Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report

Case presentation. We report the case of a 64-year-old Caucasian man diagnosed with chronic-phase chronic myeloid leukemia in April 2005. After 4 years of treatment with imatinib, he became intolerant to the drug and was switched to nilotinib. Two years later, he decided to stop nilotinib. Undetectable molecular response persisted for 30 months after discontinuation of the drug. Introduction. Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up. Conclusion: Our present case suggests that nilotinib withdrawal is safe for patients with chronic myeloid leukemia who achieve a stable undetectable molecular response. Our patient was homozygous for killer immunoglobulin-like receptor haplotype A, previously reported to be a promising immunogenetic marker for undetectable molecular response. We recommend additional studies to investigate patient immunogenetic profiles and their potential role in complete response to therap

Therapeutic approaches with intravitreal injections in geographic atrophy secondary to age-related macular degeneration: current drugs and potential molecules

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy

Bone marrow homing and engraftment defects of human hematopoietic stem and progenitor cells

Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow. We also address the problem of graft failure which remains a significant contributor to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Within this context, we discuss non-malignant and malignant hematological disorders treated with reduced-intensity conditioning regimens or grafts from human leukocyte antigen (HLA)-mismatched donor

Video Object Recognition and Modeling by SIFT Matching Optimization

In this paper we present a novel technique for object modeling and object recognition in video. Given a set of videos containing 360 degrees views of objects we compute a model for each object, then we analyze short videos to determine if the object depicted in the video is one of the modeled objects. The object model is built from a video spanning a 360 degree view of the object taken against a uniform background. In order to create the object model, the proposed techniques selects a few representative frames from each video and local features of such frames. The object recognition is performed selecting a few frames from the query video, extracting local features from each frame and looking for matches in all the representative frames constituting the models of all the objects. If the number of matches exceed a fixed threshold the corresponding object is considered the recognized objects .To evaluate our approach we acquired a dataset of 25 videos representing 25 different objects and used these videos to build the objects model. Then we took 25 test videos containing only one of the known objects and 5 videos containing only unknown objects. Experiments showed that, despite a significant compression in the model, recognition results are satisfactory

Object Recognition and Modeling Using SIFT Features

In this paper we present a technique for object recognition and modelling based on local image features matching. Given a complete set of views of an object the goal of our technique is the recognition of the same object in an image of a cluttered environment containing the object and an estimate of its pose. The method is based on visual modeling of objects from a multi-view representation of the object to recognize. The first step consists of creating object model, selecting a subset of the available views using SIFT descriptors to evaluate image similarity and relevance. The selected views are then assumed as the model of the object and we show that they can effectively be used to visually represent the main aspects of the object. Recognition is done making comparison between the image containing an object in generic position and the views selected as object models. Once an object has been recognized the pose can be estimated searching the complete set of views of the object. Experimental results are very encouraging using both a private dataset we acquired in our lab and a publicly available dataset

Therapeutic Effectiveness of Nutrition Therapy in Pediatric Patients with Chronic Liver Diseases Awaiting Liver Transplantation

Abstract It is important to prevent protein/calorie malnutrition in children with end stage liver diseases prior to transplantation. This study involved 34 patients between the ages of 10 and 156 months (mean value 25.69 months 32.2) (13 females and 21 males) on the liver transplant waiting list. Data collected as of three months before transplant and up to ten months after the procedure concerned gender, age, weight, height, Pediatric End Stage Liver Disease Score, baseline pathology, type of nutrition, type of transplant, immunosuppression, pulse steroid therapy, length of stay, and post transplant complications. Linear regression analysis showed that the length of hospital stay was 24.5 days more for females than for males, but also that intensive nutrition therapy shortens this stay for both female patients (P = 0.085) and younger patients (P = 0.023). The study population was divided into two groups according to the different nutritional therapies adopted. The Student’s t-test and Mann-Whitney test evidenced that the group receiving intensive nutrition therapy grew taller compared with the group following an oral diet (mean -1.37 and Prob = 0.043); that females grew taller compared to males (mean -1.65 +/- 0.56); and that there was an increase in height among the children in the group receiving intensive nutrition therapy despite the presence (-1.37 +/- 0.56) or absence (-14.8 +/- 5.44 and Prob = 0.035) of complications, and despite the administration (-1.03 +/- 0.33) or non administration (-1.48 +/- 0.55 and Prob = 0.019) of steroids. Intensive nutrition therapy enhances the velocity of growth in height and shortens the length of hospital stay, thus optimizing the final prognosis of the baseline pathology

High intensity X/ γ photon beams for nuclear physics and photonics

In this manuscript we review the challenges of Compton back-scattering sources in advancing photon beam performances in the1−20MeVenergy range, underlining the design criteria bringing tomaximum spectral luminosity and briefly describing the main achieve-ments in conceiving and developing new devices (multi-bunch RF cav-ities and Laser recirculators) for the case of ELI-NP Gamma BeamSystem (ELI-NP-GBS)

HLA-G expression and role in advanced-stage classical Hodgkin lymphoma

Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-

What unrelated hematopoietic stem cell transplantation in thalassemia taught us about transplant immunogenetics

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic nonmalignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS) and thalassemia-free survival (TFS) rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD) remains the most important complication in unrelated HSCT in thalassemia, leading to significant rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individualize appropriate strategies for its prevention and management. This review provides an overview of recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia