ABSTRACT

Cancer patients with venous thromboembolism (VTE) are prone to poor prognoses. Thus, we aimed to develop a nomogram to predict the risk of VTE in these patients. We retrospectively analyzed 791 patients diagnosed with solid tumors between January 2017 and May 2021 at Tongji Hospital. Univariate logistic analysis and multivariate logistic regression were adopted in this study. Our results indicated that age ≥ 60 years, tumor stages III-IV, platelet distribution width (PDW) ≤ 12.6%, albumin concentration ≤ 38.8 g/L, lactate dehydrogenase (LDH) concentration ≥ 198 U/L, D-dimer concentration ≥ 1.72 µg/mL, blood hemoglobin concentration ≤ 100 g/dL or the use of erythropoiesis-stimulating agents and cancer types were independent risk factors. The nomogram prediction model was developed based on the regression coefficients of these variables. We assessed the performance of the nomogram by calibration plot and the area under the receiver operating characteristic curve and compared it with the Khorana score. The concordance index (C- index) of the nomogram was 0.852 [95% confidence interval (CI) 0.823 to 0.880], while the Khorana score was 0.681 (95% CI 0.639 to 0.723). Given its performance, this nomogram could be used to select cancer patients at high risk for VTE and guide thromboprophylaxis treatment in clinical practice, provided it is validated in an external cohort.

PMID:37462901 | DOI:10.1007/s11239-023-02856-0

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PubMed articles on: Cancer & VTE/PE

Acute pulmonary tumour embolism and right systolic dysfunction in a hidden intrahepatic cholangiocarcinoma: case report

Eur Heart J Case Rep. 2023 Jun 28;7(7):ytad291. doi: 10.1093/ehjcr/ytad291. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Pulmonary tumour embolism is a rare entity that can arise from a wide variety of neoplasms. It can initially manifest as a pulmonary embolism with right heart failure and be refractory to thrombolytic therapy. Cholangiocarcinoma is a rare malignancy that arises from the epithelium of the biliary tree, representing 3% of all the gastrointestinal malignancies, being the intrahepatic cholangiocarcinoma the second most common liver tumour after hepatocellular carcinoma.

CASE SUMMARY: This case regards a patient that presented to our centre with acute pulmonary embolism, deep vein thrombosis, and unrevealing previous medical history. Imaging studies revealed pulmonary embolism, an ovarian mass, and multiple hepatic hypodensities. Throughout the hospitalization, the patient's haemodynamic state and right heart failure worsened, eventually leading to multi-organ failure and death. Post-mortem evaluation revealed cholangiocarcinoma cells on the pulmonary arteries.

DISCUSSION: Pulmonary tumour embolism is a rare pathology that can present with acute right heart failure. The diagnosis of occult cancer can be challenging, and the appropriate treatment for this entity remains an unexplored subject.

PMID:37457051 | PMC:PMC10347672 | DOI:10.1093/ehjcr/ytad291

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PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism following head and neck surgery

Eur Arch Otorhinolaryngol. 2023 Jul 17. doi: 10.1007/s00405-023-08112-8. Online ahead of print.

ABSTRACT

PURPOSE: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in patients undergoing surgery, but conflicting data exist on VTE risk in patients undergoing head and neck surgery for malignant and non-malignant conditions. Our aim was to examine the risk of VTE among patients with and without cancer undergoing head and neck surgery.

METHODS: We conducted a nationwide cohort study to examine the risk of VTE among patients with an otolaryngological diagnosis using data from the Danish National Patient Register between 2010 and 2018. Analyses were stratified by cancer and anatomical areas of the surgical procedure.

RESULTS: In total, 116,953 patients were included of whom 10% (n = 12,083) had active cancer. After 3 months, 1.2% of the patients with cancer and 0.3% of the patients without cancer experienced VTE, respectively. For patients undergoing mouth/throat surgery, 0.8% with cancer and 0.2% without cancer had VTE, respectively. After nose/sinuses surgery 0.7% and 0.2%, respectively. No patients experienced VTE after ear surgery; and after endoscopies the numbers were 1.3% and 0.6% respectively.

CONCLUSIONS: While the minority of patients undergoing head and neck surgery develop VTE postoperatively, the risk increases among those with cancer. To support clinical decision making on anticoagulation, risk stratification tools could be further developed to recognize this hazard in patients with cancer undergoing head and neck surgery.

PMID:37458791 | DOI:10.1007/s00405-023-08112-8

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PubMed articles on: Cardio-Oncology

From bedside to the bench: patient-specific hiPSC-EC models uncover endothelial dysfunction in genetic cardiomyopathies

Front Physiol. 2023 Jul 19;14:1237101. doi: 10.3389/fphys.2023.1237101. eCollection 2023.

ABSTRACT

Genetic cardiomyopathies are a group of inherited disorders in which myocardial structure and function are damaged. Many of these pathologies are rare and present with heterogenous phenotypes, thus personalized models are required to completely uncover their pathological mechanisms and develop valuable therapeutic strategies. Both cardiomyocytes and fibroblasts, differentiated from patient-specific human induced pluripotent stem cells, represent the most studied human cardiac cell models in the context of genetic cardiomyopathies. While endothelial dysfunction has been recognized as a possible pathogenetic mechanism, human induced pluripotent stem cell-derived endothelial cells are less studied, despite they constitute a suitable model to specifically dissect the role of the dysfunctional endothelium in the development and progression of these pathologies. In this review, we summarize the main studies in which human induced pluripotent stem cell-derived endothelial cells are used to investigate endothelial dysfunction in genetic-based cardiomyopathies to highlight new potential targets exploitable for therapeutic intervention, and we discuss novel perspectives that encourage research in this direction.

PMID:37538375 | PMC:PMC10394630 | DOI:10.3389/fphys.2023.1237101

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PubMed articles on: Cardio-Oncology

Accelerated cystogenesis by dietary protein load is dependent on, but not initiated by kidney macrophages

Front Med (Lausanne). 2023 Jul 19;10:1173674. doi: 10.3389/fmed.2023.1173674. eCollection 2023.

ABSTRACT

BACKGROUND: Disease severity of autosomal dominant polycystic kidney disease (ADPKD) is influenced by diet. Dietary protein, a recognized cyst-accelerating factor, is catabolized into amino acids (AA) and delivered to the kidney leading to renal hypertrophy. Injury-induced hypertrophic signaling in ADPKD results in increased macrophage (MФ) activation and inflammation followed by cyst growth. We hypothesize that the cystogenesis-prompting effects of HP diet are caused by increased delivery of specific AA to the kidney, ultimately stimulating MФs to promote cyst progression.

METHODS: Pkd1flox/flox mice with and without Cre (CAGG-ER) were given tamoxifen to induce global gene deletion (Pkd1KO). Pkd1KO mice were fed either a low (LP; 6%), normal (NP; 18%), or high (HP; 60%) protein diet for 1 week (early) or 6 weeks (chronic). Mice were then euthanized and tissues were used for histology, immunofluorescence and various biochemical assays. One week fed kidney tissue was cell sorted to isolate tubular epithelial cells for RNA sequencing.

RESULTS: Chronic dietary protein load in Pkd1KOmice increased kidney weight, number of kidney infiltrating and resident MФs, chemokines, cytokines and cystic index compared to LP diet fed mice. Accelerated cyst growth induced by chronic HP were attenuated by liposomal clodronate-mediated MФ depletion. Early HP diet fed Pkd1KO mice had larger cystic kidneys compared to NP or LP fed counterparts, but without increases in the number of kidney MФs, cytokines, or markers of tubular injury. RNA sequencing of tubular epithelial cells in HP compared to NP or LP diet group revealed increased expression of sodium-glutamine transporter Snat3, chloride channel Clcnka, and gluconeogenesis marker Pepck1, accompanied by increased excretion of urinary ammonia, a byproduct of glutamine. Early glutamine supplementation in Pkd1KO mice lead to kidney hypertrophy.

CONCLUSION: Chronic dietary protein load-induced renal hypertrophy and accelerated cyst growth in Pkd1KO mice is dependent on both infiltrating and resident MФ recruitment and subsequent inflammatory response. Early cyst expansion by HP diet, however, is relient on increased delivery of glutamine to kidney epithelial cells, driving downstream metabolic changes prior to inflammatory provocation.

PMID:37538309 | PMC:PMC10394241 | DOI:10.3389/fmed.2023.1173674

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PubMed articles on: Cardio-Oncology

Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients

Eur Heart J Digit Health. 2023 May 8;4(4):302-315. doi: 10.1093/ehjdh/ztad031. eCollection 2023 Aug.

ABSTRACT

AIMS: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care.

METHODS AND RESULTS: De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals.

CONCLUSION: Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.

PMID:37538144 | PMC:PMC10393891 | DOI:10.1093/ehjdh/ztad031

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PubMed articles on: Cardio-Oncology

Modulatory effect of amifostine (WR-1065) against genotoxicity and oxidative stress induced by methotrexate in human umbilical vein endothelial cells (HUVECs)

Toxicol Mech Methods. 2023 Aug 3:1-11. doi: 10.1080/15376516.2023.2238069. Online ahead of print.

ABSTRACT

Amifostine is used in chemotherapy and radiotherapy as a cytoprotective adjuvant alongside DNA-binding chemotherapeutic agents. It functions by reducing free radicals and detoxifying harmful metabolites. Methotrexate, as an antimetabolite drug has been considered for treating various cancers and autoimmune diseases. However, the cytotoxic effects of methotrexate extend beyond tumor cells to crucial organs, including the heart. This study applied the HUVEC cell line as a reference in vitromodel for researching the characteristics of vascular endothelium and cardiotoxicity. The current study aimed to assess amifostine's potential cytoprotective properties against methotrexate-induced cellular damage. Cytotoxicity was measured using the MTT assay. Apoptotic rates were evaluated by Annexin V-FITC/PI staining viaflow cytometry. The genoprotective effect of amifostine was determined using the comet assay. Cells were exposed to various amifostine doses (10-200 μg/mL) and methotrexate (2.5 μM) in pretreatment culture condition. Methotrexate at 2.5 μM revealed cytotoxicity, apoptosis, oxidative stress and genotoxicity while highlighting amifostine's cyto/geno protective properties on HUVECs. Amifostine significantly decreased the levels of ROS and LPO while preserving the status of GSH and SOD activity. Furthermore, it inhibited genotoxicity (tail length, %DNA in tail, and tail moment) in the comet assay. Amifostine markedly attenuated methotrexate-induced apoptotic cell death (early and late apoptotic rates). These findings convey that amifostine can operate as a cytoprotectant agent.

PMID:37537746 | DOI:10.1080/15376516.2023.2238069

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PubMed articles on: Cardio-Oncology

Homotypic targeted nanoplatform enable efficient chemoimmunotherapy and reduced DOX cardiotoxicity in chemoresistant cancer via TGF-β1 blockade

J Control Release. 2023 Aug 1:S0168-3659(23)00486-8. doi: 10.1016/j.jconrel.2023.07.063. Online ahead of print.