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1.
CA Cancer J Clin ; 72(6): 570-593, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35653456

RESUMO

Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high-acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up-to-date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy-induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit.


Assuntos
Hipercalcemia , Neoplasias , Idoso , Humanos , Emergências , Oncologia , Neoplasias/complicações , Neoplasias/terapia , Náusea , Hipercalcemia/etiologia
2.
Circ Res ; 133(1): 25-44, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37264926

RESUMO

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Aterosclerose/metabolismo , Inflamação , Proteína Quinase 7 Ativada por Mitógeno/genética , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
3.
Int J Mol Sci ; 24(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38069314

RESUMO

Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and the local environment (microbiomics).


Assuntos
Antineoplásicos , Neoplasias de Cabeça e Pescoço , Mucosite , Estomatite , Humanos , Estomatite/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações
4.
Cancer ; 127(4): 528-534, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33085092

RESUMO

BACKGROUND: Prior research has confirmed that persistent hypomagnesemia was predictive of shorter survival among patients with ovarian cancer who received carboplatin-based chemotherapy. In the current retrospective study, the authors examined the association between hypomagnesemia and survival in patients with head and neck cancer who received concurrent chemoradiation with weekly infusions of cisplatin and/or carboplatin. METHODS: Patients with head and neck cancers who had undergone chemoradiation with cisplatin and/or carboplatin between January 1, 2010, and December 31, 2014, were included. Patients were aged ≥18 years with pathology of squamous cell carcinoma of the larynx, oral cavity, or oropharynx who had received at least 30 fractions of radiotherapy with concurrent weekly cisplatin and/or carboplatin. Pathology features, laboratory results, Eastern Cooperative Oncology Group performance status, social histories, and survival were recorded. The association between hypomagnesemia and survival was analyzed controlling for known prognostic factors. RESULTS: The final cohort consisted of 439 patients with a median age of 59 years. A greater frequency of hypomagnesemia during the treatment course was found to be significantly associated with shorter survival (hazard ratio [HR], 1.13; P = .033) independent of age (HR, 1.65; P = .042), cancer site (nonoropharynx vs oropharynx: HR, 2.15 [P = .003]), Eastern Cooperative Oncology Group performance status (>1 vs ≤1: HR, 2.64 [P < .001]), and smoking history (smoker vs nonsmoker: HR, 1.88 [P = .012]). In addition, more severe hypomagnesemia was associated with shorter survival compared with the milder form. CONCLUSIONS: The frequency and severity of hypomagnesemia during treatment are prognostic of survival for patients with head and neck cancers who are receiving concurrent chemoradiation with cisplatin and/or carboplatin. A prospective study is needed to investigate the impact of the prevention of hypomagnesemia on survival in this patient population.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/epidemiologia , Deficiência de Magnésio/epidemiologia , Prognóstico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Sobreviventes de Câncer , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Deficiência de Magnésio/induzido quimicamente , Deficiência de Magnésio/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem
5.
BMC Cancer ; 21(1): 1304, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872526

RESUMO

BACKGROUND: Studies suggest a high prevalence of pain in head and neck cancer (HNC) patients at diagnosis, during and after treatment; however, these studies had small sample sizes and did not comprehensively assess factors known to influence pain. We surveyed a large cohort of HNC survivors to determine variations in the prevalence of pain, its treatment and management by duration of survivorship, and assessed a comprehensive list of risk factors. METHODS: A cross sectional survey of post-treatment survivors of HNC during routine follow-up clinic visits. RESULTS: A total of 505 HNC survivors with a median follow up of 3 years from cancer diagnosis were included in the study. Overall, 45% (n = 224) reported pain and 14.5, 22 and 7% reported use of prescribed pain medication, over-the-counter pain medication and alternative pain therapies, respectively. Prevalence of severe pain was 7.3% and did not vary significantly by years of survivorship (< 1 year = 5.7%; 1 to < 3 years = 7.1%; 3 to < 8 years = 7.6%; 8 years or more =9.7%; P = 0.392). However, use of prescribed pain medication significantly varied by years of survivorship (< 1 year = 45.7%; 1 to < 3 years = 24.6%; 3 to < 8 years = 18.9; 8 years or more = 18.3%; p < 0.001). Of note, a significant proportion of survivors reported moderate to severe pain (moderate to severe = 55.7% versus none to mild = 44.3%) despite step 3 analgesic use (p < 0.001). Multivariable regression shows that recurrent disease (OR 6.77, 95% CI [1.44, 31.80]), history of chemotherapy (OR 6.00, 95% CI [2.10, 17.14]), and depression (Mild-moderate OR 5.30, 95% CI [2.20, 12.78]; Major OR 8.00, 95% CI [2.67, 23.96]) were significant risk factors for severe pain. CONCLUSIONS: We identified a high prevalence of pain among HNC survivors and determined that analgesic use varied by the duration of survivorship. Therefore, routine surveillance for pain must be consistent throughout the course of survivorship.


Assuntos
Analgésicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Dor/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/farmacologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Sobrevivência , Adulto Jovem
6.
Cancer ; 126(23): 5124-5136, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32888342

RESUMO

BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. RESULTS: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data. CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Microbiota , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estomatite/etiologia , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/microbiologia , Humanos , Masculino , Microbiota/efeitos dos fármacos , Microbiota/efeitos da radiação , Pessoa de Meia-Idade , RNA Ribossômico 16S , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Estomatite/microbiologia , Fatores de Tempo
7.
Ann Emerg Med ; 75(2): 264-286, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31561995

RESUMO

In the past decade, rapid advances in therapeutic target discovery in hematologic malignancies have led to many clinical studies demonstrating efficacy of novel agents. Between 2014 and 2018, Food and Drug Administration approvals of new drugs and agents have increased, with greater than 2 dozen novel agents. Rapidly identifying the risk profiles of these cancer therapeutics that may present with acute toxicities and understanding the timing, sequence, duration, and treatment of disease processes are the most important challenges faced by practitioners in emergency medicine, even in nononcologic centers. The emergency medicine literature lags behind rapid advances in oncology, and guidelines for rapid recognition and management of these emerging entities are not familiar. In this Review Article, we discuss the most recent and clinically relevant developments in the arena of hematologic malignancies, further expanding on drug toxicities and their clinical presentations and offering suggestions for management. Specifically, we discuss immune-related adverse events after immune checkpoint inhibitor therapy (including myocarditis and hemophagocytic lymphohistiocytosis), chimeric antigen receptor-T cell therapy, cytokine release syndrome, chimeric antigen receptor-T cell-related encephalopathy syndrome, differentiation syndrome, sinusoid occlusion syndrome, QT-interval prolongation, and tumor lysis syndrome. Rapid advances in hematology and oncology will bring many new challenges for emergency health care providers in the near future; thus, the urgency to raise awareness among this community.


Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Diagnóstico Diferencial , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia
8.
Oncologist ; 24(4): 529-536, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30049883

RESUMO

BACKGROUND: The impact of noncancerous factors on the morbidity and mortality of glioblastoma multiforme (GBM) has not been well studied. Using a large surgical cohort, we examined the association between multiple clinical characteristics and postoperative morbidities and survival in patients with GBM. MATERIALS AND METHODS: The study included 404 consecutive GBM patients who underwent initial tumor resection at MD Anderson Cancer Center between January 1, 2010, and December 31, 2014. Data about clinical characteristics, treatments, and postoperative complications were collected. The associations between clinical parameters and postoperative complications and survival were analyzed. RESULTS: Charlson Comorbidity Index was positively related to a higher incidence of postoperative total (odds ratio [OR] = 1.20; p = .002) and neurological (OR = 1.18; p = .011) complications. Preoperative systolic blood pressure (SBp) over 140 mmHg was associated with a higher incidence of postoperative intracranial hemorrhage (OR = 4.42; p = .039) and longer hospital stay (OR = 2.48; p = .015). Greater postoperative fluctuation of SBp (OR = 1.14; p = .025) and blood glucose (mmol/L; OR = 1.48; p = .023) were related to a higher incidence of neurological complications, whereas higher postoperative blood glucose (OR = 0.64; p < .001) was related to a lower incidence. Long-term lower SBp (<124 mmHg; hazard ratio [HR] = 1.47; p = .010) and higher blood glucose (HR = 1.12; p < .001) were associated with shorter survival. Long-term serum albumin level (g/dL; HR = 0.32; p < .001) was positively associated with survival. CONCLUSION: Short-term SBp and blood glucose levels and fluctuations are associated with postoperative complications in GBM patients. Their long-term optimization may impact survival of these patients. Future clinical trials are needed to confirm the benefit of optimizing medical comorbidities on GBM patients' outcomes. IMPLICATIONS FOR PRACTICE: Glioblastoma multiforme (GBM) is one of the most feared cancer diagnoses because of its limited survival and treatment. This study revealed significant associations of noncancerous factors on the morbidity and mortality of GBM. The complexity of medical comorbidities, as well as short-term postoperative levels and fluctuations of blood pressure and blood glucose, was associated with postoperative complications, but not overall survival. However, long-term levels of these common clinical parameters were significantly associated with survival. Optimization of medical conditions may be critical for reducing the morbidity and mortality of GBM patients. Future clinical trials are needed to validate the observed associations in an independent cohort.


Assuntos
Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Procedimentos Neurocirúrgicos/mortalidade , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
9.
Oncologist ; 24(6): e312-e317, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30940743

RESUMO

BACKGROUND: Hypomagnesemia is a known side effect of several antineoplastic agents, but its impact on outcomes of patients with cancer is not well understood. We examined whether magnesium abnormalities affect survival in patients with ovarian cancer who receive chemotherapy containing carboplatin. MATERIALS AND METHODS: We included patients with advanced ovarian cancer who had undergone surgery and chemotherapy between January 1, 2004, and December 31, 2014, at our institution. Inclusion criteria were age 18 years or older, pathology of high-grade serous carcinoma, first treatment (surgery or chemotherapy) within 60 days of diagnosis, and chemotherapy containing carboplatin. The final cohort consisted of 229 patients. Vital signs and laboratory tests were recorded at baseline and during the treatment course. The associations between magnesium abnormalities (and other clinical characteristics) and survival were analyzed. RESULTS: The median patient age was 64 years. Higher baseline heart rate (beats per minute; hazard ratio [HR] = 1.02, p = .002) and greater frequency of hypomagnesemia during the treatment course (HR = 1.05, p = .002) were significantly associated with shorter survival independent of completeness of tumor reduction (HR = 1.60, p = .02), and International Federation of Gynecology and Obstetrics stage (HR = 1.63, p = .01). CONCLUSION: Baseline heart rate and the frequency of hypomagnesemia episodes during treatment are prognostic of survival for patients with advanced ovarian cancer receiving carboplatin-containing chemotherapy and tumor reductive surgery. Future research is needed for strategies to detect and prevent hypomagnesemia in this patient population. IMPLICATIONS FOR PRACTICE: Despite standard laboratory tests and intravenous magnesium replacement prior to each cycle of chemotherapy, hypomagnesemia remains a common side effect of platinum-based chemotherapy. This study revealed that frequent occurrence of hypomagnesemia during the course of treatment including carboplatin-containing chemotherapy and tumor reductive surgery was strongly predictive of shorter survival in patients with advanced ovarian cancer. Strategies to effectively mitigate hypomagnesemia, such as more frequent detection, dietary recommendations, and timely replacement, should be considered in the overall cancer treatment plan for these patients.


Assuntos
Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/mortalidade , Hipercalciúria/mortalidade , Nefrocalcinose/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Erros Inatos do Transporte Tubular Renal/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Feminino , Seguimentos , Humanos , Hipercalciúria/sangue , Hipercalciúria/induzido quimicamente , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Nefrocalcinose/sangue , Nefrocalcinose/induzido quimicamente , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Prognóstico , Erros Inatos do Transporte Tubular Renal/sangue , Erros Inatos do Transporte Tubular Renal/induzido quimicamente , Estudos Retrospectivos , Taxa de Sobrevida , Texas/epidemiologia
10.
Invest New Drugs ; 37(2): 345-351, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30610588

RESUMO

Background Increased adiposity is thought to result in worse clinical outcomes in patients with breast cancer through increased estrogen production, hyperinsulinemia, insulin resistance, and activation of the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (mTOR) pathway. Thus, we hypothesized that the addition of metformin to everolimus and exemestane, could lead to better outcomes in overweight and obese patients with metastatic, hormone receptor-positive, HER2-negative breast cancer. We conducted a phase II trial to evaluate the efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal women with metastatic, hormone receptor-positive, HER2-negative breast cancer. Methods Twenty-two patients with a body mass index ≥25 kg/m2 were treated with metformin 1000 mg twice daily, everolimus 10 mg daily and exemestane 25 mg daily. Median progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results Median PFS and OS were 6.3 months (95% confidence interval [CI]: 3.8-11.3 months) and 28.8 months (95% CI: 17.5-59.7 months), respectively. Five patients had a partial response and 7 had stable disease for ≥24 weeks yielding a clinical benefit rate of 54.5%. Compared with overweight patients, obese patients had an improved PFS on univariable (p = 0.015) but not multivariable analysis (p = 0.215). Thirty-two percent of patients experienced a grade 3 treatment-related adverse event (TRAE). There were no grade 4 TRAEs and 7 patients experienced a grade 3 TRAE. Conclusion The combination of metformin, everolimus and exemestane was safe and had moderate clinical benefit in overweight and obese with patients metastatic, hormone receptor-positive, HER2-negative breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Metformina/uso terapêutico , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Pós-Menopausa , Adulto , Idoso , Androstadienos/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Quimioterapia Combinada , Everolimo/administração & dosagem , Feminino , Seguimentos , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida
11.
J Natl Compr Canc Netw ; 17(2): 171-189, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30787130

RESUMO

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/terapia , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/terapia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Humanos , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/etiologia
12.
Cancer Treat Res ; 177: 183-209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30523625

RESUMO

The prevalence of anal human papillomavirus (HPV) infection and anal high-grade squamous intraepithelial lesion (HSIL) remain high among HIV-infected individuals on effective antiretroviral therapy (ART). The incidence of HPV-related anal cancers has continued to increase since the introduction of ART. Therefore, ART may confer only limited benefit with respect to reducing the risk of anal HSIL and cancer. Efforts are in progress to define the efficacy of secondary prevention programs for prevention of anal cancer. In the modern ART era, anal cancer recurrence and survival outcomes are similar in HIV-infected and HIV-uninfected patients, but HIV-infected patients may experience more toxicities. This article reviews the current literature on HPV-associated anal cancer in the HIV-infected population, including epidemiology, screening, clinical characteristics, and treatment outcomes.


Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Neoplasias do Ânus/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antirretrovirais/uso terapêutico , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/terapia , Coinfecção/virologia , Detecção Precoce de Câncer , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Infecções por Papillomavirus/complicações
13.
Ann Emerg Med ; 73(1): 79-87, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29880440

RESUMO

STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs). METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death. RESULTS: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival. CONCLUSION: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Feminino , Humanos , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Nivolumabe/efeitos adversos , Prevalência , Prognóstico , Estudos Retrospectivos , Adulto Jovem
14.
Support Care Cancer ; 27(7): 2649-2655, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30474736

RESUMO

PURPOSE: Consultation to palliative care (PC) services in hospitalized patients is frequently late after admission to a hospital. The purpose of this study is to examine the association of in-hospital mortality and timing of palliative care consultation in cancer patients admitted through the emergency department (ED) of MD Anderson Cancer Center. METHODS: Institutional databases were queried for unique medical admissions over a period of 1 year. Primary cancer type, ED versus direct admission, length of stay (LOS), presenting symptoms, and in-hospital mortality were reviewed; patient data were analyzed, and risk factors for in-hospital mortality were identified. The association of early palliative care consultation (within 3 days of admission) with these outcomes was studied. Descriptive statistics and multivariate logistic regression model were used. RESULTS: Equal numbers of patients were admitted directly versus through the ED (7598 and 7538 respectively). However, of all patients who died in the hospital, 990 (88%) were admitted through the ED, compared with 137 admitted directly (P < 0.001). Patients who died in the hospital had longer median LOS compared with patients who were discharged alive (11 vs. 4 days, respectively, P < 0.001). Early palliative care consultation was associated with decreased mortality, compared with late consultation (P < 0.001). Chief complaints of respiratory problems, neurologic issues, or fatigue/weakness were significantly associated with in-hospital mortality. CONCLUSION: We found an association between ED admission and hospital mortality. Decedent cancer patients had a prolonged LOS, and early palliative care consultation for terminally ill symptomatic patients may prevent in-hospital mortality and improve quality of cancer care.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Neoplasias/mortalidade , Neoplasias/terapia , Cuidados Paliativos/métodos , Encaminhamento e Consulta/estatística & dados numéricos , Idoso , Estudos de Coortes , Feminino , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Pacientes Internados , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
15.
Am J Emerg Med ; 37(2): 376.e1-376.e2, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30361152

RESUMO

Immune checkpoint inhibitors are a new class of anticancer drugs recently approved by the US Food and Drug Administration (FDA) for the treatment of various malignancies. Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein-1 (PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2). Pembrolizumab was first approved by the FDA in 2014 for the treatment of advanced melanoma and is currently approved for use in non-small cell lung cancer and several other neoplasms. Immune checkpoint inhibitors such as pembrolizumab have been reported to induce immune-mediated side effects, including type 1 diabetes mellitus in very rare cases (0.1% in clinical trials). Here, we report the case of a woman with no known history of diabetes who presented to our emergency department in a state of diabetic ketoacidosis within 3 weeks of receiving only a single dose of pembrolizumab therapy, and without any previous exposure to immunotherapy. This case of abrupt adult-onset type 1 diabetes mellitus is an example of the undesirable side effects that can emerge after only a brief exposure to an immune checkpoint inhibitor. Close monitoring of patients receiving immune checkpoint inhibitors is warranted for the early diagnosis and management of imminent and potentially life-threatening complications.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Diabetes Mellitus Tipo 1/induzido quimicamente , Cetoacidose Diabética/induzido quimicamente , Neoplasias Cardíacas/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Quimioterapia Adjuvante , Serviço Hospitalar de Emergência , Feminino , Neoplasias Cardíacas/cirurgia , Hemangiossarcoma/cirurgia , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante
18.
Hong Kong Med J ; 25(3): 178-182, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31178437

RESUMO

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.


Assuntos
Infecções por Clostridium/terapia , Diarreia/terapia , Transplante de Microbiota Fecal , Idoso , Colonoscopia , Endoscopia do Sistema Digestório , Fezes/microbiologia , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
19.
J Natl Compr Canc Netw ; 16(8): 986-1017, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30099375

RESUMO

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.


Assuntos
Infecções por HIV/tratamento farmacológico , Oncologia/normas , Neoplasias/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Comorbidade , Interações Medicamentosas , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Disparidades em Assistência à Saúde/normas , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Hospedeiro Imunocomprometido/efeitos da radiação , Oncologia/métodos , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias/virologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Sociedades Médicas/normas , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/normas , Estados Unidos
20.
Support Care Cancer ; 26(5): 1465-1470, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29168032

RESUMO

PURPOSE: Patients with febrile neutropenia are a heterogeneous group with a minority developing serious medical complications. Outpatient management of low-risk febrile neutropenia has been shown to be safe and cost-effective. Scoring systems, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been developed and validated to identify low-risk patients. We aimed to compare the performance of these two scores in identifying low-risk febrile neutropenic patients. METHODS: We performed a pooled analysis of patients presenting with febrile neutropenia to three tertiary cancer emergency centers in the USA, UK, and South Korea in 2015. The primary outcome measures were the occurrence of serious complications. Admission to an intensive care unit (ICU) and 30-day mortality were secondary outcomes. The predictive performance of each score was analyzed. RESULTS: Five hundred seventy-one patients presented with febrile neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall, the MASCC score had a greater discriminatory power in the detection of low-risk patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI 0.626-0.737, p = 0.0024). CONCLUSION: Both MASCC and CISNE scores have reasonable discriminatory value in predicting patients with low-risk febrile neutropenia. Risk scores should be used in conjunction with clinical judgment for the identification of patients suitable for outpatient management of neutropenic fever. Developing more accurate scores, validated in prospective settings, will be useful in facilitating more patients being managed in an outpatient setting.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Neutropenia Febril/diagnóstico , Antineoplásicos/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/diagnóstico , Serviço Hospitalar de Emergência/normas , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Valor Preditivo dos Testes , Estudos Prospectivos , República da Coreia , Medição de Risco , Fatores de Risco , Centros de Atenção Terciária/normas , Centros de Atenção Terciária/estatística & dados numéricos , Reino Unido , Estados Unidos
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