3. Attach, aseptically, in sequence

a. Platelet concentrate or bag aliquot

b. Platelet administration set, including filter

c. Three-way stopcock

d. Transfusion syringe

4. Draw volume of platelets for transfusion and tubing

dead space into syringe. Clear air bubbles.

5. Remove syringe from three-way stopcock and attach to

connecting tubing.

6. Establish IV access. If infant is at risk for hypoglycemia

with interruption of continuous glucose source, start

new IV or monitor closely throughout infusion.

7. Clear IV of glucose solution with 1 mL or more of normal saline.

8. Attach connecting tubing and syringe to IV line.

9. Monitor patient’s vital signs.

10. Infuse platelets over 1- to 2-hour period, faster if tolerated by infant.

11. After infusion is complete, flush IV line with 1 mL of

normal saline before restarting glucose solution.

12. Determine survival time of transfused platelets by

obtaining platelet counts at 1 and/or 24 hours if concern for platelet refractoriness.

F. Complications

1. Accentuated hemolysis in sensitized but indirect antiglobulin test–negative ABO setup

2. Rh sensitization in Rh-negative recipient (34)

3. Volume overload

4. Allergic reactions, including hypotension

310 Section VIII ■ Transfusions

5. Transfusion-related lung injury (TRALI) (35)

6. Increased morbidity in NEC (36)

Complications discussed in more detail in

“Complications of Blood Products” section.

Granulocyte Transfusions

A. Indications

1. Granulocyte transfusions are used infrequently because

of improvements in antimicrobial medications, supportive care, and the occasional use of granulocyte- and

granulocyte/macrophage-stimulating factors.

2. Granulocyte transfusion may be considered in the following conditions; however, reduction in morbidity or mortality have not been confirmed in randomized trials (37).

a. Neonates <14 days old with bacterial sepsis and

absolute neutrophil count (ANC) (+ band count)

<3 × 109

/L, and older neonates with bacterial sepsis

and ANC (+ band count) <0.5 × 109

/L

b. Neutropenic neonates with fungal disease not

responsive to standard antifungal therapy.

B. Equipment and Technique

1. Granulocyte concentrates for neonatal use are prepared

by automated granulocytapheresis, and should contain

1 to 2 × 109

 neutrophils/kg in a volume of 10- to 15-mL/

kg. Steroid- and G-CSF-mobilized donor preferred.

2. Daily transfusions may be necessary until there is clinical improvement and evidence of recovery of neutrophil counts.

3. Component must be ABO- and Rh-compatible with

recipient, and cross-match–compatible.

4. Product should be irradiated, CMV-negative, and

infused as soon as possible after collection.

5. The product should not be refrigerated or warmed

above room temperature.

6. Standard 120- to 170-mm filters should be used for

infusion; microaggregate and LD filters must be

avoided.

 

Chapter 43 ■ Transfusion of Blood and Blood Products 309

D. Equipment and Technique

1. Platelets

a. Random donor platelet concentrate (5.5 × 1010

platelets in 40 to 70 mL of plasma)

(1) Separated from WB by centrifugation within 8

hours of blood draw and resuspended in plasma

(2) Shelf life of 5 days

b. Volume-reduced platelets

(1) Standard platelet concentrate further concentrated to a volume of 15 to 20 mL by centrifugation

(2) Associated with loss of platelets and possible

decrease in platelet function

(3) Shelf life reduced to 4 hours

(4) Use only if infant has oliguria, severe volume

load sensitivity

c. Apheresis platelets (3 × 1011 platelets in volume of

250 mL plasma)

(1) Removes only platelets, returns RBCs and

plasma to donor

(2) Usually LD before storage

(3) Permits repeated donations from same donor

every 48 hours under select circumstances

(4) High yield of platelets

(5) More expensive product

(6) Useful when multiple platelet transfusions of a

particular antigen specificity are required, as in

neonatal alloimmune thrombocytopenia (NAIT)

or for infants on extracorporeal membrane oxygenation needing multiple platelet transfusions.

(7) May be HLA-typed or typed for HPA-1 or other

specific platelet antigen in case of NAIT.

(8) Maternal plateletpheresis product is preferred

for NAIT. Use maternal antigen-negative platelets, washed, irradiated, and resuspended in

ABO group-compatible plasma or saline.

2. Calculate volume of platelets to transfuse based on type

of product.

a. 10 to 15 mL/kg of random platelet provides 10 × 109

platelets/kg and should increase platelet count by

approximately 50 × 109

/L in the absence of ongoing

consumption. Can use same calculations for apheresis platelets, but studies do not confirm posttransfusion increments.

b. Advise use of equivalent unit (EU) calculations and

not mL/kg for dosing apheresis platelets.

c. 1 EU is the volume of a platelet aliquot that has a

minimum platelet content of 5.5 × 1010 platelets

(approximately 1 random donor platelet concentrate).

d. The standard dose based on this method is 1 EU/5

to 10 kg, with a minimum dose of 1 EU. Volume

reduction may be necessary for some extremely lowbirthweight infants.

e. Other products (HLA-matched, cross-matched

platelets) used for platelet refractoriness; washed

platelets if using HPA-matched maternal apheresis

platelets.

3. Blood administration set with 120- to 170-mm inline filter, unless platelets have been prefiltered while drawing

into a syringe. Specific sets designed for plasma/platelets have inline filters with reduced surface area to

increase platelet transfusion efficacy.

4. Sterile syringe for automated pump infusion. Use of

syringe technique will increase damage to platelets.

Administer by drip if clinically feasible.

5. Automated syringe pump

6. Connecting IV tubing

7. IV access, preferably through 23-gauge or larger needle

or through umbilical venous catheter

8. Normal saline flush solution

E. Technique for Platelet Administration by

Automated Syringe

1. Estimate by weight the volume of platelets in a single

bag to determine fluid load to infant.

2. Confirm correct platelet product.

a. Infant and unit identification

b. Infant and donor blood group, and Rh type

c. Check other restrictions: CMV negative, irradiated,

etc.

 

B. Contraindications

1. None absolute

2. Exert caution in patient with:

a. Volume overload

b. Congestive heart failure

c. T-activation

d. Increased risk for NEC (especially extremely lowbirthweight infants)

C. Technique

1. Determine total amount of blood needed.

a. Calculate volume of blood for transfusion. Most

infants are transfused 10 to 15 mL/kg of RBCs,

which will increase the hemoglobin by 3 g/dL.

b. RBC volume required: [EBV × (Hct desired – Hct

observed)] Hct of RBC unit

(1) Hct is hematocrit

(2) EBV is the estimated patient’s blood volume 80

to 85 mL/kg in full-term infants and approximately 100 to 120 mL/kg in preterm infants

(3) RBC units collected in citrate-phosphatedextrose-adenine (CPDA-1) have a Hct of

approximately 70%, RBCs in extended-storage

AP solutions (AS-1) have a Hct ≤60%

2. Include volume of blood needed for dead space of tubing, filter, pump mechanism (varies from system to system; may be as much as 30 mL).

3. Obtain blood product (see Appendix C).

a. Several studies have documented the safety of using

PRBCs stored in extended-storage anticoagulant

preservative (AP) solutions to outdate (20–22).

b. Avoid use of RBCs stored in extended-storage AP

solutions for massive transfusions, unless the additive is removed by inverted storage or centrifugation;

risks of hyperosmolality, hyperglycemia, hypernatremia, hyperkalemia, hyperphosphatemia are postulated (21,23,24).

Table 43.2

Guidelines for Transfusion of

RBCs in Patients <4 Months

of Age

Clinical Status Target Hematocrit

For severe cardiopulmonary disease (requiring

mechanical ventilation with FiO2 >0.35)

>40%–45%

For moderate cardiopulmonary disease >30%–35%

For major surgery >30%–35%

For infants with stable anemia with unexplained apnea/bradycardia, tachycardia, or

poor growth

>20%–25%

Modified from Fasano RM, Luban NL. Blood Component Therapy for the

Neonate. In: Martin R, Fanaroff A, eds. Fanaroff & Martin’s Neonatal-Perinatal

Medicine. 9th ed. St. Louis: Elsevier; 2010:1360; Strauss RG. How I transfuse red

blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity. Transfusion. 2008;48:209.

Definitions for level of severity of cardiopulmonary disease may be defined individually by institution.

 

2. The rate of transfusion may be increased to 10 to

20 mL/kg/h to replace acute blood loss.

3. 120 to 150 micron inline filters often used for complex

mechanical procedure.

Platelet Transfusions

A. Indications (Table 43.3)

The platelet count at which transfusion is recommended

has to be individualized because hemostatic competence is

determined not only by the quantity of platelets but also by

platelet function, vascular integrity, levels of coagulation

factors, and underlying disorder/disease.

B. Contraindications (33)

1. Autoimmune thrombocytopenic purpura (neonatal

ITP)

2. Heparin-induced thrombocytopenia (HIT)

3. Bleeding due to coagulopathy only (i.e., vitamin K deficiency)

4. Bleeding due to anatomic defect

5. Bleeding controllable with direct pressure/local measures (i.e., surgical bleeding)

C. Precautions

1. Use type-specific (Rh-negative) platelets when potential

for sensitization is present (i.e., in Rh-negative female).

Although platelets do not have Rh antigens, all products have some RBC contamination (less in plateletpheresis), which may cause Rh sensitization (34).

2. Use platelets from donor with ABO-compatible plasma.

Isohemagglutinins in ABO-incompatible plasma may

result in hemolysis, a positive direct antiglobulin test,

and poorer in vivo platelet survival than anticipated.

3. Transfuse platelets as soon after preparation as possible. Platelets should never be refrigerator-stored or

warmed.

Venous thromboembolism (VTE) is a common cardiovascular disease, for which several single nucleotide polymorphisms (SNPs)

 

Abstract

Venous thromboembolism (VTE) is a common cardiovascular disease, for which several single nucleotide polymorphisms (SNPs) underlying susceptibility were identified. Apart from candidate gene approach, genome-wide association studies (GWAS) have contributed to the identification of novel VTE-associated SNPs, including some with no clear role in the haemostatic system. These genetic variants constitute potential cancer-related biomarkers, particularly predictive and prognostic biomarkers, as a two-way association between VTE and cancer is well established. The present dataset comprises the data obtained from GWAS performed to identify genetic variants associated with VTE risk. Furthermore, this dataset also comprises data regarding previously reported candidate gene and validation reports performed in adults of European ancestry that also analysed the VTE GWAS-identified variants. Lastly, to evaluate the impact of these genetic variants in carcinogenesis, a broad search was made, which has let us to establish putative links between several VTE-associated genes and cancer hallmarks in a review article entitled "Venous thromboembolism GWAS reported genetic makeup and the hallmarks of cancer: linkage to ovarian tumour behaviour".

PMID: 32258274 [PubMed - as supplied by publisher]

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Could Preoperative Unintended Weight Loss Predispose to Postoperative Thrombosis in Patients Undergoing Colorectal Cancer Surgery? An Analysis of the NSQIP Data.

Related Articles

Could Preoperative Unintended Weight Loss Predispose to Postoperative Thrombosis in Patients Undergoing Colorectal Cancer Surgery? An Analysis of the NSQIP Data.

J Am Coll Nutr. 2020 Apr 07;:1-7

Authors: Temraz S, Tamim H, Mailhac A, Nassar F, Moukalled N, Jamali F, Taher A

Abstract

Objective: A significant portion of colorectal cancer patients lose weight preoperatively. Here we examine the influence of pre-operative significant weight loss on venous thromboembolism (VTE) risk and determine whether pre-operative BMI and albumin could influence VTE outcomes in patients who have lost significant weight prior to surgery.Methods: We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and identified 103,455 colorectal cancer patients undergoing major surgery from 2008 to 2012. Patients were assigned to one of two groups based on whether they lost significant weight preoperatively or not. Simple and stepwise multiple logistic regressions were used to evaluate the association between pre-operative unintended weight loss and 30-days postoperative outcomes. The association between weight loss and postoperative thrombosis was further assessed across several strata.Results: The overall prevalence of pre-operative significant weight loss was 6.8%. Significant weight loss prior to surgery was significantly and independently associated with a higher risk of VTE (adjusted OR 1.23, 95% CI 1.06-1.44), mortality (adjusted OR 1.55, 95% CI 1.35-1.78), composite morbidity (adjusted OR 1.52, 95% CI 1.42-1.62), bleeding (adjusted OR 1.78, 95% CI 1.67-1.91) and return to operation room (adjusted OR 1.29, 95% CI 1.16-1.42). The effect of pre-operative significant weight loss on thromboembolic outcome was evident across patients with a BMI <18.5 kg< bmi40kg/m2.Conclusions: Significant weight loss and BMI both need to be measured preoperatively to stratify patients who are at a higher risk of VTE.

PMID: 32255404 [PubMed - as supplied by publisher]

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Cancer therapies have been evolving from conventional chemotherapeutics to targeted agents. This has fulfilled the hope of

 

Abstract

Cancer therapies have been evolving from conventional chemotherapeutics to targeted agents. This has fulfilled the hope of greater efficacy but unfortunately not of greater safety. In fact, a broad spectrum of toxicities can be seen with targeted therapies, including cardiovascular toxicities. Among these, cardiomyopathy and heart failure have received greatest attention, given their profound implications for continuation of cancer therapies and cardiovascular morbidity and mortality. Prediction of risk has always posed a challenge and even more so with the newer targeted agents. The merits of accurate risk prediction, however, are very evident, e.g. facilitating treatment decisions even before the first dose is given. This is important for agents with a long half-life and high potential to induced life-threatening cardiac complications, such as myocarditis with immune checkpoint inhibitors. An opportunity to address these needs in the field of cardio-oncology is provided by the expanding repertoire of "-omics" and other tools in precision medicine and their integration in a systems biology approach. This may allow for new insights into patho-mechanisms and the creation of more precise and cost-effective risk prediction tools with the ultimate goals of improved therapy decisions and prevention of cardiovascular complications. Herein, we explore this topic as a future approach to translating the complexity of cardio-oncology to the reality of patient care.

PMID: 32253744 [PubMed - as supplied by publisher]

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Perinatal and Antibiotic Exposures and the Risk of Developing Childhood-Onset Inflammatory Bowel Disease: A Nested Case-Control Study Based on a Population-Based Birth Cohort.

Related Articles

Perinatal and Antibiotic Exposures and the Risk of Developing Childhood-Onset Inflammatory Bowel Disease: A Nested Case-Control Study Based on a Population-Based Birth Cohort.

Int J Environ Res Public Health. 2020 Apr 02;17(7):

Authors: Canova C, Ludvigsson JF, Di Domenicantonio R, Zanier L, Barbiellini Amidei C, Zingone F

The role of early-life environmental exposures on Inflammatory Bowel Disease (IBD) onset remains unclear. We aimed

 

Abstract

The role of early-life environmental exposures on Inflammatory Bowel Disease (IBD) onset remains unclear. We aimed to quantify the impact of perinatal conditions and antibiotic use in the first 6 and 12 months of life, on the risk of childhood-onset IBD, in a birth cohort of the region Friuli-Venezia Giulia (Italy). A nested case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate Odds Ratios (OR) with 95% confidence intervals (CI) for all analyzed risk factors. We identified 164 individuals with IBD onset before the age of 18 years and 1640 controls. None of the considered perinatal conditions were associated with IBD. Analyses on antibiotic exposure were based on 70 cases and 700 controls. Risks were significantly higher for children with ≥4 antibiotic prescriptions in the first 6 and 12 months of life (OR = 6.34; 95%CI 1.68-24.02 and OR = 2.91; 95%CI 1.31-6.45, respectively). This association was present only among patients with Crohn's disease and those with earlier IBD onset. We found that perinatal characteristics were not associated to IBD, while the frequent use of antibiotics during the first year of life was associated to an increased risk of developing subsequent childhood-onset IBD.

PMID: 32252276 [PubMed - in process]

15:06

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

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Dataset of GWAS-identified variants underlying venous thromboembolism susceptibility and linkage to cancer aggressiveness.

Related Articles

Dataset of GWAS-identified variants underlying venous thromboembolism susceptibility and linkage to cancer aggressiveness.

Data Brief. 2020 Jun;30:105399

Authors: Tavares V, Pinto R, Assis J, Pereira D, Medeiros R

Purpose: Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)

 

Abstract

Purpose: Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)- positive early breast cancer (EBC), drug resistance and disease relapse occur. Therefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone.

Methods: A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered.

Results: Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, p=0.0003) and OS (HR 0.86, p=0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, p=0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, p=0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (p=0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity.

Conclusions: Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. The correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.

PMID: 32256583 [PubMed - as supplied by publisher]

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Nutritional hazard analysis and critical control points at work (NACCPW): interdisciplinary assessment of subjective and metabolic work-related risk of the workers and their prevention.

Related Articles

Nutritional hazard analysis and critical control points at work (NACCPW): interdisciplinary assessment of subjective and metabolic work-related risk of the workers and their prevention.

Int J Food Sci Nutr. 2020 Apr 07;:1-7

Authors: Di Lorenzo L, Pipoli A, Manghisi NM, Clodoveo ML, Corbo F, De Pergola G, Sabbà C

Cardiotoxicity is a feared side effect that may limit the clinical use of anthracyclines. It may indeed affect the quality

 

Abstract

Cardiotoxicity is a feared side effect that may limit the clinical use of anthracyclines. It may indeed affect the quality of life and survival of patients with cancer, regardless of oncological prognosis. This paper provides an overview of anthracycline-induced cardiotoxicity in terms of definition, classification, incidence, risk factors, possible mechanisms, diagnosis, and treatment. We also report effective strategies for preventing cardiotoxicity. In addition, we discuss limiting current approaches, the need for a new classification, and early cardiotoxicity detection and treatment. Probably, anthracycline-induced cardiotoxicity is a continuous phenomenon that starts from myocardial cell injury; it is followed by left ventricular ejection fraction (LVEF) and, if not diagnosed and cured early, progressively leads to symptomatic heart failure. Anthracycline-induced cardiotoxicity can be detected at a preclinical phase. The role of biomarkers, in particular troponins, in identifying subclinical cardiotoxicity and its therapy with angiotensin-converting enzyme inhibitors (mainly enalapril) to prevent LVEF reduction is a recognized and effective strategy. If cardiac dysfunction has already occurred, partial or complete LVEF recovery may still be obtained in case of early detection of cardiotoxicity and prompt heart failure treatment.

PMID: 32258060 [PubMed - as supplied by publisher]

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Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience.

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Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience.

World J Clin Oncol. 2020 Mar 24;11(3):143-151

Authors: Rahardja S, Tan RYC, Sultana R, Leong FL, Lim EH

BACKGROUND: Pertuzumab is a humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal

 

Abstract

BACKGROUND: Pertuzumab is a humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer (MBC) when used in combination with a taxane and Trastuzumab, and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer. There are currently few reports on the pattern of use and value of Pertuzumab in real world settings. Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.

AIM: To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.

METHODS: A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted. Demographic and clinical data were extracted from electronic medical records. Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.

RESULTS: Thirty-one (62.0%) of the fifty (16.4%) patients who received Pertuzumab as first-line therapy. With a median follow-up of 21.5 mo, there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups [51.5 (95%CI: 35.8-60.0) vs 32.9 (95%CI: 28.1-37.5) mo; P = 0.0128]. Two (4.88%) patients in the Pertuzumab group experienced grade 3 (G3) cardiotoxicity. The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group. The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.

CONCLUSION: This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity. However, the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

PMID: 32257845 [PubMed - as supplied by publisher]

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Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Related Articles

Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

J Oncol. 2020;2020:5169278

Authors: Yu L, Fu F, Li J, Huang M, Zeng B, Lin Y, Mei Q, Lv J, Wang C

Improvements in long-term cancer survival rates have resulted in an increase in the prevalence of chemotherapy-linked

 

Abstract

Improvements in long-term cancer survival rates have resulted in an increase in the prevalence of chemotherapy-linked cardiac failure, but treatment-induced cardiac injuries may not be detected until long after therapy. Monitoring cardiac function is recommended; however, cardiovascular injury in cancer patients differs from those with primary cardiac dysfunction, which limits the utility of traditional cardiac biomarkers. Here we examined plasma levels of peptides produced by cathepsin B, which is released during chemotherapy-induced cardiac injury. We applied nanotrap fractionation to enrich plasma peptides from cancer patients treated with or without chemotherapy. Peptides associated with chemotherapy-induced cardiotoxicity, but not other cardiac injury, were identified by mass spectrometry, and their dependence on cathepsin B activity was determined using enzyme inhibition experiments. We found that a peptide (SAA-1525) derived from serum amyloid A1 was significantly increased in cardiotoxicity patients, and its production was inhibited when plasma samples were pretreated with cathepsin B specific inhibitors. Plasma SAA-1525 also correlated with other markers of cardiac injury. Analysis of plasma SAA-1525 levels may hold potential as a rapid and minimally invasive method to monitor subclinical injury, thereby allowing timely intervention to mitigate further cardiac damage and avoid more severe clinical presentation.

PMID: 32259067 [PubMed - as supplied by publisher]

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Cardiotoxicity of Anthracyclines.

Related Articles

Cardiotoxicity of Anthracyclines.

Front Cardiovasc Med. 2020;7:26

Authors: Cardinale D, Iacopo F, Cipolla CM

Introduction: Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients. Nonetheless,

 

Abstract

Introduction: Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients. Nonetheless, patients with hematological cancers receive less attention as compared with their solid tumor counterparts regarding this potentially fatal complication.Areas covered: Risk factors that are associated with the development of VTE in hematological cancers are discussed, based on a PubMed literature search. Since different hematological malignancies carry different risk of VTE, risk assessment in individual types of hematological cancers, including acute leukemias, lymphomas, myeloma and myeloproliferative neoplasms, are examined separately. Clinical relevance of VTE assessment and current guidelines on thromboprophylaxis in patients with hematological malignancies are also briefly reviewed.Expert opinion: When assessing VTE risk in patients with hematological cancers, in addition to the non-cancer specific risk factors, individual cancer-type specific and the therapy-related factors must be taken into consideration. Primary thromboprophylaxis should be considered in high risk patients.

PMID: 32249620 [PubMed - as supplied by publisher]

13:27

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

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Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

Oncologist. 2020 Apr 06;:

Authors: Reding KW, Aragaki AK, Cheng RK, Barac A, Wassertheil-Smoller S, Chubak J, Limacher MC, Hundley WG, D'Agostino R, Vitolins MZ, Brasky TM, Habel LA, Chow EJ, Jackson RD, Chen C, Morgenroth A, Barrington WE, Banegas M, Barnhart M, Chlebowski RT

Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen of porcine reproductive and respiratory syndrome

 

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen of porcine reproductive and respiratory syndrome (PRRS), which is one of the most economically harmful diseases in modern pig production worldwide. Receptor of activated protein C kinase 1 (RACK1) was previously shown to be indispensable for the PRRSV replication and NF-κB activation in Marc-145 cells. Here we identified a membrane protein, integrin β3 (ITGB3), as a RACK1-interacting protein. PRRSV infection in Marc-145 cells upregulated the ITGB3 expression. Abrogation of ITGB3 by siRNA knockdown or antibody blocking inhibited PRRSV infection and NF-κB activation, while on the other hand, overexpression of ITGB3 enhanced PRRSV infection and NF-κB activation. Furthermore, inhibition of ITGB3 alleviated the cytopathic effects and reduced the TCID50 titer in Marc-145 cells. We also showed that RACK1 and ITGB3 were NF-κB target genes during PRRSV infection, and that they regulate each other. Our data indicated that ITGB3, presumably as a co-receptor, played an imperative role during PRRSV infection and NF-κB activation in Marc-145 cells. PRRSV infection activates a positive feedback loop involving the activation of NF-κB and upregulation of ITGB3 and RACK1 in Marc-145 cells. The findings would advance our elaborated understanding of the molecular host-pathogen interaction mechanisms underlying PRRSV infection in swine and suggest ITGB3 and NF-κB signaling pathway as potential therapeutic targets for PRRS control.

PMID: 32247758 [PubMed - as supplied by publisher]

14:01

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

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Venous thromboembolism in patients hospitalized for hip joint replacement surgery.

Related Articles

Venous thromboembolism in patients hospitalized for hip joint replacement surgery.

Thromb Res. 2020 Mar 27;190:1-7

Authors: Keller K, Hobohm L, Barco S, Schmidtmann I, Münzel T, Engelhardt M, Goldhofer M, Konstantinides SV, Drees P

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms

 

Abstract

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms of the disease. The use of cardiac magnetic resonance (CMR) imaging and nuclear magnetic resonance (NMR) imaging in preclinical models allows the non-invasive study of subclinical pathophysiological processes that influence cardiac function and establish imaging parameters that can be adopted into clinical practice to predict cardiovascular outcomes. Given the rising population of cancer survivors and the current lack of effective therapies for the management of cardiotoxicity, research combining clinically relevant animal models and non-invasive cardiac imaging remains essential to improve methods to monitor, predict, and treat cardiovascular adverse events. This comprehensive review summarizes the lessons learned from animal models of cardiotoxicity employing CMR and tissue characterization techniques and discusses the ongoing challenges and hopes for the future.

PMID: 32248349 [PubMed - as supplied by publisher]

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Integrin β3, a RACK1 interacting protein, is critical for porcine reproductive and respiratory syndrome virus infection and NF-κB activation in Marc-145 cells.

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Integrin β3, a RACK1 interacting protein, is critical for porcine reproductive and respiratory syndrome virus infection and NF-κB activation in Marc-145 cells.

Virus Res. 2020 Apr 02;:197956

Authors: Yang C, Lan R, Wang X, Zhao Q, Li X, Bi J, Wang J, Yang G, Lin Y, Liu J, Yin G

INTRODUCTION: Cancer patients receiving chemotherapy are a high risk of VTE, yet the importance of thromboprophylaxis for

 

Abstract

INTRODUCTION: Cancer patients receiving chemotherapy are a high risk of VTE, yet the importance of thromboprophylaxis for cancer patients that are at high risk of developing VTE is still controversial.

AIM: To calculate the benefits and harms of thromboprophylaxis, compared to placebo, in ambulatory high-risk cancer patients that are receiving chemotherapy.

METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WANFANG Data, Chinese National Knowledge Infrastructure and Chinese Scientific Journal Database for randomized controlled trials (RCTs) describing benefits and harms of thromboprophylaxis. Statistical analysis was performed using Stata software (version 15.1).

RESULTS: We included six studies, which contained a total of 3240 cancer patients with thromboprophylaxis and 2874 cancer patients without thromboprophylaxis. Thromboprophylaxis was effective in high-risk patients with two points or higher (RR 0.51, 95% CI 0.36-0.71, I2 = 0.0%, P = 0.526). It was associated with an increase in bleeding events (RR 1.65, 95% CI 1.14-2.40, I2 = 0.0%, P = 0.498) and was mainly efficient in reducing the risk of pulmonary embolism (RR 0.56, 95% CI 0.33-0.96, I2 = 0.0%, P = 0.263). The risk of major (RR 1.85, 95% CI 0.87-3.94, I2 = 0.0%, P = 0.888) and non-major (RR 1.59, 95% CI 0.96-2.62, I2 = 16.3%, P = 0.303) bleeding showed no significant difference with or without thromboprophylaxis. There was no reduction in all-cause mortality with thromboprophylaxis (RR 0.95, 95% CI 0.78-1.18, I2 = 22.0%, P = 0.277).

CONCLUSION: Thromoboprophylaxis is effective and safe in cancer patients that are at high risk for developing VTE with chemotherapy.

PMID: 32246324 [PubMed - as supplied by publisher]

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Observational Multicenter Study on the Prognostic Relevance of Coagulation Activation in Risk Assessment and Stratification in Locally Advanced Breast Cancer. Outline of the ARIAS Trial.

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Observational Multicenter Study on the Prognostic Relevance of Coagulation Activation in Risk Assessment and Stratification in Locally Advanced Breast Cancer. Outline of the ARIAS Trial.

Cancers (Basel). 2020 Apr 01;12(4):

Authors: Pizzuti L, Krasniqi E, Mandoj C, Marinelli D, Sergi D, Capomolla E, Paoletti G, Botti C, Kayal R, Ferranti FR, Sperduti I, Perracchio L, Sanguineti G, Marchetti P, Ciliberto G, Barchiesi G, Mazzotta M, Barba M, Conti L, Vici P

BACKGROUND: Recently, the randomized EINSTEIN-Jr. study showed similar efficacy and safety for rivaroxaban and standard

 

Abstract

BACKGROUND: Recently, the randomized EINSTEIN-Jr. study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling.

METHODS: Rivaroxaban treatment with tablets or the newly-developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily or thrice-daily for children with bodyweights of ≥30, ≥12-<30,<12kg,<20kg.

RESULTS: Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable.

DISCUSSION: Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.

PMID: 32246743 [PubMed - as supplied by publisher]

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The effectiveness and safety of thromboprophylaxis in cancer patients based on Khorana score: a meta-analysis and systematic review of randomized controlled trials.

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The effectiveness and safety of thromboprophylaxis in cancer patients based on Khorana score: a meta-analysis and systematic review of randomized controlled trials.

Clin Transl Oncol. 2020 Apr 03;:

Authors: Bao Y, Gao B, Yan P, Tian L, Yang K

AIM: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous

 

Abstract

AIM: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous T cells to kill the cancer cell. Myocarditis cases have been reported in cancer patients after immunological therapy; for example, nivolumab treatment is a monoclonal antibody that blocks programmed cell death-1/programmed cell death ligand-1 ligand interaction. This project provided insight into the inflammatory response as a benchmark to investigate the potential cardiotoxic effect of T cell response to the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis in regulating cardiomyocyte injury in vitro.

METHODS AND RESULTS: We investigated cardiomyopathy resulted from the PD-1/PD-L1 axis blockade using the anti-PD-1 antibody in Rockefeller University embryonic stem cells-derived cardiomyocytes (RUES2-CMs) and a melanoma tumor-bearing murine model. We found that nivolumab alone did not induce inflammatory-related proteins, including PD-L1 expression, and did not induce apoptosis, which was contrary to doxorubicin, a cardiotoxic chemotherapy drug. However, nivolumab was able to exacerbate the immune response by increasing cytokine and inflammatory gene expression in RUES2-CMs when co-cultured with CD4+ T lymphocytes and induced apoptosis. This effect was not observed when RUES2-CMs were co-cultured with CD8+ T lymphocytes. The in vivo model showed that the heart function of tumor-bearing mice was decreased after treatment with anti-PD-1 antibody and demonstrated a dilated left ventricle histological examination. The dilated left ventricle was associated with an infiltration of CD4+ and CD8+ T lymphocytes into the myocardium. PD-L1 and inflammatory-associated gene expression were significantly increased in anti-PD-1-treated tumor-bearing mice. Cleaved caspase-3 and mouse plasma cardiac troponin I expressions were increased significantly.

CONCLUSION: PD-L1 expression on cardiomyocytes suppressed T-cell function. Blockade of PD-1 by nivolumab enhanced cardiomyocyte inflammation and apoptosis through the enhancement of T-cell response towards cardiomyocytes.

PMID: 32244307 [PubMed - as supplied by publisher]

13:08

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

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Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr Phase 3 dose-exposure-response evaluation.

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Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr Phase 3 dose-exposure-response evaluation.

J Thromb Haemost. 2020 Apr 04;:

Authors: Young G, Lensing AWA, Monagle P, Male C, Thelen K, Willmann S, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bajolle F, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaría A, Amedro P, Beyer-Westendorf J, Martinelli I, Patricia Massicotte M, Smith WT, Berkowitz SD, Schmidt S, Price V, Prins MH, Kubitza D, EINSTEIN-Jr. Phase 3 Investigators

Heart and blood vessels disorders comprise one of the main causes of death worldwide. Pharmacologically active

 

Abstract

Heart and blood vessels disorders comprise one of the main causes of death worldwide. Pharmacologically active natural compounds have been used as a complementary therapy in cardiovascular disease around the world in a traditional way. Dietary, natural bioactive compounds, as well as healthy lifestyles, are considered to prevent coronary artery diseases. Pre-clinical and clinical studies reported that consumption of plant-food bioactive derivatives including polyphenolic compounds, peptides, oligosaccharides, vitamins, unsaturated fatty acids possess protective effects on cardiovascular diseases. This review aims to summarize the cardiovascular risk factors, pre-clinical studies and clinical trials related to cardioprotective properties of the plant-food-derived bioactive compounds. Molecular mechanisms by the natural bioactive compounds exert their cardiovascular protective properties have also been highlighted.

PMID: 32235611 [PubMed - in process]

4 April 2020

12:39

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

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Quantifying the impact of surgical decompression on quality of life and identification of factors associated with outcomes in patients with symptomatic metastatic spinal cord compression.

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Quantifying the impact of surgical decompression on quality of life and identification of factors associated with outcomes in patients with symptomatic metastatic spinal cord compression.

J Neurosurg Spine. 2020 Apr 03;:1-8

Authors: Lak AM, Rahimi A, Abunimer AM, Tafel I, Devi S, Premkumar A, Ida F, Lu Y, Chi JH, Tanguturi S, Groff MW, Zaidi HA

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians

 

Abstract

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients.

METHOD: We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool.

RESULTS: We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT.

CONCLUSION: Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.

PMID: 32243404 [PubMed - as supplied by publisher]

5 April 2020

12:17

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

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Preoperative Peak Oxygen Consumption: A Predictor of Survival in Resected Lung Cancer.

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Preoperative Peak Oxygen Consumption: A Predictor of Survival in Resected Lung Cancer.

Cancers (Basel). 2020 Mar 31;12(4):

Authors: Lindenmann J, Fink-Neuboeck N, Fediuk M, Maier A, Kovacs G, Balic M, Smolle J, Smolle-Juettner FM

OBJECTIVE: Metastatic spinal cord compression (MSCC) imposes significant impairment on patient quality of life and often

 

Abstract

OBJECTIVE: Metastatic spinal cord compression (MSCC) imposes significant impairment on patient quality of life and often requires immediate surgical intervention. In this study the authors sought to estimate the impact of surgical intervention on patient quality of life in the form of mean quality-adjusted life years (QALY) gained and identify factors associated with positive outcomes.

METHODS: The authors performed a retrospective chart review and collected data for patients who had neurological symptoms resulting from radiologically and histologically confirmed MSCC and were treated with surgical decompression during the last 12 years.

RESULTS: A total of 151 patients were included in this study (mean age 60.4 years, 57.6% males). The 5 most common metastatic tumor types were lung, multiple myeloma, renal, breast, and prostate cancer. The majority of patients had radioresistant tumors (82.7%) and had an active primary site at presentation (67.5%). The median time from tumor diagnosis to cord compression was 12 months and the median time from identification of cord compression to death was 4 months. Preoperative presenting symptoms included motor weakness (70.8%), pain (70.1%), sensory disturbances (47.6%), and bowel or bladder disturbance (31.1%). The median estimated blood loss was 500 mL and the average length of hospital stay was 10.3 days. About 18% of patients had postoperative complications and the mean follow-up was 7 months. The mean pre- and postoperative ECOG (Eastern Cooperative Oncology Group) performance status grades were 3.2 and 2.4, respectively. At follow-up, 58.3% of patients had improved status, 31.5% had no improvement, and 10.0% had worsening of functional status. The mean QALY gained per year in the entire cohort was 0.55. The mean QALY gained in the first 6 months was 0.1 and in the first year was 0.4. For patients who lived 1-2, 2-3, 3-4, or 4-5 years, the mean QALY gained were 0.8, 1.4, 1.7, and 2.3, respectively. Preoperative motor weakness, bowel dysfunction, bladder dysfunction, and ASA (American Society of Anesthesiologists) class were identified as independent predictors inversely associated with good outcome.

CONCLUSIONS: The mean QALY gained from surgical decompression in the first 6 months and first year equals 1.2 months and 5 months of life in perfect health, respectively. These findings suggest that surgery might also be beneficial to patients with life expectancy < 6 months.

PMID: 32244218 [PubMed - as supplied by publisher]

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Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

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Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

Medicine (Baltimore). 2020 Apr;99(14):e19679

Authors: Danjuma MI, Mohamed MFH, ElShafei MN, Fatima H, Shokri SA, Mohamed S, Abubeker IY, Kartha A, Elzouki AN, Mohamedali MGH, Mahgboub Y, Bidmos M

PURPOSE: Little data exist for comparing cardiac safety and survival outcomes of trastuzumab/pertuzumab

 

Abstract

PURPOSE: Little data exist for comparing cardiac safety and survival outcomes of trastuzumab/pertuzumab or ado-T emtansine (TDM1) in metastatic breast cancer (MBC) patients enrolled in randomized clinical trial (RCT) vs the real-world.

METHODS: This was a retrospective population-based cohort of all patients with MBC treated with trastuzumab/pertuzumab or TDM1 (2012-2017) in Ontario, Canada. Outcomes were incident heart failure (HF) and overall survival (OS). RCT data were obtained from digitizing survival curves and compared with cohort data using Kaplan-Meier analysis. Age-based comparison of outcomes was conducted for patients ≥ 65 years old vs younger than 65.

RESULTS: The two cohorts composed of 833 and 397 patients treated with trastuzumab/pertuzumab and TDM1, of whom 5.5% and 7.6% had baseline HF, respectively. Incident HF following trastuzumab/pertuzumab or TDM1 was low (trastuzumab/pertuzumab 1.8 events/100 person years; TDM1 0.02 events/100 person years). The median OS was 39.2 and 56.4 months in the trastuzumab/pertuzumab population-based cohort and CLEOPATRA, respectively. The median OS was 15.4 and 30.9 months in the TDM1 population-based cohort and EMILIA, respectively. Cohort OS was significantly worse than RCT OS (trastuzumab/pertuzumab HR 1.67, 95% CI 1.37-2.03, p < 0.0001;< 0.0001).

CONCLUSION: HF incidence during trastuzumab/pertuzumab or TDM1 therapy in this real-world cohort was low. Survival in this cohort was worse compared to RCT, suggesting that recruitment of patients similar to the real-world population is required.

PMID: 32236828 [PubMed - as supplied by publisher]

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Diet, Lifestyle and Cardiovascular Diseases: Linking Pathophysiology to Cardioprotective Effects of Natural Bioactive Compounds.

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Diet, Lifestyle and Cardiovascular Diseases: Linking Pathophysiology to Cardioprotective Effects of Natural Bioactive Compounds.

Int J Environ Res Public Health. 2020 Mar 30;17(7):

Authors: Sharifi-Rad J, Rodrigues CF, Sharopov F, Docea AO, Can Karaca A, Sharifi-Rad M, Kahveci Karıncaoglu D, Gülseren G, Şenol E, Demircan E, Taheri Y, Suleria HAR, Özçelik B, Nur Kasapoğlu K, Gültekin-Özgüven M, Daşkaya-Dikmen C, C Cho W, Martins N, Calina D

Somatic mutations in RAS and related pathway genes such as NF1 have been strongly implicated in the development of cancer

 

Abstract

Somatic mutations in RAS and related pathway genes such as NF1 have been strongly implicated in the development of cancer whilst also being implicated in a diverse group of developmental disorders named the "RASopathies"; including Neurofibromatosis 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), and capillary malformation-arteriovenous syndrome (CM-AVM). It remains unclear why i) there is little overlap in mutational subtype between Ras-driven malignancies associated with sporadic disease and those associated with the RASopathy syndromes, and ii) RASopathy-associated cancers are usually of different histological origin to those seen with sporadic mutations of the same genes. For instance, germline variants in KRAS and NRAS are rarely found at codons 12, 13 or 61, the most common sites for somatic mutations in sporadic cancers. An exception is Costello's syndrome, where germline variants in codons 12 and 13 of HRAS occur relatively frequently. Given recent renewed drug interest following early clinical success of RAS G12C and farnesyl transferase inhibitors, an improved understanding of this relationship could help guide targeted therapies for both sporadic and germline cancers associated with the Ras pathway.

PMID: 32240795 [PubMed - as supplied by publisher]

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sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.

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sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.

Acta Pharmacol Sin. 2020 Apr 01;:

Authors: Hu YH, Liu J, Lu J, Wang PX, Chen JX, Guo Y, Han FH, Wang JJ, Li W, Liu PQ

INTRODUCTION: D-dimer is widely used in clinical pretests for venous thromboembolism exclusion, and its elevation suggests the

 

Abstract

INTRODUCTION: D-dimer is widely used in clinical pretests for venous thromboembolism exclusion, and its elevation suggests the presence of thrombus. The extent of hypercoagulability after colorectal surgery has not been systematically compared between patients who have undergone laparoscopic surgery and open surgery. The present study measured D-dimer levels sequentially in patients undergoing colorectal surgery and compared the extent of hypercoagulability between laparoscopic surgery and open surgery.

METHODS: A prospective cohort study involving 169 patients who underwent resection of colorectal cancer at Saitama Medical Center, Dokkyo Medical University, was conducted between January 2013 and September 2014. To measure D-dimer level, peripheral blood was obtained on postoperative day (POD) 1, POD4, and POD7. Enoxaparin sodium was administered twice daily as the routine prophylactic anticoagulant therapy on POD2 to 7.

RESULTS: D-dimer levels on POD1, POD4, and POD7 were significantly higher after open surgery than after laparoscopic surgery. Older age, pathologically advanced stage cancer, greater intraoperative blood loss and higher preoperative D-dimer levels were significantly associated with higher D-dimer levels on POD1, POD4, and POD7. Patients who completed the course of postoperative enoxaparin injections had significantly lower D-dimer levels on POD7 than those who did not receive postoperative enoxaparin injections. Multiple regression analyses of postoperative D-dimer level showed that laparoscopic surgery was a significant and independent factor affecting D-dimer level on POD4 and POD7.

CONCLUSION: This study showed that postoperative D-dimer levels were lower after laparoscopic surgery than after open surgery. The limited invasiveness of laparoscopic surgery may be beneficial to reduce the risk of postoperative deep vein thrombosis.

PMID: 32237071 [PubMed - as supplied by publisher]

11:24

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Urothelial carcinoma of the bladder induces endothelial cell activation and hypercoagulation.

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Urothelial carcinoma of the bladder induces endothelial cell activation and hypercoagulation.

Mol Cancer Res. 2020 Mar 31;:

Authors: John A, Robador JR, Vidal-Y-Sy S, Houdek P, Wladykowski E, Guenes C, Bolenz C, Schneider SW, Bauer AT, Gorzelanny C

Cardiac sarcoma is the commonest histology among primary cardiac tumors but it is a rare clinical entity and it is characterized

 

Abstract

Cardiac sarcoma is the commonest histology among primary cardiac tumors but it is a rare clinical entity and it is characterized by late stage presentation, poor prognosis from the time of detection and a variety of clinical presentations depending on the size and extent of the mass. We report the case of a high-grade right atrial angiosarcoma presenting with pulmonary embolism and cardiac tamponade. The patient underwent surgical resection and reconstruction of the atrial wall with bovine pericardial patch. This case report underscores the great heterogeneity of the clinical presentation, often non-specific, and the fatal prognosis of angiosarcoma, mostly related to the lack of evidence supporting a standardized therapeutic approach.

PMID: 31697274 [PubMed - indexed for MEDLINE]

11:24

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Venous thromboembolism risk assessment tools: Do we need a consensus?

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.sagepub.com-pb-assets-sage-pubmed-sage.png Related Articles

Venous thromboembolism risk assessment tools: Do we need a consensus?

Phlebology. 2019 10;34(9):579-581

Authors: Machin M, Salim S, Onida S, Davies AH

PMID: 30739582 [PubMed - indexed for MEDLINE]

14:46

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

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Germline and sporadic cancers driven by the RAS pathway: parallels and contrasts.

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Germline and sporadic cancers driven by the RAS pathway: parallels and contrasts.

Ann Oncol. 2020 Mar 30;:

Authors: Dunnett-Kane V, Burkitt-Wright E, Blackhall FH, Malliri A, Evans G, Lindsay CR

INTRODUCTION: Venous Thromboembolism (VTE) is an important cause of morbidity and mortality. The risk of recur

 

Abstract

INTRODUCTION: Venous Thromboembolism (VTE) is an important cause of morbidity and mortality. The risk of recur- rence could be very high without thromboprophylaxis. New oral anticoagulants (NOACs or DOACs) represent a new step in anticoagulation.

MATERIAL AND METHODS: We searched for papers with trials, systematic reviews and meta-analysis involving NOACs in the treatment and secondary prevention of VTE. We also searched for guidelines of two medical societies (American College of Chest Physicians and International Society of Thrombosis and Haemostasis - ISTH).

RESULTS: Six RCT (randomized controlled trial) comparing NOACs with Warfarin shew a non-inferiority in relation with recurrent VTE and major bleeding. Two RCT (SELECT-D and Hokusay cancer) and one meta-analysis shew low recurrence rate of VTE in cancer patients and higher rate of bleeding, mainly in gastrointestinal and genitourinary cancers. There are two RCTs involving NOACs in treatment of patients with Antiphospholipid Syndrome (APS).

DISCUSSION: NOACs shew non-inferiority over AVK. Guidelines of CHEST 2016 recommend NOACs for VTE treatment in no cancer patients, and Low Molecular Weight Heparin (LMWH) for cancer patients. ISTH suggest NOACs as the first option in VTE cancer patients with low risk of bleeding. A recent RCT shews no benefit and increased risk of vascular events in APS patients treated with NOACs. NOACs are the gold standard for VTE treatment and secondary prevention in no cancer patients. They could be the first option in cancer patients with low risk of bleeding.

PMID: 32239823 [PubMed - as supplied by publisher]

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Can I use direct oral anticoagulants to treat cancer-associated venous thromboembolism?

Can I use direct oral anticoagulants to treat cancer-associated venous thromboembolism?

Cleve Clin J Med. 2020 Apr;87(4):201-203

Authors: Emiloju O, Gupta S, Dourado C

PMID: 32238374 [PubMed - as supplied by publisher]

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Comparison of postoperative plasma D-dimer levels between patients undergoing laparoscopic resection and conventional open resection for colorectal cancer.

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Comparison of postoperative plasma D-dimer levels between patients undergoing laparoscopic resection and conventional open resection for colorectal cancer.

Asian J Endosc Surg. 2020 Mar 31;:

Authors: Kubota Y, Okuyama T, Oi H, Takeshita E, Mitsui T, Noro T, Sameshima S, Noie T, Oya M

Doxorubicin (DOX) is a chemotherapeutic agent broadly used in the treatment of a range of solid tumors. In spite of its high potency,

 

Abstract

Doxorubicin (DOX) is a chemotherapeutic agent broadly used in the treatment of a range of solid tumors. In spite of its high potency, as is the case for many other chemotherapeutic drugs, there are many challenges associated with the use of DOX in clinical oncology. This is particularly true for DOX in the treatment of lung cancer where in vitro potency is shown to be very high, but low lung distribution and off-target toxicity (particularly cardiotoxicity) restricts its use. Nanocarrier-based drug delivery systems (nanoDDS) have been shown to help alter biodistribution and alleviate off-target toxicity associated with DOX. While significant understanding exists regarding the design parameters to achieve those clinical benefits, much less is known regarding the design of nanoDDS capable of enhancing tumor penetration of DOX (and other drugs), which is another major factor leading to DOX's reduced efficacy. The purpose of this study was to design a dendrimer-based nanoDDS capable of enhancing the penetration of DOX as measured in an in vitro 3D lung tumor model and to correlate those results with its efficacy. Spheroids formed with A549 human lung adenocarcinoma cells/murine fibroblasts cell line (NIH/3T3 cell line) are shown to produce the essential components of the extracellular matrix (ECM), which is known as a physical barrier that hinder the transport of DOX. DOX was conjugated to generation 4, succinamic acid-terminated poly (amido-amine) (PAMAM) dendrimers (G4SA) through an enzyme-liable tetrapeptide (G4SA-GFLG-DOX) resulting in a nanoDDS with ~5.5 DOX, -17 mV surface (zeta) potential, and 10 nm in hydrodynamic diameter (HD). Penetration of DOX to the core of the spheroid in term of DOX fluorescence's was determined to be 3.1-fold greater compared to free DOX, which positively correlated with enhanced efficacy as measured by Caspase 3/7 assay. This improved penetration happens as the interactions between the G4SA-GFLG-DOX and the highly negatively charged ECM are minimized by shielding the protonatable amine of DOX upon conjugation, and the HD of the conjugate is kept smaller than the estimated mesh size of the ECM. Interestingly, the conjugate provide has more specificity for DOX to tumor cells compared to fibroblasts, while free DOX is equally distributed in both tumor and fibroblasts as assessed in the co-culture spheroids. Growth inhibition studies show that the released DOX maintains its activity, and leads to tumor reduction to the same extent as free DOX. The results obtained here are of relevance for the design of dendrimer-based nanoDDS for the treatment of solid tumors as they provide critical information regarding desirable surface characteristics and sizes for efficient tumor penetration.

PMID: 32227969 [PubMed - as supplied by publisher]

13:49

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

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Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study.

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Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study.

Ther Adv Med Oncol. 2020;12:1758835920909660

Authors: Pineda-Moncusí M, Garcia-Giralt N, Diez-Perez A, Tusquets I, Servitja S, Albanell J, Prieto-Alhambra D, Nogués X

Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape

 

Abstract

Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape of treatment approaches for several malignancies and continuing to increase patient survival. Accordingly, adverse effects of cancer therapies that interfere with the continuation of best-possible care, induce life-threatening risks or lead to long-term morbidity are gaining increasing importance. Cardiovascular toxic effects of cancer therapeutics and radiation therapy are the epitome of such concerns, and proper knowledge, interpretation and management are needed and have to be placed within the context of the overall care of individual patients with cancer. Furthermore, the cardiotoxicity spectrum has broadened to include myocarditis with immune checkpoint inhibitors and cardiac dysfunction in the setting of cytokine release syndrome with chimeric antigen receptor T cell therapy. An increase in the incidence of arrhythmias related to inflammation such as atrial fibrillation can also be expected, in addition to the broadening set of cancer therapeutics that can induce prolongation of the corrected QT interval. Therefore, cardiologists of today have to be familiar not only with the cardiotoxicity associated with traditional cancer therapies, such as anthracycline, trastuzumab or radiation therapy, but even more so with an ever-increasing repertoire of therapeutics. This Review provides this information, summarizing the latest developments at the juncture of cardiology, oncology and haematology.

PMID: 32231332 [PubMed - as supplied by publisher]

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Dendrimer Conjugation Enhances Tumor Penetration and Efficacy of Doxorubicin in Extracellular Matrix-Expressing 3D Lung Cancer Models.

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Dendrimer Conjugation Enhances Tumor Penetration and Efficacy of Doxorubicin in Extracellular Matrix-Expressing 3D Lung Cancer Models.

Mol Pharm. 2020 Mar 31;:

Authors: Almuqbil RM, Heyder RS, Bielski ER, Durymanov M, Reineke JJ, da Rocha SRP

BACKGROUND: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration

 

Abstract

BACKGROUND: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs.

METHODS: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death.

RESULTS: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002).

CONCLUSION: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

PMID: 30795818 [PubMed - indexed for MEDLINE]

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Delirium in adult cancer patients: ESMO Clinical Practice Guidelines.

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

Delirium in adult cancer patients: ESMO Clinical Practice Guidelines.

Ann Oncol. 2018 Oct;29 Suppl 4:iv143-iv165

Authors: Bush SH, Lawlor PG, Ryan K, Centeno C, Lucchesi M, Kanji S, Siddiqi N, Morandi A, Davis DHJ, Laurent M, Schofield N, Barallat E, Ripamonti CI, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org

PMID: 32169223 [PubMed - indexed for MEDLINE]

2 April 2020

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

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Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia.

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Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia.

Nat Rev Cardiol. 2020 Mar 30;:

Authors: Herrmann J