ABSTRACT

OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.

DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.

SETTING: PICUs within U.S. CHAT Consortium participating centers.

PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE.

CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.

PMID:37882641 | DOI:10.1097/PCC.0000000000003383

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PubMed articles on: Cancer & VTE/PE

Guidelines in Practice: Prevention of Venous Thromboembolism

AORN J. 2023 Nov;118(5):321-328. doi: 10.1002/aorn.14019.

 

ABSTRACT

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

PMID:37892623 | PMC:PMC10607346 | DOI:10.3390/jcm12206486

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PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium

Pediatr Crit Care Med. 2023 Oct 26. doi: 10.1097/PCC.0000000000003383. Online ahead of print.

 

ABSTRACT

OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.

RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients.

RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs.

CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.

PMID:37883026 | DOI:10.1080/17474086.2023.2276209

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PubMed articles on: Cardio-Oncology

The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats

Biomedicines. 2023 Oct 18;11(10):2820. doi: 10.3390/biomedicines11102820.

ABSTRACT

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

PMID:37893193 | PMC:PMC10604204 | DOI:10.3390/biomedicines11102820

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PubMed articles on: Cardio-Oncology

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF

J Clin Med. 2023 Oct 12;12(20):6486. doi: 10.3390/jcm12206486.

 

ABSTRACT

OBJECTIVE: To observe the effect of nurse-patient co-management mode on preventing venous thromboembolism (VTE) in lung cancer patients with carboplatin and gemcitabine chemotherapy after peripheral venipuncture central venous catheterization (PICC).

METHODS: 100 patients with lung cancer admitted to the 2nd Affiliated Hospital of Hainan Medical University from April 2020 to April 2022 were selected. All patients received a combination chemotherapy of carboplatin and gemcitabine and PICC catheterization. The patients were divided into an observation group and a control group by 1:1 simple random method, with 50 cases in each group. Patients in the control group were given routine nursing for lung cancer, and patients in the observation group were treated with nurse-patient co-management mode, and nursing intervention lasted for 2 months. General Comfort Questionnaire, self-management ability, quality of life, Self-care ability Scale, self-rating Anxiety Scale (SAS), and self-rating depression Scale were compared before and after intervention between the two groups. The recovery of immune ability indices (CD3+, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) in 2 groups were detected. Complications after PICC catheterization were recorded in the two groups.

RESULTS: After nursing, self-rating depression Scale and self-rating Anxiety Scale scores in both groups were significantly decreased, which were lower in the observation group than the control group (P < .001). After nursing, scores of self-concept, self-responsibility, self-care skills, and health knowledge level were significantly increased in both groups, which were higher in the observation group than control group (P < .001). After nursing, scores on the General Comfort Questionnaire, self-management scale, and quality of life were increased in both groups, which were higher in the observation group than control group (P < .0501). After nursing care, the immune competence indices of both patients increased significantly, and the immune indexes of CD3+, CD3+CD4+, and CD3+ CD4+/CD3+CD8+ in the observation group were significantly higher than those in the control group (P < .05). The total incidence of complications in the observation group was significantly lower than that in the control group (8.00% vs. 26.00%, P < .001), and the incidence of venous thromboembolism was significantly lower than that in the control group (2.00% vs. 14.00%, P < .001).

CONCLUSION: The nurse-patient co-management model has shown to be effective in reducing the incidence of venous thromboembolism in patients who have undergone PICC catheterization while receiving carboplatin and gemcitabine chemotherapy. This model also helps patients improve their self-care and self-management abilities, alleviates adverse psychological effects, and contributes to the recovery of their immune system.

PMID:37883756

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PubMed articles on: Cardio-Oncology

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Cancers (Basel). 2023 Oct 18;15(20):5036. doi: 10.3390/cancers15205036.

ABSTRACT

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.

PMID:37894403 | PMC:PMC10605752 | DOI:10.3390/cancers15205036

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PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients

Expert Rev Hematol. 2023 Oct 26:1-8. doi: 10.1080/17474086.2023.2276209. Online ahead of print.

 

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in lung cancer patients undergoing thoracic surgery. We examined the risk and timing of VTE following surgery for primary non-small cell lung cancer (NSCLC).

METHODS: in the Danish Lung Cancer Registry. VTE events in the year after surgery were assessed by stage, patient characteristics, and surgical procedure.

RESULTS: We identified 13,197 patients who underwent surgery for NSCLC in 2003-2021 (mean age 67.6 years, 50% female); 10,524 (79.7%) had stage I-II NSCLS and 2673 (20.3%) had stage III-IV. During one-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I versus 4.1% for stage IV), but varied little by pathological type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%, 95% CI 3.2-6.9), followed by pneumonectomy (3.6%, 95% CI 2.5-5.1). The hazard of VTE was highest during the first three months after surgery, whereafter it declined. For stage IV cancer hazards increased again after six months. At one-year, all-cause death was 12.6% (95% CI: 12.0-13.1 %).

CONCLUSIONS: Among patients undergoing surgery for NSCLC, 3.3% developed VTE, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.

PMID:37890818 | DOI:10.1016/j.athoracsur.2023.10.015

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PubMed articles on: Cardio-Oncology

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs

Int J Mol Sci. 2023 Oct 23;24(20):15466. doi: 10.3390/ijms242015466.

ABSTRACT

Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.

PMID:37895146 | PMC:PMC10607179 | DOI:10.3390/ijms242015466

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PubMed articles on: Cancer & VTE/PE

A Novel Model to Prevent Venous Thromboembolism in Patients with Lung Cancer

Altern Ther Health Med. 2023 Oct 27:AT9245. Online ahead of print.

 

ABSTRACT

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy regimen for colorectal, gastric, and breast cancers, cardiotoxicity caused by 5-fluorouracil might affect anywhere from 1.5% to 18% of patients. The precise mechanisms underlying cardiotoxicity associated with CRC treatment are complex and may involve the modulation of various signaling pathways crucial for maintaining cardiac health including TKI ErbB2 or NRG-1, VEGF, PDGF, BRAF/Ras/Raf/MEK/ERK, and the PI3/ERK/AMPK/mTOR pathway, resulting in oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, ultimately damaging cardiac tissue. Thus, the identification and management of cardiotoxicity associated with CRC drug therapy while minimizing the negative impact have become increasingly important. The purpose of this review is to catalog the potential cardiotoxicities caused by anticancer drugs and targeted therapy used to treat colorectal cancer as well as strategies focused on early diagnosing, prevention, and treatment of cardiotoxicity associated with anticancer drugs used in CRC therapy.

PMID:37895912 | PMC:PMC10610064 | DOI:10.3390/ph16101441

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PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

Medicina (Kaunas). 2023 Oct 20;59(10):1867. doi: 10.3390/medicina59101867.

ABSTRACT

Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.

PMID:37893585 | PMC:PMC10607997 | DOI:10.3390/medicina59101867

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PubMed articles on: Cardio-Oncology

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy

Life (Basel). 2023 Oct 23;13(10):2103. doi: 10.3390/life13102103.

ABSTRACT

Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions.

PMID:37895484 | PMC:PMC10608651 | DOI:10.3390/life13102103

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PubMed articles on: Cancer & VTE/PE

Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study

Ann Thorac Surg. 2023 Oct 25:S0003-4975(23)01073-1. doi: 10.1016/j.athoracsur.2023.10.015. Online ahead of print.

 

ABSTRACT

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.

PMID:37898967 | DOI:10.1007/s11739-023-03426-1

00:01

PubMed articles on: Cardio-Oncology

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy

Pharmaceuticals (Basel). 2023 Oct 11;16(10):1441. doi: 10.3390/ph16101441.

 

ABSTRACT

BACKGROUND: Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with HF.

OBJECTIVES: This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF.

METHODS: The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period.

RESULTS: The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors.

CONCLUSIONS: SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF.

PMID:37897456 | DOI:10.1016/j.jchf.2023.08.026

00:01

PubMed articles on: Cancer & VTE/PE

Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis

Intern Emerg Med. 2023 Oct 29. doi: 10.1007/s11739-023-03426-1. Online ahead of print.

 

ABSTRACT

We report an unusual case of extensive deep vein thrombosis (DVT) and pulmonary embolism (PE) in the setting of metastatic uterine leiomyosarcoma. Recognition of the associated sequelae of this condition may improve short- and long-term outcomes. A 56-year-old black female with a history of uterine leiomyosarcoma diagnosed incidentally after total abdominal hysterectomy for fibroid uterus without initiation of chemoradiation treatment presented to the emergency department complaining of generalized weakness and progressively worsening stridor for 2 weeks. The patient was experiencing shortness of breath, dysphagia, and hoarseness. Physical exam was remarkable for rhonchi but was otherwise normal. Diagnostic imaging via CT of the abdomen, pelvis, and chest revealed DVTs of the left common and external iliac veins, the superior mesenteric artery, multiple pulmonary emboli of the right pulmonary artery, several nodular lesions within the lungs, and scattered peritoneal necrotic lesions, which were suspicious for metastatic disease. Additionally, CT of the neck showed an exophytic mass protruding into the airway from the subglottic region and thyromegaly with bilateral thyroid lobe nodules. The patient was subsequently started on Eliquis and chemotherapy. The rarity of this case is rooted in the extent of the patient's DVTs and PEs secondary to hypercoagulability in metastatic cancer. This presentation should be further evaluated to exclude thrombophilias or underlying malignancies. Drawing from the lessons of this case will help guide future clinical management regarding the care of metastatic uterine leiomyosarcoma.

PMID:37900811 | PMC:PMC10601721 | DOI:10.1159/000531761

00:01

PubMed articles on: Cardio-Oncology

SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction

JACC Heart Fail. 2023 Oct 12:S2213-1779(23)00596-6. doi: 10.1016/j.jchf.2023.08.026. Online ahead of print.

 

ABSTRACT

Despite significant advancements in systemic anticancer therapies, cardiac tamponade remains a serious and potentially life-threatening complication in metastatic breast cancer (MBC). However, there is a paucity of comprehensive research investigating alternative management approaches, such as pericardiocentesis and anti-inflammatory therapy (AIT), to effectively address cardiac tamponade and mitigate the risk of heart failure arising from constrictive physiology (CP) in patients with MBC when traditional systemic anticancer drugs fail to yield favorable outcomes. Herein, we describe two cases of MBC with cardiac tamponade that occurred despite the administration of effective systemic anticancer drugs. In each case, pericardial effusion was detected in a patient who was undergoing palliative anticancer therapy for human epidermal growth factor receptor 2 (HER2)-positive MBC. The patients in these cases were successfully treated with pericardiocentesis and AIT (prednisolone and colchicine) for subsequent CP without substitution with their systemic anticancer drugs. Cardiac tamponade and CP are regarded as signs of advanced cancer and are associated with a worse clinical outcome in general; however, they can still be treated with an effective anticancer drug, pericardiocentesis, and management of CP by cardiooncology specialists.

PMID:37900575 | PMC:PMC10601458 | DOI:10.3389/fcvm.2023.1285233

00:01

PubMed articles on: Cancer & VTE/PE

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort

World J Gastroenterol. 2023 Oct 21;29(39):5494-5502. doi: 10.3748/wjg.v29.i39.5494.

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the digestive tract with increasing prevalence globally. Although venous thromboembolism (VTE) is a major complication in IBD patients, it is often underappreciated with limited tools for risk stratification.

AIM: To estimate the proportion of VTE among IBD patients and assess genetic risk factors (monogenic and polygenic) for VTE.

METHODS: Incident VTE was followed for 8465 IBD patients in the UK Biobank (UKB). The associations of VTE with F5 factor V leiden (FVL) mutation, F2 G20210A prothrombin gene mutation (PGM), and polygenic score (PGS003332) were tested using Cox hazards regression analysis, adjusting for age at IBD diagnosis, gender, and genetic background (top 10 principal components). The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve (AUC).

RESULTS: The overall proportion of incident VTE was 4.70% in IBD patients and was similar for CD (4.46%), UC (4.49%), and unclassified (6.42%), and comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers, hazard ratio (HR) was 1.94, 95% confidence interval (CI): 1.42-2.65. In contrast, patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores (middle 8 deciles), HR was 2.06 (95%CI: 1.57-2.71). The AUC for differentiating VTE diagnosis was 0.64 (95%CI: 0.61-0.67), 0.68 (95%CI: 0.66-0.71), and 0.69 (95%CI: 0.66-0.71), respectively, for F5/F2 mutation carriers, PGS, and combined.

CONCLUSION: Similar to cancer patients, VTE complications are common in IBD patients. PGS provides more informative risk information than F5/F2 mutations (FVL and PGM) for personalized thromboprophylaxis.

PMID:37900992 | PMC:PMC10600809 | DOI:10.3748/wjg.v29.i39.5494

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PubMed articles on: Cancer & VTE/PE

Venous Thromboembolism in Metastatic Uterine Leiomyosarcoma: A Case Report and Review of the Literature

Case Rep Oncol. 2023 Sep 12;16(1):900-906. doi: 10.1159/000531761. eCollection 2023 Jan-Dec.

 

ABSTRACT

OBJECTIVE: To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR).

DESIGN: In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes.

SETTING: We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China.

MAIN OUTCOMES AND MEASURES: The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach.

RESULTS: From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1-2 years, less than 1 year, and 2-3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology.

CONCLUSION AND RELEVANCE: Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.

PMID:37901406 | PMC:PMC10602811 | DOI:10.3389/fmed.2023.1203346

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PubMed articles on: Cardio-Oncology

Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report

Case Rep Oncol. 2023 Oct 11;16(1):1100-1106. doi: 10.1159/000533826. eCollection 2023 Jan-Dec.

ABSTRACT

Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.

PMID:37900846 | PMC:PMC10601787 | DOI:10.1159/000533826

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PubMed articles on: Cardio-Oncology

Case report: Successful treatment of malignant pericardial effusion with pericardiocentesis, concurrent anti-inflammatory therapy and cancer therapy

Front Cardiovasc Med. 2023 Oct 12;10:1285233. doi: 10.3389/fcvm.2023.1285233. eCollection 2023.

 

ABSTRACT

PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA).

METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups.

RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed.

CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.

PMID:37801086 | DOI:10.1007/s00520-023-08073-y

31 October 2023

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Cardiotoxicity News

PubMed articles on: Cardio-Oncology

Association between baseline blood pressure and the incidence of lenvatinib-induced hypertension in patients with thyroid cancer

Cancer Med. 2023 Oct 30. doi: 10.1002/cam4.6644. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension is the most frequently occurring adverse event of lenvatinib, recognized relatively early in its course. However, the trend in blood pressure after the initiation of lenvatinib and the outcomes with antihypertensive treatment are unclear. This study aimed to clarify the association between baseline blood pressure and the incidence of lenvatinib-induced hypertension in patients with thyroid cancer.

METHODS: This retrospective study included 65 patients without hypertension at the time of lenvatinib initiation. Patients were divided into two groups: those who developed hypertension grade ≥3 (HTN group) and those who did not develop hypertension grade ≥3 (non-HTN group).

RESULTS: Of the 65 patients, 46 (71%) developed hypertension grade ≥3. In both HTN and non-HTN groups, blood pressure significantly increased the day after lenvatinib initiation. There was no significant difference in the elevated values of both the changes in systolic blood pressure (ΔSBP) and diastolic blood pressure (ΔDBP) between the two groups, with an average increase of 20 mmHg in SBP and 13 mmHg in DBP from baseline. The median (range) time to the onset of hypertension grade ≥3 was 2 days (1-12 days). In the multivariable analysis, patients with normal (SBP 120-129 mmHg and/or DBP 80-84 mmHg) or high-normal baseline blood pressure (SBP 130-139 mmHg and/or DBP 85-89 mmHg) were at higher risk of developing hypertension grade ≥3 than those with optimal baseline blood pressure (SBP <120<80

CONCLUSIONS: Lenvatinib-induced hypertension appears the day after administration, and higher baseline blood pressure is a significant risk factor for developing hypertension grade ≥3. In cases of increased blood pressure with lenvatinib, early initiation of antihypertensives may prevent treatment interruption due to hypertension and maintain the therapeutic intensity of lenvatinib.

PMID:37902136 | DOI:10.1002/cam4.6644

00:00

PubMed articles on: Cardio-Oncology

Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories

Front Med (Lausanne). 2023 Oct 12;10:1203346. doi: 10.3389/fmed.2023.1203346. eCollection 2023.

 

ABSTRACT

Venous thromboembolism (VTE) is a common complication in patients with cancer. Data on the role of natural inhibitors of coagulation for occurrence of cancerassociated VTE are limited, thus, we investigated the association of tissue factor pathway inhibitor (TFPI) with risk of VTE and all-cause mortality in patients with cancer. Total TFPI antigen levels were measured with a commercially available ELISA in patients included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study with the primary outcome VTE. Competing risk analysis and Cox regression analysis were performed to explore the association of TFPI levels with VTE and all-cause mortality. TFPI was analyzed in 898 patients (median age: 62 years [interquartile range, IQR: 53-68]; 407 [45%] women). Sixtyseven patients developed VTE and 387 died (24-month cumulative risk: 7.5% and 42.1%, respectively). Patients had median TFPI levels at study inclusion of 56.4ng/mL (IQR: 45.7-70.0), with highest levels in tumor types known to have a high risk of VTE (gastroesophageal-, pancreatic and brain-cancer: 62.0ng/mL [IQR: 52.0-75.0]). In multivariable analysis adjusting for age, sex, cancer type and stage, TFPI levels were associated with VTE risk (SHR per doubling: 1.63, 95%CI: 1.03-2.57). When patients with high and intermediate/low VTE risk were analyzed separately, the association remained independently associated in the high risk group only (SHR: 2.63, 95%CI: 1.40-4.94). TFPI levels were independently associated with all-cause mortality (HR: 2.36, 95%CI: 1.85-3.00). In cancer patients increased TFPI levels are associated with VTE risk, specifically in patients with high risk tumor types, and with all-cause mortality.

PMID:37822244 | DOI:10.3324/haematol.2023.283581

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PubMed articles on: Cardio-Oncology

Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis

Nat Med. 2023 Oct 26. doi: 10.1038/s41591-023-02591-2. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.

PMID:37884625 | DOI:10.1038/s41591-023-02591-2

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PubMed articles on: Cancer & VTE/PE

Measurement of adherence and health-related quality of life during anticoagulation therapy in cancer-associated venous thromboembolism (VTE): a multicenter quantitative study

Support Care Cancer. 2023 Oct 6;31(10):615. doi: 10.1007/s00520-023-08073-y.

 

ABSTRACT

OBJECTIVE: While most of the evidence in CTO interventions emerge from Western and Japanese studies, few data have been published up today from the Middle East. Objective of this study was to evaluate technical success rates and clinical outcomes of an Iranian population undergoing CTO PCI in a tertiary referral hospital. Moreover, we sought to evaluate the efficacy of our CTO teaching program.

METHODS: This is a retrospective single-center cohort study including 790 patients who underwent CTO PCI performed by operators with different volumes of CTOs PCI performed per year. According to PCI result, all patients have been divided into successful (n = 555, 70.3 %) and unsuccessful (n = 235, 29.7 %) groups. Study endpoints were Major Adverse Cardiovascular Events and Health Status Improvement evaluated using the Seattle Angina Questionnaire at one year.

RESULTS: A global success rate of 70 % for antegrade and 80 % for retrograde approach was shown despite the lack of some CTO-dedicated devices. During the enrollment period, the success rate increased significantly among operators with a lower number of CTO procedures per year. One-year MACE rate was similar in both successful and unsuccessful groups (13.5 % in successful and 10.6 % in unsuccessful group, p = 0.173). One year patients' health status improved significantly only in successful group.

CONCLUSIONS: No significant differences of in-hospital and one-year MACE were found between the successful and unsuccessful groups. Angina symptoms and quality of life significantly improved after successful CTO PCI. The RAIAN registry confirmed the importance of operator expertise for CTO PCI success.

PMID:37866775 | DOI:10.1016/j.ihj.2023.10.002

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PubMed articles on: Cardio-Oncology

Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs

J Natl Compr Canc Netw. 2023 Oct;21(10):1039-1049.e10. doi: 10.6004/jnccn.2023.7047.

ABSTRACT

BACKGROUND: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied.

METHODS: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation.

RESULTS: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE.

CONCLUSIONS: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.

PMID:37856199 | DOI:10.6004/jnccn.2023.7047

19:51

PubMed articles on: Cancer & VTE/PE

Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer

Haematologica. 2023 Oct 12. doi: 10.3324/haematol.2023.283581. Online ahead of print.

 

ABSTRACT

BACKGROUND: Guidelines recommend extended venous thromboembolism (VTE) prophylaxis for high-risk populations undergoing major abdominal cancer operations. Few studies have evaluated extended VTE prophylaxis in the Medicare population who are at higher risk due to age.

METHODS: We performed a retrospective study using a 20% random sample of Medicare claims, 2012-2017. Patients ≥65 years with an abdominal cancer undergoing resection were included. Primary outcome was the proportion of patients receiving new extended VTE prophylaxis prescriptions at discharge. Secondary outcomes included postdischarge VTE and hemorrhagic events.

RESULTS: The study included 72 983 patients with a mean age of 75. Overall, 8.9% of patients received extended VTE prophylaxis. This proportion increased (7.2% in 2012, 10.6% in 2017; p < 0.001). Incidence of postdischarge hemorrhagic events was 1.0% in patients receiving extended VTE prophylaxis and 0.8% in those who did not. The incidence of postdischarge VTE events was 5.2% in patients receiving extended VTE prophylaxis and 2.4% in those who did not.

CONCLUSION: Adherence to guideline-recommended extended VTE prophylaxis in high-risk patients undergoing major abdominal cancer operations is low. The higher rate of VTE in the prophylaxis group may suggest we captured some therapeutic anticoagulation, which would mean the actual rate of thromboprophylaxis is lower than reported herein.

PMID:37800390 | DOI:10.1002/jso.27473

19:51

PubMed articles on: Cancer & VTE/PE

An etiological assessment of a deep vein thrombosis led to the discovery of a renal tumor collision: Case report

Int J Surg Case Rep. 2023 Oct;111:108922. doi: 10.1016/j.ijscr.2023.108922. Epub 2023 Oct 5.

ABSTRACT

INTRODUCTION AND IMPORTANCE: The thromboembolic complication of kidney's tumor is rare, and they can be the reason for the discovery of those tumor. Also the collision kidney tumor, such as a simultaneous occurrence of different histological types of adjacent neoplasms in the same organ is rare.

CASE PRESENTATION: We report a patient diagnosed with a kidney tumor discovered in the context of an etiological assessment of thrombosis, presenting with pulmonary embolism and deep vein thrombosis of the lower limb. This tumor treated by a cytoreductive nephrectomy. The histologic diagnosis of PRCC (Papillary Renal Cell Carcinoma) associated with a chromophobe cell carcinoma and sarcomatoid component was rendered.

CLINICAL DISCUSSION: The development of the tumor process and its progression to the metastatic stage is largely favored by the hypercoagulable state, and the cancer itself promotes the appearance of thrombo-enmbolic phenomena due to this phenomenon. Two major studies recommend that immediate cytoreductive nephrectomy should be offered to metastatic patients with a good general condition.

CONCLUSION: A renal tumor collision is rare, whereas the risk factors for a renal tumor collision are the same as a renal tumor without collision, just as the management of a metastatic renal tumor is the same. Understanding the thromboembolic physiopathology in the case of kidney cancer has made it possible to optimize management.

PMID:37812961 | PMC:PMC10568267 | DOI:10.1016/j.ijscr.2023.108922

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PubMed articles on: Cardio-Oncology

Outcomes of chronic total occlusion percutaneous coronary intervention from the RAIAN (RAjaie - Iran) registry

Indian Heart J. 2023 Oct 20:S0019-4832(23)00166-9. doi: 10.1016/j.ihj.2023.10.002. Online ahead of print.

 

ABSTRACT

OBJECTIVE: Craniopharyngiomas are extremely rare (incidence rate of 1.34 per million). Due to its proximity to the sellar/suprasellar prefrontal regions region, cognitive impairment, behavioral changes, and adverse endocrinological outcomes are common. Further, surgery and radiotherapy can further impact functioning. Currently, there is no parsimonious cognitive profile of adult patients following interventions. This case highlights the role of neuropsychological evaluations in monitoring global psychological functioning and frontal behavioral syndrome in an adult with recurrent craniopharyngioma.

METHOD: The patient is a 39-year-old Black female first evaluated as an inpatient prior to resection surgery. She was evaluated on four additional times post-surgically. At the most recent evaluation, she and her family reported memory problems, apathy, and gait instability. Complicating factors included hypothyroidism, chronic kidney disease, diabetes, obstructive sleep apnea, pulmonary embolism, hypotension, COVID-19, and recurrent tachycardia, with inconsistent adherence to treatment recommendations.

RESULTS: She displayed global cognitive deficits two years post-surgery, particularly in language and memory. Neurobehaviorally, she exhibited pervasive signs of severe frontal lobe syndrome, including, abulia, hypophonic and dysarthric speech, psychomotor retardation, bradyphrenia, and anosognosia.

CONCLUSION: Neuropsychological evaluations remain critical in monitoring the patient's neurocognitive status and provide valuable insights into treatment planning and need for additional support and care to optimize patients' quality of life in the context of significant cognitive disability.

PMID:37807245 | DOI:10.1093/arclin/acad067.136

19:51

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse

Res Pract Thromb Haemost. 2023 Aug 20;7(7):102173. doi: 10.1016/j.rpth.2023.102173. eCollection 2023 Oct.

ABSTRACT

BACKGROUND: Evidenced-based interventions have been developed to prevent venous thromboembolism (VTE) in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis. Our previous work identified barriers and facilitators to using VTE prevention interventions in oncology practice.

OBJECTIVES: To identify potential strategies that address the identified barriers and leverage facilitators to achieve successful implementation of evidence-based interventions for VTE prevention in oncology practice.

METHODS: We used the Implementation Research Logic Model, an implementation science framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies.

RESULTS: We identified 12 discrete implementation strategies (eg, conducting clinician education and training and staged implementation scale-up) that address barriers and leverage facilitators through their mechanisms of action (eg, increased clinician awareness of evidence and targeting the highest effectiveness). We identified key implementation (eg, penetration, adoption, acceptability, fidelity, appropriateness, and sustainability), system (eg, integration of VTE-risk assessment into clinical workflow), and clinical (eg, lower VTE rates) outcomes targeted by the selected strategies.

CONCLUSION: Using the Implementation Research Logic Model framework and building on our knowledge of barriers and facilitators, we identified implementation strategies and important outcomes to evaluate these strategies. We will use these results to test and measure the strategies to improve the uptake of evidence-based recommendations for VTE prevention in oncology practice.

PMID:37822563 | PMC:PMC10562910 | DOI:10.1016/j.rpth.2023.102173

19:51

PubMed articles on: Cancer & VTE/PE

Persistent underuse of extended venous thromboembolism prophylaxis in patients undergoing major abdominal cancer operations

J Surg Oncol. 2023 Oct 6. doi: 10.1002/jso.27473. Online ahead of print.

 

ABSTRACT

BACKGROUND: The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high-risk for bleeding.

METHODS: We used the RIETE registry to compare the 6-month incidence rates of: 1) VTE recurrences vs. major bleeding; and 2) fatal pulmonary embolism (PE) vs. fatal bleeding in 3 subgroups (those with mild, moderate, or severe RI) of cancer patients receiving enoxaparin monotherapy.

RESULTS: From January 2009 through June 2022, 2,844 patients with RI received enoxaparin for ≥6 months: 1,432 (50%) had mild, 1,168 (41%) moderate, and 244 (8.6%) had severe RI. Overall, 68%, 62% and 12% respectively, received the recommended doses. Among patients with mild RI, the rates of VTE recurrences vs. major bleeding (4.6% vs. 5.4%) and fatal PE vs. fatal bleeding (1.3% vs. 1.2%) were similar. Among patients with moderate RI, VTE recurrences were half as common as major bleeding (3.1% vs. 6.3%), but fatal PE and fatal bleeding were close (1.8% vs. 1.2%). Among patients with severe RI, VTE recurrences were 3-fold less common than major bleeding (4.1% vs. 13%), but fatal PE was 3-fold more frequent than fatal bleeding (2.5% vs. 0.8%). During the first 10 days, fatal PE was 5-fold more common than fatal bleeding (2.1% vs. 0.4%).

CONCLUSIONS: Among cancer patients with severe RI, fatal PE was 5-fold more common than fatal bleeding. The recommended doses of enoxaparin in these patients should be revisited.

PMID:37832588 | DOI:10.1055/a-2191-7510

19:51

PubMed articles on: Cardio-Oncology

Cancer and Atrial Fibrillation Comorbidities Among 25 Million Citizens in Shanghai, China: Medical Insurance Database Study

JMIR Public Health Surveill. 2023 Oct 17;9:e40149. doi: 10.2196/40149.

ABSTRACT

BACKGROUND: With population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China.

OBJECTIVE: We aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations.

METHODS: Data from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed.

RESULTS: A total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P<.001).

CONCLUSIONS: Patients with AF are associated with increased prevalence, heightened male predominance, and younger peak age of cancer. Further studies are needed to determine whether early screening of specific cancers is cost-effective and beneficial for patients with AF.

PMID:37847541 | DOI:10.2196/40149

19:51

PubMed articles on: Cardio-Oncology

Smoking, Diabetes Mellitus, and Previous Cardiovascular Disease as Predictors of Anticancer Treatment-Induced Cardiotoxicity in Non-Small-Cell Lung Cancer: A Real-World Study

Clin Lung Cancer. 2023 Oct 4:S1525-7304(23)00187-0. doi: 10.1016/j.cllc.2023.09.007. Online ahead of print.

ABSTRACT

PURPOSE: Cardiotoxicity is a common and under-reported side effect of tyrosine-kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI). Baseline risk factors may help in risk-stratifying patients at increased risk of cardiotoxicity. This real-world study investigated the effects of baseline risk factors in cardiotoxicity on patients with non-small-cell lung cancer (NSCLC) treated with TKIs and ICIs.

METHODS: This is a retrospective study carried out at The Royal Marsden Hospital, UK. Newly diagnosed patients with localized or metastatic NSCLC who received anticancer therapy with TKIs and/or ICIs were eligible. Patients who received only chemotherapy were excluded. Patients were followed up from the time of diagnosis until death or discharge. The relationship between cardiotoxicity and risk factors were tested by logistic regression.

RESULTS: Of 88/451 (19.5%) patients developed cardiotoxicity. Risk factors hypothesized to have a causal relationship with anticancer treatment-induced cardiotoxicity were analyzed. Cardiotoxicity risk was increased with prior diabetes mellitus (OR = 1.93, 95% CI, 1.04-3.61, P = .038), history of smoking (OR = 1.91, 95% CI, 1.13-3.22, P = .016) and presence of baseline cardiovascular disease (OR = 2.03, 95% CI, 1.13-3.64, P = .018). The risk of developing cardiotoxicity increased in patients for smokers with diabetes mellitus (OR = 3.03, 95% CI, 1.40-6.55, P < .01) and for smokers with previous cardiovascular disease (OR = 1.99, 95% CI, 1.03-3.84, P = .041).

CONCLUSION: Diabetes mellitus, smoking and baseline cardiovascular disease may synergistically contribute to cardiotoxicity when a patient is exposed to potentially cardiotoxic anticancer agents. Risk stratification at baseline may improve cardio-oncology care.

PMID:37880075 | DOI:10.1016/j.cllc.2023.09.007

19:51

PubMed articles on: Cancer & VTE/PE

A - 119 A Case Study: the Cognitive Functioning of an Adult Patient with Recurrent Craniopharyngiomas

Arch Clin Neuropsychol. 2023 Oct 20;38(7):1291. doi: 10.1093/arclin/acad067.136.

 

ABSTRACT

(1) Background: Central venous access devices (CVADs) have been commonly employed during various courses of anticancer treatment. Currently, there are a few types of clinically available CVADs, which are associated with short-term and long-term complications. However, little is known about the complication rates when CVADs are used only in palliative care settings. We therefore performed a systematic review and meta-analysis of all the published literature to evaluate the complication rates of CVADs in this clinical setting. (2) Methods: A systematic review and meta-analysis were conducted to identify publications from PubMed/MEDLINE, Embase (Ovid), Scopus, Cochrane Library, CINAHL, Google Scholar, and trial registries. Publications reporting the complication rates of PICCs, central lines, and PORTs in palliative settings for terminally ill cancer patients were included, while those on the use of systemic anticancer therapy and peripheral venous catheters were excluded. The outcome measures included overall complication rate, rate of catheter-related bloodstream infection (CRBSI), and rate of thromboembolism (TE). This systematic review was registered with PROSPERO (CRD42023404489). (3) Results: Five publications with 327 patients were analyzed, including four studies on PICCs and one study on central lines. No studies on PORTs were eligible for analysis. The overall complication rate for PICCs (pooled estimate 7.02%, 95% CI 0.27-19.10) was higher than that for central lines (1.44%, 95% CI 0.30-4.14, p = 0.002). The risk of CRBSI with PICCs (2.03%, 95% CI 0.00-9.62) was also higher than that with central lines (0.96%, 95% CI 0.12-3.41, p = 0.046). PICCs also had a trend of a higher risk of TE (2.10%, 95% CI 0.00-12.22) compared to central lines (0.48%, 95% CI 0.01-2.64, p = 0.061). (4) Conclusions: PICCs for palliative cancer care were found to have greater complications than central lines. This might aid in the formulation of future recommendation guidelines on the choice of CVAD in this setting.

PMID:37835406 | PMC:PMC10571956 | DOI:10.3390/cancers15194712

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PubMed articles on: Cardio-Oncology

High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer

J Pathol. 2023 Oct 16. doi: 10.1002/path.6212. Online ahead of print.

ABSTRACT

A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRASG12D . The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRASG12D detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

PMID:37842959 | DOI:10.1002/path.6212

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PubMed articles on: Cancer & VTE/PE

Enoxaparin for the long-term therapy of venous thromboembolism in patients with cancer and renal insufficiency

Thromb Haemost. 2023 Oct 13. doi: 10.1055/a-2191-7510. Online ahead of print.

 

ABSTRACT

BACKGROUND: Cardiotoxicity among breast cancer survivors is associated with chemotherapy and radiation therapy. The risk of cardiovascular disease (CVD) among Asian, Native Hawaiian and Pacific Islander (ANHPI) breast cancer survivors in the US is unknown.

METHODS: We used the SEER-Medicare linked database to estimate the risk of CVD among older breast cancer survivors. ICD diagnosis codes were used to identify incident CVD outcomes. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) comparing ANHPI to Non-Hispanic White (NHW) breast cancer patients for CVD, and among ANHPI race and ethnicity groups.

RESULTS: A total of 7,122 ANHPI breast cancer survivors and 21,365 NHW breast cancer survivors were identified. The risks of incident heart failure and ischemic heart disease were lower among ANHPI compared to NHW breast cancer survivors (HRheart failure=0.72, 95%CI=0.61, 0.84; HRheart disease=0.74, 95%CI=0.63, 0.88). Compared to Japanese breast cancer patients, Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer survivors had higher risks of heart failure. ischemic heart disease and death. Among ANHPI breast cancer survivors, risk factors for heart failure included older age, higher comorbidity score, distant cancer stage and chemotherapy.

CONCLUSIONS: Our results support heterogeneity in CVD outcomes among breast cancer survivors among ANHPI race and ethnicity groups. Further research is needed to elucidate the disparities experienced among ANHPI cancer survivors.

IMPACT: Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer patients had higher risks of heart failure, ischemic heart disease and death among ANHPI breast cancer patients.

PMID:37843411 | DOI:10.1158/1055-9965.EPI-23-0679

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PubMed articles on: Cancer & VTE/PE

Increased risk of venous and arterial thromboembolism in patients with colorectal cancer receiving cetuximab-based combination chemotherapy: A population-based study in Korea

Thromb Res. 2023 Oct 4;231:50-57. doi: 10.1016/j.thromres.2023.10.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Limited data exist on the risk of venous and arterial thromboembolisms (VTE and ATE) in patients receiving cetuximab plus chemotherapy. We aimed to determine the thromboembolic risk of patients with recurrent/metastatic colorectal cancer (CRC) treated with cetuximab plus chemotherapy compared to chemotherapy alone.

METHODS: This population-based study used nationwide claims data from the Health Insurance Review and Assessment Service of South Korea from 2013 to 2020. Patients with recurrent/metastatic CRC treated with first-line oxaliplatin- or irinotecan-based doublets with or without cetuximab and no secondary prevention for VTE and ATE were included. Primary outcomes were the occurrence of any thromboembolic events, VTE, and ATE, which were determined using the cumulative incidence method incorporating death as a competing event.

RESULTS: We identified 19,723 patients (cetuximab plus chemotherapy, N = 7630; chemotherapy alone, N = 12,093). The cumulative incidence of any thromboembolic events in patients with cetuximab plus chemotherapy was significantly higher than in those receiving chemotherapy alone (6-month, 5.62 % vs. 3.58 %, P < 0.0001). The rates of VTE (6-month, 5.11 % vs. 3.28 %, P < 0.0001) and ATE (6-month, 0.53 % vs. 0.32 %, P = 0.0218) were also higher in patients receiving cetuximab plus chemotherapy. In multivariable analysis, cetuximab plus chemotherapy was independently associated with developing any thromboembolic events (hazard ratio [HR], 1.63; 95 % confidence interval [CI], 1.42-1.87), VTE (HR, 1.62; 95 % CI, 1.40-1.87), and ATE (HR, 1.77; 95 % CI, 1.16-2.71).

CONCLUSIONS: Cetuximab with irinotecan- or oxaliplatin-based doublet chemotherapy was associated with an increased risk of any thromboembolic events, VTE, and ATE; further studies are warranted to examine the underlying mechanisms.

PMID:37804738 | DOI:10.1016/j.thromres.2023.10.005

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PubMed articles on: Cancer & VTE/PE

Complications of Central Venous Access Devices Used in Palliative Care Settings for Terminally Ill Cancer Patients: A Systematic Review and Meta-Analysis

Cancers (Basel). 2023 Sep 25;15(19):4712. doi: 10.3390/cancers15194712.

 

ABSTRACT

BACKGROUND: Despite recent improvements in the treatment of cancer, little is known about the long-term survival in patients with cancer and venous thromboembolism. We aimed to examine the five-year mortality of venous thromboembolism in cancer patients in a large population-based cohort study.

METHODS: Using Danish healthcare registries from 1995 to 2020, we obtained data on cancer patients with venous thromboembolism and comparison cohorts of cancer patients without venous thromboembolism, matched in terms of cancer type, age, sex, and year of cancer diagnosis, and adjusted for level of comorbidity and frailty using the Charlson Comorbidity Index Score and Hospital Frailty Risk Score, marital status, use of selected medications, and recent surgery (<90

FINDINGS: During the study period, 886,536 patients were diagnosed with cancer. Of 1882 cancer patients diagnosed at the time of their venous thromboembolism, 44.4% (835/1882) had distant metastases. In this cohort, the one- and five-year mortality cumulative incidences were 68% (1284/1882) and 84% (1578/1882), respectively, in contrast to 38% (2135/5549) and 67% (3653/5549) in the comparison cohort. The mortality rate ratio was 4.34 (95% confidence interval [CI], 3.95-4.78) for the first year of follow-up and 3.44 (95% CI 3.17-3.73) for the five-year follow-up period. Of the 23,366 patients diagnosed with venous thromboembolism after cancer diagnosis, 18% (4183/23,366) had distant metastases at the time of cancer diagnosis. The cumulative incidence of death at one year was 45% (10,465/23,366; mortality rate ratio 3.48, 95% CI 3.37-3.60) and at five years 69% (15,669/23,366; mortality rate ratio 2.57, 95% CI 2.50-2.63).

INTERPRETATION: Despite improved cancer treatment, venous thromboembolism in cancer patients is strongly associated with a poor prognosis.

FUNDING: The study was supported by grants from the Independent Research Fund Denmark (record no. 3101-00102B) and the Karen Elise Jensen Foundation.

PMID:37809052 | PMC:PMC10558815 | DOI:10.1016/j.lanepe.2023.100739

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PubMed articles on: Cancer & VTE/PE

Acute venous thromboembolism in patients with brain cancer: clinical course

Res Pract Thromb Haemost. 2023 Aug 20;7(6):102172. doi: 10.1016/j.rpth.2023.102172. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH).

OBJECTIVES: The aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer.

METHODS: This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome.

RESULTS: Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors.

CONCLUSION: In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

PMID:37810416 | PMC:PMC10551887 | DOI:10.1016/j.rpth.2023.102172

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PubMed articles on: Cardio-Oncology

Incident Cardiovascular Disease Risk Among Older Asian, Native Hawaiian and Pacific Islander Breast Cancer Survivors

Cancer Epidemiol Biomarkers Prev. 2023 Oct 16. doi: 10.1158/1055-9965.EPI-23-0679. Online ahead of print.