Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, ...coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.
•This consensus article provides guidance on prevention, screening, monitoring and treatment of cardiovascular toxicities.•Authorship includes a multidisciplinary group of experts from different institutions and countries in Europe and abroad.•Cardiovascular toxicities of cancer therapies can have significant impact on cancer patients' morbidity and mortality.•A multidisciplinary approach to the cardiovascular care of cancer patients is essential to achieve optimal long-term outcomes.•A summary of recommendations is provided, including levels of evidence and grades of recommendation where applicable.
Purpose
HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding ...HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction.
Methods
Patients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%.
Results
Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%.
Conclusion
This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.
is an important pathogen for both humans and animals. It can infect livestock, as well as pets and wild animals. During recent years, a number of reports have described the isolation of
from zoo ...animals, mainly birds and mammals, for which the infection was mostly lethal. Between 2005 and 2019, there were at least 17 cases of deceased mammals, belonging to five different species, which suffered from a
infection at the Zoo Wuppertal, Germany. Since only scarce information exists on the properties of
from zoo animals, we characterized eight isolates, covering all infected species, in detail. All isolates were members of biotype 1, but belonged to five serotypes, five sequence types (STs), and seven core-genome multilocus sequence types (cgMLSTs). Using pulsed-field gel electrophoresis (PFGE) analysis and whole-genome sequencing (WGS), the seven isolates could be discriminated from each other. They differed significantly regarding their virulence genes and mobile genetic elements. While the virulence plasmid pYV existed in all serotypes (five isolates), a complete high-pathogenicity island (HPI) was detected only in the serotypes O:1a, O:1b, and O:13 (four isolates), but not in O:2a and O:2b. Similarly, the content of other plasmids and prophages varied greatly between the isolates. The data demonstrate that the deceased mammals were infected by seven individual isolates and not by a single type predominating in the zoo animals.
The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many ...difficulties in real life. Improvement of patients' adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD.
The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up.
A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients' usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients' subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires.
Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively;
<0.001). Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively;
<0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively;
<0.001). Patients' subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (
<0.001).
Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients' inhalation technique with different devices, resulting in better long-term disease control and improved quality of life.
•Evaluation of antifungal effect of T. vulgaris and C. cassia against A. flavus.•Application of logistic kinetic model to the experimental data for optimal ratio calculation.•Optimal mixture has the ...synergistic effect with lower MIC and MFC values.•Modeling of results can advance synergistic studies by predicting optimal mixture.
The antifungal effect of essential oils (EOs) of Thymus vulgaris L. (EOT. vulgaris) and Cinnamomum cassia L. (EOC. cassia) against Aspergillus flavus spores was evaluated by determining minimum inhibitory concentration, minimum fungicidal concentrations and fungicidal kinetics. Kinetic model of fungicidal activity of individual EOT. vulgaris and EOC. cassia was developed and its parameters were used to make EO mixture with optimal ratio of individual EOs. Synergism and speed of fungicidal effect of EO mixtures against A. flavus spores were evaluated.
Kinetic model revealed optimal ratio EOT. vulgaris: EOC. cassia as 14:1 in mixture. Observed result was validated by comparing fungicidal effect of this mixture to commonly used ratio 1:1 and intermediate 7:1 EO mixtures. All three mixtures showed partial fungicidal synergism, but the time point of fungicidal effect was different. The fastest fungicidal effect was observed in 14:1 EO mixture (after 90min), followed by 7:1 (110min) and 1:1 (180min). The difference in the speed of fungicidal effect could not be detected using standard microdilution susceptibility tests, which demonstrated the importance and usefulness of developed kinetic model for further investigations.
Candida parapsilosis is one of the main emerging non-Candida albicans species leading to superficial and systemic fungal infections in humans. Candida has the ability to produce biofilms associated ...with pathogenesis. The aim of the study was to estimate biofilm-producing ability of clinical isolates of C. parapsilosis sp. complex.
Clinical samples of C. parapsilosis complex have been analyzed. Crystal violet (CV) staining and tetrazolium reduction assay (MTT) have been used to analyze the clinical isolates ability to produce biofilms. The biofilm's structural characteristics have been assessed by using scanning electron microscopy.
All 65 isolates were able to form biofilm. In addition, no significant difference was found between biofilm quantification based on two assays at different time intervals (24h, 48h, 72h, 96h) (P>0.05), with the exception of Candida orthopsilosis, which exhibited higher metabolic activity at 24h time point (P<0.05). Moreover, metabolic activity and production of biofilm biomass demonstrated statistically significant correlation (r=0.685, P<0.01). According to microscopic observations, the investigated clinical strains formed the similar surface topography with the slight differences in morphology; in addition, there was no statistically significant difference between efficiency of two assays to quantify biofilm.
It was shown that, similar to C. parapsilosissensu stricto, two cryptic identified species (C. orthopsilosis and Candida metapsilosis) obtained from different clinical samples, were biofilm producers, while C. parapsilosissensu stricto exhibited the highest biofilm production.
Dermatophytes are a group of keratinophilic fungi that invade and infect the keratinized tissues and cause dermatophytosis. We investigated effectiveness of novel triazole (luliconazole and ...lanaconazole) in comparison with available antifungal agents against dermatophyte species isolated from patients with tinea pedis.
A total of 60 dermatophytes species were isolated from the patients with tinea pedis. Identification of species was done by DNA sequencing of the ITS1-5.8S rDNA-ITS2 rDNA region. In vitro antifungal susceptibility testing with luliconazole and lanaconazole and available antifungal agent was done in accordance with the Clinical and Laboratory Standards Institute, M38-A2 document.
In all investigated isolates, luliconazole had the lowest minimum inhibitory concentration (MIC) (MIC range=0.0005–0.004μg/mL), while fluconazole (MIC range=0.4–64μg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008μg/mL), followed by lanoconazole (0.003μg/mL), terbinafine (0.019μg/mL), itraconazole (0.085 μg/mL), ketoconazole (0.089μg/mL), econazole (0.097μg/mL), griseofulvin (0.351 μg/mL), voriconazole (0.583μg/mL) and fluconazole (11.58μg/mL).
The novel triazoles showed potent activity against dermatophytes and promising candidates for the treatment of tinea pedis caused by Trichophyton and Epidermophyton species. However, further studies are warranted to determine the clinical implications of these investigations.
Abstract
Aims
To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity.
Methods and results
We followed the European ...Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy.
Conclusion
We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.
Randomized controlled trials have reported a 4–5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin
®
) compared to patients who do not receive ...trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77–2.44,
p
< 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66–75 years and HR = 1.44 for 76 years and older,
p
< 0.001) and diagnosed in recent years (HR = 2.58 for 2006–2007 vs. 1.86 for 1998–2005,
p
= 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients’ diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.
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