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ObjectiveIndividuals with Autism Spectrum Disorder (ASD) often exhibit a low dietary diversity due to food selectivity that leads them to a marked preference for high-energy-density food, exposing them to risk of malnutrition. Despite these aspects, specific recommendations and targeted menus for this population are missing. The pilot study FOOD-AUT addresses this issue by developing canteen menus meeting the nutritional and sensory needs of adults with ASD, aiming to reduce their food selectivity, and consequently improving their health.MethodsThe project, funded by Gruppo Pellegrini S.p.A, was conducted at the daycare service of Sacra Famiglia Onlus Foundation, between March-2022 to March-2023. The study was divided into two phases. Observational phase: a comparison was made between the enrolled subjects’ nutritional needs and the nutrient content of the administered menus during the daycare service. Then mealtime compliance was assessed using standardized meal evaluation forms, both quantitative and qualitative. Intervention phase: canteen menus targeted to the individuals’ nutritional and sensory needs were administered and their acceptability was evaluated.ResultsTwenty-two individuals with ASD, aged 19–48, 72.7% males, were enrolled. Overweight and obesity prevalence were 54.5 and 18.2%, respectively. The observational phase showed how the most accepted foods had specific sensorial characteristics in line with the scientific literature. Adapting the menus improved food acceptance and reduced food waste.ConclusionThe results highlighted the need for adapted menus and greater attention to the way meals are delivered and consumed to improve nutritional status and therefore health of this population at increased risk of malnutrition.Clinical trial registrationClinicalTrial.gov, unique identifier: NCT05978895.

Abstract Background Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) comprise several rare hematologic malignancies with shared concomitant dysplastic and proliferative clinicopathologic features of bone marrow failure and propensity of acute leukemic transformation, and have significant impact on patient quality of life. The only approved disease-modifying therapies for any of the MDS/MPN are DNA methyltransferase inhibitors (DNMTi) for patients with dysplastic CMML, and still, outcomes are generally poor, making this an important area of unmet clinical need. Due to both the rarity and the heterogeneous nature of MDS/MPN, they have been challenging to study in dedicated prospective studies. Thus, refining first-line treatment strategies has been difficult, and optimal salvage treatments following DNMTi failure have also not been rigorously studied. ABNL-MARRO (A Basket study of Novel therapy for untreated MDS/MPN and Relapsed/Refractory Overlap Syndromes) is an international cooperation that leverages the expertise of the MDS/MPN International Working Group (IWG) and provides the framework for collaborative studies to advance treatment of MDS/MPN and to explore clinical and pathologic markers of disease severity, prognosis, and treatment response. Methods ABNL MARRO 001 (AM-001) is an open label, randomly allocated phase 1/2 study that will test novel treatment combinations in MDS/MPNs, beginning with the novel targeted agent itacitinib, a selective JAK1 inhibitor, combined with ASTX727, a fixed dose oral combination of the DNMTi decitabine and the cytidine deaminase inhibitor cedazuridine to improve decitabine bioavailability. Discussion Beyond the primary objectives of the study to evaluate the safety and efficacy of novel treatment combinations in MDS/MPN, the study will (i) Establish the ABNL MARRO infrastructure for future prospective studies, (ii) Forge innovative scientific research that will improve our understanding of pathogenetic mechanisms of disease, and (iii) Inform the clinical application of diagnostic criteria, risk stratification and prognostication tools, as well as response assessments in this heterogeneous patient population. Trial registration This trial was registered with ClinicalTrials.gov on August 19, 2019 (Registration No. NCT04061421).

Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatible living donor. The desensitization protocol consisted of Rituximab administration and immunoadsorption while the pre-transplant protocol, which was initiated 14 days before the transplant, included Tacrolimus, Mofetil Mycophenolate (MMF), antimicrobial and antiviral prophylaxis. Induction therapy consisted of anti-thymocyte globulins and steroids, while maintenance after transplantation consisted of steroid, tacrolimus and MMF. When the first occurrence of leukopenia was observed six weeks after the transplant, firstly antimicrobial/antiviral prophylaxis was stopped and later also MMF treatment was interrupted but severe neutropenia relapsed after MMF resuming treatment. Immunological and virological causes were excluded. The patient was treated with Filgrastim. Bone marrow biopsy, which was performed to exclude a hematological cause of severe persistent neutropenia, revealed a bone marrow hypoplasia with neutrophils maturation interrupted at the early stages. This case highlights the need to establish diagnostic and therapeutic guidelines for PTN which take in consideration all the therapeutic steps including the pre-transplant phase in particular in the context of AB0i where immunosuppression is more consistent.

Mastocytosis encompasses a subset of rare diseases, characterized by the presence and accumulation of abnormal neoplastic MC in various organ systems, including skin, bone marrow, spleen and gastrointestinal tract. Clinical manifestations are highly heterogeneous, as they result from both MC mediator release and MC organ infiltration. Both pregnancy, a lifetime dominated by huge physiological changes, and labor can provide triggers that could induce worsening of mastocytosis symptoms. On the other hand, mastocytosis has relevant implications in obstetric management and prenatal care during all the pregnancy. In this review article, current knowledge about the impact of mastocytosis on fertility and pregnancy outcome will be reviewed and discussed, with the aim to provide clinical practice guidance for the evaluation and management of pregnancy and delivery in patients with cutaneous and systemic mastocytosis.

Abstract: Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.

Non-invasive screening tools to identify children at high risk of vitamin D (VitD) deficiency are proactive measures in preventive care. Recently, a validated questionnaire (Evaluation dEficieNCy Questionnaire, EVIDENCe-Q) for identifying newly diagnosed VitD-insufficient adults has been developed. We tested the EVIDENCe-Q modified for children with obesity and evaluated the correlation between VitD and questionnaire scores to adapt this tool to the pediatric population. We enrolled 120 children with obesity (BMI ≥ 2). Clinical evaluation and VitD levels were considered. The modified EVIDENCe-Q included information regarding factors affecting control of VitD, with scores ranging between 0 (best) and 36 (worst). VitD and adiposity indices were inversely correlated. The threshold values for identifying severe deficiency (

Achievement of deep molecular response following treatment with a tyrosine kinase inhibitor (TKI) allows for treatment-free remission (TFR) in many patients with chronic myeloid leukemia (CML). Successful TFR is defined as the achievement of a sustained molecular response after cessation of ongoing TKI therapy. The phase 3 ENESTPath study was designed to determine the required optimal duration of consolidation treatment with the second-generation TKI, nilotinib 300 mg twice-daily, to remain in successful TFR without relapse after entering TFR for 12 months. The purpose of this Italian ‘patient’s voice CML’ substudy was to evaluate patients’ psycho-emotional characteristics and quality of life through their experiences of stopping treatment with nilotinib and entering TFR. The purpose of the present contribution is to early present the study protocol of an ongoing study to the scientific community, in order to describe the study rationale and to extensively present the study methodology. Patients aged ≥18 years with a confirmed diagnosis of Philadelphia chromosome positive BCR-ABL1+ CML in chronic phase and treated with front-line imatinib for a minimum of 24 months from the enrollment were eligible. Patients consenting to participate the substudy will have quality of life questionnaires and in-depth qualitative interviews conducted. The substudy will include both qualitative and quantitative design aspects to evaluate the psychological outcomes as assessed via patients’ emotional experience during and after stopping nilotinib therapy. Randomization is hypothesized to be a timepoint of higher psychological alert or distress when compared to consolidation and additionally any improvement in health-related quality of life (HRQoL) due to nilotinib treatment is expected across the timepoints (from consolidation, to randomization, and TFR). An association is also expected between dysfunctional coping strategies, such as detachments and certain personality traits, and psychological distress and HRQoL impairments. Better HRQoL outcomes are expected in TFR compared to the end of consolidation. This substudy is designed for in-depth assessment of all potential psycho-emotional variables and aims to determine the need for personalized patient care and counselling, and also guide clinicians to consider the psychological well-being of patients who are considering treatment termination.NCT number: NCT01743989, EudraCT number: 2012-005124-15

Abstract: Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark − count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10−4), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively (P < 10−4). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860.

Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk of transforming into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed. However, many questions remain regarding prognostication and optimal therapy. In addition, there is a need to define potential pre-phases of CMML and special CMML variants, and to separate these entities from each other and from conditions mimicking CMML. To address these unmet needs, an international consensus group met in a Working Conference in August 2018 and discussed open questions and issues around CMML, its variants, and pre-CMML conditions. The outcomes of this meeting are summarized herein and include diag nostic criteria and a proposed classification of pre-CMML conditions as well as refined minimal diagnostic criteria for classical CMML and special CMML variants, including oligomonocytic CMML and CMML associated with systemic mastocytosis. Moreover, we propose diagnostic standards and tools to distinguish between ‘normal’, pre-CMML and CMML entities. These criteria and standards should facilitate diagnostic and prognostic evaluations in daily practice and clinical studies in applied hematology.

It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P

Chronic myeloid leukemia (CML) is characterized by the constitutive tyrosine kinase activity of the oncoprotein BCR-ABL1 in myeloid progenitor cells that activates multiple signal transduction pathways leading to the leukemic phenotype. The tyrosine-kinase inhibitor (TKI) nilotinib inhibits the tyrosine kinase activity of BCR-ABL1 in CML patients. Despite the success of nilotinib treatment in patients with chronic-phase (CP) CML, a population of Philadelphia-positive (Ph+) quiescent stem cells escapes the drug activity and can lead to drug resistance. The molecular mechanism by which these quiescent cells remain insensitive is poorly understood. The aim of this study was to compare the gene expression profiling (GEP) of bone marrow (BM) CD34+/lin- cells from CP-CML patients at diagnosis and after 12 months of nilotinib treatment by microarray, in order to identify gene expression changes and the dysregulation of pathways due to nilotinib action. We selected BM CD34+/lin- cells from 78 CP-CML patients at diagnosis and after 12 months of first-line nilotinib therapy and microarray analysis was performed. GEP bioinformatic analyses identified 2,959 differently expressed probes and functional clustering determined some significantly enriched pathways between diagnosis and 12 months of nilotinib treatment. Among these pathways, we observed the under expression of 26 genes encoding proteins belonging to the cell cycle after 12 months of nilotinib treatment which led to the up-regulation of chromosome replication, cell proliferation, DNA replication, and DNA damage checkpoint at diagnosis. We demonstrated the under expression of the ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCD3 encoding proteins which pumped drugs out of the cells after 12 months of nilotinib. Moreover, GEP data demonstrated the deregulation of genes involved in the JAK-STAT signaling pathway. The down-regulation of JAK2, IL7, STAM, PIK3CA, PTPN11, RAF1, and SOS1 key genes after 12 months of nilotinib could demonstrate the up-regulation of cell cycle, proliferation and differentiation via MAPK and PI3K-AKT signaling pathways at diagnosis.

El objetivo de este escrito es describir y analizar los aportes e implicancias de la inclusión de prácticas comunitarias en la formación universitaria a partir de una experiencia de extensión desarrollada en la Facultad de Psicología de la Universidad de Buenos Aires (UBA), y su articulación a procesos de investigación y docencia. Partiendo de breves viñetas, abordamos los atravesamientos subjetivos de esta experiencia y cuestionamos la construcción de roles profesionales rígidos y estáticos, así como una formación universitaria centrada en la relación asimétrica y distante entre docente–estudiante, alejada de las problemáticas sociocomunitarias concretas. Se concluye que uno de los principales aportes de esta experiencia está en la creación colectiva de una posición reflexiva, implicada y activa, con relación a las problemáticas psicosociales. Consideramos que este proceso aporta en la construcción de un puente entre universidad y realidad social, el que esperamos fortalecer a partir de articulaciones múltiples entre prácticas de extensión e investigación participativa.

Primary resistance to tyrosine-kinase inhibitors (TKIs) is quite uncommon in chronic-phase Chronic Myeloid Leukemia (CML) and related to still poorly understood mechanisms, as ABL mutations are rarely detected in primary resistant patients. We report the challenging case of a CML patient who was resistant to multiple TKIs because of different emerging ABL mutations and became pregnant while on Nilotinib therapy despite repeated and clear discouragement to conceive. She decided to continue with her pregnancy, showing an admirable and incredible perseverance in the pursuit of her personal aims.

Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.

Somatic mutations of MPL exon 10, mainly involving a W515 substitution, have been described in JAK2 (V617F)-negative patients with essential thrombocythemia and primary myelofibrosis. We used direct sequencing and high-resolution melt analysis to identify mutations of MPL exon 10 in 570 patients with myeloproliferative neoplasms, and allele specific PCR and deep sequencing to further characterize a subset of mutated patients. Somatic mutations were detected in 33 of 221 patients (15%) with JAK2 (V617F)-negative essential thrombocythemia or primary myelofibrosis. Only one patient with essential thrombocythemia carried both JAK2 (V617F) and MPL (W515L). High-resolution melt analysis identified abnormal patterns in all the MPL mutated cases, while direct sequencing did not detect the mutant MPL in one fifth of them. In 3 cases carrying double MPL mutations, deep sequencing analysis showed identical load and location in cis of the paired lesions, indicating their simultaneous occurrence on the same chromosome.

Within a cohort of 1,915 consecutive patients with myeloproliferative neoplasm followed for a median time of 5.2 years (range 0–33.3), we investigated the occurrence of lymphoid neoplasm with the aim of defining this risk and to investigate the role of genetic predisposing factors. We identified 22 patients with myeloproliferative neoplasm who developed lymphoid neoplasm over their lifetime. We found that the risk of developing lymphoid neoplasm was 2.79-fold higher (95% CI, 1.80–4.33; P

Risk stratification in primary myelofibrosis is currently based on two international prognostic scoring systems, neither of which takes into consideration red blood cell transfusion-dependency. In 288 consecutive patients with primary myelofibrosis, red blood cell transfusion-dependency at diagnosis affects survival independently of the International Prognostic Scoring System (P

Background Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia.Design and Methods We studied 605 patients with essential thrombocythemia (follow-up 4596 person-years) with the aim of defining prognostic factors for thrombosis, myelofibrosis, and leukemia during follow-up.Results Sixty-six patients (11%) developed thrombosis with a 10-year risk of 14%. Age >60 years (p60 years (p

In this report, we present images from a patient with acute promyelocytic leukemia who experienced several central nervous system relapses.

This document summarizes a study on the effects of CFTR modulators on patients with cystic fibrosis (CF) and leukocyte adhesion deficiency type IV (LAD-IV). The study found that CFTR modulators improved certain cellular functions in CF patients, suggesting that they may correct both CF and LAD-IV phenotypes. However, there were some patients who showed improvement in CF symptoms but not in LAD-IV characteristics, indicating the need for further research. The study also suggests that measuring certain cellular markers could be a useful method for monitoring patients in the long term. [Extracted from the article]

Nerve sheath myxoma (NSM) is a rare benign peripheral nerve sheath tumor that affects young adults. NSMs are asymptomatic, slow-growing swellings located in the upper extremities, more rarely in the lower extremities. Given the high risk of recurrence, it is recommended to perform a complete exeresis. To our knowledge, the evolution and management of NMS during pregnancy have not been described yet. We report the first case of recurrent pretibial NSM in a pregnant girl and its follow-up and outcome during and after pregnancy. NSM is difficult to diagnose clinically or using imaging. The final diagnosis remains histopathological. It is known how various types of benign and malignant skin tumors can develop or change during pregnancy. With our case, however, we documented that pregnancy does not affect the growth and evolution of NSM. Given the benign nature of the lesions and their tendency to grow slowly, during pregnancy, follow-up of NSMs can be conducted through ultrasonography and surgical treatment postponed after delivery. Our case highlights the importance of careful monitoring and individualized decision making, especially in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Our case highlights the importance of a careful monitoring and a tailored treatment in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Considering the benign nature of the lesions and their tendency to grow slowly, follow-up of NSMs during pregnancy can be conducted through ultrasonography, and surgical treatment can be postponed after delivery. [ABSTRACT FROM AUTHOR]