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1.
Medicine (Baltimore) ; 98(41): e17348, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593084

RESUMO

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças do Sistema Imunitário/induzido quimicamente , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos
2.
Curr Treat Options Oncol ; 20(7): 53, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31119396

RESUMO

In the original version of this article, which published in Current Treatment Options in Oncology, Volume 20, Issue 12, December 2018, the surname of the third author was captured incorrectly. The name shown above is correct.

3.
Int J Mol Sci ; 19(12)2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513765

RESUMO

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) has led to the development of biologically-driven targeted therapies. Hypoxia-inducible factors (HIFs), angiogenic growth factors, von Hippel⁻Lindau (VHL) gene mutations, and oncogenic microRNAs (miRNAs) play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of vascular endothelial growth factor (VEGF) inhibitors, Mechanistic target of rapamycin (mTOR) inhibitors, and immunotherapeutic agents, which have significantly improved the outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC) inhibitors, selenium, and agents like PT2385 and PT2977 are being explored in various clinical trials as potential HIF inhibitors, to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in clear cell RCC (ccRCC) tumors.

4.
Curr Treat Options Oncol ; 19(12): 79, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30554335

RESUMO

OPINION STATEMENT: Checkpoint inhibitors have monumentally transformed the treatment of metastatic urothelial carcinoma. While the efficacy and safety of the different agents are similar in platinum-refractory metastatic urothelial carcinoma, pembrolizumab is the only agent that was superior to chemotherapy in a randomized phase III trial. Pembrolizumab and atezolizumab are also approved as first-line therapies in cisplatin-ineligible metastatic urothelial carcinoma. Several immunotherapy trials are ongoing in non-metastatic setting to maximize responses upfront. Despite the promising responses with immunotherapy, majority of patients do not respond to monotherapy and combination approaches would be the path moving forward to maximize responses. In addition, novel therapies are needed for patients who progress on checkpoint inhibitors. There is still a lot to be done to better understand predictive biomarkers, optimal combination, and sequences to improve clinical outcomes in urothelial carcinoma.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias da Bexiga Urinária/terapia , Antígeno B7-H1/antagonistas & inibidores , Humanos , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Bexiga Urinária/patologia , Urotélio/patologia
5.
Sci Rep ; 8(1): 17921, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30560897

RESUMO

Diabetes mellitus (DM) serves as an important prognostic indicator in patients with cardiac-related illness. Our objective is to compare survival and neurological outcomes among diabetic and non-diabetic patients who were admitted to the hospital after an out-of-hospital cardiac arrest (OHCA). We searched MEDLINE and EMBASE for relevant articles from database inception to July 2018 without any language restriction. Studies were included if they evaluated patients who presented with OHCA, included mortality and neurological outcome data separately for DM patients and Non-DM patients and reported crude data, odds ratio (OR), relative risk (RR) or hazard ratio (HR). Two investigators independently reviewed the retrieved citations and assessed eligibility. The quality of included studies was evaluated using Newcastle-Ottawa quality assessment scale for cohort studies. Random-effect models using the generic variance method were used to create pooled odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 value. Survival and neurological outcomes (using modified rankin scale and cerebral performance category scale) after OHCA in hospitalized patients with DM compared with patients without DM. Out of 57 studies identified, six cohort studies met the inclusion criteria. In an analysis of unadjusted data, patients with DM had lower odds of survival, pooled OR 0.64; 95% CI, 0.52-0.78, [I2 = 90%]. When adjusted ORs were pooled, the association between DM and survival after OHCA was still significantly reduced, pooled OR 0.78, 95% CI, 0.68-0.89 [I2 = 55%]. Unadjusted pooled OR revealed poor neurological outcomes in patients with DM, pooled OR 0.55, 95% CI, 0.38-0.80 [I2 = 90%]. The result demonstrates significant poor outcomes of in-hospital survival and neurological outcomes among DM patients after OHCA.


Assuntos
Diabetes Mellitus/epidemiologia , Parada Cardíaca Extra-Hospitalar/epidemiologia , Diabetes Mellitus/mortalidade , Hospitalização , Humanos , Modelos Teóricos , Razão de Chances , Parada Cardíaca Extra-Hospitalar/mortalidade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
6.
J Investig Med High Impact Case Rep ; 6: 2324709618806332, 2018 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30349834

RESUMO

Urothelial carcinoma, the most common histologic subtype of bladder cancer in the United States, most frequently presents as non-muscle invasive disease. Initially, therapy involves transurethral endoscopic resection and subsequent intravesical therapies with extended surveillance for high-risk disease. Even with the best treatments, recurrence and progression can occur. However, metastasis of non-muscle invasive bladder cancer to distant sites without evidence of progression or regional metastasis is rare. In this article, we present the case of a patient with high-grade papillary urothelial carcinoma who developed an unusual metastasis to the mandible, confirmed by GATA-3 immunostaining, over 4 years after initial transurethral resection. Prior to the development of metastatic disease, this patient had no evidence of local recurrence during maintenance Bacillus Calmette-Guerin intravesical therapy and concurrent surveillance. Positron emission tomography-computed tomography taken after presentation with mandibular metastasis did not show any evidence of regional metastasis. This case highlights an unusual location for distant metastasis of urothelial carcinoma occurring in a patient without evidence of muscle invasive disease or regional metastasis. We additionally highlight the utility of GATA-3 immunostaining in identifying urothelial carcinoma histologically.

7.
J Immunother ; 41(1): 42-44, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29111983

RESUMO

In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active autoimmune disorders. Here, we report a rare case of quiescent bullous pemphigoid which flared after initiation of pembrolizumab, a programmed death ligand-1 inhibitor.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Pênfigo/tratamento farmacológico , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/patologia , Neoplasias Urológicas/tratamento farmacológico , Doença Aguda , Progressão da Doença , Exantema , Humanos , Masculino , Pessoa de Meia-Idade , Pênfigo/diagnóstico , Prednisona/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Dermatopatias Vesiculobolhosas/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias Urológicas/diagnóstico , Suspensão de Tratamento
8.
BMJ Case Rep ; 20172017 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-28052946

RESUMO

Dabigatran is a non-vitamin K antagonist oral anticoagulant that has been approved for atrial fibrillation and prevention of venous thromboembolism. Its use has been increasing in the USA since serum drug levels do not need monitoring. To date, no significant skin side effects have been reported other than 4 cases of non-specific skin lesion and 2 cases of leukocytoclastic vasculitis (LCV), which is a small vessel inflammatory disease that presents as palpable purpura in lower extremities. We present a man aged 57 years with chronic deep vein thrombosis who developed palpable purpura, petechiae, swelling in lower extremities, torso and distal upper extremities on the third day after dabigatran initiation. The present case highlights the potential risk for LCV with dabigatran use and provides insight into its management.


Assuntos
Antitrombinas/efeitos adversos , Dabigatrana/efeitos adversos , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Vasculite Leucocitoclástica Cutânea/tratamento farmacológico , Trombose Venosa/tratamento farmacológico
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