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1.
J Urol ; : 101097JU0000000000000714, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899651

RESUMO

PURPOSE: To describe the cardiovascular risk profile in a representative cohort of prostate cancer patients treated with or without androgen deprivation therapy (ADT). MATERIALS AND METHODS: We prospectively characterized in detail 2492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe ADT for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores. RESULTS: Most (92%) had new prostate cancer (intermediate-risk in 41%; high-risk in 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers; 22% had known cardiovascular disease; 16% diabetes; 45% hypertension; 31% body-mass index ≥30kg/m2; 24% had low levels of physical activity; the mean handgrip strength was 37.3kg; 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom ADT was planned had higher Framingham risk scores than those not intending to receive ADT; this risk was abolished after adjustment for confounders. CONCLUSIONS: Two-thirds of men with prostate cancer is at high cardiovascular risk. There is a positive association between a plan to use ADT and baseline cardiovascular risk factors; however, this association is explained by confounding factors.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31977016

RESUMO

AIMS: Atrial fibrillation (AF) and frailty are common, and the prevalence is expected to rise further. We aimed to investigate the prevalence of frailty and the ability of a frailty index (FI) to predict unplanned hospitalizations, stroke, bleeding and death in patients with AF. METHODS AND RESULTS: Patients with known AF were enrolled in a prospective cohort study in Switzerland. Information on medical history, lifestyle-factors and clinical measurements were obtained. The primary outcome was unplanned hospitalization; secondary outcomes were all-cause mortality, bleeding and stroke. The FI was measured using a cumulative deficit approach, constructed according to previously published criteria and divided into three groups (non-frail, pre-frail, frail). The association between frailty and outcomes was assessed using multivariable adjusted Cox regression models. Of the 2369 included patients, prevalence of pre-frailty and frailty was 60.7% and 10.6%, respectively. Pre-frailty and frailty were associated with a higher risk of unplanned hospitalizations (adjusted hazard ratio [aHR] 1.82; 95% confidence interval [CI], 1.49-2.22, p < 0.001; and aHR 3.59; 95%CI 2.78-4.63, p < 0.001), all-cause mortality (aHR 5.07; 95%CI 2.43-10.59, p < 0.001; and aHR 16.72; 95%CI 7.75-36.05, p < 0.001), and bleeding (aHR 1.53; 95%CI 1.11-2.13, p = 0.01; and aHR 2.46; 95%CI 1.61-3.77, p < 0.001). Frailty, but not pre-frailty was associated with a higher risk of stroke (aHR 3.29; 95%CI 1.29-8.39, p = 0.01). CONCLUSION: Over two thirds of patients with AF are pre-frail or frail. These patients have a high risk for unplanned hospitalizations and other adverse events. These findings emphasize the need to carefully evaluate these patients. However, whether screening for pre-frailty and frailty and targeted prevention strategies improve outcomes needs to be shown in future studies.

3.
Lancet ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31492501

RESUMO

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

4.
J Am Coll Cardiol ; 74(12): 1519-1528, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31537259

RESUMO

BACKGROUND: In patients with coronary or peripheral artery disease, the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events and mortality and increased bleeding. OBJECTIVES: This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study. METHODS: This study reports, by treatment group, the number and proportion of patients; hazard rate ratios for bleeding according to site and severity; the timing of bleeding using landmark analyses; and the number and proportion of patients who received blood products and other hemostatic treatments. RESULTS: Of 27,395 patients enrolled (mean age 68 years, 22% women), 18,278 were randomized to the combination of rivaroxaban and aspirin or to aspirin alone and followed for a mean of 23 months. Compared with aspirin alone, the combination increased modified International Society on Thrombosis and Hemostasis major bleeding (288 of 9,152 [3.1%] vs. 170 of 9,126 [1.9%]), (HR: 1.70; 95% CI: 1.40 to 2.05; p < 0.001), International Society on Thrombosis and Hemostasis major bleeding (206 of 9,152 [2.3%] vs. 116 of 9,126 [1.3%]), (HR: 1.78; 95% CI: 1.41 to 2.23; p < 0.0001), and minor bleeding (838 of 9,152 [9.2%] vs. 503 of 9,126 [5.5%]), (HR: 1.70; 95% CI 1.52 to 1.90; p < 0.0001); the combination also increased the need for any red cell transfusion (87 of 9,152 [1.0%] vs. 44 of 9,126 [0.5%]), (HR: 1.97; 95% CI 1.37 to 2.83, p = 0.0002). The gastrointestinal (GI) tract was the most common site of increased major bleeding (140 of 9,152 [1.5%] vs. 65 of 9,126 [0.7%]), (HR: 2.15; 95% CI: 1.60 to 2.89; p < 0.001), and the increase in bleeding was predominantly in the first year after randomization. Approximately one-third of major GI bleeding was gastric or duodenal, one-third was colonic or rectal, and one-third was from an unknown GI site. The study investigators reported that approximately three-quarters of major bleeding episodes were of mild or moderate intensity. A similar proportion of patients in each treatment group who experienced major bleeding received platelets, clotting factors, or other hemostatic agents. CONCLUSIONS: The combination of rivaroxaban and aspirin compared with aspirin alone increased major bleeding, mainly from the GI tract. Most excess bleeding occurred during the first year after randomization, was of mild or moderate intensity, and was managed with conventional supportive therapy. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424).

5.
J Am Heart Assoc ; 8(16): e010870, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31394972

RESUMO

Background The predictive value of adiposity indices and the newly developed index for cardiometabolic risk factors and cardiovascular diseases (CVDs) remains unclear in the Chinese population. This study aimed to compare the predictive value of A Body Shape Index with other 5 conventional obesity-related anthropometric indices (body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio) in Chinese population. Methods and Results A total of 44 048 participants in the study were derived from the baseline data of the PURE-China (Prospective Urban and Rural Epidemiology) study in China. All participants' anthropometric parameters, CVDs, and risk factors (dyslipidemia, abnormal blood pressure, and hyperglycemia) were collected by standard procedures. Multivariable logistic regression models and receiver operator characteristic curve analysis were used to evaluate the predictive values of obesity-related anthropometric indices to the cardiometabolic risk factors and CVDs. A positive association was observed between each anthropometric index and cardiometabolic risk factors and CVDs in all models (P<0.001). Compared with other anthropometric indices (body mass index, waist circumference, hip circumference, waist-to-hip ratio, and A Body Shape Index), waist-to-height ratio had significantly higher areas under the curve (AUCs) for predicting dyslipidemia (AUCs: 0.646, sensitivity: 65%, specificity: 44%), hyperglycemia (AUCs: 0.595, sensitivity: 60%, specificity: 45%), and CVDs (AUCs: 0.619, sensitivity: 59%, specificity: 41%). Waist circumference showed the best prediction for abnormal blood pressure (AUCs: 0.671, sensitivity: 66%, specificity: 40%) compared with other anthropometric indices. However, the new body shape index did not show a better prediction to either cardiometabolic risk factors or CVDs than that of any other traditional obesity-related indices. Conclusions Waist-to-height ratio appeared to be the best indicator for dyslipidemia, hyperglycemia, and CVDs, while waist circumference had a better prediction for abnormal blood pressure.

6.
J Am Coll Cardiol ; 74(5): 672-682, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31370960

RESUMO

As new treatments continue to improve clinical outcomes in coronary artery disease (CAD) and heart failure, it is necessary to characterize the appropriate use of ß-adrenergic receptor blockers (ß-blockers) in the contemporary management of these conditions. This review examines the current evidence supporting ß-blocker use in heart failure with preserved ejection fraction (HFpEF), heart failure with midrange ejection fraction (HFmEF), and heart failure with reduced ejection fraction (HFrEF), following acute coronary syndrome and in stable CAD. ß-Blockers remain essential in the treatment of HFrEF, but limited evidence supports their use in HFmEF or HFpEF. They should still be considered routinely following acute coronary syndrome, but there is a need for contemporary trials that re-examine this in patients without left ventricular dysfunction, as well as in patients with stable CAD. From a global perspective, more studies are needed to characterize the extent of ß-blocker use in CAD and heart failure, and how evidence-based use can be improved in these conditions.

7.
J Am Coll Cardiol ; 74(5): 683-698, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31370961

RESUMO

The pharmacological inhibition of the renin-angiotensin-aldosterone system as a therapeutic strategy is one of the most significant advances in the treatment and prevention of cardiovascular disease in heart failure with reduced ejection fraction and in coronary artery disease. Recently, the addition of neprilysin inhibition to angiotensin receptor blockade has been shown to be even more effective than angiotensin-converting enzyme inhibition alone in heart failure with reduced ejection fraction, marking an important new milestone in heart failure treatment. This review summarizes the major trials that have informed the clinical role of inhibition of the renin-angiotensin-aldosterone and neprilysin pathways, as well as the limitations of these strategies.

8.
Oncologist ; 24(11): 1405-1409, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31315962

RESUMO

Trastuzumab is an effective treatment for HER2-positive breast cancer. Current guidelines recommend withholding trastuzumab in patients experiencing a significant asymptomatic decline in left ventricular function. In this commentary, we discuss the survival benefits afforded by trastuzumab juxtaposed against the risk of trastuzumab-mediated cardiotoxicity. It is not known whether the net benefit of continuing trastuzumab in the setting of mild cardiotoxicity outweighs the associated risks. We describe a potential approach undertaken by our group, and others, and call for a randomized trial.

10.
Can J Cardiol ; 35(4): 544.e1-544.e2, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935646

RESUMO

Cabozantinib is a multitargeted tyrosine kinase inhibitor, with activity against vascular endothelial growth factor receptor, as well as MET, RET, and AXL. It is currently approved for treating advanced thyroid and kidney cancers, and is being investigated in other cancers. We present a case of reversible heart failure due to cabozantinib use in a 70-year-old man with metastatic renal cell carcinoma. This is, to our knowledge, one of the first reported cases of cardiomyopathy associated with cabozantinib use.

11.
Eur Heart J ; 40(9): 712-714, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30821325
12.
Urol Oncol ; 37(4): 282-288, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630735

RESUMO

Prostate cancer is the most common malignancy among men. Given its prevalence and relatively low mortality rates, several biopsychosocial survivorship issues have garnered recent attention. This article reviews the literature on the association between depression and prostate cancer, emphasizing key practice points relevant for clinicians. Depression is prevalent among men with prostate cancer, with approximately 1 in 6 patients experiencing clinical depression. Suicidal ideation is also not uncommon in this population and does not always present in those with other depressive symptoms. While choice of definitive cancer treatment (radiation or surgery) does not seem to affect depressive symptoms, receipt of androgen deprivation therapy appears to have a negative effect. Not only are patients at increased risk for depression following a prostate cancer diagnosis, but depression itself seems to adversely affect oncologic outcomes. We were not able to identify any clinical trials examining the efficacy of antidepressant medications for depressive symptoms in these patients, however population-based studies suggest antidepressant prescriptions are commonly utilized. Taken together, the literature on the intersection between urologic oncology and psychology/psychiatry affirms the importance of depression among men with prostate cancer. Clinicians should consider assessment of this symptom domain and treat or refer judiciously. Clinical trials represent a priority for future research.

13.
Int J Cardiol ; 280: 124-129, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30679073

RESUMO

BACKGROUND: Presence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM. METHODS: Consecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA. RESULTS: Fifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015). CONCLUSIONS: The presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up.

14.
PLoS One ; 13(12): e0209486, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30571754

RESUMO

BACKGROUND: Preclinical evidence suggests statins may have anti-tumor properties. Large observational studies are also consistent with improved survival and cancer-specific outcomes among cancer patients on statins. We sought to evaluate the randomized controlled trials of statins in addition to usual anti-cancer therapy. METHODS: A systematic search of MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, Papers First and Clinicaltrials.gov was performed from inception through to July 4, 2017 to identify randomized clinical trials that investigated statin therapy in cancer patients. Our primary outcome was overall survival and our secondary outcome was progression-free survival. We calculated summary hazard ratio's (HR) and 95% confidence intervals (CI) based on random-effects models using aggregate data. PROSPERO (CRD42017065503). RESULTS: Ten studies with 1,881 individuals were included with 1,572 deaths and a median follow-up of 23 months. All trials included patients with advanced (stage 3 or higher) disease. There was minimal between-study statistical heterogeneity (I2 = 1.8%, for OS; I2 = 0%, for PFS). The pooled HR for overall survival in patients randomized to statins plus standard anti-cancer therapy versus standard therapy alone was 0.94 (95% CI, 0.85 to 1.04). In the 9 studies that reported progression-free survival (1,798 participants), the pooled HR for statin plus standard therapy versus standard therapy alone was 0.97 (95% CI, 0.87 to 1.07). CONCLUSIONS: In patients with advanced cancer and a prognosis <2 years, the addition of statins to standard anti-cancer therapy does not appear to improve overall survival or progression-free survival. Future research should assess if cancer patients with better prognosis benefit from longer-term statin therapy.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
15.
Pilot Feasibility Stud ; 4: 149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30258648

RESUMO

Background: Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine deficiency occurs in 33% of patients with HF. However, the effectiveness of thiamine supplementation in HF is not known. Methods: In a placebo-controlled randomized two-period crossover feasibility trial, patients age ≥ 60 years with HF and reduced ejection fraction (HFrEF, EF ≤ 45%) will be randomized to thiamine 500 mg oral capsule once daily or placebo for 3 months, then crossed over to the other intervention after a 6-week washout period. The primary outcome is recruitment rate. Secondary outcomes include feasibility and clinical measures. Feasibility outcomes include refusal rate, retention rate, and compliance rate. Secondary clinical outcomes include left ventricular ejection fraction, peak global longitudinal strain measured by echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) quality of life score, and clinical outcomes (all-cause mortality, HF hospitalizations, and HF emergency room visits). Discussion: Thiamine is potentially a safe and low-cost treatment for older patients with HFrEF. Results from this study will inform the feasibility of a large clinical trial with clinical endpoints. The findings will be published in a peer review journal and presented at a relevant conference. This study has received full approval from the Hamilton Integrated Research Ethics Board (18-4537) and Health Canada (210603). This trial is funded by the Hamilton Health Sciences New Investigator Grant (15-387) and the McMaster/St. Peter's Hospital Chair of Aging. Trial registration: NCT03228030 (ClinicalTrials.gov), registered July 24, 2017.

16.
Blood Adv ; 2(15): 1935-1945, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30093531

RESUMO

We completed a phase 1 dose-escalation trial to evaluate the safety of a dopamine receptor D2 (DRD2) antagonist thioridazine (TDZ), in combination with cytarabine. Thirteen patients 55 years and older with relapsed or refractory acute myeloid leukemia (AML) were enrolled. Oral TDZ was administered at 3 dose levels: 25 mg (n = 6), 50 mg (n = 4), or 100 mg (n = 3) every 6 hours for 21 days. Intermediate-dose cytarabine was administered on days 6 to 10. Dose-limiting toxicities (DLTs) included grade 3 QTc interval prolongation in 1 patient at 25 mg TDZ and neurological events in 2 patients at 100 mg TDZ (gait disturbance, depressed consciousness, and dizziness). At the 50-mg TDZ dose, the sum of circulating DRD2 antagonist levels approached a concentration of 10 µM, a level noted to be selectively active against human AML in vitro. Eleven of 13 patients completed a 5-day lead-in with TDZ, of which 6 received TDZ with hydroxyurea and 5 received TDZ alone. During this period, 8 patients demonstrated a 19% to 55% reduction in blast levels, whereas 3 patients displayed progressive disease. The extent of blast reduction during this 5-day interval was associated with the expression of the putative TDZ target receptor DRD2 on leukemic cells. These preliminary results suggest that DRD2 represents a potential therapeutic target for AML disease. Future studies are required to corroborate these observations, including the use of modified DRD2 antagonists with improved tolerability in AML patients. This trial was registered at www.clinicaltrials.gov as #NCT02096289.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/efeitos adversos , Feminino , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Tioridazina/administração & dosagem , Tioridazina/efeitos adversos
17.
Can J Cardiol ; 34(8): 1059-1068, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29980467

RESUMO

BACKGROUND: Immune checkpoint inhibitors, including programmed cell death-1, programmed cell death ligand-1 and cytotoxic lymphocyte antigen-4 inhibitors, have emerged as important therapeutic alternatives for advanced malignancies. This drug class upregulates T-cell activity, leading to an immune response against cancer cells. However, the increased activity of T cells can lead to autoimmune reactions. METHODS: We conducted a systematic review of all published articles and grey literature in PubMed, Medline, and Embase on cardiac complications associated with checkpoint inhibitor use from September 1, 1996 to November 10, 2017. RESULTS: The search strategy yielded 908 unique articles. Of these, 835 were excluded on the basis of abstract and full-text review. A total of 73 studies met eligibility criteria and were included. We found a total of 99 cases of cardiotoxicity with the use of checkpoint inhibitors. Myocarditis (45%) was the most common cardiotoxicity. The overall case fatality rate was 35%. This was notably higher in patients with myocarditis, complete heart block, or conduction abnormalities, and ventricular arrhythmias. There was no difference in outcomes for patients treated with or without steroids. Immunosuppressive therapies such as infliximab, mycophenolate, intravenous immunoglobulin, antithymocyte globulin, and/or plasmapheresis were used in 12 patients leading to survival in 9 of these patients (75%). CONCLUSIONS: Immune checkpoint inhibitors are associated with cardiotoxicity. Because of the high case fatality rate, close surveillance and prompt empiric therapy for cardiovascular complications of checkpoint inhibitors should be considered. Aggressive treatment with immunosuppressive agents and/or plasmapheresis might lead to clinical improvement and increased survival.


Assuntos
Cardiopatias/induzido quimicamente , Imunossupressores/efeitos adversos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Linfócitos T/microbiologia , Cardiotoxicidade , Humanos , Imunossupressores/uso terapêutico
19.
Leuk Res ; 70: 62-66, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29885533

RESUMO

Therapy in Polycythemia Vera (PV), a myeloproliferative neoplasm, focuses on reducing cardiovascular (CV) risk without increasing bleeding or hematological progression. However, the real-world practice of treating PV in North America is understudied. We performed a retrospective cohort study of newly diagnosed PV (JAK2V617F mutation positive) patients in Hamilton, Canada to fill this knowledge gap. Out of 108 patients included, (n = 45, 41.7%) patients did not receive therapy consistent with contemporary treatment guidelines. Multivariable analysis showed increased white blood cell count at diagnosis (HR, 1.09; 95% CI, 1.04-1.14; p < 0.001), older age (HR, 1.15; 95% CI, 1.07-1.23; p < 0.001) and diabetic history (HR, 3.71; 95% CI, 1.27-10.78; p = 0.012) associated with greater mortality. Not receiving pharmacological treatment according to guidelines was also independently associated with increased mortality (HR, 3.12; 95% CI, 1.13-8.65; p = 0.029).


Assuntos
Policitemia Vera/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Canadá , Gerenciamento Clínico , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Policitemia Vera/diagnóstico , Policitemia Vera/mortalidade , Guias de Prática Clínica como Assunto , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto Jovem
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