ABSTRACT

Gefitinib (GEF) may increase the risk of corrected QT prolongation (QTc). We aimed to evaluate whether gefitinib increases the risk of corrected QT interval (QTc) prolongation and analyze the associated risk factors.A total of 122 cases of advanced EGFR-mutated non-small cell lung cancer (NSCLC) who received gefitinib therapy from January 2015 to December 2020 were evaluated. The results of at least two resting 12-lead electrocardiogram before and after gefitinib treatment were obtained. The Bazett and Fridericia formulas were used to calculate the QTc interval, and the changes of QTc interval values before and after treatment were evaluated. The correlation between gefitinib and QTc interval prolongation and related risk factors were analyzed.After gefitinib-targeted therapy, 23 patients (18.9%) had a prolonged QTc interval, which increased from a mean of 446 ± 25 ms at baseline to 478 ± 18 ms (P < 0.001). Three of the patients met criteria for Grade 3 QTc prolongation in the common term V5.0 for clinical adverse events. Univariate analysis showed that age (ORR, 1.054; 95% confidence interval [CI], 1.003-1.107; P = 0.038), history of hypertension (ORR, 3.409; 95% CI, 1.334-8.713; P = 0.01), CCB medication history (ORR, 0.259; 95% CI, 0.094-0.712; P = 0.009), history of lung cancer surgery (ORR, 0.231; 95% CI, 0.064-0.829; P = 0.025), and baseline QT interval (ORR, 0.978; 95% CI, 0.964-0.993; P = 0.004) were important predictors of QTc interval prolongation in patients treated with gefitinib. The results of multivariate analysis showed that the history of lung cancer surgery and the baseline QT interval were important factors affecting QTc interval prolongation in patients treated with gefitinib.Gefitinib increases the risk of QTc prolongation in NSCLC patients, which may be more pronounced in patients with advanced age, hypertension, CCB therapy, lung cancer surgery, and a long QT interval at baseline.

PMID:37258113 | DOI:10.1536/ihj.22-583

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PubMed articles on: Cardio-Oncology

Natriuretic Peptides, Cardio-Oncology

Anatol J Cardiol. 2023 Jun;27(6):298. doi: 10.14744/AnatolJCardiol.2023.6.

NO ABSTRACT

PMID:37257014 | DOI:10.14744/AnatolJCardiol.2023.6

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PubMed articles on: Cardio-Oncology

Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - a nationwide database analysis from Hungary

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PubMed articles on: Cardio-Oncology

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series

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PubMed articles on: Cancer & VTE/PE

Correction to: Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis

Support Care Cancer. 2023 Jun 3;31(6):373. doi: 10.1007/s00520-023-07851-y.

NO ABSTRACT

PMID:37269357 | DOI:10.1007/s00520-023-07851-y

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PubMed articles on: Cancer & VTE/PE

D-dimer testing: A narrative review

Adv Clin Chem. 2023;114:151-223. doi: 10.1016/bs.acc.2023.02.006. Epub 2023 Mar 29.

ABSTRACT

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

PMID:37268332 | DOI:10.1016/bs.acc.2023.02.006

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PubMed articles on: Cancer & VTE/PE

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial

JAMA. 2023 Jun 2. doi: 10.1001/jama.2023.7843. Online ahead of print.

ABSTRACT

IMPORTANCE: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.

OBJECTIVE: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.

DESIGN, SETTING, AND PARTICIPANTS: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.

INTERVENTION: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.

MAIN OUTCOMES AND MEASURES: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.

RESULTS: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.

CONCLUSIONS AND RELEVANCE: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02744092.

PMID:37266947 | DOI:10.1001/jama.2023.7843

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PubMed articles on: Cancer & VTE/PE

Cerebral infarction related to nonbacterial thrombotic endocarditis in a middle-aged woman with uterine adenomyosis: A case report

Medicine (Baltimore). 2023 Jun 2;102(22):e33871. doi: 10.1097/MD.0000000000033871.

ABSTRACT

RATIONALE: Few isolated case reports and case series have reported arterial and venous thromboembolism related to adenomyosis; however, the underlying mechanism remains unclear.

PATIENT CONCERNS: A 47-year-old woman presented with dizziness, nausea, vomiting, and loss of consciousness after red blood cell transfusion. She was being treated for menorrhagia and severe anemia.

DIAGNOSES: Magnetic resonance imaging showed multiple infarctions in right cerebellum and bilateral frontal, parietal, and occipital lobes. Echocardiography performed during the evaluation for the source of emboli revealed multiple echogenic masses on the tricuspid aortic valve. There was no evidence of infection, and the masses on the aortic valve were diagnosed as nonbacterial thrombotic endocarditis. The levels of autoimmune antibodies and tumor markers except for carbohydrate antigen 19-9 and cancer antigen 125 were within the normal range. Uterine ultrasound showed a large adenomyosis. The patient was diagnosed with multiple cerebral and cerebellar infarctions due to nonbacterial thrombotic endocarditis, and hormone therapy and anticoagulation with warfarin were initiated.

INTERVENTIONS: The patient did not develop recurrent infarction during anticoagulant therapy; however, menorrhagia worsened requiring total hysterectomy.

OUTCOMES: The patient did not experience recurrent infarction despite the absence of anticoagulant therapy during the 3-year follow-up period.

LESSONS: The present case adds to the limited number of previously reported cases and supports that, albeit rare, adenomyosis can be associated with embolic infarction and suggests that nonbacterial thrombotic endocarditis might be the link between adenomyosis and embolic infarction.

PMID:37266639 | PMC:PMC10238019 | DOI:10.1097/MD.0000000000033871

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PubMed articles on: Cancer & VTE/PE

Body Mass Index (BMI) Related Morbidity with Thyroid Surgery

Laryngoscope. 2023 Jun 2. doi: 10.1002/lary.30789. Online ahead of print.

ABSTRACT

OBJECTIVES: The increase in incidence of thyroid cancer correlates with strict increases in body mass index (BMI) and obesity in the United States. Thyroid hormone dysregulation has been shown to precipitate circulatory volume, peripheral resistance, cardiac rhythm, and even cardiac muscle health. Theoretically, thyroid surgery could precipitate injury to the cardiopulmonary system.

METHODS: The American College of Surgery National Quality Improvement Program database was queried for thyroidectomy cases in the 2007-2020 Participant User files. Continuous and categorical associations between BMI and cardiopulmonary complications were investigated as reported in the database.

RESULTS: The query resulted 186,095 cases of thyroidectomy procedures in which the mean age was 51.3 years and sample was 79.3% female. No correlation was evident in univariate and multivariate analyses between BMI and the incidence of postoperative stroke or myocardial infarction. The incidence of complications was extremely low. However, risk of deep venous thrombosis correlated with BMI in the categorical, univariate, and multivariate (OR 1.036, CI 1.014-1.057, p < 0.01) regression analysis. Additionally, increased BMI was associated with increased risk of pulmonary embolism (PE) (OR 1.050 (1.030, 1.069), p < 0.01), re-intubation (OR 1.012 (1.002, 1.023), p = 0.02), and prolonged intubation (OR 1.031 (1.017, 1.045), p < 0.01).

CONCLUSION: Despite the rarity of cardiopulmonary complications during thyroid surgery, patients with very high BMI carry a significant risk of deep venous thrombosis, PE, and prolonged intubation.

LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2023.

PMID:37265205 | DOI:10.1002/lary.30789

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PubMed articles on: Cancer & VTE/PE

Prevention of venous thromboembolism in patients with cancer

BMJ. 2023 Jun 1;381:e072715. doi: 10.1136/bmj-2022-072715.

ABSTRACT

Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population. Various risk models predictive of venous thromboembolism in patients with cancer have been developed, and knowledge of these rubrics is essential for the treating oncologist. Subgroups of particular interest are inpatients receiving chemotherapy, postoperative patients after surgical debulking, and patients undergoing radiotherapy. Numerous newer drugs have become available for the prevention of venous thromboembolism in patients with cancer who are at high risk of developing the disease. These include the class of drugs called direct oral anticoagulants, (DOACs) which do not require the same monitoring that other modalities have previously required and are taken by mouth, preventing the discomfort associated with subcutaneous strategies. The appropriate risk stratification and intervention to prevent venous thromboembolism are vital to the treatment of patients with cancer.

PMID:37263632 | DOI:10.1136/bmj-2022-072715

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PubMed articles on: Cancer & VTE/PE

Accuracy of the Physicians' Intuitive Risk Estimation in the Diagnostic Management of Pulmonary Embolism: An Individual Patient Data Meta-Analysis

J Thromb Haemost. 2023 May 30:S1538-7836(23)00438-5. doi: 10.1016/j.jtha.2023.05.023. Online ahead of print.

ABSTRACT

BACKGROUND: In patients clinically suspected of pulmonary embolism (PE), physicians often rely on an intuitive estimation ('gestalt') of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization.

OBJECTIVES: To assess the diagnostic accuracy of gestalt in diagnosing PE and gain insight into its possible variation.

METHODS: We performed an individual patient data meta-analysis including patients suspected of PE. The primary outcome was the diagnostic accuracy of gestalt for diagnosing PE, quantified as a risk ratio (RR) between gestalt and PE from a two-stage random-effect log-binomial meta-analysis regression as well as gestalts' sensitivity and specificity. Variability of these measures was explored across different healthcare settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age.

RESULTS: We analysed 20,770 patients suspected of PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% versus 9.1%, respectively. The overall RR was 3.02 (95%CI 2.35, 3.87) and overall sensitivity and specificity were 74% (95%CI 68-79%) and 61% (95%CI 53-68%). Although variation was observed across individual studies (I2-90.63%), diagnostic accuracy was consistent across all subgroups and healthcare settings.

CONCLUSIONS: A positive gestalt was associated with a threefold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and healthcare settings, exemplifying its diagnostic value for all patients suspected of PE.

PMID:37263381 | DOI:10.1016/j.jtha.2023.05.023

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PubMed articles on: Cancer & VTE/PE

Thrombotic Complications in Children with COVID-19 and MIS-C

J Thromb Haemost. 2023 May 31:S1538-7836(23)00434-8. doi: 10.1016/j.jtha.2023.05.020. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19) associated coagulopathy is multifactorial and involves inflammation driven hypercoagulability, endothelial dysfunction, platelet activation and impaired fibrinolysis. Hospitalized adults with COVID-19 are at an increased risk of both venous thrombo-embolism (VTE) and ischemic stroke, resulting in adverse outcomes including mortality. While children with COVID-19 follow a less severe course, both arterial and venous thrombosis have been reported in hospitalized children with COVID-19. Additionally, some children develop a post-infectious, hyper-inflammatory illness termed Multisystem Inflammatory Syndrome of Childhood (MIS-C), which is also associated with hypercoagulability and thrombosis. Several randomized trials have evaluated the safety and efficacy of antithrombotic therapy in adults with COVID-19, though similar pediatric data are lacking. In this narrative review we discuss the postulated pathophysiology of COVID-19 coagulopathy, and summarize principal findings of the recently completed adult trials of antithrombotic therapy. We provide an up-to-date summary of pediatric studies investigating the rate of VTE and ischemic stroke in COVID-19 and MIS-C, in addition to reviewing the findings of the single, non-randomized pediatric trial investigating the safety of prophylactic anticoagulation. Lastly, we outline the adult and pediatric consensus guidelines on the use of antithrombotic therapy in this cohort. A detailed discussion of the practical implementation and current limitations of published data will hopefully address knowledge deficits surrounding the use of antithrombotic therapy in children with COVID-19, and generate hypotheses for future research.

PMID:37268064 | DOI:10.1016/j.jtha.2023.05.020

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PubMed articles on: Cancer & VTE/PE

A systemic review and meta-analysis of Aflibercept plus FOLFIRI regimen as a second-line treatment for metastatic colorectal cancer: A PRISMA compliant pooled analysis of randomized controlled trials and single arm studies to assess efficacy and safety

Crit Rev Oncol Hematol. 2023 May 29:104034. doi: 10.1016/j.critrevonc.2023.104034. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.

METHOD: PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.

RESULT: Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%-37%, p = 0.00) for 12m PFS and 61% (95% CI, 53% - 68%, p = 0.00) for 12m OS. The pooled prevalences were 69% (95% CI, 55% - 82%, p = 0.00) for any grade 3-4 toxicities, 10% (95% CI, 5% - 16%, p = 0.00) for grade 3-4 diarrhea, 13% (95% CI, 5% - 24%, p = 0.00) for grade 3-4 hypertension, 31% (95% CI, 22% - 40%, p = 0.00) for grade 3-4 neutropenia and 5% (95% CI, 2% - 7%, p = 0.00) for grade 3-4 venous thromboembolic event.

CONCLUSION: Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.

PMID:37257732 | DOI:10.1016/j.critrevonc.2023.104034

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PubMed articles on: Cancer & VTE/PE

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State

West Afr J Med. 2023 May 27;40(5):533-540. ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated.

OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer.

METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23.

RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001).

CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events.

CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d’évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d’une thromboprophylaxie. Les scores de risque des patients dans notre environnement n’ont pas été étudiés de manière adéquate.

OBJECTIF: L’étude évalue l’association des scores d’évaluation du risque thrombotique (en utilisant l’outil modifié d’évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d’un cancer lymphoïde.

MÉTHODES: Il s’agit d’une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d’Anambra). Quarante-cinq patients atteints d’un cancer lymphoïde et 45 sujets apparemment sains ont participé à l’étude. Le score modifié d’évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l’estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23.

RÉSULTATS: L’âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que l[...]

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PubMed articles on: Cardio-Oncology

Finally Getting to the Heart of the Matter: Imaging Multiorgan Treatment Response in AL Amyloidosis

JACC Cardiovasc Imaging. 2023 May 5:S1936-878X(23)00190-0. doi: 10.1016/j.jcmg.2023.03.022. Online ahead of print.

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PMID:37269271 | DOI:10.1016/j.jcmg.2023.03.022

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PubMed articles on: Cardio-Oncology

Long COVID syndrome after SARS-CoV-2 survival in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Pulm Circ. 2023 May 31;13(2):e12244. doi: 10.1002/pul2.12244. eCollection 2023 Apr.