of ALK is the therapy of choice for ALK-fusion patients. Unfortunately, all patients under this kind of treatment eventually develop acquired resistance through several well-known mechanisms, such as acquisition of a secondary mutation within the kinase domain, activation of a bypass signaling pathway, or a histological change like small-cell lung cancer transformation. At the time of progression, a tissue re-biopsy may give important molecular and morphological information regarding the mechanisms driving resistance to ALK TKIs. However, this procedure is not always feasible and it may not reflect the tumor heterogeneity, and therefore gives incomplete information. To overcome these drawbacks, the analysis of circulating tumor DNA (ctDNA) isolated from plasma, the so-called liquid biopsy, is emerging as a noninvasive and useful tool for detecting resistance mutations. Secondary resistance mutations are common in second-generation TKIs resistant patients and among these, Gly1202Arg (p.G1202R) emerged as the most frequent mutation. Case presentation: We have treated an ALK-positive lung adenocarcinoma patient with a sequential strategy of ALK TKIs. Patient follow-up was performed combining clinical, radiological, and molecular profiling. ctDNA was isolated from plasma and by means of ultra-deep next generation sequencing; we searched for secondary ALK resistance mutations on exons 21–25. ALK mutation Gly1202Arg (G1202R) was detected. We have documented consistency between plasma levels of G1202R mutation and radiological progression or improvement. Conclusion: Liquid biopsy appears to be a promising tool to anticipate progression and to drive the therapeutic strategy based upon ALK resistance mutations. Keywords: non-small-cell lung cancer, EML4-ALK, ALK tyrosine kinase inhibitors, G1202R resistance mutation, liquid biopsy

ClassyFarm is an integrated system aiming at the categorization of the farms according to a risk assessment methodology (RA). It is an Italian innovation that allows to facilitate and improve the collaboration and the dialogue between the breeders and the competent authority, in order to raise the level of safety and quality of food of animal origin. ClassyFarm collects, gather and process data, referred to the following evaluation areas: biosecurity, animal welfare, health and production parameters, animal nutrition, antimicrobial usage, injuries detected at slaughterhouse. ClassyFarm can be applied to several livestock species, included buffalo farms. On the request of the Italian Ministry of Health, CreNbuf in collaboration with CReNBa, have develop a checklist (CL) for the animal welfare assessment in buffalo species, based on RA and included in the ClassyFarm system. The multiple-choice CL consists of 80 Items. Each Item is scored according to 3 choice categories: “insufficient”, “acceptable” and “excellent”. The assessment system includes non-animal based (N-ABMs) and animal-based measures (ABMs). N-ABMs are divided into 2 macro-areas: Area A (28 Items) “Management factors”; Area B (30 Items) “Housing factors”. ABMs are assessed in Area C (14 Items). The CL has been tested in 341 farms, with an average of 353 head (min10, max 2240). The average overall welfare value was 61.27% (on a scale of 0 to 100%). The values of the specific areas were: Area A 60.20%; Area B 41.34%; Area C 71.55%. At least one potential legislative non-compliance was recorded in 39.8% of the farms. These CL represent a functional and smart instrument to assign an animal welfare index to each farm, and to provide to veterinarians and breeders a tool for improving farm management and housing conditions by using the data collected in each Area, while respecting farm sustainability, giving answers to consumers and add value to farmers’ correct activities. The Italian Ministry of Health is promoting this system, unique in its kind, also in the European and international context, raising a wide and strong interest.

An expert opinion elicitation, based on a modified Delphi technique, was organized to collect the opinion of 14 Italian veterinarians with the aim of conducting a hazard and a welfare promoter characterization for defining and weighing a list of management and housing factors potentially associated with negative or positive welfare outcomes in buffalo kept in loose housing systems. In addition, the 14 experts judged a set of animal-based measures (ABMs), rating their appropriateness and the level of animal pain and suffering due to the welfare consequences they measure. Experts were asked to score 52 hazards, 45 welfare promoters and 14 ABMs. Management and housing hazards, that were determined to be associated with a very high negative impact on the welfare of buffalo, were: lack of water availability, uncorrected animal grouping strategy, dirty and unmanaged lying area, incorrect milking routine, poor maintenance of the milking system, lack of litter for calves, insufficient shaded lying area and/or lack of any cooling system and presence of inadequate or slippery floor in walking areas. Management and housing welfare promoters dealing with optimal buffalo comfort around resting obtained the highest ratings, in particular: housing free for all animals and the possibility for adult buffaloes to access a loafing area of at least 7 m²and/or to a pasture for at least 60 days a year; cleanleness of the calf boxes, a hospital pen of at least 8 m²/parturient animal. In addition, high scores were given to appropriate grouping, adequate temperature, humidity and ventilation, presence of experienced and trained stockpersons. As to ABMs, the highest rankings were given to mortality of calves and adult buffaloes, percentage of animals showing vaginal and/or uterine prolapses, body condition scoring and percentage of deformed claws in adult buffaloes. Our results represent the starting point for the development of the first protocol for the assessment of the welfare of buffalo farmed in loose housing systems.

BACKGROUND AND PURPOSE: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses. MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library. RESULTS: Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus. CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

INTRODUCTION: Nicoletella semolina is gram-negative bacterium recently described as member of the Pasteurellaceae family(1). N. semolina has been isolated from horses with respiratory disorders (2) however it is still unclear if this bacterium plays a role as potential pathogen, opportunistic or just as commensal of the normal bacteriological flora. To the best of authors’ knowledge there are no descriptions of the isolation of this bacterium in donkeys. The aim of the present report is to describe, for the first time, the isolation of N. semolina in a donkey foal from Italy. MATERIALS AND METHODS: Three 2-3-month-old crossbreed donkey carcass (A-B-C) were submitted to the necropsy. Anamnesis reported severe respiratory disorders before death. At necropsy in all foals was reported generalized pneumonia associated with purulent-catarrhal collection and emphysema diffuse; the foal A showed lesions in all lung lobes, pericardial effusion and subsequent cardiac tamponade. Samples were collected from lungs and were plated onto two Blood Agar Base and MacConkey agar SS plates, and incubated aerobically and in microaerophilia at 37°C±1°C for 72h. The plates were observed every 24h. On all isolates were performed identification using the Vitek 2 Compact system (bioMérieux). On the strain isolated from the foal A was performed the sequencing and analysis of 16S rRNA genes. PCR was performed with MicroSeq 500 rDNA PCR Kit (Life Thecnoligies). Amplification products of the 16SrRNA genes were used for cycle sequencing with MicroSeq 500 rDNA Sequencing Kit. Sequence analysis and alignment were carried out using SeqScape v.2.5 (Applied Biosystem) and NCBI/BLAST/blastn suite. RESULTS: After 24h of incubation aerobic bacterial cultures of all 3 foals (A-B-C) in Blood Agar Base yielded heavy growth of Streptococcus equi subsp. zooepidemicus; at the same time point in MacConkey agar plates (foal C) was detected the co-presence of Salmonella kasenyi. After 48h of incubation in Blood Agar Base plates (foal B) was isolated Nocardia spp. Furthermore at 72h in in Blood Agar Base plates (foal A) was detected the appearance of colonies gray, rounded, waxy, nonhaemolytic, nonadherent, similar to a grain of semolina wheat (1). The organism was identified as a pleomorphic gram-negative coccobacillus, nonmotile, catalase and oxidase positive and negative for indole test. 16S rDNA sequencing revealed 99% homology with N. semolina. DISCUSSION AND CONCLUSIONS: The present report described in the donkey is fairly similar to that noted recently in young horses (3) where is described the isolation of N. semolina associated with Streptococcus equi subsp. zooepidemicus with respiratory disorders (2). In the donkey is still be determined whether N. semolina is a primary pathogen or a commensal which can occasionally cause disease. Further studies are required to clarify the potential pathogen of this bacterium in the donkeys. REFERENCES: 1.Kuhnert P., Korczak B., Falsen E., Straub R., Hoops A., Boerlin P., Frey J., Mutters R., 2004. Nicoletella semolina gen. nov., sp. nov., a New Member of Pasteurellaceae Isolated from Horses with Airway Disease.