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10/30/23

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality following distal pancreatectomy (DP)

Abstract

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality following distal pancreatectomy (DP). However, the influence of operative technique on VTE risk after DP is unknown.

OBJECTIVE: The purpose of this study was to examine the association between the MIS technique versus the open technique and the development of postoperative VTE after DP.

METHODS: Patients who underwent DP from 2014 to 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program pancreas-specific database. Multivariable logistic regression was then used to identify independent associations with the development of postoperative VTE after DP.

RESULTS: A total of 3558 patients underwent DP during this time period. Of these cases, 47.8% (n = 1702) were performed via the MIS approach. After adjusting for significant covariates, the MIS approach was independently associated with the development of any VTE (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.06-2.40; p = 0.025), as well as increasing the risk of developing a postdischarge VTE (OR 1.80, 95% CI 1.05-3.08; p = 0.033) when compared with the open approach. There was an association between VTE and the development of numerous postoperative complications, including pneumonia, unplanned intubation, need for prolonged mechanical ventilation, and cardiac arrest.

CONCLUSION: Compared with the open approach, the MIS approach is associated with higher rates of postoperative VTE in patients undergoing DP. The majority of these events are diagnosed after hospital discharge.

PMID: 31919713 [PubMed - as supplied by publisher]

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Risk of venous thromboembolism in patients undergoing gastric cancer surgery: protocol for a systematic review and meta-analysis.

BMJ Open. 2020 Jan 08;10(1):e033267

Authors: Wang D, Yu Y, Tao P, Wang D, Chen Y, Chen H

OBJECTIVE: To evaluate the Caprini score as an independent predictor of venous thromboembolism (VTE) in patients undergoing robotic-

Abstract

OBJECTIVE: To evaluate the Caprini score as an independent predictor of venous thromboembolism (VTE) in patients undergoing robotic-assisted radical prostatectomy (RARP) and to identify appropriate cut-points for clinical use.

MATERIAL AND METHODS: We performed a retrospective review of patients who underwent RARP for prostate cancer between December 2003 and February 2016. VTE cases developed the condition within 90 days of discharge. The control group was comprised of patients whose RARP most closely preceded and followed each VTE case in time and who were matched on lymph node dissection and surgeon. The Caprini score was calculated for each patient, and the groups were compared on a number of clinical variables. Multiple logistic regression was used to evaluate whether the Caprini score was an independent predictor of VTE. Receiver operating characteristics (ROC) curves were used to establish appropriate clinical cut-points.

RESULTS: A total of 3719 patients underwent RARP during the study period. A total of 52 (1.4%) of patients met the criteria for cases. Data were available for 97 patients who met the criteria for controls. Multiple logistic regression indicated that the Caprini score and operative time were independently both significant predictors of VTE (p=0.005 and p=0.044, respectively). ROC indicated that the Caprini score showed a significant but moderate relationship to VTE (area under curve [AOC]=0.64; p=0.004). A Caprini score >6 was the best arithmetic balance for sensitivity (61.5; 95% confidence interval [CI]: 47.0-74.7) and specificity (59.8; 95% CI: 49.3-69.6).

CONCLUSION: The Caprini score predicts postoperative VTE in patients undergoing RARP.

PMID: 31922483 [PubMed - as supplied by publisher]

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Minimally Invasive Surgery is Associated with an Increased Risk of Postoperative Venous Thromboembolism After Distal Pancreatectomy.

Ann Surg Oncol. 2020 Jan 09;:

Authors: Willobee BA, Dosch AR, Allen CJ, Macedo FI, Bartholomew TS, Picado O, Gaidarski AA, Dudeja V, Yakoub D, Merchant NB

Radiation therapy (RT) is commonly used to treat solid tumors of the breast, lung, and esophagus; however, the heart is an unintentional

Abstract

Radiation therapy (RT) is commonly used to treat solid tumors of the breast, lung, and esophagus; however, the heart is an unintentional target of ionizing radiation (IR). IR exposure to the heart results in chronic toxicities including heart failure. We hypothesize that the circadian system plays regulatory roles in minimizing the IR-induced cardiotoxicity. We treated mice in control (Day Shift), environmentally disrupted (Rotating Shift), and genetically disrupted (Per 1/2 mutant) circadian conditions with 18 Gy of IR to the heart. Compared to control mice, circadian clock disruption significantly exacerbated post-IR systolic dysfunction (by ultrasound echocardiography) and increased fibrosis in mice. At the cellular level, Bmal1 protein bound to Atm, Brca1, and Brca2 promoter regions and its expression level was inversely correlated with the DNA damage levels based on the state of the clock. Further studies with circadian synchronized cardiomyocytes revealed that Bmal1 depletion increased the IR-induced DNA damage and apoptosis. Collectively, these findings suggest that the circadian clock protects from IR-induced toxicity and potentially impacts RT treatment outcome in cancer patients through IR-induced DNA damage responses.

PMID: 31919902 [PubMed - as supplied by publisher]

15:04

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Caprini score and surgical times linked to the risk for venous thromboembolism after robotic-assisted radical prostatectomy.

Turk J Urol. 2020 Jan 06;:1-7

Authors: Frankel J, Belanger M, Tortora J, McLaughlin T, Staff I, Wagner J

QTc prolongation has been observed during arsenic trioxide and realgar's clinical use, and become a huge obstacle for the application. Our lab

Abstract

QTc prolongation has been observed during arsenic trioxide and realgar's clinical use, and become a huge obstacle for the application. Our lab has obtained the soluble arsenic from realgar named realgar transforming solution or RTS. In this study, we first evaluated the cytotoxicity on NB4 cell and found that RTS could remarkably inhibit proliferation of NB4 than arsenic trioxide. Then we figured out the QTc prolongation of RTS treatment contrasted with arsenic trioxide; results revealed that arsenic trioxide prolonged corrected QTc of mice by 20.1% and showed 1.9-fold higher cytotoxicity on H9c2 cell than RTS. On the contrary, there could not find any QTc prolongation of mice in RTS treatment. Also, arsenic trioxide elevated the intercellular calcium accumulation of H9c2 cell by 2.02-fold v.s control and RTS. HE staining and Masson's trichrome staining had shown that there was no injured section after RTS treatments. IK1 currents of rat ventricular cardiomyocytes were diminished by 45.0% after treating with arsenic trioxide while RTS showed no significance than the control group. The results above indicated that RTS could serve as an alternative arsenic agent on leukemia and had a lower risk of cardiotoxicity.

PMID: 31285125 [PubMed - indexed for MEDLINE]

11 January 2020

12:35

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Trastuzumab emtansine (T-DM1)-associated cardiotoxicity: Pooled analysis in advanced HER2-positive breast cancer.

Eur J Cancer. 2020 Jan 07;126:65-73

Authors: Pondé N, Amaye L, Lambertini M, Paesmans M, Piccart M, de Azambuja E

Abstract

INTRODUCTION: T-DM1 has been approved for the treatment of HER2+ breast cancer. Cardiac dysfunction is a side effect of trastuzumab, a component of T-DM1. However, little is known about T-DM1-associated cardiotoxicity.

METHODS: We have conducted a pooled analysis of T-DM1 trials in advanced HER2+ breast cancer cases to understand the incidence, clinical presentation as well as to establish possible risk factors for T-DM1-associated cardiotoxicity. The primary endpoint was the incidence of cardiac events (CEs). CEs were categorized as follows: (1) congestive heart failure (CHF) or grade 3/4 LVEF drop; (2) cardiac ischemia, (3) cardiac arrhythmia, (4) grade 1/2 LVEF drop. Secondary endpoints included CE recovery rate and impact of CEs on treatment discontinuation. Logistic regression was used to assess possible risk factors for CEs.

RESULTS: Individual patient-level data from 1961 patients exposed to T-DM1 in seven trials were pooled. Of these, 1544 received T-DM1 and 417 T-DM1 + pertuzumab. CHF/LVEF drop grade 3/4 was reported in 0.71%, cardiac ischemia in 0.1%, cardiac arrhythmia in 0.71% and grade 1/2 LVEF drop in 2.04%. The total CE rate was 3.37% (95% confidence interval (CI), 2.6%-4.3%). Multivariate analysis showed patient's age ≥65 (OR 3.0; 95% CI, 1.77-5.14; P-value <0.001)<55%

CONCLUSION: The incidence of CEs in patients receiving T-DM1 was low. Older patients receiving T-DM1 should be carefully followed for cardiac safety during treatment.

PMID: 31923729 [PubMed - as supplied by publisher]

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The circadian clock protects against ionizing radiation-induced cardiotoxicity.

FASEB J. 2020 Jan 10;:

Authors: Dakup PP, Porter KI, Gajula RP, Goel PN, Cheng Z, Gaddameedhi S

PURPOSE: It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory

Abstract

PURPOSE: It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory cytokines. Dapsone, an antibiotic drug which is the principal in a multidrug regimen for the treatment of leprosy, is a sulfone with anti-inflammatory and antioxidant immunosuppressive properties. Therefore, we designed this study to investigate the possible effects of dapsone on doxorubicin-induced cardiotoxicity.

METHODS: Male rats were administrated doxorubicin (2.5 mg/kg) and dapsone (1, 3, 10 mg/kg) intraperitoneally six times in 2 weeks. Then electrocardiographic (ECG) parameters (QRS complexes, RR and QT intervals) alternation, papillary muscle contraction and excitation, and histopathological changes were assessed. Also, the heart tissue levels of malondialdehyde (MDA) as oxidant factor and superoxide dismutase (SOD) as antioxidant enzyme, tumor necrosis factor-alpha (TNF-α) and serum level of CK-MB were analyzed.

RESULTS: Administration of dapsone with doxorubicin significantly reversed alterations induced by doxorubicin in serum levels of CK-MB, ECG parameters, papillary muscle contractility and excitation. Furthermore, the measurement of MDA, SOD and TNF-α tissue level indicated that dapsone significantly reduced oxidative stress and inflammation. These findings were consistent with histopathological analysis.

CONCLUSION: Dapsone exerts cardioprotective effects on doxorubicin-induced cardiotoxicity through its anti-inflammatory and antioxidant mechanism.

PMID: 31915967 [PubMed - as supplied by publisher]

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Realgar transforming solution as a novel arsenic agent with a lower risk of cardiotoxicity.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Realgar transforming solution as a novel arsenic agent with a lower risk of cardiotoxicity.

J Pharmacol Sci. 2019 Jun;140(2):162-170

Authors: Hai Y, Song P, Wang X, Zhao L, Xie Q, Li J, Li Y, Li H

PURPOSE OF REVIEW: Inflammation has been shown to be an important factor in the development and progression of heart failure (HF)

Abstract

PURPOSE OF REVIEW: Inflammation has been shown to be an important factor in the development and progression of heart failure (HF), regardless of the etiology. There have been many studies that demonstrated roles of inflammatory biomarkers in diagnosis, prognosis of chronic and acute HF patients, and also markers of cardiotoxicity from chemotherapy. These cytokines are high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), soluble growth stimulation expressed gene 2 (sST2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), growth differentiation factor-15 (GDF-15), endothelin-1 (ET-1), and galectin-3. In this review, we discuss the past and present insights of those inflammatory biomarkers in order to gain more understanding in pathogenesis of HF, risk stratification of HF patients, and early detection of cardiotoxicity from cancer therapy.

RECENT FINDINGS: Many inflammatory cytokines have been shown to be associated with mortality of both chronic and acute HF patients, and some of them are able to track treatment responses, especially sST2 and galectin-3, which are the only two inflammatory biomarkers recommended to use in clinical setting by the recent standard HF guidelines, while some studies described ET-1 and MPO as potential predictors of cardiotoxicity from cancer drugs. The prognostic implications of inflammatory biomarkers in HF patients have been demonstrated more consistently in chronic than acute HF, with some suggestions of ET-1 and MPO in patients receiving chemotherapy. However, further studies are necessary for the use of inflammatory biomarkers in routine clinical practice.

PMID: 31916187 [PubMed - as supplied by publisher]

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Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats.

Cancer Chemother Pharmacol. 2020 Jan 08;:

Authors: Sheibani M, Nezamoleslami S, Faghir-Ghanesefat H, Emami AH, Dehpour AR

Dysregulation of calcium homeostasis is a major mechanism of doxorubicin (DOX)-induced cardiotoxicity.

Abstract

Dysregulation of calcium homeostasis is a major mechanism of doxorubicin (DOX)-induced cardiotoxicity. Treatment with DOX causes activation of sarcoplasmic reticulum (SR) ryanodine receptor (RYR) and rapid release of Ca2+ in the cytoplasm resulting in depression of myocardial function. The aim of this study was to examine the effect of dantrolene (DNT) a RYR blocker on both the cardiotoxicity and antitumor activity of DOX in a rat model of breast cancer. Female F344 rats with implanted MAT B III breast cancer cells were randomized to receive intraperitoneal DOX twice per week (12 mg/kg total dose), 5 mg/kg/day oral DNT or a combination of DOX + DNT for 3 weeks. Echocardiography and blood troponin I levels were used to measure myocardial injury. Hearts and tumors were evaluated for histopathological alterations. Blood glutathione was assessed as a measure of oxidative stress. The results showed that DNT improved DOX-induced alterations in the echocardiographic parameters by 50%. Histopathologic analysis of hearts showed reduced DOX induced cardiotoxicity in the group treated with DOX + DNT as shown by reduced interstitial edema, cytoplasmic vacuolization, and myofibrillar disruption, compared with DOX-only-treated hearts. Rats treated with DNT lost less body weight, had higher blood GSH levels and lower troponin I levels than DOX-treated rats. These data indicate that DNT is able to provide protection against DOX cardiotoxicity without reducing its antitumor activity. Further studies are needed to determine the optimal dosing of DNT and DOX in a tumor-bearing host.

PMID: 31918212 [PubMed - as supplied by publisher]

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Reappraisal of Inflammatory Biomarkers in Heart Failure.

Curr Heart Fail Rep. 2020 Jan 08;:

Authors: Chaikijurajai T, Tang WHW

The clinical application of doxorubicin (DOX) for cancer treatment is limited due to its cardiotoxicity. However, the basic pathophysiological

Abstract

The clinical application of doxorubicin (DOX) for cancer treatment is limited due to its cardiotoxicity. However, the basic pathophysiological molecular mechanisms underlying DOX-induced cardiomyopathy have not yet been completely clarified, and the disease-specific therapeutic strategies are lacking. The aim of the present study was to investigate the potential cardioprotective effect of cardamonin (CAR), a flavone found in Alpinia plant, on DOX-induced cardiotoxicity in a mouse model. At first, in DOX-treated mouse cardiomyocytes, CAR showed significantly cytoprotective effects through elevating nuclear factor erythroid-2 related factor 2 (Nrf2) signaling, and reducing the degradation of Nrf2. This process then improved the anti-oxidant system, as evidenced by the up-regulated expression levels of haem oxygenase-1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). In contrast, DOX-induced increases in malondialdehyde (MDA) and reactive oxygen species (ROS) were highly inhibited by CAR treatments. Additionally, DOX-induced apoptosis and inflammatory response in cardiomyocytes were diminished by CAR through reducing the Caspase-3 and nuclear factor-κB (NF-κB) signaling pathways, respectively. Then, in the DOX-induced animal model with cardiotoxicity, we confirmed that through improving Nrf2 signaling, CAR markedly suppressed oxidative stress, apoptosis and inflammatory response in hearts of mice, improving cardiac function eventually. Together, our findings demonstrated that CAR activated Nrf2-related cytoprotective system, and protected the heart from oxidative damage, apoptosis and inflammatory injury, suggesting that CAR might be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy.

PMID: 31918264 [PubMed - as supplied by publisher]

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Dantrolene Attenuates Cardiotoxicity of Doxorubicin Without Reducing its Antitumor Efficacy in a Breast Cancer Model.

Transl Oncol. 2020 Jan 06;13(2):471-480

Authors: Todorova VK, Siegel ER, Kaufmann Y, Kumarapeli A, Owen A, Wei JY, Makhoul I, Klimberg VS

Venous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B

Abstract

Venous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B cell lymphoblastic lymphoma (T/B cell LL) can result not only in life-threatening acute complications but also contribute to significant long-term sequelae. The PREVAPIX-ALL study is an open-label randomized controlled study comparing outcomes of treatment with prophylactic dose apixaban versus no anticoagulation (standard of care) in children and adolescents with ALL and T/B cell LL receiving standard induction chemotherapy with asparaginase and the presence of a central venous access device. On day 29 of induction, all patients undergo screening imaging with duplex ultrasonography and echocardiography. The primary efficacy endpoint of the study is a composite of symptomatic and asymptomatic VTE that includes deep vein thrombosis, pulmonary embolism, cerebral sinovenous thrombosis or VTE-related death. The primary safety outcome is major bleeding. Secondary outcomes are central line-associated infections, patency and line replacement, superficial thrombosis, arterial events and death. A planned sample size of 500 randomized paediatric patients enrolled over a period of 5 years is based on the estimation of VTE rates of 20 and 10% in the standard of care and apixaban groups, respectively. An optional biomarker study in 150 patients will examine predictors of increased VTE risk and study in vivo anticoagulant effects of apixaban in children by measuring specific biomarkers in the haemostatic system and inflammatory pathway. This study will provide valuable information for the safety and efficacy of apixaban in VTE prevention during induction in paediatric ALL.

PMID: 30861550 [PubMed - indexed for MEDLINE]

14:14

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Cardamonin protects against doxorubicin-induced cardiotoxicity in mice by restraining oxidative stress and inflammation associated with Nrf2 signaling.

Biomed Pharmacother. 2019 Dec 13;122:109547

Authors: Qi W, Boliang W, Xiaoxi T, Guoqiang F, Jianbo X, Gang W

BACKGROUND: Venous thromboembolism (VTE) is a significant source of postoperative morbidity and mortality in patients undergoing

Abstract

BACKGROUND: Venous thromboembolism (VTE) is a significant source of postoperative morbidity and mortality in patients undergoing common oncologic procedures. We sought to estimate the effect of surgical approach on the risk of developing a VTE.

METHODS: IBM Watson Health Marketscan Database was used to conduct this retrospective study. In total, 12 938 patients who underwent either a radical prostatectomy, partial colectomy, or hysterectomy via a minimally invasive or open approach. We used a propensity-weighted logistic regression analysis to assess the independent effect of surgical approach on VTE. The primary outcome of interest was the 90-day rate of VTE after surgery.

RESULTS: Patients undergoing minimally invasive surgery across all three surgical procedures were noted to have a lower odds of developing a VTE: (radical prostatectomy, odds ratio [OR]: 0.667, 95% confidence interval [CI]: 0.500-0.891; P = .006 |partial colectomy: OR, 0.620, 95% CI: 0.477-0.805; P < .001|

CONCLUSION: We found that a minimally invasive approach was associated with significantly lower odds of VTE compared with undergoing the same open procedure. This study highlights how surgical approach may be an independent risk factor for development of VTE and may elucidate potential risk mitigation strategy.

PMID: 31916588 [PubMed - as supplied by publisher]

12:39

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PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)-Rationale and Design.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.thieme.de-classic-images-tc-logo_tc.jpg Related Articles

PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)-Rationale and Design.

Thromb Haemost. 2019 May;119(5):844-853

Authors: O'Brien SH, Li D, Mitchell LG, Hess T, Zee P, Yee DL, Newburger JW, Sung L, Rodriguez V

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is t

Abstract

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cause of vascular death after heart attack and stroke. Anticoagulation therapy is the cornerstone of VTE treatment. Despite such therapy, up to 50% of DVT patients develop post-thrombotic syndrome and up to 4% of PE patients develop chronic thromboembolic pulmonary hypertension. Therefore, better therapies are needed. Although the direct oral anticoagulants are more convenient and safer than warfarin for VTE treatment, bleeding remains the major side effect, particularly in cancer patients. Factor XII and factor XI have emerged as targets for new anticoagulants that may be safer. To reduce the complications of VTE, attenuation of thrombin activatable fibrinolysis inhibitor activity is under investigation in PE patients to enhance endogenous fibrinolysis whereas blockade of leukocyte interaction with the vessel wall is being studied to reduce the inflammation, which contributes to post-thrombotic syndrome in DVT patients. Focusing on these novel antithrombotic strategies, this paper (a) explains why safer anticoagulants are needed, (b) provides the rationale for factor XII and XI as targets for such agents, (c) reviews the data on the factor XII- and XI-directed anticoagulants under development, (d) describes novel therapies to enhance fibrinolysis and decrease inflammation in PE and DVT patients, respectively, and (e) offers insights into the opportunities for these novel VTE therapies.

PMID: 31917385 [PubMed - as supplied by publisher]

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Minimally invasive cancer surgery is associated with a lower risk of venous thromboembolic events.

J Surg Oncol. 2020 Jan 08;:

Authors: Krimphove MJ, Reese S, Chen X, Marchese M, Cone E, Tully KH, Paciotti M, Kibel AS, Melnitchouk N, Kluth LA, Dasgupta P, Trinh QD

All patients with venous thromboembolism should receive anticoagulant treatment in the absence of absolute contraindications

Abstract

All patients with venous thromboembolism should receive anticoagulant treatment in the absence of absolute contraindications. Initial anticoagulant treatment is crucial to reduce mortality, prevent early recurrences and improve long-term outcome. Treatment and patient disposition should be tailored on the severity of clinical presentation, on comorbidities and on the potential to receive appropriate care in the outpatient setting. Direct oral anticoagulants used in fixed doses without laboratory monitoring are the agents of choice for the treatment of acute venous thromboembolism in the majority of patients. In comparison with conventional anticoagulation (parenteral anticoagulants followed by vitamin K antagonists), these agents showed an improved safety (relative risk [RR] of major bleeding 0.61, 95% CI 0.45-0.83) with a similar risk of recurrence (RR 0.90, 95% CI 0.77-1.06). Vitamin K antagonists or low-molecular weight heparins are still an alternative to direct oral anticoagulants for the treatment of venous thromboembolism in specific patient categories as those with severe renal failure and the antiphospholipid syndrome or cancer, respectively. On the top of therapeutic anticoagulation, probably less than 10% of patients require reperfusion by thrombolysis or interventional treatments and these are hemodynamically unstable patients with acute pulmonary embolism and a minority of patients with proximal limb-threatening deep vein thrombosis. The choice should be driven by the combination of evidence from clinical trials and local expertise. The majority of patients with acute deep vein thrombosis and a proportion of selected hemodynamically stable patients with acute pulmonary embolism can be safely managed as outpatients.

PMID: 31917399 [PubMed - as supplied by publisher]

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Novel Antithrombotic Strategies for Treatment of Venous Thromboembolism.

Blood. 2020 Jan 09;:

Authors: Weitz JI, Chan NC

The most important decision in the long-term treatment of VTE is how long to anticoagulate. VTE provoked by a reversible risk

Abstract

The most important decision in the long-term treatment of VTE is how long to anticoagulate. VTE provoked by a reversible risk factor, or a first unprovoked isolated distal DVT, generally should be treated for 3 months. VTE provoked by a persistent or progressive risk factor (eg, cancer), or a second unprovoked proximal DVT or PE, is generally treated indefinitely. First proximal DVT or PE may be treated for 3 to 6 months, or indefinitely. Male sex, presentation as PE (particularly if concomitant proximal DVT), a positive D-dimer test after stopping anticoagulation, an antiphospholipid antibody, low risk of bleeding and patient preference favor indefinite anticoagulation. The type of indefinite anticoagulation is of secondary importance. Low dose oral Xa inhibitors are convenient and thought to have a lower risk of bleeding; they are less suitable if there is a higher risk of recurrence. For cancer-associated VTE, we prefer full-dose oral Xa inhibitors over low molecular weight heparin, with gastrointestinal lesions being a relative contraindication. Graduated compression stockings are not routinely indicated after DVT but are encouraged if there is persistent leg swelling or if a trial of stockings improves symptoms. Medications have a limited role in the treatment of post-thrombotic syndrome. After PE, patients should have clinical surveillance for chronic thromboembolic pulmonary hypertension (CTEPH), with ventilation-perfusion scanning and echocardiography being the initial diagnostic tests if CTEPH is a concern. Patients with CTEPH, and other symptomatic patients with extensive residual perfusion defects, should be evaluated for endarterectomy, balloon pulmonary angioplasty or vasodilator therapies.

PMID: 31917402 [PubMed - as supplied by publisher]

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ACUTE TREATMENT OF VENOUS THROMBOEMBOLISM.

Blood. 2019 Jan 09;:

Authors: Becattini C, Agnelli G

Background: Takotsubo cardiomyopathy (TTS) is an extremely rare complication of fluorouracil containing chemotherapy

Abstract

Background: Takotsubo cardiomyopathy (TTS) is an extremely rare complication of fluorouracil containing chemotherapy regimes such as FOLFOX used for colorectal cancer, occurring in only five previous case reports. Due to its potentially fatal outcomes, yet infrequent presence in the literature, it is worthwhile reviewing the clinical features and outcomes of this phenomenon.

Case summary: A 54-year-old lady was admitted with cardiogenic shock. A cardiac magnetic resonance imaging (CMR) showed mid-ventricle to apical hypokinesis and confirmed TTS. She was managed with inotropes and non-invasive ventilation after which she recovered fully both clinically and in her CMR features 6 weeks following discharge.

Discussion: This is the first case showing the acute CMR features of this complication and highlights the need for awareness of this rarely occurring cardiotoxicity. It also shows the potentially fatal phenomenon can be fully reversible when diagnosed and managed promptly even in patients with metastatic cancer and critical illness.

PMID: 31911978 [PubMed]

10 January 2020

12:39

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Long-term treatment of venous thromboembolism.

Blood. 2020 Jan 09;:

Authors: Kearon C, Kahn SR

Children surviving cancer and chemotherapy are at risk for adverse health events including heart failure that may be delayed by years

Abstract

Children surviving cancer and chemotherapy are at risk for adverse health events including heart failure that may be delayed by years. Although the early effects of doxorubicin-induced cardiotoxicity may be attributed to a direct effect on the cardiomyocytes, the mechanisms underlying the delayed or late effects (8-20 years) are unknown. The goals of this project were to develop a model of late-onset doxorubicin-induced cardiotoxicity to better delineate the underlying pathophysiology responsible. The underlying hypothesis was that doxorubicin-induced "late-onset cardiotoxicity" was the result of mitochondrial dysfunction leading to cell failure and death. Wistar rats, 3 to 4 weeks of age, were randomly assigned to vehicle or doxorubicin injection groups (1-45 mg/kg). Cardiovascular function was unaltered at the lower dosages (1-15 kg/mg), but beginning at 6 months post injection significant cardiac degradation was observed in the 45 mg/kg group. Doxorubicin significantly increased myocardial mtDNA damage. In contrast, in isolated c-kit+ left ventricular (LV) cells, doxorubicin treatment did not increase mtDNA damage. Biomarkers of senescence within the LV were significantly increased, suggesting accelerated aging of the LV. Doxorubicin also significantly increased LV histamine content suggestive of mast cell activation. Using flow cytometry, a significant expansion of the c-kit+ and SSEA1+ cell populations within the left ventricle were concomitant with significant decreases in the circulating peripheral blood population of these cells. These results are consistent with the concept that doxorubicin induced significant damage to the cardiomyocyte population and that although the heart attempted to compensate it eventually succumb to an inability for self-repair.

PMID: 31913702 [PubMed - as supplied by publisher]

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Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features.

Eur Heart J Case Rep. 2019 Dec;3(4):1-6

Authors: Joy G, Eissa H, Al Karoudi R, White SK

Objective: To evaluate the effectiveness of sequential compression devices (SCDs) for venous thromboembolism (VTE) prevention in medically ill hospitalized patients

Abstract

Objective: To evaluate the effectiveness of sequential compression devices (SCDs) for venous thromboembolism (VTE) prevention in medically ill hospitalized patients.

Materials and Methods: Adult patients admitted to a teaching hospital from April 2015 to March 2016 were included. Patients on anticoagulants with or without SCDs were excluded. We analyzed VTE risk, length of hospital stay, and other comorbidities among propensity score-matched patients on SCDs and those without thromboprophylaxis (NONE).

Results: Among 30,824 patients, 67 patients (0.22%) developed VTE during their hospital stays, with deep vein thrombosis (DVT) in 55 cases and pulmonary embolism (PE) in 12. VTE was seen in 47 out of 20,018 patients on SCDs (41 DVT, 6 PE) and 20 out of 10,819 patients without SCDs (14 DVT, 6 PE). Risk-adjusted analysis showed no significant difference in VTE incidence in the SCD group compared to NONE (odds ratio 0.99, 95% confidence interval 0.57-1.73, p=0.74).

Conclusion: Compared to the NONE group, SCDs are not associated with decreased VTE incidence during hospital stay.

PMID: 31042860 [PubMed - indexed for MEDLINE]

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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pubmed: ctoall&ca or conall

Accelerated cardiomyocyte senescence contributes to late-onset doxorubicin-induced cardiotoxicity.

Am J Physiol Cell Physiol. 2020 Jan 08;:

Authors: Mitry MA, Laurent D, Keith BL, Sira E, Eisenberg CA, Eisenberg LM, Joshi S, Gupte S, Edwards JG

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications o

Abstract

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures.

METHODS: A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples.

RESULTS: The mean age was 51 ± 8.4 (range 21-86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group.

CONCLUSIONS: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.

PMID: 31291926 [PubMed - indexed for MEDLINE]

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pubmed: caandvteortroorpul

Effectiveness of Sequential Compression Devices in Prevention of Venous Thromboembolism in Medically Ill Hospitalized Patients: A Retrospective Cohort Study

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--galenos.com.tr-icon-PUBMED-galenosyay.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Effectiveness of Sequential Compression Devices in Prevention of Venous Thromboembolism in Medically Ill Hospitalized Patients: A Retrospective Cohort Study

Turk J Haematol. 2019 08 02;36(3):193-198

Authors: Dhakal P, Wang L, Gardiner J, Shrotriya S, Sharma M, Rayamajhi S

BACKGROUND: There is increasing evidence to support extended thromboprophylaxis after colorectal surgery to minimize the incidence of postdischarge venous

Abstract

BACKGROUND: There is increasing evidence to support extended thromboprophylaxis after colorectal surgery to minimize the incidence of postdischarge venous thromboembolic events. However, the absolute number of events is small, and extended thromboprophylaxis requires significant resources from the health care system.

OBJECTIVE: This study aimed to determine the cost-effectiveness of extended thromboprophylaxis in patients undergoing colorectal surgery for malignancy or IBD.

DESIGN: An individualized patient microsimulation model (1,000,000 patients; 1-month cycle length) comparing extended thromboprophylaxis (28-day course of enoxaparin) to standard management (inpatient administration only) after colorectal surgery was constructed.

SETTINGS: The sources for this study were The American College of Surgeons National Surgical Quality Improvement Project Participant User File and literature searches.

OUTCOMES: Costs (Canadian dollars), quality-adjusted life-years, and venous thromboembolism-related deaths prevented over a 1-year time horizon starting with hospital discharge were determined. The results were stratified by malignancy or IBD.

RESULTS: In patients with malignancy, extended prophylaxis was associated with higher costs (+113$; 95% CI, 102-123), but increased quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), resulting in an incremental cost-effectiveness ratio of 2473$/quality-adjusted life-year. For IBD, extended prophylaxis also had higher costs (+116$; 95% CI, 109-123), more quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), and an incremental cost-effectiveness ratio of 2475$/quality-adjusted life-year. Extended prophylaxis prevented 16 (95% CI, 4-27) venous thromboembolism-related deaths per 100,000 patients and 22 (95% CI, 6-38) for malignancy and IBD. There was a 99.7% probability of cost-effectiveness at a willingness-to-pay threshold of 50,000$/quality-adjusted life-year. To account for statistical uncertainty around variables, sensitivity analysis was performed and found that extended prophylaxis is associated with lower overall costs when the incidence of postdischarge venous thromboembolic events reaches 1.8%.

LIMITATIONS: Significant differences in health care systems may affect the generalizability of our results.

CONCLUSIONS: Despite the rarity of venous thromboembolic events, extended thromboprophylaxis is a cost-effective strategy. See Video Abstract at http://links.lww.com/DCR/A976. COSTO-EFECTIVIDAD DE LA TROMBOPROFILAXIS EXTENDIDA EN PACIENTES SOMETIDOS A CIRUGÍA COLORRECTAL DESDE UNA PERSPECTIVA DEL SISTEMA DE SALUD CANADIENSE:: Cada vez hay más pruebas que apoyen la tromboprofilaxis extendida después de la cirugía colorrectal para minimizar la incidencia de eventos tromboembólicos venosos después del alta hospitalaria. Sin embargo, el número absoluto de eventos es pequeño y la tromboprofilaxis extendida requiere recursos significativos del sistema médico.Determinar la rentabilidad (relación costo-efectividad) de la tromboprofilaxis extendida en pacientes sometidos a cirugía colorrectal por neoplasia maligna o enfermedad inflamatoria intestinal.Un modelo de microsimulación de paciente individualizado (1,000,000 de pacientes; ciclo de 1 mes) que compara la tromboprofilaxis extendida (curso de enoxaparina de 28 días) con el [...]

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tratamiento estándar (solo para pacientes hospitalizados) después de la cirugía colorrectal.Archivo de usuario participante del Proyecto de Mejoramiento de la Calidad Quirúrgica del Colegio Nacional de Cirujanos Americanos (ACS-NSQIP) y búsquedas bibliográficas.Costos (en dólares Canadienses), años de vida ajustados por la calidad y muertes relacionadas con el tromboembolismo venoso prevenidas en un horizonte temporal de 1 año a partir del alta hospitalaria. Los resultados fueron estratificados por malignidad o enfermedad inflamatoria intestinal.En pacientes con neoplasias malignas, la profilaxis extendida se asoció con costos más altos (+113 $; IC del 95%, 102-123), pero con un aumento de la calidad de vida ajustada por años de vida (+0.05; IC del 95%, 0.04-0.06), lo que resultó en un incremento de relación costo-efectividad de 2473 $/año de vida ajustado por calidad. Para la enfermedad inflamatoria intestinal, la profilaxis extendida también tuvo costos más altos (+116 $; 95% IC, 109-123), más años de vida ajustados por calidad (+0.05; 95% IC, 0.04-0.06) y una relación costo-efectividad incremental de 2475 $/año de vida ajustado por calidad. La profilaxis prolongada evitó 16 (95% IC, 4-27) muertes relacionadas con tromboembolismo venoso por cada 100,000 pacientes y 22 (95% IC, 6-38) por malignidad y enfermedad inflamatoria intestinal, respectivamente. Hubo un 99.7% de probabilidad de costo-efectividad en un límite de disposición a pagar de 50,000 $/año de vida ajustado por calidad. Para tener en cuenta la incertidumbre estadística en torno a los variables, se realizó un análisis de sensibilidad y se encontró que la profilaxis extendida se asocia con menores costos generales cuando la incidencia de eventos tromboembólicos venosos después del alta hospitalaria alcanza 1.8%.Las diferencias significativas en los sistemas de salud pueden afectar la generalización de nuestros resultados.A pesar de la escasez de eventos tromboembólicos venosos, la tromboprofilaxis extendida es una estrategia rentable. Vea el video del resumen en http://links.lww.com/DCR/A976.

PMID: 31318768 [PubMed - indexed for MEDLINE]

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pubmed: caandvteortroorpul

Safety and complications of medical thoracoscopy in the management of pleural diseases.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--s3-service-broker-live-ddda94b7-dbb0-4917-917d-776dae91ebba.s3.amazonaws.com-bmc-linkout-fulltext.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Safety and complications of medical thoracoscopy in the management of pleural diseases.

BMC Pulm Med. 2019 Jul 10;19(1):125

Authors: Wan YY, Zhai CC, Lin XS, Yao ZH, Liu QH, Zhu L, Li DZ, Li XL, Wang N, Lin DJ

10/11/23

OBJECTIVE: This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary

Abstract

OBJECTIVE: This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary objective of this systematic review was to examine the comparative safety of the Food and Drug Administration-approved vaginal estrogen preparations among postmenopausal women.

METHODS: We performed a PubMed search of the primary literature from January 1, 1966 to July 16, 2019 for English-language clinical trials. Manual review of retrieved citations identified additional citations.

RESULTS: Of 882 retrieved citations, 75 clinical trials met inclusion criteria. Maximum trial duration was 52 weeks. None of the trials predesignated breast or endometrial cancer, cardiovascular events, or venous thromboembolism as primary outcomes. Studies were not designed to rule out an increase in endometrial carcinoma risk with long-term use of vaginal estrogen. There were few head-to-head comparisons. Fifty trials examined serum sex steroid and gonadotrophin levels; assay methodologies varied. Serum estradiol levels were 11 pg/mL at baseline or during placebo use and increased to a mean of 30 pg/mL after treatment. Estradiol levels were usually highest during the first 12 weeks of treatment, and were higher for estrogen creams than for inserts or rings. The 22 trials of endometrial thickness and the 15 trials of endometrial biopsy did not clearly demonstrate endometrial proliferation after vaginal estrogen treatment, but data were limited, and studies did not always perform systematic endometrial biopsy.

CONCLUSIONS: Newer low-dose estradiol rings, tablets, and inserts appear to induce the least increases in serum hormones, possibly indicating greater safety. Limited evidence in trials lasting up to 52 weeks suggest endometrial safety of vaginal estrogen use. Long-term trials are needed. : Video Summary:http://links.lww.com/MENO/A513.

PMID: 31913230 [PubMed - as supplied by publisher]

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pubmed: caandvteortroorpul

Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg Related Articles

Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

Dis Colon Rectum. 2019 11;62(11):1381-1389

Authors: Trepanier M, Alhassan N, Sabapathy CA, Liberman AS, Charlebois P, Stein BL, S Feldman L, Lee L

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