-
Vaccines Jan 2021Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and... (Review)
Review
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids contribute to serious adverse events (SAEs) following live varicella vaccination and live zoster vaccination. To this end, we examined multiple published reports of SAEs following varicella vaccination (Varivax) and zoster vaccination (Zostavax). We observed that five of eight viral SAEs following varicella vaccination, including two deaths, occurred in children receiving corticosteroids, while one of three fatal viral SAEs following live zoster vaccination occurred in an adult being treated with low-dosage prednisone. The latter death after live zoster vaccination occurred in a 70 year-old man with rheumatoid arthritis, being treated with prednisone 10 mg daily. Thus, corticosteroids contributed to more severe infectious complications in subjects immunized with each of the two live virus vaccines. Further, when we surveyed the rheumatology literature as well as individual case reports, we documented examples where daily dosages of 7.5-20 mg prednisone were associated with increased rates of severe wild-type varicella-zoster virus infections in children and adults.
PubMed: 33418856
DOI: 10.3390/vaccines9010023 -
The Journal of Biological Chemistry 2021Meningiomas (MNs), arising from the arachnoid/meningeal layer, are nonresponsive to chemotherapies, with ∼50% showing loss of the Neurofibromatosis 2 (NF2) tumor...
Meningiomas (MNs), arising from the arachnoid/meningeal layer, are nonresponsive to chemotherapies, with ∼50% showing loss of the Neurofibromatosis 2 (NF2) tumor suppressor gene. Previously, we established NF2 loss activates mechanistic target of rapamycin complex 1 (mTORC1) and mechanistic target of rapamycin complex 2 (mTORC2) signaling, leading to clinical trials for NF2 and MN. Recently our omics studies identified activated ephrin (EPH) receptor and Src family kinases upon NF2 loss. Here, we report increased expression of several ligands in NF2-null human arachnoidal cells (ACs) and the MN cell line Ben-Men-1, particularly neuregulin-1/heregulin (NRG1), and confirm increased NRG1 secretion and activation of V-ERB-B avian erythroblastic leukemia viral oncogene homolog 3 (ERBB3) receptor kinase. Conditioned-medium from NF2-null ACs or exogenous NRG1 stimulated ERBB3, EPHA2, and mTORC1/2 signaling, suggesting pathway crosstalk. NF2-null cells treated with an ERBB3-neutralizing antibody partially downregulated mTOR pathway activation but showed no effect on viability. mTORC1/2 inhibitor treatment decreased NRG1 expression and downregulated ERBB3 while re-activating pAkt T308, suggesting a mechanism independent of NRG1-ERBB3 but likely involving activation of another upstream receptor kinase. Transcriptomics after mTORC1/2 inhibition confirmed decreased ERBB3/ERBB4 while revealing increased expression of insulin-like growth factor receptor 1 (IGF1R). Drug treatment co-targeting mTORC1/2 and IGF1R/insulin receptor attenuated pAkt T308 and showed synergistic effects on viability. Our findings indicate potential autocrine signaling where NF2 loss leads to secretion/activation of NRG1-ERBB3 signaling. mTORC1/2 inhibition downregulates NRG1-ERBB3, while upregulating pAkt T308 through an adaptive response involving IGF1R/insulin receptor and co-targeting these pathways may prove effective for treatment of NF2-deficient MN.
Topics: Antibodies, Monoclonal, Humanized; Autocrine Communication; Benzamides; Benzoxazoles; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Lapatinib; Meningeal Neoplasms; Meningioma; Morpholines; Neuregulin-1; Neurofibromin 2; Proto-Oncogene Proteins c-akt; Pyrazoles; Pyrimidines; Receptor, EphA2; Receptor, ErbB-3; Receptor, IGF Type 1; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Transcriptome; Triazines
PubMed: 33273014
DOI: 10.1074/jbc.RA120.014960 -
Transplant Infectious Disease : An... Apr 2021We report a case of tuberculosis (TB) meningitis after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed acute myeloid leukemia. The patient was...
We report a case of tuberculosis (TB) meningitis after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed acute myeloid leukemia. The patient was 52-year-old woman who had relapsed leukemia with a remission duration of 7 months, and she received re-induction with consolidation, allogeneic HSCT. After 4 days of engraftment, she had headache with fever and cerebrospinal fluid (CSF) analysis presented increased intracerebral pressure, white blood cell counts with dominant neutrophils, elevated glucose and protein level. Brain imaging showed diffuse leptomeningeal enhancement with scattered miliary TB lesions suggesting disseminated TB disease. Mycobacterium tuberculosis was detected in CSF and sputum anti-TB medication was started. She was IGRA positive before transplantation but did not receive treatment for LTBI prior or during the transplant. Unfortunately, she expired because of intracerebral hemorrhage. TB meningitis is a rare but important complication of HSCT as it can cause serious neurologic sequelae, even death. So in transplant recipients having high risk of TB reactivation, LTBI treatment is recommended before or along with transplantation. If latent TB is not treated, vigilant suspicion and early diagnosis of TB meningitis could improve the transplant outcome.
Topics: Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Middle Aged; Recurrence; Tuberculosis, Meningeal
PubMed: 33012077
DOI: 10.1111/tid.13482 -
Turkish Journal of Haematology :... Nov 2020
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cerebral Cortex; Humans; Magnetic Resonance Imaging; Male; Meningeal Neoplasms
PubMed: 32830474
DOI: 10.4274/tjh.galenos.2020.2020.0376 -
Annals of Palliative Medicine Sep 2020This study was conducted to summarize the clinical, magnetic resonance imaging (MRI) and pathological features of IgG4-realated hypertrophic pachymeningitis (IgG4-RHP)...
BACKGROUND
This study was conducted to summarize the clinical, magnetic resonance imaging (MRI) and pathological features of IgG4-realated hypertrophic pachymeningitis (IgG4-RHP) and its differential diagnosis from similar diseases.
METHODS
Data of IgG4-RHP patients admitted to Department of Neurology, Neurosurgery and Infection, the First Affiliated Hospital of Medical School of Zhejiang University from January 1, 2015 to July 31, 2019 were collected and their clinical symptoms, laboratory examinations, imaging and pathological features were investigated. At the same time, the clinicopathological and imaging findings of other dura thickening diseases diagnosed in our hospital were compared and analyzed.
RESULTS
The clinical symptoms of 4 IgG4-RHP patients include chronic headache and cranial nerves injury, etc. Levels of serum IgG4 and cerebrospinal fluid (CSF) IgG4 increased in all patients. Focal enhancement of dura mater could be seen on plain and enhanced cranial MRI. Pathological results were consistent with IgG4-RHP symptoms. Among other diseases that cause dural thickening, the content of serum C-reactive protein in patients with Rosai-Dorfman disease declined. Patients with intracranial hypotension syndrome often have postural headache. Patients with tuberculous meningitis can have previous pulmonary tuberculosis. The diagnosis of patients with atypical meningioma depends on the results of operation and pathology. Patients with central nervous system leukemia can be diagnosed with reference to the results of laboratory results.
CONCLUSIONS
The clinicopathological and imaging manifestations of IgG4-RHP are summarized in this study. Meanwhile, the clinical data of several other diseases with similar imaging characteristics are analyzed in order to clarify the diagnostic strategy of IgG4-RHP and provide help for the next treatment.
Topics: Humans; Hypertrophy; Immunoglobulin G; Magnetic Resonance Imaging; Meningitis; Skull
PubMed: 32819129
DOI: 10.21037/apm-19-452 -
Haematologica Aug 2020
Topics: Central Nervous System; Drug Resistance, Neoplasm; Humans; Leukemia; Meninges
PubMed: 32739886
DOI: 10.3324/haematol.2020.253609 -
Cureus Jun 2020is a multidrug-resistant gram-positive bacterium of the human skin flora and one of the most clinically important nondiphtherial corynebacteria in the acute care...
is a multidrug-resistant gram-positive bacterium of the human skin flora and one of the most clinically important nondiphtherial corynebacteria in the acute care setting. can cause different forms of infections, especially in immunocompromised patients with underlying risk factors and comorbidities. was initially described in 1976 as a highly resistant coryneform bacteria causing severe sepsis in patients with hematologic malignancies and profound neutropenia. infection has also been reported in the setting of endocarditis, septicemia, meningitis, pneumonia, and soft tissue infections. Management of disseminated infection in immunocompromised cancer patients can be challenging due to its high virulence and rapid skin colonization. We present two cases of disseminated infection in patients with acute myelogenous leukemia (AML) and underlying comorbidities. Both patients presented with neutropenic fever resistant to initial standard empiric antibiotic therapy.
PubMed: 32714702
DOI: 10.7759/cureus.8764 -
Blood Jul 2020
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Meningitis, Aseptic; Methotrexate; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32702128
DOI: 10.1182/blood.2019004195 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... May 2020
Topics: Adenine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Meningitis, Cryptococcal; Piperidines; Pyrazoles; Pyrimidines
PubMed: 32536143
DOI: 10.3760/cma.j.issn.0253-2727.2020.05.013 -
Blood Aug 2020Cytokine storm syndromes (CSS) are severe hyperinflammatory conditions characterized by excessive immune system activation leading to organ damage and death....
Cytokine storm syndromes (CSS) are severe hyperinflammatory conditions characterized by excessive immune system activation leading to organ damage and death. Hemophagocytic lymphohistiocytosis (HLH), a disease often associated with inherited defects in cell-mediated cytotoxicity, serves as a prototypical CSS for which the 5-year survival is only 60%. Frontline therapy for HLH consists of the glucocorticoid dexamethasone (DEX) and the chemotherapeutic agent etoposide. Many patients, however, are refractory to this treatment or relapse after an initial response. Notably, many cytokines that are elevated in HLH activate the JAK/STAT pathway, and the JAK1/2 inhibitor ruxolitinib (RUX) has shown efficacy in murine HLH models and humans with refractory disease. We recently reported that cytokine-induced JAK/STAT signaling mediates DEX resistance in T cell acute lymphoblastic leukemia (T-ALL) cells, and that this could be effectively reversed by RUX. On the basis of these findings, we hypothesized that cytokine-mediated JAK/STAT signaling might similarly contribute to DEX resistance in HLH, and that RUX treatment would overcome this phenomenon. Using ex vivo assays, a murine model of HLH, and primary patient samples, we demonstrate that the hypercytokinemia of HLH reduces the apoptotic potential of CD8 T cells leading to relative DEX resistance. Upon exposure to RUX, this apoptotic potential is restored, thereby sensitizing CD8 T cells to DEX-induced apoptosis in vitro and significantly reducing tissue immunopathology and HLH disease manifestations in vivo. Our findings provide rationale for combining DEX and RUX to enhance the lymphotoxic effects of DEX and thus improve the outcomes for patients with HLH and related CSS.
Topics: Animals; Apoptosis; CD8-Positive T-Lymphocytes; Cytokine Release Syndrome; Cytokines; Dexamethasone; Disease Models, Animal; Drug Resistance; Drug Therapy, Combination; Humans; Interleukin-2; Janus Kinase Inhibitors; Janus Kinases; Lymphocytic Choriomeningitis; Lymphohistiocytosis, Hemophagocytic; Mice; Mice, Inbred C57BL; Nitriles; Perforin; Pyrazoles; Pyrimidines; STAT5 Transcription Factor; Signal Transduction; Specific Pathogen-Free Organisms
PubMed: 32530039
DOI: 10.1182/blood.2020006075