Il ruolo delle mutazioni di KRAS e BRAF nella prognosi dei pazienti affetti da carcinoma colorettale con metastasi epatiche resecate

RIASSUNTO Il trattamento del carcinoma colorettale metastatico si è rapidamente evoluto negli ultimi 10 anni. I progressi maggiori sono stati resi possibili dall'introduzione di farmaci biologici, l'identificazione di specifici markers biomolecolari prognostici e predittivi, il progressivo miglioramento delle tecniche chirurgiche di resezione delle metastasi epatiche e quindi, quale naturale conseguenza, l'espandersi delle indicazioni per questo tipo di chirurgia. Nonostante notevoli e incessanti progressi la caratterizzazione prognostica dei pazienti e la definizione di specifiche indicazioni terapeutiche sulla base di fattori biomolecolari può dirsi ancora agli albori e certamente rappresenta tuttora una delle più attuali sfide dell’oncologia moderna. Il setting dei pazienti affetti da carcinoma colorettale metastatico candidati a resezione delle metastasi epatiche con intento curativo è stato fin ad oggi ben poco esplorato dal punto di vista biomolecolare. I criteri attuali di selezione dei pazienti che possano beneficiare in misura clinicamente rilevante di un intervento di resezione di metastasi epatiche sono esclusivamente clinici. Molti score prognostici sono stati elaborati, proposti e variamente testati per poter definire specifiche classi di rischio di recidiva. Purtroppo ad oggi, pur conoscendosi molti fattori condizionanti un alto rischio di recidiva e, quindi, ridotte possibilità di sopravvivenza a lungo termine non esistono determinanti specifici in grado di definire in maniera assoluta quali pazienti debbano essere sottoposti a resezione epatica e quali definitivamente esclusi. Muovendo da un consistente background clinico e biologico diversi gruppi di ricerca in varie parti del mondo hanno ipotizzato che un aiuto consistente nella definizione di nuove categorie di rischio possa venire dallo studio di specifiche alterazioni biomolecolari. Tra queste in particolare, le mutazioni di oncogeni ampiamente studiati e di storica importanza nella cancerogenesi colorettale quali KRAS e BRAF. In questo elaborato vi è un'estesa revisione della letteratura sull'argomento e sono presentati nel dettaglio i risultati di un ampio studio retrospettivo che ha indagato il possibile ruolo delle mutazioni dei geni KRAS e BRAF nel definire un sottogruppo di pazienti con carcinoma colorettale metastatico clinicamente candidati a resezione epatica potenzialmente curativa con minime possibilità di guarigione o di sopravvivenza libera da ricaduta

Influence of Omega-3 fatty acids on the learning ability of the Guide Dog during the training

Some studies show the usefulness of supplementation with long chain poliunsatured fatty acids (LCPUFA) in puppies during training through the evaluation of the ability of learning and memory. The purpose of this preliminary study was to evaluate the effect of DHA supplementation on learning abilities in a group of future Guide Dogs for the Blind during the phases of education and training. Two groups of six Labrador dogs (A, study group and B, control group), belonging to School of Guide Dogs of Tuscany (Italy), random selected, were included in the study. To evaluate the effect of supplementation, we used the standardized tests of the School as they are internationally recognized and can establish both character and learning skills of puppies. Some differences were observed between the two groups in some tests results; in particular in those that require a greater visual and sensory capacity and motor coordination as the grid (or abnormal surface) test and the tilting table test. The results obtained in this study could confirm the usefulness of a 35 mg/kg DHA supplementation during the first year of life for improving cognitive skills in dogs

More Real than Real: A Study on Human Visual Perception of Synthetic Faces

Deep fakes became extremely popular in the last years, also thanks to their increasing realism. Therefore, there is the need to measures human's ability to distinguish between real and synthetic face images when confronted with cutting-edge creation technologies. We describe the design and results of a perceptual experiment we have conducted, where a wide and diverse group of volunteers has been exposed to synthetic face images produced by state-of-the-art Generative Adversarial Networks (namely, PG-GAN, StyleGAN, StyleGAN2). The experiment outcomes reveal how strongly we should call into question our human ability to discriminate real faces from synthetic ones generated through modern AI

INVESTIGATION OF CRP AND OTHER HEMATIC INFLAMMATION MARKERS IN DOGS

The systemic reaction to acute inflammation, also known as acute phase response, induces some hemato-biochemical changes, which can be evidenced in laboratory findings. The C Reactive Protein (CRP) is a main acute phase response protein elective in dogs to detect inflammatory disease. Other blood parameters have been described as useful inflammation markers i.e. Fibrinogen and Leukocytes (1, 2, 3). The aim of this retrospective study was to investigate the CRP values in comparison to Fibrinogen (Fib), Albumin (Alb), and Iron (Fe) values, total White Blood Cell (WBC), Segmented Neutrophil (NeuSeg) and Band Neutrophil (Band) counts, and the occurrence of Toxic Neutrophils (Neu TOX), Activated Monocytes (Mon ATT), and Reactive Lymphocytes (Linf REA) in blood smears. For this purpose, data of 1,837 blood samples was collected over a three-year period (2012-2015). Data collected for each sample included: Fib, Alb, Fe, WBC, NeuSeg, Band, Neu TOX, Mon ATT, Linf REA and CRP, as well as information regarding dog’s age, breed, and gender. Blood samples were divided into 2 groups: "inflammatory";; CRP ≥0.30 mg/dL (#1080) and non-inflammatory;; CRP ≤0.29 mg/dL (#757). The 2 groups were compared using: Chi squared for sex, breed, and age; Relative risk (RR) for age; Spearman Rank correlation test (SRct) for all parameters studied; Multiple regression (MR) to assess the relationship between CRP and other inflammation markers; Receiver Operating Characteristic (ROC) curves for diagnostic accuracy of each parameter in comparison to CRP (MedCalc®, 14.8). Dogs belonging to inflammatory group were significantly older (>7 years old) than those of non-inflammatory group (P<0.05), (RR, 1.38). Low yet significant (p<0.01) correlations between CRP and the other markers were noted using the SRct (R): CRP/Fib, +0.26; CRP/NeuSeg, +0.26; CRP/WBC, +0.24; CRP/Alb, -0.21; CRP/Band, +0.14; CRP/Fe, -0.08; CRP/NeuTOX, +0.23; MonATT, +0.22. On the contrary, the MR analysis did not show any relationship between CRP and other markers (R2: 0.05 for CRP ≥ 0.30 mg/dL;; 0.02 for CRP ≤ 0.29 mg/dL). ROC analysis of the parameters yielded the following results: NeuSeg is a moderately accurate inflammation marker with Area Under the Curve (AUC) of 0.71. The other parameters are less accurate markers of inflammation (AUC) compared to CRP: WBC, 0.70; Fib, 0.67; Alb, 0.64; Fe, 0.64; Band, 0.59. The markers with the best combination of Sensitivity (SS) and Specificity (SP) were: Fib (SS, 52.7; SP, 77.5 for 400 mg/dL cut-off) and Band (SS, 17.6; SP, 98.0 for 0.3 K/μL cut-off). The correlation between CRP and all the parameters studied, except Linf REA, is significant but low because they are affected by many conditions aside from inflammation. None of them is able to predict CRP values. The diagnostic accuracy of each single inflammatory marker is lower in comparison to CRP. In order to increase the diagnostic accuracy of inflammation markers, an evaluation of several parameters simultaneously is warranted, particularly in the absence of CRP measurement

Small-for-gestational-age fetus diagnosed in the second trimester: Possible etiologies and short-term neonatal outcomes

Introduction: The aim of our study was to investigate the causes of fetal growth <10th centile diagnosed <26 weeks' gestation in singleton pregnancies and compare pregnancy outcomes in relation to the identified etiology. Material and methods: Historical cohort study conducted in two Italian hospitals which included all small-for-gestational-age fetuses diagnosed between 18+0 and 26+0 weeks over a 10-year period. Fetuses were divided into three groups depending on the prenatally suspected etiology: chromosomal abnormalities (Group 1), malformations (Group 2) and isolated (Group 3). These groups were compared regarding pregnancy outcomes. Fetuses in Group 3 were divided into small-for-gestational-age and fetal growth restriction following the Delphi Consensus criteria and the outcomes were further compared. Fisher's Exact or Mann-Whitney test were used for comparison of groups. Results: In all, 435 fetuses were included. Of these, 20 cases (4.6%) were associated with chromosomal abnormalities (Group 1), 98 (22.5%) with fetal malformations (Group 2) and 317 (72.9%) were isolated (Group 3). A higher percentage of live births was reported for Group 3 (P < 0.001). Termination of pregnancy was more common in Group 1 (P < 0.001). No differences in gestational age at delivery, birthweight, intrauterine death or neonatal death were detected within groups. Growth-restricted fetuses had lower gestational age at delivery, birthweight and number of live births (P < 0.001), higher rates of termination of pregnancy, intrauterine death (P < 0.001) and neonatal death <10 days (P = 0.002) compared to small-for-gestational-age. In 17 cases a chromosomal abnormality, genetic syndrome or adverse neurological outcome was diagnosed after birth: six from Group 2 (11.3% of live births in this group) and 11 from Group 3 (4.3%). Conclusions: We report that fetal growth <10th percentile diagnosed before 26 weeks is not isolated before birth in 27% of cases. Malformations and chromosomal abnormalities are common etiologies; therefore, detailed anomaly scans and invasive testing should be offered. In addition, there is a residual risk of neonatal death and postnatal diagnosis of a genetic syndrome or neurodevelopmental impairment despite normal prenatal tests. These results expand the small amount of information on the outcome of cases with very early diagnosis of impaired fetal growth currently available and highlight the importance of detailed counseling with couples

VENOUS BLOOD GAS ANALYSIS WITH RADIOMETERTM ABL 735 GLA XP® INSTRUMENT: REFERENCE INTERVALS IN DOGS

Background: The Venous Blood Gas (VBG) analysis is ultimate in Veterinary Emergency and Critical Care (VECC) because provides a quick and complete picture of oximetry, fluid, electrolyte and acid-base balance. Accurate Reference Intervals (RI) are necessary to interpret correctly the patient’s values. Objective: To establish RI for VBG in dogs performed with the RadiometerTM ABLGLA735XP® instrument used at a Veterinary Teaching Hospital, VECC Unit. Methods: Over a period of 2 years 1,341 VBG reports were analyzed retrospectively. The data were selected according to the American Society Veterinary Clinical Pathology guidelines for RI (indirect method, post hoc) and analysed with the MedCalc® software. New RIs were compared and validated to the RIs already in use derived from the reference consultation. Results: RIs for measured parameters have been assessed: pO2 (48.1-56.2 mmHg); pCO2 (38.0-43.4 mmHg); ctHb (15.1-19.8 g/dL); pH (7.351-7.409); Na+ (140-154 mEq/L); K+ (3.9-5.3 mEq/L); Cl- (109–124 mEq/L); Ca2+ (2.26-2.78 mEq/L); Glucose (81–124 mg/dL); Lactate (0.5-2.48 mmol/L). RIs for calculated parameters were also established: sO2 (72.1-83.9%); tCO2 (22.1–27.0%); HCO3- (20.8-25.2 mmol/L); AG (12.1-19.9 mEq/L); BE (-2.0-2.2 mmol/L); mOsm (302.1-314.4 mmol/Kg). RIs for Hematocrit and bilirubin were not considered as methods used from the instrument relies on human techniques with a reduced analytical sensitivity. Conclusions: The new RIs were found almost overlapping to previous used RIs with exception of mOsm. Pre-analytical errors such as blood sampling, sample collection devices and input data for patient in the device (i.e. body temperature) are crucial to supply an accurate VBG analysis

Endoscopic transsphenoidal approach as a promising surgical option in the treatment of craniopharyngioma

10.1530/endoabs.32.P85

The Language of Pain in the Hypermobile Ehlers–Danlos Syndrome: Metaphors as a Key to Understanding the Experience of Pain and as a Rehabilitation Tool

Ehlers-Danlos syndromes are a heterogeneous group of Heritable Connective Tissue Disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile Ehlers-Danlos syndrome is the most frequent and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hypermobile Ehlers-Danlos syndrome is often associated with pain that does not always allow the use of effective pain-reducing treatments. Patients with hEDS constantly describe their pain in detail. Eighty-nine patients with hEDS diagnoses were recruited and evaluated. They were asked to describe their pain in writing. The texts were examined through Linguistic Inquiry and Word Count. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and the quality of metaphors was carried out. The results showed that language quality varies depending on how much pain is perceived. The greater the pain is perceived, the lesser the positive effects and the greater the negative effects and dehumanizing metaphors are being used. Moreover, a greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for examining illness experience and may help clinicians in the rehabilitation program