Infection and massive bone marrow necrosis in the treatment of thrombotic thrombocytopenia purpura (TTP) [abstract]

Bone marrow necrosis (BMN) is a rare entity and until recently has been a postmortem phenomenon. Most ante-mortem cases are associated with underlying malignancy, primarily leukemias and lymphomas. Rarely, it is the result of other etiologies. BMN is characterized by sheets of poorly defined necrotic cells over an eosinophilic amorphous background with preserved cortical bone. The pathophysiology of BMN is not fully understood. This case report is of an adult female who presented initially with thrombotic thrombocytopenia purpura (TTP), was treated with plasma exchange, rituximab, vincristine, and subsequently developed marked pancytopenia. The bone marrow biopsy revealed profound bone marrow necrosis and mixed bacterial infection. Shortly after the patient was treated with antibiotics her peripheral blood cell count recovered. The patient has survived to date with no underlying malignancy identified. The etiology of this patients bone marrow necrosis is unknown, however four scenarios are possible. The most likely of these, is that the patient, immunosuppressed from her TTP therapy, became infected, the infection starved the marrow and then the marrow subsequently died. The source of infection was undiscovered. Other possible causes include undetected malignancy and TTP, which can plug the microcirculation of the bone marrow and cause necrosis. A single case reporting a patient having an acute reaction to rituximab therapy with bone marrow necrosis appearing 2 weeks later. There are no reports in the literature of bone marrow infection and necrosis associated with the treatment of TTP, without a concurrent diagnosis of cancer

Papillary thyroid carcinoma arising from a mature teratoma in a cryptorchid testis : a case report

Struma testis is a rare entity, and malignant transformation of a testicular teratoma to papillary thyroid carcinoma (PTC) has only once been previously described. Furthermore, sold tumor metastases to the testis are rare, with a less than 1% rate of testicular metastases from solid tumors, and there are no reports of primary thyroid carcinomas metastasizing to the testis. We report the case of a 56 year old man who was found to have a cryptorchid testis containing a mature teratoma with malignant somatic component in the form of a 1.6 centimeter PTC

Bone marrow failure associated with CD8 T-cell expansion in a patient with trichorhinophalangeal syndrome and common variable immunodeficiency [abstract]

Objective: To report a case of trichorhinophalangeal syndrome coexistent with common variable immunodeficiency (CVID)-like phenotype with a polyclonal expansion of CD8 T-cells Case: A 34-year-old white woman with multiple congenital abnormalities, autoimmune endocrinopathies, and chronic neutropenia with splenomegaly presented with daily low-grade fever. Laboratory examination showed pancytopenia and persistent neutropenia now unresponsive to G-CSF. A bone marrow biopsy revealed 95% cellularity, myelofibrosis, increased histiocytes and eosinophils, and extensive lymphoid infiltration all interpreted to represent a T-cell proliferative diseasepossibly malignant or as secondary to either long-term G-CSF treatment or CVID. To better understand her problems, her full history was reviewed, the literature was searched, and a T-cell receptor gene rearrangement analysis was performed. Discussion: CVID is clinically diverse: several potential genetic and immunopathogenic mechanisms may account for these heterogeneous and poorly defined clinical phenotypes. Polyclonal expansion of large granular lymphocytes with neutropenia has been reported in a substantial proportion of CVID patients and is associated with elevated levels of soluble Fas ligand. Molecular genetic analysis of the marrow showed that the T cells were polyclonal, ruling out malignancy. Although this patient's congenital abnormalities are likely unrelated, we hypothesize at least some of her endocrinopathies and all of her hematologic abnormalities are a manifestation of immunodysregulation due to CVID. This stresses the need to more precisely define distinct clinical phenotypes and to develop guidelines for diagnosis and treatment of a very heterogeneous syndrome, CVID

How Low Can You Go? Feature Selection for Drug Discovery

The cost of bringing a drug to market depends on how quickly a candidate drug can be “discovered” and evaluated to ensure safety and effectiveness. In this work we develop a method for predicting whether a given drug and protein compound will “bind.” Our aim is to select a set of features to predict drug-protein interactions. This study focuses on kinases. Kinase inhibitors are the largest class of new cancer therapies. Selective inhibition is difficult due to high sequence similarity, leading to off-target interactions and side-effects. Pictured here human c-SRC

Unique challenges for glioblastoma immunotherapy—discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank

Cancer immunotherapy has made remarkable advances with over 50 separate Food and Drug Administration (FDA) approvals as first- or second-line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T cells, and bispecific T-cell-engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights into the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells, T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner

Unique challenges for glioblastoma immunotherapy - Discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology.

Cancer immunotherapy has made remarkable advances with over fifty separate Food and Drug Administration (FDA) approvals as first or second line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T-cells and bispecific T-cell-engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights in the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells and T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

© 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975)