topics / مواضيع: 12/08/23

INTRODUCTION: Respiratory distress is an uncommon clinical event after caesarean section and occurs due to pulmonary

Abstract

INTRODUCTION: Respiratory distress is an uncommon clinical event after caesarean section and occurs due to pulmonary thromboembolism. Various causes of pulmonary thromboembolism are thrombophlebitis, ovarian venous thrombosis and mesenteric vein thrombosis.

PRESENTATION OF CASE: We report a case of 30 year old female who presented with respiratory distress after eight days of uneventful caesarian section. On emergency explorative laparotomy, small gut was found to be gangrenous, so resection of the segment was performed. On histopathological examination, there was ischaemic necrosis of bowel with presence of large thrombus in mesenteric vessel. On correlating radiological findings of pulmonary thromboembolism and mesenteric vessel thrombosis with bad obstetric history, a possibility of Antiphospholipid syndrome (APS) was suggested in this case. Unfortunately, patient died the day following laparotomy so there was insufficient time to evaluate the patient for thrombophilic disorders.

DISCUSSION: Pregnancy and perpeurium are associated with higher risk of thrombosis as these are hypercoagulable states. Operative delivery and history of thrombophilia in previous pregnancies (APS) are other predisposing factors which lead to increased thrombotic state and pulmonary thromboembolism.

CONCLUSION: High index of suspicion for thrombophilic disorders is required in postpartum patients presenting with respiratory distress as prompt diagnosis and urgent intervention can save patient's life.

PMID: 32169825 [PubMed - as supplied by publisher]

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Uses of pharmacovigilance databases: An overview.

Therapie. 2020 Feb 26;:

Authors: Bihan K, Lebrun-Vignes B, Funck-Brentano C, Salem JE

Over the past decades, assessment of drug safety and of their benefits harms balance has been profoundly modified by the availability

Abstract

Over the past decades, assessment of drug safety and of their benefits harms balance has been profoundly modified by the availability of large databases and computerized automated statistical approaches. Improvement of digital data storage capacity has been applied to pharmacovigilance reports. VigiBase, the international pharmacovigilance database, is now aggregating over 21 million individual case safety reports in 2020. Identification and investigation of drug safety signals - concerning notably rare and unknown adverse drug reactions - is one of the major tasks in pharmacovigilance that can be amplified by automated signal detection. Several quantitative statistical methods exist, each with its own strengths and limits. Integrating signal detection, pharmacovigilance databases can be used for a wide variety of retrospective observational studies illustrated here by concrete examples. Confirming these signals by orthogonal validation using pre-clinical platforms and prospective trials is helpful. Pharmacovigilance databases represent a considerable source of information. However, the quality of signal detection and of pharmacoepidemiology studies in the field of adverse drug reaction closely depends on the quality of the individual data recorded.

PMID: 32169289 [PubMed - as supplied by publisher]

17 March 2020

13:30

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Clinical factors associated with the development of postoperative atrial fibrillation in esophageal cancer patients receiving multimodality therapy before surgery.

J Gastrointest Oncol. 2020 Feb;11(1):68-75

Authors: Song EY, Venkat P, Fradley M, Frakes JM, Klocksieben F, Fontaine J, Mehta R, Saeed S, Hoffe SE, Pimiento JM

Objective: To evaluate the cardio-protective effect of Ginkgo Biloba (GB) on doxorubicin induced-cardiotoxicity.

Abstract

Objective: To evaluate the cardio-protective effect of Ginkgo Biloba (GB) on doxorubicin induced-cardiotoxicity.

Methods: The experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from January to March, 2016, and comprised thirty Wistar Sprague male rats aged 3-4 months and weighing 200-400 g. The rats were divided into three equal groups (n=10); Group І (control): rats were treated with distilled water, Group ІІ (doxorubicin): rats were treated with distilled water and doxorubicin 20 mg/kg, and Group ІІІ (GB): rats were treated with GB and doxorubicin 20mg/kg. Serum malondialdehyde (MDA), glutathione reductase (GSH), lipid peroxidise (LPO), tumour necrosis factor-alpha (TNF-α), cardiac troponin (cTnI), brain natriuretic peptide (BNP) and caspase-3 (Cas-3) were measured using enzyme-linked immunosorbent assay kits. SPSS 20 was used to compare the effect GB with doxorubicin on the biomarkers of doxorubicin induced-cardiotoxicity.

Results: Doxorubicin led to cardiotoxicity through elevation of cTnI, BNP, Cas-3 and LPO compared with controls (p<0.01).also,<0.01)<0.05).0.05) compared with the doxorubicin.

Conclusions: GB has significant cardio-protective effect through attenuation of oxidative stress during doxorubicin induced-cardiotoxicity in rats.

PMID: 31603888 [PubMed - indexed for MEDLINE]

15 March 2020

12:21

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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A rare case of mesenteric vessel thrombosis post caesarian section-An underdiagnosed entity.

Int J Surg Case Rep. 2020 Feb 19;68:170-173

Authors: Pawar R, Brar K, Malhotra C, Chhabra S, Rana D, Gupta A

AIMS: The prognostic importance of post-diagnosis assessment of cardiorespiratory fitness (CRF) in cancer patients is not well established. We sought to

Abstract

AIMS: The prognostic importance of post-diagnosis assessment of cardiorespiratory fitness (CRF) in cancer patients is not well established. We sought to examine the association between CRF and mortality in cancer patients.

METHODS AND RESULTS: This was a single-center cohort analysis of 1,632 patients (58% male; 64±12 years) with adult onset cancer who were clinically referred for exercise treadmill testing a median of 7 (IQR: 3, 12) years after primary diagnosis. CRF was defined as peak metabolic equivalents (METs) achieved during standard Bruce protocol, and categorized by tertiles. The association between CRF and all-cause and cause-specific mortality was assessed using multivariable Cox proportional hazard models adjusting for important covariates.

RESULTS: Median follow-up was 4.6 (IQR: 2.6, 7.0) years; a total of 411 deaths (229, 50, and 132 all-cause, cardiovascular, and cancer related, respectively) occurred during this period. Compared with low CRF (range: 1.9-7.6 METs), the adjusted hazard ratio (HR) for all-cause mortality was 0.38 (95% CI: 0.28-0.52) for intermediate CRF (range: 7.7-10.6 METs) and 0.17 (95% CI: 0.11-0.27) for high CRF (range: 10.7-22.0 METs). The corresponding HRs were 0.40 (95% CI: 0.19-0.86) and 0.41 (95% CI: 0.16-1.05) for cardiovascular mortality and 0.40 (95% CI: 0.26-0.60) and 0.16 (95% CI: 0.09-0.28) for cancer mortality, respectively. The adjusted risk of all-cause, cardiovascular, and cancer mortality decreased by 26%, 14%, and 25% with each 1 MET increment in CRF.

CONCLUSION: CRF is a strong, independent predictor of all-cause, cardiovascular, and cancer mortality, even after adjustment for important clinical covariates in patients with certain cancers.

PMID: 32167560 [PubMed - as supplied by publisher]

13:04

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Gingko Biloba protects cardiomyocytes against acute doxorubicin induced cardiotoxicity by suppressing oxidative stress.

J Pak Med Assoc. 2019 Aug;69(Suppl 3)(8):S103-S107

Authors: Jasim ST, Al-Kuraishy HM, Al-Gareeb AI

BACKGROUND: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for

Abstract

BACKGROUND: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab.

METHODS: TRIBE2 was an open-label, phase 3, randomised study of patients aged 18-75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatme[...]

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nt given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov, NCT02339116.

FINDINGS: Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1-41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3-21·4) in the experimental group and 16·4 months (15·1-17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63-0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3-4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis).

INTERPRETATION: Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria.

FUNDING: The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann-La Roche.

PMID: 32164906 [PubMed - as supplied by publisher]

13:04

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Association of Post-Diagnosis Cardiorespiratory Fitness with Cause-Specific Mortality in Cancer.

Eur Heart J Qual Care Clin Outcomes. 2020 Mar 13;:

Authors: Groarke JD, Payne DL, Claggett B, Mehra MR, Gong J, Caron J, Mahmood SS, Hainer J, Neilan TG, Partridge AH, Di Carli M, Jones LW, Nohria A

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic

Abstract

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.

PMID: 32163687 [PubMed - as supplied by publisher]

12:22

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Religious observance and perceptions of end-of-life care.

Nurs Inq. 2020 Mar 12;:e12347

Authors: Tarabeih M, Bokek-Cohen Y, Abu Rakia R, Nir T, Coolidge NE, Azuri P

BACKGROUND: This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating

Abstract

BACKGROUND: This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)-derived exosomes, epithelial ovarian cancer (EOC)-derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome's payload(s) upon its uptake and regulation of the TME.

EVIDENCE: Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications.

CONCLUSION: Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.

PMID: 32162012 [PubMed - as supplied by publisher]

15:04

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Development and Validation of a Risk Score for Prediction of Venous Thromboembolism in Patients With Lung Cancer.

Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620910793

Authors: Li Z, Zhang G, Zhang M, Mei J, Weng H, Peng Z

This study examines the impact of the level of religious observance on the attitudes toward end-of-life (EOL) decisions and euthanasia

Abstract

This study examines the impact of the level of religious observance on the attitudes toward end-of-life (EOL) decisions and euthanasia of Jews in Israel-where euthanasia is illegal-as compared to Jews living in the USA, in the states where euthanasia is legal. A self-reporting questionnaire on religiosity and personal beliefs and attitudes regarding EOL care and euthanasia was distributed, using a convenience sample of 271 participants from Israel and the USA. Findings show that significant differences were found in attitudes between Jews of different levels of religious observance with respect to patient autonomy, right to die with dignity, and dying in familiar and supportive surroundings. The USA and Israeli Jews have similar knowledge regarding EOL care and expressed similar attitudes and perceptions toward the issues of authority of medical staff and religious figures and patient's autonomy. Findings indicate that the level of religious observance has more potency in shaping their attitudes and perceptions of EOL decisions than the state law. We conclude by discussing the implications of our findings with regard to multicultural health systems and providing practical recommendations.

PMID: 32162408 [PubMed - as supplied by publisher]

12:22

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Tumor-derived exosomes in the regulation of macrophage polarization.

Inflamm Res. 2020 Mar 11;:

Authors: Baig MS, Roy A, Rajpoot S, Liu D, Savai R, Banerjee S, Kawada M, Faisal SM, Saluja R, Saqib U, Ohishi T, Wary KK

This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A

Abstract

This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A total of 827 patients with lung cancer from February 2013 to February 2018 in our hospital were retrospectively analyzed. Demographic and clinicopathological variables independently correlated to VTE were applied to develop the risk score in the development group while examined in the validation group. The regression coefficients of multivariable logistic regression test were applied to assign a risk score system. The incidence of VTE was 12.3%, 12.7%, and 11.8% in all patients, in the development and validation groups, respectively. The 496 patients in the development group were classified into 3 groups: low risk (scores ≤3), moderate risk (scores 4-5), and high risk (scores ≥6). The risk of VTE was significantly and positively related to the risk scores in both development and validation groups. The risk score system aided proper stratification of patients with either high or low risk of VTE in the development and validation groups (c statistic = 0.819 and 0.827, respectively). This risk score system based on the factors with most significant correlation showed good predictive ability and is potentially useful for predicting VTE in patients with lung cancer. However, it was developed and validated by a retrospective analysis and has significant limitations, and a prospective validation with all the classic variables assessing the thrombotic risk is needed for a solid conclusion.

PMID: 32162530 [PubMed - in process]

14 March 2020

11:45

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial.

Lancet Oncol. 2020 Mar 09;:

Authors: Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, Bordonaro R, Latiano TP, Tamburini E, Santini D, Passardi A, Marmorino F, Grande R, Aprile G, Zaniboni A, Murgioni S, Granetto C, Buonadonna A, Moretto R, Corallo S, Cordio S, Antonuzzo L, Tomasello G, Masi G, Ronzoni M, Di Donato S, Carlomagno C, Clavarezza M, Ritorto G, Mambrini A, Roselli M, Cupini S, Mammoliti S, Fenocchio E, Corgna E, Zagonel V, Fontanini G, Ugolini C, Boni L, Falcone A, GONO Foundation Investigators

Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer.

Abstract

Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer. The cardiotoxicity of DOX is related to the accumulation of its main metabolite doxorubicinol (DOXOL) in the cardiac tissue. Although the pharmacokinetics of DOX shows high interindividual variability, there are no significant covariates to improve dose adjustment. The present study reports the pharmacokinetics of both DOX and DOXOL in a homogeneous population of young female patients with breast cancer (n = 12) making use of a standardized drug association, evaluated in the very first chemotherapy cycle, using plasma and urine data that allowed the calculation of the renal clearance of DOX, the formation clearance of DOXOL and the hepatic clearance of DOX. The extensive data availability also made it possible to estimate the hepatic extraction ratio of DOX for the investigated population, as well as to determine DOXOL unbound fraction in plasma for the first time in humans. DOX and DOXOL simultaneous analysis in plasma, plasma ultrafiltrate, and urine were performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The pharmacokinetics profile of both DOX and DOXOL showed high variability (geometric coefficient of variation of area under the plasma concentration versus time curve extrapolated to infinity was approximately 215 %). The geometrics means were 0.26 for DOXOL/DOX AUC ratio, 15 % and 17 % for unbound fractions of DOX and DOXOL, respectively, 30.70 L⋅h-1 for total clearance, 0.66 L⋅h-1 for renal clearance, 29.97 L⋅h-1 for hepatic clearance and 0.39 L⋅h-1 for the formation clearance of the metabolite DOXOL. The 95 % confidence interval of the estimated hepatic extraction ratio of DOX ranged from 0.14 to 0.79, which characterizes DOX as a drug of low, intermediate or high hepatic extraction ratio.

PMID: 32163849 [PubMed - as supplied by publisher]

12:22

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[Сurrent views on predictors and biomarkers of early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer (review of literature).]

Klin Lab Diagn. 2020;65(3):141-148

Authors: Kit OI, Gvaldin DY, Omelchuk EP, Timoshkina NN

An increasingly aged population, early cancer diagnosis and new oncology and surgical therapies that improve survival favor the

Abstract

An increasingly aged population, early cancer diagnosis and new oncology and surgical therapies that improve survival favor the presentation of cancer patients who are simultaneously affected by a cardiac disease requiring surgery. Oncological therapy can lead to cardiovascular injury, impacting surgical strategies and risk. Current opinion in patients affected by concomitant heart disease and cancer is to give priority to the surgical treatment of cardiac disease, thus allowing the treatment of neoplasm in an active or advanced stage, either by surgical resection or by means of radiation and oncology therapies. Therefore, prior to heart surgery, tumor staging, assessment of prognosis, as well as the interaction between tumor and extracorporeal circulation and the possibility of being able to improve survival with appropriate therapies even in advanced stages, are crucial. Then, an adequate preoperative screening of cardiovascular abnormalities related to antitumoral therapy and the assessment of other conditions linked to the type of cancer, are both extremely important to decide the most appropriate surgical approach. Careful evaluation of the association of cardiovascular diseases and the prognosis of the active or remitted malignancy should be established to improve the prediction of short-, medium- and long-term outcomes. This article aims to review the literature on cardiovascular effects of antitumoral therapy in cardiac surgery candidates. Moreover, the authors provide an overview of the factors that should be considered in patients with a prior history of malignancy or with active cancer, who need cardiac surgery.

PMID: 31530950 [PubMed - indexed for MEDLINE]

13 March 2020

12:22

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio.

J Pharm Biomed Anal. 2020 Mar 04;185:113231

Authors: Pippa LF, Oliveira ML, Rocha A, de Andrade JM, Lanchote VL

Patients with malignant tumors are usually accompanied with hypercoagulability state and high incidence risk of venous thromboembolism (VTE)

Abstract

Patients with malignant tumors are usually accompanied with hypercoagulability state and high incidence risk of venous thromboembolism (VTE), especially in patients with pancreatic ductal adenocarcinoma (PDAC). However, conventional coagulation test is failed to identify this abnormity. We retrospectively reviewed clinical data of 78 PDAC patients and 79 age-matched controls with rapid thromboelastography (r-TEG) and conventional coagulation test. The main index of r-TEG include TEG-ACT (second), R (second), K (second), angleα (°) and MA (mm), and a short TEG-ACT, short R, a short K, a broad angleα and a prolonged MA can identify hypercoagulability. Compared with age-matched controls, the PADC patients were analyzed to have a shorter K value (72. + 24 ± 22.90 vs. 85.63 ± 32.81, P = 0.0014), increased angleα value (76.20 ± 3.68 vs. 74.415 ± 4.73, P = 0.009) and MA value (63.33 ± 7.19 vs. 60.89 ± 5.52, P = 0.18). Both TEG-ACT (101.72 ± 7.57 vs. 103.78 ± 7.33, P = 0.086) and R (32.95 ± 4.72 vs. 34.34 ± 4.61, P = 0.085) value showed no significant difference in two groups. The laboratory values for conventional coagulation test were within normal ranges: PT (11.65 ± 0.95 vs. 11.38 ± 0.79, P = 0.049), INR (1.01 ± 0.09 vs. 0.98 ± 0.08, P = 0.101), aPTT (28.75 ± 3.45 vs. 28.00 ± 2.98, P = 0.149) and TT (19.44 ± 1.12 vs. 19.69 ± 1.35, P = 0.212). Incidence rates of VTE were 3.8% (3 of 78 patients) and 1.3% (1 of 79 patients) respectively (Fisher's exact test: P = 0.367). Several r-TEG indexes can indicate coagulation disorders within PDAC patients, but the incidence rates of VTE for both PDAC patients and normal controls had no significant difference. Compare to the control group, the potential hypercoagulability of PDAC patients did not correlate to thrombotic complications.

PMID: 31250338 [PubMed - indexed for MEDLINE]

12:51

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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((cardiotoxicity OR cardio-toxicity) AND cancer) OR Cardio-oncology OR Cardioncology OR cardiooncology; +22 new citations

22 new pubmed citations were retrieved for your search.

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((cardiotoxicity OR cardio-toxicity) AND cancer) OR Cardio-oncology OR Cardioncology OR cardiooncology

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PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.

Citations may include links to full-text content from PubMed Central and publisher web sites.

12 March 2020

13:20

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented.

Cancers (Basel). 2020 Mar 06;12(3):

Authors: Farge D, Bournet B, Conroy T, Vicaut E, Rak J, Zogoulous G, Barkun J, Ouaissi M, Buscail L, Frere C

Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy.

Abstract

Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy. Despite recent advances in the use of adjuvant chemotherapy in PC, the prognosis remains poor, with fewer than 8% of patients being alive at 5 years after diagnosis. The prevalence of PC has steadily increased over the past decades, and it is projected to become the second-leading cause of cancer-related death by 2030. In this context, optimizing and integrating supportive care is important to improve quality of life and survival. Venous thromboembolism (VTE) is a common but preventable complication in PC patients. VTE occurs in one out of five PC patients and is associated with significantly reduced progression-free survival and overall survival. The appropriate use of primary thromboprophylaxis can drastically and safely reduce the rates of VTE in PC patients as shown from subgroup analysis of non-PC targeted placebo-controlled randomized trials of cancer patients and from two dedicated controlled randomized trials in locally advanced PC patients receiving chemotherapy. Therefore, primary thromboprophylaxis with a Grade 1B evidence level is recommended in locally advanced PC patients receiving chemotherapy by the International Initiative on Cancer and Thrombosis clinical practice guidelines since 2013. However, its use and potential significant clinical benefit continues to be underrecognized worldwide. This narrative review aims to summarize the main recent advances in the field including on the use of individualized risk assessment models to stratify the risk of VTE in each patient with individual available treatment options.

PMID: 32155940 [PubMed]

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Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review.

Cancers (Basel). 2020 Mar 06;12(3):

Authors: Rossel A, Robert-Ebadi H, Marti C

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also

Abstract

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.

PMID: 32158597 [PubMed]

14:50

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[Cardiac surgery in patients with malignancy: a literature review and recommendations for perioperative management].

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pensiero.it-images-linkout.jpg Related Articles

[Cardiac surgery in patients with malignancy: a literature review and recommendations for perioperative management].

G Ital Cardiol (Rome). 2019 Sep;20(9):491-498

Authors: Jiritano F, Matteucci M, Guareschi A, Fina D, Vizzardi E, Mariscalco G, Sciatti E, Lorusso R

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cance

Abstract

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cancer associated thrombosis (CAT) within the first year after cancer diagnosis. This risk may vary according to patient characteristics, cancer location, cancer stage, or the type of chemotherapeutic regimen. Landmark studies evaluating thrombophrophylaxis with low molecular weight heparin (LMWH) for ambulatory cancer patients have shown a relative reduction in the rate of symptomatic VTE of about one half. However, the absolute risk reduction is modest among unselected patients given a rather low risk of events resulting in a number needed to treat (NNT) of 40 to 50. Moreover, this modest benefit is mitigated by a trend towards an increased risk of bleeding, and the economic and patient burden due to daily injections of LMWH. For these reasons, routine thromboprophylaxis is not recommended by expert societies. Advances in VTE risk stratification among cancer patients, and growing evidence regarding efficacy and safety of direct oral anticoagulants (DOACs) for the treatment and prevention of CAT have led to reconsider the paradigms of this risk-benefit assessment. This narrative review aims to summarize the recent evidence provided by randomized trials comparing DOACs to placebo in ambulatory cancer patients and its impact on expert recommendations and clinical practice.

PMID: 32155855 [PubMed]

14:50

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors.

Immune Netw. 2020 Feb;20(1):e9

Authors: Choi J, Lee SY

Anthracycline-associated cardiomyopathy and peripartum cardiomyopathy are nonischemic cardiomyopathies that often afflict

Abstract

Anthracycline-associated cardiomyopathy and peripartum cardiomyopathy are nonischemic cardiomyopathies that often afflict previously healthy young patients; both diseases have been well described since at least the 1970s and both occur in the settings of predictable stressors (ie, cancer treatment and pregnancy). Despite this, the precise mechanisms and the ability to reliably predict who exactly will go on to develop cardiomyopathy and heart failure in the face of anthracycline exposure or childbirth have proven elusive. For both cardiomyopathies, recent advances in basic and molecular sciences have illuminated the complex balance between cardiomyocyte and endothelial homeostasis via 3 broad pathways: reactive oxidative stress, interference in apoptosis/growth/metabolism, and angiogenic imbalance. These advances have already shown potential for specific, disease-altering therapies, and as our mechanistic knowledge continues to evolve, further clinical successes are expected to follow.

PMID: 31120822 [PubMed - indexed for MEDLINE]

15:14

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Representation of Patients With Cardiovascular Disease in Pivotal Cancer Clinical Trials.

Circulation. 2019 05 28;139(22):2594-2596

Authors: Bonsu J, Charles L, Guha A, Awan F, Woyach J, Yildiz V, Wei L, Jneid H, Addison D

PMID: 30882246 [PubMed - indexed for MEDLINE]

11 March 2020

11:16

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Phase II Multicenter, Open-Label Study of Oral ENMD-2076 for the Treatment of Patients with Advanced Fibrolamellar Carcinoma.

Oncologist. 2020 Mar 10;:

Authors: Abou-Alfa GK, Mayer R, Venook AP, O'Neill AF, Beg MS, LaQuaglia M, Kingham PT, Kobos R, Basturk O, Brennan C, Yopp A, Harding JJ, Leong S, Crown J, Hoti E, Leonard G, Ly M, Bradley M, Valentino E, Markowitz D, Zukiwski A, Ren K, Gordan JD

LESSONS LEARNED: The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain

Abstract

LESSONS LEARNED: The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and, thus, overexpression of Aurora kinase A. ENMD-2076 showed a favorable toxicity profile. The limited results, one patient (3%) with a partial response and 57% of patients with stable disease, do not support further evaluation of ENMD-2076 as single agent. Future studies will depend on the simultaneous targeting approach of DNAJB1-PRKACA and the critical downstream components.

BACKGROUND: Fibrolamellar carcinoma (FLC) represents approximately 0.85% of liver cancers. The associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and overexpression of Aurora kinase A (AURKA). ENMD-2076 is a selective anti-AURKA inhibitor.

METHODS: Patients aged >12 years with pathologically confirmed incurable FLC, with measurable disease, Eastern Cooperative Oncology Group performance status 0-2 or Lansky 70-100, and adequate organ function were eligible. Patients were prescribed ENMD-2076 based on body surface area. The primary endpoint was overall objective response rate by RECIST v1.1, with a null hypothesis of true response rate of 2% versus one-sided alternative of 15%. Secondary endpoints included 6-month progression-free survival (PFS) rate (Fig. 1), median PFS, time to progression (TTP), and overall survival (OS). Safety was evaluated throughout the study.

RESULTS: Of 35 patients who enrolled and received treatment, 1 (3%) had a partial response (PR) and 20 (57%) had stable disease (SD). Median TTP, PFS, and OS were 5, 3.9, and 19 months, respectively. The most frequently reported drug-related serious adverse event was hypertension in three patients. Three deaths were reported on-study-two due to disease progression and one due to pulmonary embolism not related to ENMD-2076.

CONCLUSION: The study provided no rationale for further studying ENMD-2076 as a single agent in FLC.

PMID: 32154962 [PubMed - as supplied by publisher]

11:16

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"Wolverine, I think it's called: Blood thinners but in tablets." Patients experience of living with cancer associated thrombosis in New Zealand (PELICANZ).

Thromb Res. 2020 Mar 02;189:35-38

Authors: Woulfe T, Mann K, Pollack D, Swarnkar P, Nelson A, Noble S

PMID: 32151801 [PubMed - as supplied by publisher]

11:16

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Corrigendum to "Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study" [Thromb. Res. vol. 185, January 2020, pages 13-19].

Thromb Res. 2020 Mar 06;:

Authors: Mulder FI, van Es N, Kraaijpoel N, Di Nisio M, Carrier M, Duggal A, Gaddh M, Garcia D, Grosso MA, Kakkar AK, Mercuri MF, Middeldorp S, Royle G, Segers A, Shivakumar S, Verhamme P, Wang T, Weitz JI, Zhang G, Büller HR, Raskob G

PMID: 32151398 [PubMed - as supplied by publisher]

11:16

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Thromboprophylaxis in the End-of-Life Cancer Care: The Update.

Cancers (Basel). 2020 Mar 05;12(3):

Authors: Zabrocka E, Sierko E

Cancer patients are at increased risk for venous thromboembolism (VTE), which further increases with advanced stages of malignancy,

Abstract

Cancer patients are at increased risk for venous thromboembolism (VTE), which further increases with advanced stages of malignancy, prolonged immobilization, or prior history of thrombosis. To reduce VTE-related mortality, many official guidelines encourage the use of thromboprophylaxis (TPX) in cancer patients in certain situations, e.g., during chemotherapy or in the perioperative period. TPX in the end-of-life care, however, remains controversial. Most recommendations on VTE prophylaxis in cancer patients are based on the outcomes of clinical trials that excluded patients under palliative or hospice care. This translates to the paucity of official guidelines on TPX dedicated to this group of patients. The problem should not be underestimated as VTE is known to be associated with symptoms adversely impacting the quality of life (QoL), i.e., limb or chest pain, dyspnea, hemoptysis. In end-of-life care, where the assurance of the best possible QoL should be the highest priority, VTE prophylaxis may eliminate the symptom burden related to thrombosis. However, large randomized studies determining the benefits and risks profiles of TPX in patients nearing the end of life are lacking. This review summarized available data on TPX in this population, analyzed potential tools for VTE risk prediction in the view of this group of patients, and summarized the most current recommendations on TPX pertaining to terminal care.

PMID: 32150978 [PubMed]

11:16

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Assessment of preoperative hypercoagulability in patients with pancreatic ductal adenocarcinoma (PDAC) using rapid thromboelastography (r-TEG).

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles

Assessment of preoperative hypercoagulability in patients with pancreatic ductal adenocarcinoma (PDAC) using rapid thromboelastography (r-TEG).

J Thromb Thrombolysis. 2019 Nov;48(4):648-652

Authors: Mou Y, Li M, Hou S, Ren X, Tian B

The public health sector faces a huge challenge as a result of the high prevalence and burden of disability caused by ischemic cardio

Abstract

The public health sector faces a huge challenge as a result of the high prevalence and burden of disability caused by ischemic cardio-cerebrovascular disease (CVD) and depression. Although studies have explored the underlying mechanisms and potential therapies to address conditions, there is no treatment breakthrough, especially for depression which is highly influenced by social stressors. However, accumulating evidence reveals that CVD and depression are correlated and share common risk factors, particularly obesity, diabetes, and hypertension. They also share common mechanisms, including oxidative stress (OS), inflammation and immune response, cell death signaling pathway, and microbiome-gut-brain axis. This review summarizes the relationship between ischemic CVD and depression and describes the interactions among common risk factors and mechanisms for these two diseases. In addition, we propose that OS mediates the crosstalk between these diseases. We also reveal the potential of antioxidants to ameliorate OS-related injuries.

PMID: 32148646 [PubMed - in process]

15:14

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Anthracycline and Peripartum Cardiomyopathies.

Circ Res. 2019 05 24;124(11):1633-1646

Authors: Cowgill JA, Francis SA, Sawyer DB

Chemotherapy faces challenges, including poor aqueous solubility of the drugs, and cardiotoxicity. Micellar drug delivery

Abstract

Chemotherapy faces challenges, including poor aqueous solubility of the drugs, and cardiotoxicity. Micellar drug delivery systems (DDS) are used to encapsulate anticancer drugs for better therapeutic effects, however, with poor loading content. Herein, we synthesized a micellar DDS using -benzyloxy substituted poly(ε-caprolactone) as the hydrophobic block, and co-loaded anticancer doxorubicin (Dox) and antioxidant quercetin (Que). -Substituted oligo(ethylene) glycol (OEG) poly(ε-caprolactone)s were used as hydrophilic blocks to make the polymers thermoresponsive. Variation of the OEG chain allowed the tunability of the lower critical solution temperature. Moreover, drug loading and release were studied. Thermodynamic stability, size, and morphology were determined by fluorescence measurements, dynamic light scattering, and transmission electron microscopy. Combination loading demonstrated improved loading of Dox and Que. Biological studies were performed using HepG2 human liver cancer and H9c2 rat heart cells. The use of biodegradable, biocompatible and thermoresponsive polymers along with the co-loading approach is a good strategy in developing DDSs.

PMID: 32149500 [PubMed - as supplied by publisher]

15:14

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The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression.

Oxid Med Cell Longev. 2019;2019:2491927

Authors: Lin D, Wang L, Yan S, Zhang Q, Zhang JH, Shao A

Venous thromboembolism is a common complication of malignancy. Lung cancer is considered one of the most thrombogenic cancer

Abstract

Venous thromboembolism is a common complication of malignancy. Lung cancer is considered one of the most thrombogenic cancer types. Primary thromboprophylaxis is not currently recommended for all ambulatory patients with active cancer. In the present narrative review we aim to summarize recent data on the safety and efficacy of primary thromboprophylaxis as well as on venous thromboembolism risk assessment, focusing on ambulatory patients with lung cancer. A potential benefit from prophylactic anticoagulation with low molecular weight heparins in terms of venous thromboembolism risk reduction and increased overall survival in patients with lung cancer, without a significant increase in bleeding risk, has been reported in several studies. Recent studies also reveal promising results of direct oral anticoagulants regarding their efficacy as primary thromboprophylaxis in patients with cancer, including those with lung cancer. However, the use of different study methodologies and the heterogeneity of study populations among the trials limit the extraction of definite results. More randomized, controlled trials, restricted to a well-characterized population of patients with lung cancer, are greatly anticipated. The use of risk assessment tools for stratification of venous thromboembolic risk is warranted. The development of an accurate and practical risk assessment model for patients with lung cancer represents an unmet need.

PMID: 32146869 [PubMed - as supplied by publisher]

15:14

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Enhancement of Loading Efficiency by Co-loading of Doxorubicin and Quercetin in Thermoresponsive Polymeric Micelles.

Biomacromolecules. 2020 Mar 09;:

Authors: Soltantabar P, Calubaquib EL, Mostafavi E, Biewer MC, Stefan MC

AIM: Postoperative pulmonary embolism can be a fatal surgical complication and is thought to occur secondary to asymptomatic

Abstract

AIM: Postoperative pulmonary embolism can be a fatal surgical complication and is thought to occur secondary to asymptomatic venous thromboembolism (VTE) that exists preoperatively in some patients. The purpose of this study was to clarify the frequency and risk factors of pretreatment VTE in gynecological cancer patients.

METHODS: This study investigated 2086 patients with gynecological cancer (cervix, n = 754; endometrium, n = 862; ovary, n = 470) who underwent initial treatment between 2004 and 2017. Pretreatment VTE screening was performed with D-dimer (DD) levels in these patients. Based on this, the associated risk factors were retrospectively analyzed.

RESULTS: Pretreatment VTE was discovered in 7.3% of patients with cervical cancer, 11.5% of those with endometrial cancer and 27.0% of those with ovarian cancer. Significant independent risk factors were: age greater than or equal to 60 years and tumor long diameter greater than or equal to 40 mm for cervical cancer; age greater than or equal to 60 years, stage III/IV advanced disease, clear cell carcinoma and tumor long diameter greater than or equal to 60 mm for endometrial cancer; and age greater than or equal to 60 years, clear cell carcinoma and massive ascites for ovarian cancer.

CONCLUSION: Pretreatment asymptomatic VTE is very frequent in gynecological cancer patients. It may be beneficial to consider measuring DD or performing venous ultrasonography in patients with the above risk factors.

PMID: 32147891 [PubMed - as supplied by publisher]

13:39

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Do we need prophylactic anticoagulation in ambulatory patients with lung cancer? A review.

Vasc Med. 2020 Mar 07;:1358863X19899160

Authors: Dimakakos E, Kotteas E, Gomatou G, Katsarou T, Vlahakos V, Vathiotis I, Talagani S, Dimitroulis I, Syrigos K

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis)

Abstract

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients' values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients' lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values.

PMID: 32150612 [PubMed - as supplied by publisher]

13:39

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Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer.

J Obstet Gynaecol Res. 2020 Mar 08;:

Authors: Tasaka N, Minaguchi T, Hosokawa Y, Takao W, Itagaki H, Nishida K, Akiyama A, Shikama A, Ochi H, Satoh T

OBJECTIVES: There is a scarcity of literature exploring the consequences of Failure To Extubate (FTE) and Delayed Reintubation (DRI)

Abstract

OBJECTIVES: There is a scarcity of literature exploring the consequences of Failure To Extubate (FTE) and Delayed Reintubation (DRI) in spine surgery. While it is reasonable to believe that patients who FTE or undergo DRI after Posterior Lumbar Fusion (PLF) and Transforaminal Lumbar Interbody Fusion (TLIF) are at risk for graver outcomes, there is minimal data to explicitly support that. The goal of this study was to investigate the morbidity and mortality associated with FTE and DRI after lumbar spine surgery in a large pool of patients.

PATIENTS AND METHODS: We conducted a retrospective multicenter study of patients that underwent elective posterior lumbar fusion (PLF) and transforaminal lumbar interbody fusion (TLIF) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2006 to 2016. We excluded patients with disseminated cancer, metastatic disease to the neural axis, patient with spinal epidural abscess, and patients with ventilator dependency prior to the operation.

RESULTS: 57,677 patients from 2006 to 2016 were identified; 55 patients (0.1 %) had FTE and 262 patients (0.46 %) had DRI. The incidence of pneumonia was 27.2-fold greater in the FTE group and septic shock was 63.5-fold greater. All complications listed below are significance to p < 0.001.

CONCLUSION: FTE and DRI were highly predictive of morbidity and mortality. Overall, investigations of the effects of FTE and DRI following spine procedures are lacking. This large multi-center national database review is one of the first to provide insight into the consequences of FTE and DRI in lumbar fusion cases. Future investigation into the consequences and predictors of FTE and DRI in spine surgery are required.

PMID: 32146234 [PubMed - as supplied by publisher]

14:07

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Ovarian cancer subtypes and survival in relation to three comprehensive imaging parameters.

J Ovarian Res. 2020 Mar 07;13(1):26

Authors: Sartor H, Bjurberg M, Asp M, Kahn A, Brändstedt J, Kannisto P, Jirström K

Several cancer treatments cause cardiotoxicity that can lead to heart failure, coronary artery disease, arrhythmia, and pericardial

Abstract

Several cancer treatments cause cardiotoxicity that can lead to heart failure, coronary artery disease, arrhythmia, and pericardial disease. In this review, representative cases of heart failure following cardiotoxicity caused by trastuzumab, anthracycline, and hematopoietic stem cell transplantation are described with case notes. Additionally, other important points regarding cardiotoxicity related to heart failure are reported. During and after potentially cardiotoxic therapy, periodic cardiac examinations are recommended to detect any cardiovascular disorders; these are ameliorated if appropriately diagnosed at an earlier stage. It is important for cardiologists and oncologists to understand the pathophysiology of representative cardiovascular disease cases following cancer treatment.

PMID: 32143767 [PubMed - as supplied by publisher]

9 March 2020

12:40

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Failure to extubate and delayed reintubation in elective lumbar fusion: An analysis of 57,677 cases.

Clin Neurol Neurosurg. 2020 Mar 02;193:105771

Authors: Gelfand Y, Longo M, De la Garza Ramos R, Sharfman ZT, Echt M, Hamad M, Kinon M, Yassari R, Kramer DC

BACKGROUND: Ovarian cancer (OC) is usually detected in late clinical stages, and imaging at diagnosis is crucial. Peritoneal carcinomatosis (PC)

Abstract

BACKGROUND: Ovarian cancer (OC) is usually detected in late clinical stages, and imaging at diagnosis is crucial. Peritoneal carcinomatosis (PC) and cardio phrenic lymph nodes (CPLN) are pathological findings of computed tomography (CT) and are relevant for surgical planning. Furthermore, mammographic breast density (BD) has shown an association with OC risk and might be prognostically relevant. However, it is not known if PC, CPLN, and BD are associated with aggressive OC subtypes and impaired OC survival. Herein, we investigated associations between three comprehensive image parameters and OC subtypes and survival.

METHODS: The Malmö Diet and Cancer Study is a prospective study that included 17,035 women (1991-1996). Tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. The CT and mammography closest to diagnosis were evaluated (Peritoneal Carcinomatosis Index PCI, CPLN, and BD). Associations between CT-PCI, CPLN, and BD vs. clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed by logistic and Cox regression.

RESULTS: There was a significant association between higher CT-PCI score and advanced clinical stage (adjusted OR 1.26 (1.07-1.49)), adjusted for age at diagnosis and histological type/grade. Increasing CT-PCI was significantly associated with impaired OC specific survival (adjusted HR 1.04 (1.01-1.07)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There was no significant association between PCI and histological type/grade, nor between BD or CPLN vs. the studied outcomes.

CONCLUSIONS: Image PCI score was significantly associated with advanced clinical stages and impaired OC survival. An objective approach (based on imaging) to scoring peritoneal carcinomatosis in ovarian cancer could help surgeons and oncologists to optimize surgical planning, treatment, and care.

PMID: 32145749 [PubMed - as supplied by publisher]

10 March 2020

13:39

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Patient values and preferences regarding VTE disease: a systematic review to inform American Society of Hematology guidelines.

Blood Adv. 2020 Mar 10;4(5):953-968

Authors: Etxeandia-Ikobaltzeta I, Zhang Y, Brundisini F, Florez ID, Wiercioch W, Nieuwlaat R, Begum H, Cuello CA, Roldan Y, Chen R, Ding C, Morgan RL, Riva JJ, Zhang Y, Charide R, Agarwal A, Balduzzi S, Morgano GP, Yepes-Nuñez JJ, Rehman Y, Neumann I, Schwab N, Baldeh T, Braun C, Rodríguez MF, Schünemann HJ

Risk factors for venous thromboembolism in cancer vary between tumours. Leucocytosis,

Abstract

Risk factors for venous thromboembolism in cancer vary between tumours. Leucocytosis, thrombocytosis, tumour histology and vascular compression may drive thrombosis in ovarian cancer. Thrombosis developed in 13.4% of our patients. Higher median leucocyte, neutrophil and monocyte counts were related to thrombosis. Thrombocytosis >350 × 109 /L was frequent (63.8%), but not predictive of thrombosis. Identification of prothrombotic biomarkers may help personalise preventive treatments.

PMID: 32141210 [PubMed - in process]

15:46

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[Pulmonary artery sarcoma that simulates pulmonary thromboembolism].

Medicina (B Aires). 2019;79(2):158

Authors: Serra AM, Kleinert MM, Núñez OT, Nogués I, Hunter B, Osatnik JD

PMID: 31048285 [PubMed - indexed for MEDLINE]

8 March 2020

12:10

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Do asymptomatic clots in children matter?

Thromb Res. 2020 Feb 19;189:24-34

Authors: Jones S, Monagle P, Newall F

Asymptomatic venous thrombosis is a common complication among hospitalised paediatric patients. Previous guidelines recommend the treatment

Abstract

Asymptomatic venous thrombosis is a common complication among hospitalised paediatric patients. Previous guidelines recommend the treatment of all asymptomatic venous thrombosis, even when the diagnosis is made incidentally or the risk factor is no longer present. Whether clinicians need to treat all asymptomatic thrombosis in children, given the likelihood of long-term sequelae, is unclear and there are significant risks associated with anticoagulation treatment. Asymptomatic thrombosis in children is most frequently associated with central venous catheters (CVCs). The incidence of asymptomatic CVC-related VTE is highest in cohorts of children with cancer, but also reported in neonates, children with congenital heart disease and critically ill children. There is significant variation in reported rates of CVC-related thrombosis among cohorts of children with different underlying diseases and of various ages. As asymptomatic thrombosis is often an incidental finding, rates of asymptomatic VTE in children are most likely underestimated. Evidence about the incidence, characteristics and long-term outcomes associated with asymptomatic thrombosis in children often lacks precision as data is presented collectively with symptomatic thrombosis. This review discusses the current evidence pertaining to the necessity for screening for asymptomatic thrombosis, the risk benefit ratio of treatment and the risk of long-term morbidity. To confidently determine the clinical significance of asymptomatic VTE in children, prospective studies with extended follow up are needed.

PMID: 32145462 [PubMed - as supplied by publisher]

13:35

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Acute Coronary Syndrome With Immune Checkpoint Inhibitors: A Proof-of-Concept Case and Pharmacovigilance Analysis of a Life-Threatening Adverse Event.

Can J Cardiol. 2019 Dec 11;:

Authors: Cautela J, Rouby F, Salem JE, Alexandre J, Scemama U, Dolladille C, Cohen A, Paganelli F, Ederhy S, Thuny F

Isolated cases of acute coronary syndrome (ACS) associated with immune checkpoint inhibitors (ICIs) have been described without

Abstract

Isolated cases of acute coronary syndrome (ACS) associated with immune checkpoint inhibitors (ICIs) have been described without the establishment of a formal cause-and-effect relationship between treatment and adverse event. We reported a case of ACS after the first administration of an ICI and with a fatal recurrence in another coronary area immediately after readministration. According to guidelines, causality was considered to be certain. Subsequently, we queried the French pharmacovigilance database and found 4 cases of ACS with coronary artery thrombosis. Causality was probable in those patients. These data suggest that ACS may be another life-threatening cardiac adverse event occurring with ICI exposure.

PMID: 32144037 [PubMed - as supplied by publisher]

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Acute and Chronic Effects of Cancer Drugs on the Cardiovascular System.

Heart Fail Clin. 2020 Apr;16(2):231-241

Authors: Moriyama S, Fukata M, Kusaba H, Maruyama T, Akashi K

Nonbacterial thrombotic endocarditis is a form of a thrombotic angiopathy involving the endothelial lined endocardial surfaces of the heart

Abstract

Nonbacterial thrombotic endocarditis is a form of a thrombotic angiopathy involving the endothelial lined endocardial surfaces of the heart which includes valves and the chamber walls. Underlying etiologies for nonbacterial thrombotic endocarditis include autoimmune diseases, hypercoagulable states, in the setting of certain malignant neoplasms, and physical injury. The pathogenesis for these processes is that of primary endothelial injury resulting in a thrombotic angiopathy. We present a patient with heart failure being evaluated before hematopoietic stem cell transplantation who had previously been provided with chemotherapy and whose cardiac magnetic resonance imaging reveals findings suggestive of amyloidosis. A subsequent endomyocardial biopsy instead showed nonbacterial thrombotic endocarditis characterized by the endocardium with fibromyxoid thickening and overlying fresh fibrin. This case highlights histopathologic findings of chemotherapy-associated nonbacterial thrombotic endocarditis involving the right ventricle wall of the endocardium, therefore expanding the radiological differential in patients with cardiac magnetic resonance imaging findings suggestive of amyloidosis.

PMID: 32142924 [PubMed - as supplied by publisher]

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Thoracic and cardiovascular surgeries in Japan during 2017 : Annual report by the Japanese Association for Thoracic Surgery.

Gen Thorac Cardiovasc Surg. 2020 Mar 05;:

Authors: Committee for Scientific Affairs, The Japanese Association for Thoracic Surgery, Shimizu H, Okada M, Tangoku A, Doki Y, Endo S, Fukuda H, Hirata Y, Iwata H, Kobayashi J, Kumamaru H, Miyata H, Motomura N, Natsugoe S, Ozawa S, Saiki Y, Saito A, Saji H, Sato Y, Taketani T, Tanemoto K, Tatsuishi W, Toh Y, Tsukihara H, Watanabe M, Yamamoto H, Yokoi K, Okita Y

PMID: 32140991 [PubMed - as supplied by publisher]

15:46

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Tranexamic Acid in Patients With Cancer Undergoing Endoprosthetic Reconstruction: A Retrospective Review.

J Am Acad Orthop Surg. 2020 Mar 15;28(6):248-255

Authors: Haase DR, Templeton KJ, Rosenthal HG, Sweeney KR

INTRODUCTION: Endoprosthetic reconstruction presents a significant risk of perioperative blood loss. Tranexamic acid (TXA)

Abstract

INTRODUCTION: Endoprosthetic reconstruction presents a significant risk of perioperative blood loss. Tranexamic acid (TXA) is an antifibrinolytic agent used to reduce blood loss in orthopaedic procedures. The safety and efficacy of TXA in arthroplasty are well documented. There is, however, a dearth of literature exploring the safety and efficacy of TXA in musculoskeletal oncology patients. This retrospective, comparative study explores the effects of TXA on perioperative blood loss, blood transfusion rates, venous thromboembolism (VTE) occurrence, and hospital stay in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction.

METHODS: For the study, charts from a total of 90 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction were reviewed; of these patients, 34 were in the TXA group and 56 in the non-TXA group. Study participants composed of a heterogeneous group of patients with primary bone sarcoma and metastatic osseous disease. Patients in the TXA group received 1 g of topical TXA administered into the wound bed before closure. The Hemoglobin Balance method was used to calculate blood loss. Patients were followed for 6 weeks.

RESULTS: Patients undergoing proximal femur replacement and distal femur replacement in the TXA group experienced a 796 and 687 mL reduction in 72-hour mean blood loss, respectively (P = 0.0003 and P = 0.006). Average blood transfusions decreased by 0.45 U of packed red blood cells per patient in the TXA group (P = 0.048) and transfusion incidence decreased by 21.1% compared with the non-TXA group (P = 0.04). Patients undergoing proximal femur replacement in the TXA group left the hospital 2.2 days earlier than those in the non-TXA group (P = 0.0004). No increase in VTE rate was observed with TXA use.

DISCUSSION: This study found results similar to total joint arthroplasty with regard to TXA's effect on perioperative blood loss, transfusion rates, hospital stay, and VTE occurrence. It provides initial data to support the efficacy of topical TXA use in this patient cohort.

LEVEL OF EVIDENCE: Level III, retrospective cohort study.

PMID: 32142488 [PubMed - as supplied by publisher]

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Variations in Incidence of Venous Thromboembolism in Low-, Middle- and High-Income Countries.

Cardiovasc Res. 2020 Mar 06;:

Authors: Siegal DM, Eikelboom JW, Lee SF, Rangarajan S, Bosch J, Zhu J, Yusuf S, Venous Thromboembolism Collaboration

AIM: To examine the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification).

Abstract

AIM: To examine the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification).

METHODS AND RESULTS: We examined the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, COMPASS). The primary outcome was a composite of pulmonary embolism, deep vein thrombosis and thrombophlebitis. We calculated age- and sex- standardized incidence rates (per 1000 person-years) and used a Cox frailty model adjusted for covariates to examine associations between the incidence of VTE and country income level. A total of 215,307 individuals (1·5 million person-years of follow-up) from high-income (n = 60,403), upper middle-income (n = 42,066) and lower middle/low-income (n = 112,838) countries were included. The age- and sex-standardized incidence rates of VTE per 1000 person-years in high-, upper middle- and lower middle/low-income countries were 0·87, 0·25 and 0·06, respectively. After adjusting for age, body mass index, smoking, antiplatelet therapy, anticoagulant therapy, education level, ethnicity, and incident cancer diagnosis or hospitalization, individuals from high-income and upper middle-income countries had a significantly higher risk of VTE than those from lower middle/low-income countries (hazard ratio [HR] 3·57, 95% confidence interval [CI] 2·40-5·30 and HR 2·27, 95%CI 1·59-3·23, respectively). The effect of country income level on VTE risk was markedly stronger in people with a lower BMI, hypertension, diabetes, non-white ethnicity and higher education.

CONCLUSION: The rates of VTE are substantially higher in high-income than low-income countries. The factors underlying the increased VTE risk in higher income countries remain unknown.

TRANSLATIONAL PERSPECTIVE: We investigated the burden of VTE by country income by combining information from 4 large prospective studies (215,307 individuals from 53 countries). This is the largest study on the global incidence of VTE published to date. We observed a higher incidence of VTE in richer compared to poorer countries. We also demonstrated that differences in rates of VTE are not explained by risk factors commonly associated with VTE. Further study is needed to understand whether these findings can be explained by differences in genetic or other markers, or whether they are due to differences in access to health care.

PMID: 32142099 [PubMed - as supplied by publisher]

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Cancer-associated prothrombotic pathways: leucocytosis, but not thrombocytosis, correlates with venous thromboembolism in women with ovarian cancer.

Intern Med J. 2020 Mar;50(3):366-370

Authors: López-Salazar J, Ramírez-Tirado LA, Gómez-Contreras N, Pacheco-Bravo I, Cortés E, Gallardo D, Arrieta O, Cesarman-Maus G

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with increased risk for venous

Abstract

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with increased risk for venous and arterial thromboembolism. The aim of this study was to evaluate outcomes following elective posterior lumbar fusion (PLF) and/or posterior interbody fusion (PLIF) among patients with PV.

METHODS: Using PearlDiver retrospective national database, Medicare patients <85

RESULTS: Selected study participants included 1491 patients with PV and 29,056 patients in the matched control group. Patients with PV had a significantly increased rate of 90-day acute pulmonary embolism (1.9% vs. 1.2%, odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10-2.38, P = 0.010), 90-day lower extremity deep vein thrombosis (3.4% vs. 1.9%, OR 1.81, 95% CI 1.33-2.40, P < 0.001), and 1-year diagnosis of surgical site infection (5.4% vs. 4.2%, OR 1.30, 95% CI 1.02-1.63, P = 0.027) compared with patients without PV. Nonetheless, PV was not associated with other major medical complications, including stroke, myocardial infarction, and mortality, following PLF and/or PLIF.

CONCLUSIONS: Patients with PV undergoing elective PLF and/or PLIF have a significantly increased risk for pulmonary embolism, lower extremity deep vein thrombosis, and surgical site infection.

PMID: 31639499 [PubMed - indexed for MEDLINE]

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7 March 2020

13:10

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Chemotherapy-associated nonbacterial thrombotic endocarditis: A radiological mimicker of cardiac amyloidosis requiring histopathologic examination for definitive diagnosis.

Cardiovasc Pathol. 2020 Feb 11;47:107210

Authors: Sekulic M, Gupta A, Patterson A, Oliveira G, Rajagopalan S

BACKGROUND: Venous thromboembolism is a well-known complication of Cushing syndrome. Deep vein thrombosis and pulmonary

Abstract

BACKGROUND: Venous thromboembolism is a well-known complication of Cushing syndrome. Deep vein thrombosis and pulmonary embolic events have been widely reported in patients with Cushing syndrome, but cerebral venous sinus thrombosis remains a much less common finding in these patients.

CASE DESCRIPTION: We report one of the first cases of cerebral venous sinus thrombosis in a patient with Cushing disease. An 18-year-old man presented to our clinic with accelerated weight gain despite an active lifestyle and unchanged diet. Workup revealed adrenocorticotrophic hormone-dependent hypercortisolism, and magnetic resonance imaging demonstrated a 6-mm pituitary microadenoma, consistent with Cushing disease. He underwent endoscopic transsphenoidal resection and achieved the desired postoperative adrenal insufficiency. The patient was discharged home, but presented again in a delayed fashion with profound cerebral venous sinus thrombosis requiring a prolonged hospitalization.

CONCLUSIONS: Previous studies have suggested that the coagulation profile of patients with Cushing syndrome normalizes when measured 12 months after correction of hypercortisolism, but these patients may remain hypercoagulable for an undefined period postoperatively, despite becoming adrenally insufficient. Although there have been scarce reports of cerebral venous sinus thrombosis in non-adrenocorticotrophic hormone-dependent Cushing syndrome, we report the first case of cerebral venous sinus thrombosis postoperatively in a patient with Cushing disease in remission.

PMID: 31639504 [PubMed - indexed for MEDLINE]

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Outcomes Following Posterior Lumbar Fusion in Patients with Polycythemia Vera.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Outcomes Following Posterior Lumbar Fusion in Patients with Polycythemia Vera.

World Neurosurg. 2020 Feb;134:e372-e378

Authors: Labaran LA, Vatani J, Bell J, Puvanesarajah V, Sequeira S, Raad M, Jain A, Hassanzadeh H

Doxorubicin is a standard treatment option for breast cancer, lymphoma, and leukemia, but its benefits are limited by its potential

Abstract

Doxorubicin is a standard treatment option for breast cancer, lymphoma, and leukemia, but its benefits are limited by its potential for cardiotoxicity. The primary objective of this study was to compare cardiac magnetic resonance imaging (CMRI) versus echocardiography (ECHO) to detect a reduction in left ventricular ejection function, suggestive of doxorubicin cardiotoxicity. We studied eligible patients who were 18 years or older, who had breast cancer or lymphoma, and who were offered treatment with doxorubicin with curative intent dosing of 240 to 300 mg/m 2 body surface area between March 1, 2009 and October 31, 2013. Patients underwent baseline CMRI and ECHO. Both imaging studies were repeated after four cycles of treatment. Ejection fraction (EF) calculated by both methods was compared and analyzed with the inferential statistical Student's t test. Twenty-eight eligible patients were enrolled. Two patients stopped participating in the study before undergoing baseline CMRI; 26 patients underwent baseline ECHO and CMRI. Eight of those 26 patients declined posttreatment studies, so the final study population was 18 patients. There was a significant difference in EF pre- and posttreatment in the CMRI group ( p = 0.009) versus the ECHO group that showed no significant differences in EF ( p = NS). It appears that CMRI is superior to ECHO for detecting doxorubicin-induced reductions in cardiac systolic function. However, ECHO is less expensive and more convenient for patients because of its noninvasive character and bedside practicality. A larger study is needed to confirm these findings.

PMID: 32132816 [PubMed]

20:50

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Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-01406736-TL.gif Related Articles

Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.

Lancet. 2020 02 15;395(10223):492-493

Authors: Earl HM, Hiller L, Plummer C, Miles D, Wardley AM, Cameron DA, Dunn JA

PMID: 32061290 [PubMed - indexed for MEDLINE]

20:50

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Protective strategies to prevent trastuzumab-induced cardiotoxicity.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-01406736-TL.gif Related Articles

Protective strategies to prevent trastuzumab-induced cardiotoxicity.

Lancet. 2020 02 15;395(10223):491-492

Authors: Guo S, Tse G, Liu T

PMID: 32061289 [PubMed - indexed for MEDLINE]

23:26

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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The Women's Health Initiative Estrogen-alone Trial had differential disease and medical expenditure consequences across age groups.

Menopause. 2020 Mar 02;:

Authors: Donneyong MM, Chang TJ, Roth JA, Guilds M, Ankrah D, Najafzadeh M, Xu WY, Chlebowski RT, Margolis K, Manson JE

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use

Abstract

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use. The impact of WHI trial on disease-associated medical expenditures attributable to subsequent decreased ET utilization has, however, not been measured. Therefore, the objective of this analysis was to quantify the age-specific disease-associated medical expenditures attributable to reduced ET utilization after the WHI Hormone Therapy (HT) trials.

METHODS: Population-level disease counts and associated expenditures between 2003 and 2015 were compared between an observed ET-user population versus a hypothetical ET-user population assuming absence of the WHI HT trials, constructed by extrapolating ET utilization rates from 1996 to 2002 assuming pre-WHI HT rates would have continued without publication of the WHI HT trial data (2002-2004). Analyses were stratified by age (50-59, 60-69, and 70-79 years). Input data were extracted from Medical Expenditure Panel Survey and the literature. The primary outcomes were: ET utilization, chronic diseases (breast cancer, stroke, coronary heart disease, colorectal cancer, pulmonary embolism, and hip fracture) and disease-associated direct medical expenditures.

RESULTS: Over 13 years, the decline in ET utilization was associated with $4.1 billion expenditure for excess chronic diseases (37,549 excess events) among women in their 50s, compared to savings of $1.5 billion and $4.4 billion for diseases averted by lower ET utilization among women in their 60s (13,495 fewer events) and 70s (40,792 fewer events), respectively.

CONCLUSION: The decline in ET utilization had differential disease and expenditure consequences by age groups in the United States. These results are limited by the lack of inclusion of vasomotor symptom benefit and costs of alternative medications for these symptoms in the analysis.

PMID: 32132440 [PubMed - as supplied by publisher]

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23:26

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Cerebral Venous Sinus Thrombosis After Transsphenoidal Resection: A Rare Complication of Cushing Disease-Associated Hypercoagulability.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Cerebral Venous Sinus Thrombosis After Transsphenoidal Resection: A Rare Complication of Cushing Disease-Associated Hypercoagulability.

World Neurosurg. 2020 Feb;134:86-89

Authors: Soni P, Koech H, Silva D, Das P, Sindwani R, Dobri G, Recinos PF

BACKGROUND AND PURPOSE: Doxorubicin anti-cancer therapy is associated with cardiotoxicity, resulting from DNA damage

Abstract

BACKGROUND AND PURPOSE: Doxorubicin anti-cancer therapy is associated with cardiotoxicity, resulting from DNA damage response (DDR). Hepatocyte growth factor (HGF) protects cardiomyocytes from injury, but its administration is hampered by low biodistribution. In this study we investigated whether the activation of the HGF receptor - encoded by the Met gene - by an agonist monoclonal antibody (mAb) protects from doxorubicin-induced cardiotoxicity.

EXPERIMENTAL APPROACH: MAb (5 mg/kg) was injected in vivo into C57BL/6J mice prior to doxorubicin (three doses of 7 mg/kg). The cardiac functions were evaluated through magnetic resonance imaging (MRI) after treatment termination. Heart histological staining and mRNA levels of genes associated with heart failure (Acta1, Nppa), inflammation (IL-6) and fibrosis (Ctgf, Col1a2, Timp1, and Mmp9) were assessed. MAb (100 nM) was administered in vitro to H9c2 cardiomyoblasts before addition of doxorubicin (25 μM). DDR and apoptosis markers were evaluated by quantitative western blotting, flow cytometry and immunofluorescence. Stattic was used for pharmacological inactivation of signal transducer and activation of transcription 3 (Stat3).

KEY RESULTS: In vivo, administration of mAb alleviated doxorubicin-induced cardiac dysfunction and fibrosis. In vitro, mAb mimicked the response to HGF by (i) inhibiting histone H2AX phosphorylation at S139, (ii) quenching the expression of the DNA repair enzyme poly (ADP-ribose) polymerase 1, and (iii) reducing the proteolytic activation of caspase 3. The Met-driven cardioprotection involved, at least in vitro, the phosphorylation of Stat3.

CONCLUSION AND IMPLICATIONS: This paper shows that Met agonist mAb provides a new tool for cardioprotection against anthracycline cardiotoxicity.

PMID: 32133617 [PubMed - as supplied by publisher]

20:50

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Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?

Cond Med. 2019 Oct;2(5):204-212

Authors: Chong J, Ho AF, Yap J, Bulluck H, Hausenloy DJ

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology

Abstract

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology. Coronary artery vasospasm is one of the most commonly reported effects of cancer therapy that can lead to myocardial ischemia or infarction. The chemotherapy agent 5-fluorouracil (5-FU) or its oral pro-drug capecitabine can result in coronary vascular endothelial dysfunction causing coronary artery spasm, and possibly coronary thrombosis. These drugs have also been shown to be associated with myocardial infarction, malignant ventricular arrhythmias, heart failure, cardiogenic shock, and sudden death. The proposed mechanisms underlying cardiotoxicity induced by 5-FU are vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium, and thrombogenicity. There remains a pressing need to discover novel and effective therapies that can prevent or ameliorate 5-FU associated cardiotoxicity. To this point, promising overlap has been observed between proposed remote ischemic conditioning (RIC) cardioprotective mechanisms and 5FU-associated cardiotoxic cellular pathways. RIC, in which transient episodes of limb ischemia and reperfusion (induced by inflations and deflations of a pneumatic cuff placed on the upper arm or thigh), confer both cardioprotective and vasculoprotective effects, and may therefore prevent 5-FU coronary artery spasm/cardiotoxicity. In this review, we will be discussing the following potentially therapeutic aspects of RIC in ameliorating 5-FU associated cardiotoxicity: sequential phases of 5-FU cardiotoxicity as possible targets for dual windows of cardioprotection characteristic of RIC; protective effects of RIC on endothelial function and microvasculature in relation to 5-FU induced endothelial dysfunction/microvascular dysfunction; reduction in platelet activation by RIC in the context of 5-FU induced thrombogenicity; and the utility of improvement in mitochondrial function conferred by RIC in 5-FU induced cellular toxicity secondary to mitochondrial dysfunction.

PMID: 32133437 [PubMed]

20:50

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Measurement of Ejection Fraction by Cardiac Magnetic Resonance Imaging and Echocardiography to Monitor Doxorubicin-Induced Cardiotoxicity.

Int J Angiol. 2020 Mar;29(1):45-51

Authors: Tak T, Jaekel CM, Gharacholou SM, Dworak MW, Marshall SA

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly

Abstract

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly expressed in heart and brain tissue. HERG plays critical role in cardiac repolarization, and mutations in HERG can cause long QT syndrome. More recently, evidence has emerged that HERG channels are aberrantly expressed in many kinds of cancer cells and play important roles in cancer progression. HERG could therefore be a potential biomarker for cancer and a possible molecular target for anticancer drug design. HERG affects a number of cellular processes, including cell proliferation, apoptosis, angiogenesis and migration, any of which could be affected by dysregulation of HERG. This review provides an overview of available information on HERG channel as it relates to cancer, with focus on the mechanism by which HERG influences cancer progression. Molecular docking attempts suggest two possible protein-protein interactions of HERG with the ß1-integrin receptor and the transcription factor STAT-1 as novel HERG-directed therapeutic targeting which avoids possible cardiotoxicity. The role of epigenetics in regulating HERG channel expression and activity in cancer will also be discussed. Finally, given its inherent extracellular accessibility as an ion channel, we discuss regulatory roles of this molecule in cancer physiology and therapeutic potential. Future research should be directed to explore the possibilities of therapeutic interventions targeting HERG channels while minding possible complications.

PMID: 32135169 [PubMed - as supplied by publisher]

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Cardio-oncology for better lymphoma therapy outcomes.

Lancet Haematol. 2020 Mar 02;:

Authors: Jurczak W, Długosz-Danecka M, Szmit S

PMID: 32135129 [PubMed - as supplied by publisher]

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Activation of the Met receptor attenuates doxorubicin-induced cardiotoxicity in vivo and in vitro.

Br J Pharmacol. 2020 Mar 04;:

Authors: Gallo S, Spilinga M, Albano R, Ferrauto G, Di Gregorio E, Casanova E, Balmativola D, Bonzano A, Boccaccio C, Sapino A, Comoglio PM, Crepaldi T

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