Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients — a 25‐year Italian experience

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Protocollo EuroNet-PHL-C2 per il trattamento del Linfoma di Hodgkin classico in bambini e adolescenti: risultati della U.O. Oncoematologia Pediatrica

Il linfoma di Hodgkin (LH) rappresenta circa l’8% delle neoplasie pediatriche. Con i recenti schemi terapeutici, la sopravvivenza cumulativa a 5 anni dalla diagnosi raggiunge il 94-95% a seconda dell’età d’esordio e dello stadio. Lo studio EuroNet-PHL-C2, “European Network of Paediatric Hodgkin Lymphoma Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents”, è un trial clinico internazionale multicentrico, randomizzato e controllato per il trattamento del linfoma di Hodgkin classico in bambini ed adolescenti. Il protocollo prevede una terapia di prima linea per tutti i pazienti, costituita da chemioterapia in base al rischio alla diagnosi (risk stratified), seguita da una eventuale radioterapia, la cui indicazione dipende dalla risposta alla chemioterapia (response adapted). Il trial si propone come obiettivo principale la riduzione dell’indicazione alla radioterapia senza compromissione dei tassi di guarigione. In questa tesi sono descritte le caratteristiche dei pazienti con Linfoma di Hodgkin Classico, arruolati dalla nostra unità operativa nel trial EuroNet-PHL-C2 nel periodo ottobre 2015 - novembre 2019. Vengono descritte le caratteristiche all’esordio, la stadiazione, la stratificazione secondo il livello di trattamento, il tipo di trattamento chemio e radioterapico, la risposta al trattamento e il follow-up

Bone Fragility in Acromegalic Patients: A Mystery Almost Solved?

Background: a high prevalence of vertebral fractures, despite normal bone mineral density (BMD), is reported in acromegalic patients in both the active and inactive phases of the disease. Aim of the study: to analyze the prevalence of vertebral fractures, bone turnover, BMD and histomorphometric parameters including bone microarchitecture in a group of acromegalic patients. Patients and methods: 42 acromegalic patients (26 males, 16 females, mean age 58 \ub112,5 and 58,8 \ub113,8 years), divided in 2 subgroups: one with active disease and one in remission (13, 29 patients respectively) underwent bone turnover evaluation (serum calcium, serum phosphate, PTH, 25- hydroxyvitamin (OH) D , ALP, CTX, urinary calcium/creatinine) and bone densitometry by Dual-Energy X-Ray Absorptiometry (DXA). Vertebral fractures were assessed by morphometric analysis during DXA. In 4 patients iliac crest bone biopsy was performed.Results: the prevalence of vertebral fractures was 64% in the whole population, 69% in the active group, 59% in the remission group. Among fractured patients, vertebral t-score was normal in 59% and it showed osteoporosis in only 11%. Vertebral BMD was higher in fractured patients compared to non-fractured (mean SD 1,108 \ub10,175 vs 0,961\ub1 0,118 g/cm2, p=0,009), also considering the active (1,147\ub10,241 vs 1,107\ub10,169 g/cm2) and inactive subgroups (1,093 \ub10,15 vs 0,945 \ub10,106g/cm2, p0,01). Disease duration was significantly higher in fractured compared to non-fractured patients (respectively 8,67 \ub16,65 and 6,93 \ub13,41 years, p<0,05). As regards bone metabolism parameters, urinary calcium/creatinine was significantly higher in fractured patients compared to non-fractured patients (0,125 \ub10,096 vs 0,074 \ub10,031, p<0,01). 25-OH vitamin D was low in both groups (fractures 24,93 \ub111,5 ng/ml, non-fractured patients 25,02 \ub17,28 ng/ml). Hypogonadism was a risk factor for vertebral fractures in active patients (p=0,04). The preliminary results regarding histomorphometric evaluation showed a greater cortical thickness and an increased porosity compared to that of normal subjects (cortical width 1882\ub1250 vs 816\ub1291 \u3bcm, cortical porosity index 10 \ub14% vs 5,79 \ub12,76%). IGF-1 positively correlated with porosity index (p<0,05).Conclusions: our data confirm a high prevalence of vertebral fractures in acromegalic patients despite a normal BMD. This apparent paradox could be explained by an increased cortical thickness associated with abnormal cortical porosity, mediated by IGF-1

Runx2 overexpression compromises bone quality in acromegalic patients

Acromegalic patients, characterized by excessive secretion of GH and IGF-1, show a high fracture risk but Bone Mineral Density is a poor predictor for bone fractures in these patients. The effects of an excess of GH/IGF1 on skeleton as well as on osteogenic progenitors, i.e. mesenchymal stem cells, have not been investigated in these patients. We aimed to elucidate the skeletal conditions of acromegalic patients by means of bone microarchitecture analysis and evaluation of MSCs osteogenic commitment. In particular, we performed histomorphometric analyses and we quantified the expression levels of the osteogenic transcription factor RUNX2 in circulating MSCs. Our results showed an abnormal microarchitecture and demonstrated that bone impairment in APs is associated with the upregulation of RUNX2 expression. Furthermore, osteoblastic activity was significantly reduced in patients under pharmacological treatment, compared to untreated patients. In conclusion, this study demonstrates the key role of RUNX2 gene overexpression in causing bone impairment in acromegalic patients. It also suggests a therapeutic approach for the improvement of bone quality, focused on the osteoblastic lineage rather than the inhibition of osteoclastic activity

Author Correction: The spread of steppe and Iranian-related ancestry in the islands of the western Mediterranean

Correction to: Nature Ecology & Evolution https://doi.org/10.1038/s41559-020-1102-0, published online 24 February 2020.D.M.F. was supported by an Irish Research Council grant GOIPG/2013/36. Radiocarbon work was supported in part by the NSF Archaeometry program BCS-1460369 (to D.J.K. and B.J.C). C.L.-F. was supported by Obra Social La Caixa and by FEDER-MINECO (BFU2015-64699-P and PGC2018-095931-B-100). D.C. was supported by grant 20177PJ9XF MIUR PRIN 2017. D.Reich is an Investigator of the Howard Hughes Medical Institute, and his ancient-DNA laboratory work was supported by National Science Foundation HOMINID grant BCS-1032255, a National Institutes of Health grant GM100233, an Allen Discovery Center grant, and grant no. 61220 from the John Templeton Foundation

The spread of steppe and Iranian-related ancestry in the islands of the western Mediterranean

Steppe-pastoralist-related ancestry reached Central Europe by at least 2500 bc, whereas Iranian farmer-related ancestry was present in Aegean Europe by at least 1900 bc. However, the spread of these ancestries into the western Mediterranean, where they have contributed to many populations that live today, remains poorly understood. Here, we generated genome-wide ancient-DNA data from the Balearic Islands, Sicily and Sardinia, increasing the number of individuals with reported data from 5 to 66. The oldest individual from the Balearic Islands (~2400 bc) carried ancestry from steppe pastoralists that probably derived from west-to-east migration from Iberia, although two later Balearic individuals had less ancestry from steppe pastoralists. In Sicily, steppe pastoralist ancestry arrived by ~2200 bc, in part from Iberia; Iranian-related ancestry arrived by the midsecond millennium bc, contemporary to its previously documented spread to the Aegean; and there was large-scale population replacement after the Bronze Age. In Sardinia, nearly all ancestry derived from the island’s early farmers until the first millennium bc, with the exception of an outlier from the third millennium bc, who had primarily North African ancestry and who—along with an approximately contemporary Iberian—documents widespread Africa-to-Europe gene flow in the Chalcolithic. Major immigration into Sardinia began in the first millennium bc and, at present, no more than 56–62% of Sardinian ancestry is from its first farmers. This value is lower than previous estimates, highlighting that Sardinia, similar to every other region in Europe, has been a stage for major movement and mixtures of people

Prospects for quarkonium studies at the high-luminosity LHC

International audienceProspects for quarkonium-production studies accessible during the upcoming high-luminosity phases of the CERN Large Hadron Collider operation after 2021 are reviewed. Current experimental and theoretical open issues in the field are assessed together with the potential for future studies in quarkonium-related physics. This will be possible through the exploitation of the huge data samples to be collected in proton–proton, proton–nucleus and nucleus–nucleus collisions, both in the collider and fixed-target modes. Such investigations include, among others, those of: (i) J/ψ and Υ produced in association with other hard particles; (ii) χc,b and ηc,b down to small transverse momenta; (iii) the constraints brought in by quarkonia on gluon PDFs, nuclear PDFs, TMDs, GPDs and GTMDs, as well as on the low-x parton dynamics; (iv) the gluon Sivers effect in polarised-nucleon collisions; (v) the properties of the quark–gluon plasma produced in ultra-relativistic heavy-ion collisions and of collective partonic effects in general; and (vi) double and triple parton scatterings

Perspectives for quarkonium studies at the high-luminosity LHC

We review the prospects for quarkonium-production studies in proton and nuclear collisions accessible during the upcoming phases of the CERN Large Hadron Collider operation after 2021, including the ultimate high-luminosity phase, with increased luminosities compared to LHC Runs 1 and 2. We address the current experimental and theoretical open issues in the field and the perspectives for future studies in quarkonium-related physics through the exploitation of the huge data samples to be collected in proton-proton, with integrated luminosities reaching up to 3/ab, in proton-nucleus and in nucleus-nucleus collisions, both in the collider and fixed-target modes. Such investigations include, among others, those of: (i) the quarkonia produced in association with other hard particles; (ii) the chi(Q) and eta(Q) down to small transverse momenta; (iii) the constraints brought in by quarkonia on gluon PDFs, nuclear PDFs, TMDs, GPDs and GTMDs, as well as on the low-x parton dynamics; (iv) the gluon Sivers effect in polarised-nucleon collisions; (v) the properties of the quark-gluon plasma produced in ultra-relativistic heavy-ion collisions and of collective partonic effects in general; and (vi) double and triple parton scatterings

Prospects for quarkonium studies at the high-luminosity LHC

International audienceProspects for quarkonium-production studies accessible during the upcoming high-luminosity phases of the CERN Large Hadron Collider operation after 2021 are reviewed. Current experimental and theoretical open issues in the field are assessed together with the potential for future studies in quarkonium-related physics. This will be possible through the exploitation of the huge data samples to be collected in proton–proton, proton–nucleus and nucleus–nucleus collisions, both in the collider and fixed-target modes. Such investigations include, among others, those of: (i) J/ψ and Υ produced in association with other hard particles; (ii) χc,b and ηc,b down to small transverse momenta; (iii) the constraints brought in by quarkonia on gluon PDFs, nuclear PDFs, TMDs, GPDs and GTMDs, as well as on the low-x parton dynamics; (iv) the gluon Sivers effect in polarised-nucleon collisions; (v) the properties of the quark–gluon plasma produced in ultra-relativistic heavy-ion collisions and of collective partonic effects in general; and (vi) double and triple parton scatterings