ABSTRACT

BACKGROUND: Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal.

AIM: To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes.

METHODS: Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed.

RESULTS: A total of 37 patients were identified (median age: 84 years, range: 70-98); n= 30 females median age: 84 years, range: 70-97); n= 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P= 0.008, stroke P= 0.001, length of stay > 33 d P= 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P= 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P< 0.001, number of operations P< 0.001, diabetes P= 0.041).

CONCLUSION: An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

PMID:37485433 | PMC:PMC10359747 | DOI:10.5312/wjo.v14.i7.554

06:56

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PubMed articles on: Cancer & VTE/PE

Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery

Clin Spine Surg. 2023 Jul 24. doi: 10.1097/BSD.0000000000001498. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort study.

OBJECTIVES: Venous thromboembolism (VTE) is a potentially high-risk complication for patients undergoing spine surgery. Although guidelines for assessing VTE risk in this population have been established, development of new techniques that target different aspects of the medical history may prove to be of further utility. The goal of this study was to develop a predictive machine learning (ML) model to identify nontraditional risk factors for predicting VTE in spine surgery patients.

SUMMARY OF BACKGROUND DATA: A cohort of 63 patients was identified who had undergone spine surgery at a single center from 2015 to 2021. Thirty-one patients had a confirmed VTE, while 32 had no VTE. A total of 113 attributes were defined and collected via chart review. Attribute categories included demographics, medications, labs, past medical history, operative history, and VTE diagnosis.

METHODS: The Waikato Environment for Knowledge Analysis (WEKA) software was used in creating and evaluating the ML models. Six classifier models were tested with 10-fold cross-validation and statistically evaluated using t tests.

RESULTS: Comparing the predictive ML models to the control model (ZeroR), all predictive models were significantly better than the control model at predicting VTE risk, based on the 113 attributes (P<0.001).

CONCLUSION: Further development of these tools may provide high diagnostic value and may guide chemoprophylaxis treatment in this setting of high-risk patients.

PMID:37482644 | DOI:10.1097/BSD.0000000000001498

06:56

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PubMed articles on: Cancer & VTE/PE

Automated detection and segmentation of pulmonary embolisms on computed tomography pulmonary angiography (CTPA) using deep learning but without manual outlining

Med Image Anal. 2023 Jul 14;89:102882. doi: 10.1016/j.media.2023.102882. Online ahead of print.

ABSTRACT

We present a novel computer algorithm to automatically detect and segment pulmonary embolisms (PEs) on computed tomography pulmonary angiography (CTPA). This algorithm is based on deep learning but does not require manual outlines of the PE regions. Given a CTPA scan, both intra- and extra-pulmonary arteries were firstly segmented. The arteries were then partitioned into several parts based on size (radius). Adaptive thresholding and constrained morphological operations were used to identify suspicious PE regions within each part. The confidence of a suspicious region to be PE was scored based on its contrast in the arteries. This approach was applied to the publicly available RSNA Pulmonary Embolism CT Dataset (RSNA-PE) to identify three-dimensional (3-D) PE negative and positive image patches, which were used to train a 3-D Recurrent Residual U-Net (R2-Unet) to automatically segment PE. The feasibility of this computer algorithm was validated on an independent test set consisting of 91 CTPA scans acquired from a different medical institute, where the PE regions were manually located and outlined by a thoracic radiologist (>18 years' experience). An R2-Unet model was also trained and validated on the manual outlines using a 5-fold cross-validation method. The CNN model trained on the high-confident PE regions showed a Dice coefficient of 0.676±0.168 and a false positive rate of 1.86 per CT scan, while the CNN model trained on the manual outlines demonstrated a Dice coefficient of 0.647±0.192 and a false positive rate of 4.20 per CT scan. The former model performed significantly better than the latter model (p<0.01).

PMID:37482032 | DOI:10.1016/j.media.2023.102882

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PubMed articles on: Cancer & VTE/PE

Incidence and Risk Factors of Venous Thromboembolism in Patients with Lung Adenocarcinoma Receiving Anti-tumor Therapy

Zhongguo Fei Ai Za Zhi. 2023 Jun 20;26(6):439-448. doi: 10.3779/j.issn.1009-3419.2023.102.22.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE.

METHODS: The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test.

RESULTS: The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P<0.05).

CONCLUSIONS: History of VTE, radiotherapy and targeted therapy are found as independent risk factors for the occurrence of VTE, which should be identified and monitored for reduction of VTE incidence. .

PMID:37488081 | PMC:PMC10365962 | DOI:10.3779/j.issn.1009-3419.2023.102.22

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PubMed articles on: Cancer & VTE/PE

Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study

J Thromb Haemost. 2023 Jul 20:S1538-7836(23)00571-8. doi: 10.1016/j.jtha.2023.07.009. Online ahead of print.

ABSTRACT

BACKGROUND: Guidelines recommend thromboprophylaxis for cancer patients at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction, but have not yet been evaluated in cancer patients.

METHODS: We assessed the performance of the 5-SNP, 37-SNP, 297-SNP, extended 297-SNP (additionally including factor V Leiden and prothrombin G20210A), and 100-SNP scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study. The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios (SHR) in the upper vs three lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification.

FINDINGS: Of 36,150 cancer patients (median age, 66 years; 48.7% females), 1,018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95%CI, 0.54-0.58) for the 5-SNP to 0.60 (95%CI, 0.58-0.62) for the extended 297-SNP scores. SHRs ranged from 1.36 (95%CI, 1.19-1.56) for the 5-SNP to 1.90 (95%CI, 1.68-2.16) for the extended 297-SNP scores, and were consistent after adjusting for cancer type. For the Khorana cancer type classification the c-index was 0.60 (95%CI, 0.58-0.61), which increased to 0.65 (95%CI, 0.63-0.67; +0.05, 95%CI, 0.04-0.07) when combined with the extended 297-SNP score.

INTERPRETATION: These findings demonstrate that polygenic VTE risk scores can identify cancer patients with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.

PMID:37481074 | DOI:10.1016/j.jtha.2023.07.009

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PubMed articles on: Cancer & VTE/PE

Risk of thromboembolic events in patients with metastatic solid tumors treated with PARP inhibitors: A systematic review and meta-analysis of phase 3 randomized controlled trials

Cancer Treat Rev. 2023 Jul 17;119:102601. doi: 10.1016/j.ctrv.2023.102601. Online ahead of print.

ABSTRACT

BACKGROUND AND SCOPE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized cancer treatment in recent years. These drugs present a favorable safety profile, even though the potential risk of thromboembolic events (TEs) during their use has not been addressed yet. In addition, PARPi have been involved in an active scientific debate regarding non-oncologic indications, particularly during the Coronavirus Disease 2019 pandemic, including potential anti-thromboembolic effect.

METHODS: To clarify whether patients treated with PARPi for metastatic solid tumors are either at increased or decreased risk of TEs, we conducted a systematic review of the literature and meta-analysis, including all phase 3 randomized controlled trials (RCTs) which investigated PARPi in this setting. Search was conducted through Medline, EMBASE, Pubmed, SCOPUS and Google Scholar in February 2023, including the proceedings of the principal oncology meetings of the last 10 years, with no time restriction. For each included study, frequencies of TEs in experimental and control arm were collected.

RESULTS: Our search identified 2,369 reports, of which 20 were lastly selected. A total of 4,946 patients were included, across 12 different RCTs. The meta-analysis did not demonstrate either an increased or a reduced risk in TEs in patients treated with PARPi for metastatic disease (OR 1.50, range: 1.00-2.24; 95% CI; P = 0.050), with low heterogeneity and low publication bias.

CONCLUSION: Although our research did not confirm either increased or decreased risk of TEs for PARPi use, no safety alerts emerged. Thromboembolic risk assessment models should always be integrated in daily clinical routine, to identify high-risk patients.

PMID:37473517 | DOI:10.1016/j.ctrv.2023.102601

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PubMed articles on: Cancer & VTE/PE

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis

J Clin Oncol. 2023 Jul 20:JCO2300429. doi: 10.1200/JCO.23.00429. Online ahead of print.

ABSTRACT

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer.

METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT.

RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58).

CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

PMID:37471683 | DOI:10.1200/JCO.23.00429

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PubMed articles on: Cancer & VTE/PE

Comment on: Silent Pulmonary Thromboembolism in Patients Undergoing Craniotomy for Brain Tumor

Turk Neurosurg. 2023;33(4):711. doi: 10.5137/1019-5149.JTN.44181-23.0.

NO ABSTRACT

PMID:37470514 | DOI:10.5137/1019-5149.JTN.44181-23.0

C

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Cardiotoxicity News

PubMed articles on: Cardio-Oncology

Radiotherapy-induced diffuse myocardial fibrosis in early-stage breast cancer patients - multimodality imaging study with six-year follow-up

Radiat Oncol. 2023 Jul 26;18(1):124. doi: 10.1186/s13014-023-02319-z.

ABSTRACT

BACKGROUND: Breast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up.

METHODS: Thirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed.

RESULTS: Regional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00-5.75) and 3 (1.25-4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography (OR 1.26, 95% Cl. 1.00-1.59, p = 0.047).

CONCLUSIONS: After radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.

PMID:37496091 | DOI:10.1186/s13014-023-02319-z

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PubMed articles on: Cardio-Oncology

Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine

Sci Rep. 2023 Jul 26;13(1):12061. doi: 10.1038/s41598-023-38450-w.

ABSTRACT

GDF15 has recently emerged as a key driver of the development of various disease conditions including cancer cachexia. Not only the tumor itself but also adverse effects of chemotherapy have been reported to contribute to increased GDF15. Although regulation of GDF15 transcription by BET domain has recently been reported, the molecular mechanisms of GDF15 gene regulation by drugs are still unknown, leaving uncertainty about the safe and effective therapeutic strategies targeting GDF15. We screened various cardiotoxic drugs and BET inhibitors for their effects on GDF15 regulation in human cardiomyocytes and cancer cell lines and analyzed in-house and public gene signature databases. We found that DNA damaging drugs induce GDF15 in cardiomyocytes more strongly than drugs with other modes of action. In cancer cells, GDF15 induction varied depending on drug- and cell type-specific gene signatures including mutations in PI3KCA, TP53, BRAF and MUC16. GDF15 suppression by BET inhibition is particularly effective in cancer cells with low activity of the PI3K/Akt axis and high extracellular concentrations of pantothenate. Our findings provide insights that the risk for GDF15 overexpression and concomitant cachexia can be reduced by a personalized selection of anticancer drugs and patients for precision medicine.

PMID:37495707 | DOI:10.1038/s41598-023-38450-w

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PubMed articles on: Cardio-Oncology

Cardio-oncology: Shared Genetic, Metabolic, and Pharmacologic Mechanism

Curr Cardiol Rep. 2023 Jul 26. doi: 10.1007/s11886-023-01906-6. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: The article aims to investigate the complex relationship between cancer and cardiovascular disease (CVD), with a focus on the effects of cancer treatment on cardiac health.

RECENT FINDINGS: Advances in cancer treatment have improved long-term survival rates, but CVD has emerged as a leading cause of morbidity and mortality in cancer patients. The interplay between cancer itself, treatment methods, homeostatic changes, and lifestyle modifications contributes to this comorbidity. Recent research in the field of cardio-oncology has revealed common genetic mutations, risk factors, and metabolic features associated with the co-occurrence of cancer and CVD. This article provides a comprehensive review of the latest research in cardio-oncology, including common genetic mutations, risk factors, and metabolic features, and explores the interactions between cancer treatment and CVD drugs, proposing novel approaches for the management of cancer and CVD.

PMID:37493874 | DOI:10.1007/s11886-023-01906-6

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PubMed articles on: Cardio-Oncology

Multimodality imaging in cardio-oncology: the added value of CMR and CCTA

Br J Radiol. 2023 Jul 26:20220999. doi: 10.1259/bjr.20220999. Online ahead of print.

ABSTRACT

During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent increase of cancer survivors and decreased mortality. This has led to an ongoing interest about the possible therapy-related side-effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. As a consequence cardio-oncology was born, involving several different specialties, among which radiology plays a relevant role. Till the end of August 2022, when European Society of Cardiology (ESC) developed the first guidelines on cardio-oncology, no general indications existed to guide diagnosis and treatment of cancer therapy-related cardiovascular toxicity (CTR-CVT). They defined multimodality imaging role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management.Cardiac computed tomography angiography (CCTA) has acquired a central role in coronary assessment, as far as coronary artery disease (CAD) exclusion is concerned; but on the side of this well-known application, it also started to be considered in left ventricular function evaluation, interstitial fibrosis quantification and cardiac perfusion studies.Cardiac magnetic resonance (CMR), instead, has been acknowledged as the gold standard alternative to trans-thoracic echocardiography (TTE) poor acoustic window in quantification of heart function and strain modifications, as well as pre- and post-contrast tissue characterization by means of T1-T2 mapping, early Gadolinium enhancement (EGE), late Gadolinium enhancement (LGE) and extracellular volume (ECV) evaluation.Our review is intended to provide a focus on the actual role of CMR and CCTA in the setting of a better understanding of cardiotoxicity and to draw some possible future directions of cardiac imaging in this field, starting from the recently published ESC guidelines.

PMID:37493228 | DOI:10.1259/bjr.20220999

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PubMed articles on: Cardio-Oncology

Penpulimab-induced complete atrioventricular block in a patient with metastatic renal cancer

HeartRhythm Case Rep. 2023 Apr 23;9(7):451-455. doi: 10.1016/j.hrcr.2023.04.007. eCollection 2023 Jul.

NO ABSTRACT

PMID:37492041 | PMC:PMC10363469 | DOI:10.1016/j.hrcr.2023.04.007

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PubMed articles on: Cardio-Oncology

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer

Curr Cardiol Rep. 2023 Jul 25. doi: 10.1007/s11886-023-01909-3. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy.

RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

PMID:37490155 | DOI:10.1007/s11886-023-01909-3

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PubMed articles on: Cardio-Oncology

Identification and protection of early cardiotoxicity in acute myeloid leukemia patients undergoing transplantation

Hematology. 2023 Dec;28(1):2239569. doi: 10.1080/16078454.2023.2239569.

ABSTRACT

Cardiotoxicity of antitumor therapy results in declining survival rates. More specifically, cardiotoxicity is positively correlated with cumulative dose of anthracyclines and eventually develops from reversible to irreversible. In this context, early monitoring methods should be explored for the timely detection of cardiotoxicity and cardioprotective therapy should be performed in patients under consideration for potentially cardiotoxic therapy. This paper reports a 22-year-old male patient with acute myeloid leukemia who underwent whole-course cardiac monitoring after receiving antileukemia therapy. After the early detection of an asymptomatic decrease in left ventricular ejection fraction (LVEF), along with a significant decrease in global longitudinal strain (GLS), the patient was treated with sacubitril/valsartan (Sac/Val). Finally, the patient completed four courses of chemotherapy and subsequent hematopoietic stem cell transplantation as planned. The measurements of LVEF and GLS also recovered after 2 months treatment of Sac/Val. Therefore, the early identification and protection of patients with cardiotoxicity are of paramount importance and future prospective studies are expected to develop the management and treatment of cancer treatment-related cardiac dysfunction.

PMID:37489927 | DOI:10.1080/16078454.2023.2239569

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PubMed articles on: Cardio-Oncology

DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes

Noncoding RNA. 2023 Jul 13;9(4):39. doi: 10.3390/ncrna9040039.