Can the new and old drugs exert an immunomodulatory effect in acute myeloid leukemia?

Acute myeloid leukemia (AML) is considered an immune-suppressive neoplasm capable of evading immune surveillance through cellular and environmental players. Increasing knowledge of the immune system (IS) status at diagnosis seems to suggest ever more attention of the crosstalk between the leukemic clone and its immunologic counterpart. During the last years, the advent of novel immunotherapeutic strategies has revealed the importance of immune dysregulation and suppression for leukemia fitness. Considering all these premises, we reviewed the “off-target” effects on the IS of different drugs used in the treatment of AML, focusing on the main advantages of this interaction. The data reported support the idea that a successful therapeutic strategy should consider tailored approaches for performing leukemia eradication by both direct blasts killing and the engagement of the IS

Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, distinct subtype of T-ALL characterized by genomic instability, a dismal prognosis and refractoriness to standard chemotherapy. Since its first description in 2009, the expanding knowledge of its intricate biology has led to the definition of a stem cell leukemia with a combined lymphoid-myeloid potential: the perfect trick. Several studies in the last decade aimed to better characterize this new disease, but it was recognized as a distinct entity only in 2016. We review current insights into the biology of ETP-ALL and discuss the pathogenesis, genomic features and their impact on the clinical course in the precision medicine era today

Salivary gland ultrasonography: a highly specific tool for the early diagnosis of primary Sjögren's syndrome

INTRODUCTION:Recently, a great interest has arisen for salivary gland ultrasonography (SGUS) as a valuable tool for the assessment of major salivary gland involvement in primary Sjögren's syndrome (pSS. The aims of this study were to test the accuracy of SGUS for the early detection of pSSand to compare the diagnostic performance of SGUS with minor salivary gland biopsy (MSGB) and unstimulated salivary flow (USFR) in this context. METHOD:Patients with suspected pSS and symptoms duration of ≤5 years were consecutively enrolled in this study. The diagnosis of pSS was made according to the AECG criteria. SGUS was performed by two radiologists blinded to the diagnosis and a previously reported ultrasound scoring system (De Vita et al. 1992, cut-off ≥ 1) was used to grade the echostructure alterations of the salivary glands. Statistical analysis was performed using SPSS v16. RESULTS: This study included 50 pSS patients and 57 controls with no-SS sicca symptoms. The mean(SD) age of the pSS group was lower than non-SS group (47(13) vs 53(12)yrs, p = 0.006). No further differences between the two groups were observed. Patients with pSS showed a significantly higher SGUS score in comparison with controls (mean(SD) = 2.1(1.8) vs 0.0(0.4), p = 0.000). The SGUS cut-off ≥ 1 showed a sensitivity (SE) of 66 %, a specificity (SP) of 98 %, a positive predictive value (PPV) of 97 % and a negative predictive value (NPV) of 73 % for pSS diagnosis. The SGUS score correlated also with patients' MSGB/FS and USFR. CONCLUSIONS: This study confirmed the good performance of SGUS for the early non-invasive diagnosis of pSS. Further research in larger international cohort of patients is mandatory in order to assess the role of SGUS in the diagnostic algorithm of pSS

Site fidelity of Hippocampus guttulatus Cuvier, 1829 at Mar Piccolo of Taranto (Southern Italy; Ionian Sea)

Lack of detailed knowledge on ecological niche, life cycles, spatial distribution, reproductive biology and space use strongly affects the selection of useful tools and measures in the conservation of threatened marine species. Especially for sedentary and slow species, behaviour and movement capacities are supposed to be the most important functional traits. Indeed, behavioural variability concerning available space and the close presence of individuals is considered a crucial trait for the population dynamics assessments, especially when disturbances of various causes are present in the environment. The present study aimed to investigate the site fidelity and degree of movement of Hippocampus guttulatus, an emblematic and threatened Mediterranean seahorse species. With this aim, a number of seahorses were tagged and monitored throughout two years within a limited area of the lagoon of Mar Piccolo of Taranto (Southern Italy). The studied individuals were initially morphometrically measured for size, sex and life-cycle stage and subsequently monitored through repeated four-month surveys each year. Obtained results indicated high site fidelity regardless of habitat type. Movement pattern was in line with the data on congeneric species, although values were slightly higher. The analyses showed differences in movement degree among different sexes and life-cycle stages and indicated greater mobility of adult females compared to males and juveniles. The investigated parameters showed a great variability suggesting that even small-scale environmental factors can influence the species mobility. Finally, a change in the population structure has been observed, with the loss of large individuals in 2016 and reduced recruitment in 2017. These findings indicated the possible presence of stressors that could lead to the alteration of the seahorse population at Mar Piccolo of Taranto

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A Contemporary Reappraisal

Percutaneous alcohol septal ablation (ASA) is an effective and minimally invasive therapeutic strategy to resolve left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy who remain symptomatic on maximally tolerated medical therapy. First performed by Sigwart in 1994, the procedure consists in determining an iatrogenic infarction of the basal interventricular septum to reduce LVOTO and alleviate symptoms. Since its first description, numerous studies have demonstrated its efficacy and safety, proposing ASA as a valid and attractive alternative to surgical septal myectomy. The success rate of the intervention is profoundly affected by patient selection and centre experience. In this review, we sought to summarise current evidence on ASA, describing the procedure and proposing a cardiomyopathy team-based approach to resolve clinical disputes in clinical practice

Placental promoter methylation of DNA repair genes and prenatal exposure to particulate air pollution: an ENVIRONAGE cohort study

BACKGROUND: Exposure to particulate air pollution has been linked with risk of carcinogenesis. Damage to repair pathways might have long-term adverse health effects. We aimed to investigate the association of prenatal exposure to air pollution with placental mutation rate and the DNA methylation of key placental DNA repair genes. METHODS: This cohort study used data from the ongoing ENVironmental Influence ON early AGEing (ENVIRONAGE) birth cohort, which enrols pairs of mothers and neonates (singleton births only) at the East-Limburg Hospital (Genk, Belgium). Placental DNA samples were collected after birth. We used bisulfite-PCR-pyrosequencing to investigate the mutation rate of Alu (a marker for overall DNA mutation) and DNA methylation in the promoter genes of key DNA repair and tumour suppressor genes (APEX1, OGG1, PARP1, ERCC1, ERCC4, p53, and DAPK1). We used a high-resolution air pollution model to estimate exposure to particulate matter with a diameter less than 2·5 μm (PM2·5), black carbon, and NO2 over the entire pregnancy on the basis of maternal address. Alu mutation was analysed with a linear regression model, and methylation values of the selected genes were analysed in mixed-effects models. Effect estimates are presented as the relative percentage change in methylation for an ambient air pollution increment of one IQR (ie, the difference between the first and third quartiles of exposure in the entire cohort). FINDINGS: 500 biobanked placental DNA samples were randomly selected from 814 pairs of mothers and neonates who were recruited to the cohort between Feb 1, 2010, and Dec 31, 2014, of which 463 samples met the pyrosequencing quality control criteria. IQR exposure increments were 3·84 μg/m3 for PM2·5, 0·36 μg/m3 for black carbon, and 5·34 μg/m3 for NO2. Among these samples, increased Alu mutation rate was associated with greater exposure to PM2·5 (r=0·26, p<0·0001) and black carbon (r=0·33, p<0·0001), but not NO2. Promoter methylation was positively associated with PM2·5 in APEX1 (7·34%, 95% CI 0·52 to 14·16, p=0·009), OGG1 (13·06, 3·88 to 22·24, p=0·005), ERCC4 (16·31%, 5·43 to 27·18, p=0·01), and p53 (10·60%, 4·46 to 16·74, p=0·01), whereas promoter methylation of DAPK1 (-12·92%, -22·35 to -3·49, p=0·007) was inversely associated with PM2·5 exposure. Black carbon exposure was associated with elevated promoter methylation in APEX1 (9·16%, 4·06 to 14·25, p=0·01) and ERCC4 (27·56%, 17·58 to 37·55, p<0·0001). Promoter methylation was not associated with pollutant exposure in PARP1 and ERCC1, and NO2 exposure was not associated with methylation in any of the genes studied. INTERPRETATION: Transplacental in-utero exposure to particulate matter is associated with an increased overall placental mutation rate (as measured with Alu), which occurred in concert with epigenetic alterations in key DNA repair and tumour suppressor genes. Our results suggest that exposure to air pollution can induce changes to fetal and neonatal DNA repair capacity. Future studies will be essential to elucidate whether these changes persist and have a role in carcinogenic insults later in life. The work is supported by the European Research Council (ERC-2012-StG.310898 and ERC-2011-StG. 282413) and by the Flemish Scientific Fund (FWO,G073315N/G082317N)