Rearrangements of the RAR-α gene in acute promyelocytic leukaemia:

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.     

Malignant gastric outlet obstruction: Which is the best therapeutic option?

Malignant gastric outlet obstruction(MGOO) is a clinical condition characterized by the mechanical obstruction of the pylorus or the duodenum due to tumor compression/infiltration, with consequent reduction or impossibility of an adequate oral intake. MGOO is mainly secondary to advanced pancreatic or gastric cancers, and significantly impacts on patients' survival and quality of life.Patients suffering from this condition often present with intractable vomiting and severe malnutrition, which further compromise therapeutic chances. Currently,palliative strategies are based primarily on surgical gastrojejunostomy and endoscopic enteral stenting with self-expanding metal stents. Several studies have shown that surgical approach has the advantage of a more durable relief of symptoms and the need of fewer re-interventions, at the cost of higher procedure-related risks and longer hospital stay. On the other hand, enteral stenting provides rapid clinical improvement, but have the limit of higher stent dysfunction rate due to tumor ingrowth and a subsequent need of frequent reinterventions. Recently, a third way has come from interventional endoscopic ultrasound, through the development of endoscopic ultrasound-guided gastroenterostomy technique with lumen-apposing metal stent. This new technique may ideally encompass the minimal invasiveness of an endoscopic procedure and the long-lasting effect of the surgical gastrojejunostomy, and brought encouraging results so far, even if prospective comparative trial are still lacking. In this Review, we described technical aspects and clinical outcomes of the above-cited therapeutic approaches, and discussed the open questions about the current management of MGOO.     

Artificial intelligence technologies for the detection of colorectal lesions: The future is now

Several studies have shown a significant adenoma miss rate up to 35% during screening colonoscopy, especially in patients with diminutive adenomas. The use of artificial intelligence(AI) in colonoscopy has been gaining popularity by helping endoscopists in polyp detection, with the aim to increase their adenoma detection rate(ADR) and polyp detection rate(PDR) in order to reduce the incidence of interval cancers. The efficacy of deep convolutional neural network(DCNN)-based AI system for polyp detection has been trained and tested in ex vivo settings such as colonoscopy still images or videos. Recent trials have evaluated the real-time efficacy of DCNN-based systems showing promising results in term of improved ADR and PDR. In this review we reported data from the preliminary ex vivo experiences and summarized the results of the initial randomized controlled trials.     

Milestone Achievement and Neurodevelopment of Rural Amazonian Toddlers (12 to 24 Months) with Different Methylmercury and Ethylmercury Exposure

Neurological outcomes (Gesell development schedules [GDS]), age of walking, and age of talking were studied in 299 toddlers (12 to 24 mo) in relation to environmental (fish consumption and tin mining) exposure. Exposure to fish methylmercury (MeHg) consumption and iatrogenic ethylmercury (EtHg) in Thimerosal-containing vaccines (TCV) was quantified in toddlers from two rural villages (n?=?91, Itapuã; n?=?218, Bom Futuro) respectively populated by fishers and cassiterite miners. Median total hair Hg (HHg) concentrations of infants from Itapuã (3.5 μg/g) were significantly higher than those of infants from Bom Futuro (2.2 μg/g). Median EtHg exposure from TCV was also significantly higher in toddlers from Itapuã (137.5 μg) than in those from Bom Futuro (112.5 μg). There were no significant differences between groups for any of the Gesell schedules; however, there were proportionally more compromised toddlers (GDS < 70) in Itapuã than Bom Futuro. Median age of talking was not statistically different but median age of walking was significantly higher in Bom Futuro. In toddlers from both villages, of fishers and miners, HHg concentrations were significantly correlated with family fish consumption. A logistic regression model was applied to all infants after classification into two groups: above or below the median Gesell schedules. Overall, there was no distinctive pattern of neurodevelopment associated with either HHg or EtHg exposure; however, nutritional status was significantly associated with GDS. In conclusion, milestone achievement was delayed in toddlers from tin-ore mining communities. Despite significantly higher exposure to both forms of organic Hg (MeHg from maternal fish consumption, and EtHg from TCV) in toddlers from the fishing village, significant differences were seen only among the proportions of most severely affected toddlers (GDS < 70).     

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

BACKGROUNDIn a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIMTo clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODSWe performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication.RESULTSDSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development.CONCLUSIONDSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.     

Cardiovascular magnetic resonance of cardiac tumors and masses

Cardiac masses diagnosis and treatment are a true challenge, although they are infrequently encountered in clinical practice. They encompass a broad set of lesions that include neoplastic (primary and secondary), non-neoplastic masses and pseudomasses. The clinical presentation of cardiac tumors is highly variable and depends on several factors such as size, location, relation with other structures and mobility. The presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy, which is still the diagnostic gold standard. The findings should always be interpreted in the clinical context to avoid misdiagnosis, particularly in specific conditions (e.g., infective endocarditis or thrombi). The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac masses. Cardiovascular magnetic resonance (CMR) allows an optimal non-invasive localization of the lesion, providing multiplanar information on its relation to surrounding structures. Moreover, with the additional feature of tissue characterization, CMR can be highly effective to distinguish pseudomasses from masses, as well as benign from malignant lesions, with further differential diagnosis of the latter. Although histopathological assessment is important to make a definitive diagnosis, CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient management. This literature review aims to provide a comprehensive overview of cardiac masses, from clinical and imaging protocol to pathological findings.     

Multimodality imaging in COVID-19 patients: A key role from diagnosis to prognosis

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, evaluation and monitoring of the patient's therapy in coronavirus disease 2019 pneumonia. The ideal imaging approach in this context is not yet well defined. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. The "bedside" pulmonary ultrasound has an undeniable series of advantages in the patient at high infectious risk and can provide incremental data in the respiratory intensive care for the serial control of the individual patient as well as for the home delivery of the stabilized subjects. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative and in the late phase the imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability to assess ventricular function and pulmonary pressures.