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3.
J Stroke Cerebrovasc Dis ; 31(1): 106163, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34763262

RESUMO

The SARS-CoV-2 virus, which causes Coronavirus disease 2019 (COVID-19), has resulted in millions of worldwide deaths. When the SARS-CoV-2 virus emerged from Wuhan, China in December 2019, reports of patients with COVID-19 revealed that hospitalized patients had acute changes in mental status, cognition, and encephalopathy. Neurologic complications can be a consequence from overall severity of the systemic infection, direct viral invasion of the SARS-CoV-2 virus in the central nervous system, and possible immune mediated mechanisms. We will examine the landscape regarding this topic in this review in addition to current understandings of COVID-19 and hemostasis, treatment, and prevention, as well as vaccination.


Assuntos
COVID-19 , Sistema Nervoso Central/virologia , Doenças do Sistema Nervoso , Trombofilia/prevenção & controle , Anticoagulantes , Hemostasia , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , SARS-CoV-2 , Trombofilia/diagnóstico
4.
Clin Case Rep ; 9(11): e04845, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34853682

RESUMO

Aplastic anemia is a disorder of bone marrow failure characterized by a hypocellular bone marrow. We report two cases with an initial hypercellular bone marrow at the time of presentation, suggesting a new phase in the pathogenesis of the disease.

5.
Case Rep Transplant ; 2020: 3954165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765921

RESUMO

Erdheim-Chester disease is a rare inflammatory disease that infiltrates skeletal and extra-skeletal tissue. Chronic kidney disease (CKD) in Erdheim-Chester disease is usually attributed to retroperitoneal lesions that lead to urologic obstruction and hydronephrosis. In this report, we describe a patient diagnosed with Erdheim-Chester disease who eventually developed end-stage kidney disease (ESKD). After complete remission of Erdheim-Chester disease by vemurafenib therapy and 2 years of hemodialysis, the patient underwent a deceased donor kidney transplantation with basiliximab induction and tacrolimus/mycophenolic acid maintenance. After conversion of mycophenolic acid to azathioprine due to cost, acute cellular rejection had occurred, and he was treated with steroid therapy. The patient remained in complete remission from Erdheim-Chester disease and dialysis-free 16 months after transplant. Kidney transplantation is another treatment option for those patients with Erdheim-Chester disease who suffer from renal failure in the setting of complete remission.

7.
Leuk Lymphoma ; 61(8): 1965-1973, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32432489

RESUMO

Gemtuzumab ozogamicin (GO) remained available to US clinicians through an open-label expanded-access protocol (NCT02312037) until GO was reapproved. Patients were aged ≥3 months with relapsed/refractory (R/R) acute myeloid leukemia (AML), high-risk myelodysplastic syndrome, or acute promyelocytic leukemia (APL), and had exhausted other treatment options. Three hundred and thirty one patients received GO as monotherapy for R/R AML (n = 139), combination therapy for R/R AML (n = 183), or treatment for R/R APL (n = 9). Corresponding treatment discontinuations occurred in 68, 39, and 33% of patients. All-causality grade 5 AEs occurred in 52, 22, and 22% of patients in the monotherapy, combination, and APL groups, respectively. Corresponding grades 3 and 4 treatment-related AEs were reported in 60, 55 and 78% of patients. Hepatotoxicity occurred in five patients: veno-occlusive disease (n = 4) and drug-induced liver injury (n = 1). GO was generally well tolerated in patients with R/R AML or APL. Most frequent treatment-related grade ≥3 AEs were hematologic AEs.Clinicaltrials.gov identifier: NCT02312037.


Assuntos
Aminoglicosídeos , Leucemia Mieloide Aguda , Aminoglicosídeos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Gemtuzumab , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico
8.
J Hematol ; 8(4): 149-154, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32300462

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive systemic inflammation which causes tissue damage due to abnormal immune system activation and has a high fatality rate even with treatment. HLH continues to be a difficult diagnosis to make because of lack of awareness and its overlap with other illnesses. This disorder is well defined in pediatric patients under the age of 18, but there is also a paucity of data in the adult population. The goals of this study were to describe associated disorders, clinical course and outcomes, and to determine if additional clinical criteria can be used to help with the diagnosis of HLH in adult patients. METHODS: Patients' electronic medical records from 2007 to 2017 (who were ≥ 18 years old at the time of the search) were screened by ICD 9 and ICD 10 codes which contain the diagnosis of HLH or hemophagocytic syndrome, infection-associated. We identified 41 adult cases of HLH that were treated at our medical center over the course of 10 years and assessed these patients using both the historical and newly proposed diagnostic criteria. We also identified underlying diagnoses related to the development of HLH and fatality rates. RESULTS: Median age at diagnosis was 55 years old (18 - 87 years old) and 22 were male. Twenty-two had an infection, 16 with malignancy, seven had an autoimmune disorder and one with Sweet syndrome. Fifteen patients were treated with steroids alone, 18 with steroids and chemotherapy, three with steroids and antiviral agents, and two with chemotherapy alone. Sixteen (39%) died and 25 (60%) survived discharge. Seven patients died after discharge. Median survival of all patients was 1,095 days. CONCLUSIONS: Our data show that HLH is primarily associated with infections and malignancies. Newly proposed diagnostic criteria are not as specific, but can be helpful in making the diagnosis of HLH. We also showed that the fatality rate at our institution was lower than currently published rates of adult HLH.

9.
Leukemia ; 33(2): 371-378, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30315234

RESUMO

Here we quantify and compare the absolute and relative overall survival (OS) benefits conveyed by complete remission (CR) in AML and high-risk MDS, and by CR with incomplete count recovery (CRi) in AML and by hematologic improvement (HI) in MDS, following treatment with 7 + 3 versus azacytidine. We compared patients receiving 7 + 3 in SWOG studies S0106 (n = 301) and S1203 (n = 261) enrolling adults ≤ 60 years, with patients receiving azacytidine therapies in S0703 (n = 133 AML patients ≥ 60) and S1117 (n = 277 MDS patients ≥ 18). Absolute survival benefit was evaluated with 1-year, 3-year, and median OS; relative benefit was evaluated with univariate and covariate-adjusted hazard ratios. CR conveyed a relative survival advantage in multivariable analysis, with a similar relative effect of CR across studies. CR also conferred an absolute survival benefit, but with a smaller magnitude of absolute benefit in the azacytidine trials. In AML, OS was similar for CRi and failure to achieve CR/CRi. In MDS, CR conferred a survival advantage versus HI and HI versus failure. The relative survival benefit of CR was similar regardless of initial therapy for AML or high-risk MDS. With both therapies, CR has a beneficial effect on survival compared with CRi or HI.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Leucemia Mieloide Aguda/mortalidade , Síndromes Mielodisplásicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Azacitidina/administração & dosagem , Citarabina/administração & dosagem , Feminino , Seguimentos , Gemtuzumab , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
10.
Neurosurg Clin N Am ; 29(4): 493-501, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30223962

RESUMO

Hemostasis is the normal process of blood coagulation in vivo to stop pathologic bleeding. Virchow triad includes venous stasis, hypercoagulability, and vascular injury. Natural anticoagulants include protein C, protein S, and antithrombin. Factor V Leiden is the most common inherited thrombophilia, followed by prothrombin gene mutation. All inherited thrombophilias are passed down in an autosomal dominant fashion. Patients harboring the antiphospholipid antibodies have an increased risk for thrombosis. von Willebrand disease is the most common inherited bleeding disorder; the pattern of inheritance is autosomal. Hemophilia A and B are the only hereditary bleeding disorders inherited in a sex-linked recessive pattern.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/genética , Trombofilia/genética , Coagulação Sanguínea , Hemofilia A/genética , Humanos , Mutação , Doenças de von Willebrand/genética
11.
Blood ; 131(25): 2782-2788, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29618479

RESUMO

Patients may be deemed ineligible for a clinical trial for reasons that do not directly impact efficacy or safety. We identified reasons for ineligibility and compared outcomes of ineligible with eligible patients treated on Southwest Oncology Group (SWOG) Leukemia Committee protocols. Patients enrolled in SWOG phase 2, 2/3, or 3 protocols open since 2005 were analyzed for eligibility status, reasons for ineligibility, baseline characteristics, Eastern Cooperative Oncology Group (ECOG) performance status (PS), serious adverse events (SAEs), complete remission (CR) status, and overall survival. A total of 2361 patients were enrolled in the 13 included studies. Of these, 247 (10%) were deemed ineligible; 78 were excluded from analyses, and 169 were included. Of the 169 included in analyses, 60% (101/169) were excluded due to missing baseline documentation. Baseline characteristics comparing ineligible to eligible patients were similar, with the exception of ECOG PS for S0325 (P = .02) and S0530 (P = .002). In multivariable analyses, neither the proportion of patients with ECOG PS ≥ 2 (P = .12) nor the rate of grade 5 SAEs (P = .62) differed between groups. There was no difference in survival between eligible and ineligible patients (P = .25), and CR rates were similar, with the exception of S0325 (P < .001) and S0703 (P = .004). The findings of this study suggest that nonessential eligibility criteria can be less restrictive, thus expanding patient enrollment and avoiding protocol deviations. The clinical trials included in this study were registered at www.clincialtrials.gov as #NCT00085709, #NCT00066794, #NCT00070499, #NCT00109837, #NCT00093418, #NCT00492856, #NCT00337168, #NCT00352365, #NCT00658814, #NCT00792948, #NCT00945815, #NCT00840177, and #NCT01522976.


Assuntos
Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/métodos , Leucemia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Definição da Elegibilidade/métodos , Feminino , Humanos , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
N Engl J Med ; 377(9): 895, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28854087
13.
Curr Neurol Neurosci Rep ; 17(2): 13, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28229399

RESUMO

PURPOSE OF REVIEW: Acute and chronic leukemias are heterogeneous diseases and can affect any part of the body upon initial discovery. Understanding the sequela of systemic involvement is key for proper diagnosis and treatment. RECENT FINDINGS: Over the decades, new research has emerged regarding neurological complications of the myeloid or lymphoid leukemias. Central nervous system involvement usually confers a poor prognosis and requires emergent treatment. Standard of care still involves systemic therapy, intrathecal administration of chemotherapeutic agents, and cranial radiation. Treatment-related side effects can occur and need to be recognized by any practitioner involved with patient care. It is imperative to understand neurologic complications from leukemia to prevent delays and initiate necessary treatment to maintain neurologic and cognitive function.


Assuntos
Leucemia/complicações , Doenças do Sistema Nervoso/complicações , Antineoplásicos/efeitos adversos , Tratamento Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Leucemia/diagnóstico , Leucemia/tratamento farmacológico , Leucemia/radioterapia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/radioterapia
14.
Oncotarget ; 8(5): 8420-8435, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28039479

RESUMO

We previously reported that autocrine TNF-α (TNF) is responsible for JNK pathway activation in a subset of acute myeloid leukemia (AML) patient samples, providing a survival/proliferation signaling parallel to NF-κB in AML stem cells (LSCs). In this study, we report that most TNF-expressing AML cells (LCs) also express another pro-inflammatory cytokine, IL1ß, which acts in a parallel manner. TNF was produced primarily by LSCs and leukemic progenitors (LPs), whereas IL1ß was mainly produced by partially differentiated leukemic blasts (LBs). IL1ß also stimulates an NF-κB-independent pro-survival and proliferation signal through activation of the JNK pathway. We determined that co-inhibition of signaling stimulated by both TNF and IL1ß synergizes with NF-κB inhibition in eliminating LSCs both ex vivo and in vivo. Our studies show that such treatments are most effective in M4/5 subtypes of AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Etanercepte/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Células-Tronco Neoplásicas/efeitos dos fármacos , Nitrilas/farmacologia , Sulfonas/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Interleucina-1beta/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Receptores Tipo I de Interleucina-1/genética , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/deficiência , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/deficiência , Receptores Tipo II do Fator de Necrose Tumoral/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/metabolismo
16.
Leuk Res ; 42: 68-74, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26818573

RESUMO

Treatment options for older patients with acute myeloid leukemia (AML) range from supportive care alone to full-dose chemotherapy. Identifying factors that predict response to therapy may help increase efficacy and avoid toxicity. The phase II SWOG S0703 study investigated the use of hydroxyurea and azacitidine with gemtuzumab ozogamicin in the elderly AML population and found survival rates similar to those expected with standard AML regimens, with less toxicity. As part of this study, global DNA methylation along with promoter DNA methylation and expression analysis of six candidate genes (CDKN2A, CDKN2B, HIC1, RARB, CDH1 and APAF1) were determined before and during therapy to investigate whether very early changes are prognostic for clinical response. Global DNA methylation was not associated with a clinical response. Samples after 3 or 4 days of treatment with azacitidine showed significantly decreased CDKN2A promoter DNA methylation in patients achieving complete remission (CR) compared to those who did not. Samples from day 7 of treatment showed significantly decreased RARB, CDKN2B and CDH1 promoter DNA methylation in responders compared to nonresponders. Gene-specific DNA methylation analysis of peripheral blood samples may help early identification of those older AML patients most likely to benefit from demethylating agent therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metilação de DNA/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Idoso , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Gemtuzumab , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Transcriptoma , Resultado do Tratamento
17.
Fed Pract ; 33(Suppl 4): 23S-25S, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-30766216

RESUMO

This unique presentation may help in further characterizing and understanding this uncommon disease and in developing more effective therapies.

18.
Cell Rep ; 10(12): 2055-68, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25801032

RESUMO

Mutations and inactivation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) are observed in 15%-25% of cases of human T cell acute lymphoblastic leukemia (T-ALL). Pten deletion induces myeloproliferative disorders (MPDs), acute myeloid leukemia (AML), and/or T-ALL in mice. Previous studies attributed Pten-loss-related hematopoietic defects and leukemogenesis to excessive activation of phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling. Although inhibition of this signal dramatically suppresses the growth of PTEN-null T-ALL cells in vitro, treatment with inhibitors of this pathway does not cause a complete remission in vivo. Here, we report that focal adhesion kinase (Fak), a protein substrate of Pten, also contributes to T-ALL development in Pten-null mice. Inactivation of the FAK signaling pathway by either genetic or pharmacologic methods significantly sensitizes both murine and human PTEN-null T-ALL cells to PI3K/AKT/mTOR inhibition when cultured in vitro on feeder layer cells or a matrix and in vivo.


Assuntos
Proteína-Tirosina Quinases de Adesão Focal/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Humanos , Leucemia/metabolismo , Camundongos , Camundongos Knockout , Transdução de Sinais/efeitos dos fármacos
19.
Diagn Cytopathol ; 43(1): 60-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24623571

RESUMO

T cell-derived malignant lymphoma is rarely detected as a bladder neoplasm. A literature review for anaplastic large cell lymphoma (ALCL) involving urinary bladder reveals only seven previously reported cases. Here, we report a case of a 59-year-old HIV-negative man with ALK-positive ALCL. He presented an unusual clinical course with initial consideration of adult onset Still's Disease (AOSD) due to his negative results searching for malignancy and infectious diseases. He rapidly developed macrophage activation (hemophagocytic) syndrome and experienced an unusual rapid disease progression and died in 39 days after onset of symptoms. Compared to previously reported cases, the current case of ALK-1-positive ALCL is a rare case with an unusual presentation. From this case, we learned that ALCL is one malignancy that should be considered and screened in patients with suspected AOSD. Also, T-cell lymphoma associated hemophagocytic syndrome should be considered in a patient with sustained corticosteroid-resistant spike fever, high serum ferritin, and rapid exacerbation of the disease course.


Assuntos
Linfoma Anaplásico de Células Grandes/patologia , Bexiga Urinária/patologia , Receptores de Activinas Tipo II/genética , Diagnóstico Diferencial , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/genética , Masculino , Pessoa de Meia-Idade , Doença de Still de Início Tardio/diagnóstico
20.
J Exp Med ; 211(6): 1093-108, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24842373

RESUMO

Leukemic stem cells (LSCs) isolated from acute myeloid leukemia (AML) patients are more sensitive to nuclear factor κB (NF-κB) inhibition-induced cell death when compared with hematopoietic stem and progenitor cells (HSPCs) in in vitro culture. However, inadequate anti-leukemic activity of NF-κB inhibition in vivo suggests the presence of additional survival/proliferative signals that can compensate for NF-κB inhibition. AML subtypes M3, M4, and M5 cells produce endogenous tumor necrosis factor α (TNF). Although stimulating HSPC with TNF promotes necroptosis and apoptosis, similar treatment with AML cells (leukemic cells, LCs) results in an increase in survival and proliferation. We determined that TNF stimulation drives the JNK-AP1 pathway in a manner parallel to NF-κB, leading to the up-regulation of anti-apoptotic genes in LC. We found that we can significantly sensitize LC to NF-κB inhibitor treatment by blocking the TNF-JNK-AP1 signaling pathway. Our data suggest that co-inhibition of both TNF-JNK-AP1 and NF-κB signals may provide a more comprehensive treatment paradigm for AML patients with TNF-expressing LC.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Leucemia Mieloide Aguda/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antracenos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Células K562 , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Camundongos , Camundongos Knockout , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Nitrilas/farmacologia , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sulfonas/farmacologia , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia , Células U937
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