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11/1/23

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and causes considerable morbidity and mortality. The risk of VTE

Abstract

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and causes considerable morbidity and mortality. The risk of VTE is higher in patients with pancreatic cancer and is often associated with treatment delays or interruptions. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing.

PATIENTS AND METHODS: We conducted a retrospective study to determine the incidence of VTE and to evaluate the ONKOTEV score as a VTE predictive tool in a population of patients with pancreatic cancer.

RESULTS: Between February 2012 and May 2017, 165 patients were included in the study. The median age was 73 years, 45.5% of patients were female, and 55.8% had stage IV disease. Fifty-one patients had a VTE (30.9%); 23.5% had pulmonary embolism, 25.5% had deep venous thrombosis, and 51.0% had visceral VTE (VsT). At a median follow-up time of 6.3 months, cumulative incidence of VTE was less than 10% for ONKOTEV scores 0 or 1 and approximately 40% and 70% for scores 2 and ≥3, respectively.

CONCLUSION: The high VTE incidence observed in this study is consistent with prior reports. Patients at high risk for VTE with no increase in hemorrhagic risk should be considered for primary thromboprophylaxis. The ONKOTEV score may stratify VTE risk in patients with pancreatic cancer, with ONKOTEV score ≥2 being associated with a higher VTE occurrence.

IMPLICATIONS FOR PRACTICE: Venous thromboembolism (VTE) is a frequent complication of patients with pancreatic cancer and causes considerable morbidity, treatment delays or interruptions, and mortality. Thromboprophylaxis is not used routinely in ambulatory patients. Tools to stratify the risk of VTE are important to help select patients who may benefit from thromboprophylaxis. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing. In this patient series, ONKOTEV score ≥2 was associated with high VTE occurrence and may stratify VTE risk in patients with pancreatic cancer, suggesting that ONKOTEV can be considered to select patients with pancreatic cancer for primary thromboprophylaxis.

PMID: 32043787 [PubMed - in process]

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Prevention of Venous Thromboembolism in Pancreatic Cancer: Breaking Down a Complex Clinical Dilemma.

Oncologist. 2020 Feb;25(2):132-139

Authors: Dallos MC, Eisenberger AB, Bates SE

Venous thromboembolic disease (VTE)

Abstract

Venous thromboembolic disease (VTE) in hospitalized adults has high morbidity and mortality, is the origin of chronic complications and increased cost for the health system. Since the publication of recommendations for thromboprophylaxis in hospitalized patients in 2013, new alternatives and strategies have emerged, which motivated us to update our recommendations. Although there are different consensus and clinical practice guidelines, adherence to them is suboptimal. The different therapeutic alternatives for hospitalized adult patients (non-surgical, surgical non-orthopedic, with and without cancer, orthopedic an d pregnant) have been updated, paying particular attention to the drugs available in Argentina.

PMID: 32044743 [PubMed - in process]

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ONKOTEV Score as a Predictive Tool for Thromboembolic Events in Pancreatic Cancer-A Retrospective Analysis.

Oncologist. 2020 Feb;25(2):e284-e290

Authors: Godinho J, Casa-Nova M, Moreira-Pinto J, Simões P, Paralta Branco F, Leal-Costa L, Faria A, Lopes F, Teixeira JA, Passos-Coelho JL

BACKGROUND: There is an elevated risk of venous thromboembolism in patients treated for colon cancer. Postoperative venous thromboembolism has

Abstract

BACKGROUND: There is an elevated risk of venous thromboembolism in patients treated for colon cancer. Postoperative venous thromboembolism has been studied previously, but no large study has compared the risks during different stages of treatment.

OBJECTIVE: This study aimed to quantify and compare the risks of venous thromboembolism before surgery, after surgery, during adjuvant chemotherapy, and up to 365 days after surgery among patients with resected colon cancer.

DESIGN: This is a population-based retrospective cohort study.

SETTING: This study was conducted in a single-payer, universal health care setting (Ontario) between 2002 and 2008.

PATIENTS: A total of 6806 patients with stage I to III colon cancer treated with surgical resection were included.

INTERVENTIONS: Phases of treatment were evaluated, including preoperative, in-hospital, postoperative, during adjuvant chemotherapy, and 365 days postoperatively.

MAIN OUTCOME MEASURES: Venous thromboembolism, as defined using diagnostic codes from administrative data sources, was the primary outcome measured.

RESULTS: Of the 6806 patients included, 327 (5%) developed venous thromboembolism. Patients receiving adjuvant chemotherapy had a higher risk versus surgery-alone patients (6% vs 4%, p < 0.001). Of the 327 who developed venous thromboembolism, 32% (1.6% overall) were diagnosed during hospital admission and 13.5% (0.6% overall) were diagnosed between discharge and 30 days after surgery. The majority of venous thromboembolisms diagnosed in patients receiving adjuvant chemotherapy (53%, 3.1% of all patients receiving adjuvant chemotherapy) were diagnosed within 180 days of starting adjuvant chemotherapy. Venous thromboembolism was an independent risk factor for worse 5-year overall survival (HR, 1.65; 95% CI, 1.43-1.91; p < 0.001).

LIMITATIONS: This study was limited by the potential for misclassification of venous thromboembolism and unknown compliance with prophylaxis recommendations.

CONCLUSION: Patients who undergo treatment for stage I to III colon cancer are at considerable risk of developing venous thromboembolism. The risk is elevated in those who require adjuvant chemotherapy, and venous thromboembolism is associated with worse long-term outcomes. There may be a role of venous thromboembolism prophylaxis during all phases of treatment, including both after surgery and during adjuvant chemotherapy. See Video Abstract at http://links.lww.com/DCR/B123. UN ESTUDIO DE COHORTE POBLACIONAL DE LAS TASAS DE TROMBOEMBOLISMO VENOSO DESPUÉS DE CIRUGÍA Y DURANTE QUIMIOTERAPIA ADYUVANTE EN PACIENTES CON CÁNCER DE COLON: Existe un riesgo elevado de tromboembolismo venoso en pacientes tratados por cáncer de colon. El tromboembolismo venoso postoperatorio se ha estudiado previamente, pero ningún estudio grande ha comparado los riesgos durante las diferentes etapas del tratamiento.Cuantificar y comparar los riesgos de tromboembolismo venoso antes de la cirugía, después de la cirugía, durante quimioterapia adyuvante y hasta 365 días después de cirugía en pacientes con cáncer de colon resecado.Estudio retrospectivo de cohorte poblacional.Escenario de atención médica universal con pagador único (Ontario) entre 2002-2008.6,806 pacientes con cáncer de colon en estadio I-III tratados con resección quirúrgica.Fase de tratamiento, incluyendo preoperatorio, hospitalización, postoperatorio, durante quimioterapia adyu[...]

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vante y 365 días después de la operación.Tromboembolismo venoso, tal como se define utilizando códigos de diagnóstico de fuentes de datos administrativos.Se incluyeron 6,806 pacientes, con 327 (5%) que desarrollaron tromboembolismo venoso. Los pacientes que recibieron quimioterapia adyuvante tuvieron un mayor riesgo en comparación con los pacientes con cirugía solamente (6% vs 4%, p <0.001).<0.001).potencial

PMID: 32045399 [PubMed - in process]

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[Updated recommendations for venous thromboembolic prophylaxis in Argentina].

Medicina (B Aires). 2020;80(1):69-80

Authors: Vazquez FJ, Korin J, Baldessari EM, Capparelli FJ, Gutierrez P, Pale C, Bocanegra F, Grand B, Vilaseca A, Penchasky D, González Alcantara MM, Prémoli MS, Tabares A, Wainsztein N, Odetto D, Vaccaro C, Martínez Aquino E, Cumpian O, Falabella V, García SA, Saadi J, Siccardi M, Gandara E

BACKGROUND: Venous thromboembolism is an important patient safety issue in thoracic surgery patients. The optimal enoxaparin dos

Abstract

BACKGROUND: Venous thromboembolism is an important patient safety issue in thoracic surgery patients. The optimal enoxaparin dose remains unclear. This multicenter pre/post clinical trial compared the pharmacokinetics of fixed versus weight-tiered enoxaparin, and their impact on 90-day venous thromboembolism and bleeding.

METHODS: Thoracic surgery patients were prospectively enrolled using a pre/post study design Cohort 1 received enoxaparin 40mg daily, and Cohort 2 received a weight-tiered regimen (<70kg

RESULTS: One hundred thirty one patients were prospectively enrolled, including 65 in the fixed dose and 66 in the weight-tiered cohort. No patient was lost to followup. Weight-tiered enoxaparin was not significantly more likely to produce adequate anticoagulation (peak anti-Factor Xa ≥0.3 IU/mL) when compared to fixed dose enoxaparin (44.3% vs. 48.2%, p=0.67). Weight-tiered enoxaparin was not more likely to avoid over-anticoagulation (peak aFXa ≥0.5 IU/mL) when compared to fixed dose enoxaparin (3.3% vs. 3.6%, p=1.00). The groups had no significant difference in trough anti-Factor Xa. Observed rates of 90-day symptomatic VTE and clinically relevant bleeding were low (0% and 3.1%, respectively) and were not significantly different between groups.

CONCLUSIONS: This multicenter pre/post clinical trial did not show a pharmacokinetic advantage to weight-tiered enoxaparin, when compared fixed dose enoxaparin, in thoracic surgery patients.

PMID: 32045583 [PubMed - as supplied by publisher]

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A Population-Based Cohort Study of Venous Thromboembolism Rates Following Surgery and During Adjuvant Chemotherapy in Patients With Colon Cancer.

Dis Colon Rectum. 2020 Mar;63(3):336-345

Authors: Patel SV, Zhang L, Wei XS, Merchant SJ, Nanji S, James PD, Booth CM

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the

Abstract

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall inci[...]

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sion(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.

PMID: 32042728 [PubMed]

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

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Fixed or weight-tiered enoxaparin after thoracic surgery for venous thromboembolism prevention.

Ann Thorac Surg. 2020 Feb 08;:

Authors: Pannucci CJ, Fleming KI, Bertolaccini C, Moulton L, Stringham J, Barnett S, Lin J, Varghese TK

Purpose: Testicular cancer survivors (TCSs) have increased risk of reduced kidney function related to treatment burden, but longitudinal studies

Abstract

Purpose: Testicular cancer survivors (TCSs) have increased risk of reduced kidney function related to treatment burden, but longitudinal studies of renal outcome in aging TCSs have been lacking. This longitudinal study describes age- and treatment-related kidney function changes in TCSs compared to a comparison group from the general population.Patients and methods: Estimated glomerular filtration rate (eGFR) was determined in blood samples from Norwegian TCSs (diagnosed 1980-1994) and surveyed median 11, 19 and 26 years since diagnosis (Survey1 [N = 1273], 2 [N = 849] and 3 [N = 670]) defining four treatment groups; Surgery only, Radiotherapy (RT) only, Cisplatin-based chemotherapy (CBCT) ≤850 mg and High CBCT/RT >850 mg cisplatin or any combination of CBCT with RT. A comparison group was constructed from similarly aged men who participated in a population-based health survey. By multiple linear regressions and generalized mixed models for repeated measurements, we studied difference in eGFR between TCSs and the Comparison Group for all TCSs combined and stratified by treatment modality.Results: At Survey 1, the kidney function for the youngest TCSs combined versus the Comparison Group was significantly reduced by mean six units (mL/min/1.73 m2) with further decline to mean 12 units at Survey 3. The kidney function was significantly reduced in all treatment groups with the largest differences emerging for TCSs from the High CBCT/RT Group, thus indicating a deteriorating impact of high cumulative doses of cisplatin.Conclusion: Collated to the Comparison Group, the kidney function in TCSs became increasingly impaired during nearly three post-treatment decades, related to the treatment modality. Early detection and intervention of kidney dysfunction is important to reduce the risk of TCSs' long-term morbidity and mortality related to nephrotoxicity, such as cardio-vascular diseases.

PMID: 32043400 [PubMed - as supplied by publisher]

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International expert consensus on the management of bleeding during VATS lung surgery.

Ann Transl Med. 2019 Dec;7(23):712

Authors: Liu L, Mei J, He J, Demmy TL, Gao S, Li S, He J, Liu Y, Huang Y, Xu S, Hu J, Chen L, Zhu Y, Luo Q, Mao W, Tan Q, Chen C, Li X, Zhang Z, Jiang G, Xu L, Zhang L, Fu J, Li H, Wang Q, Liu D, Tan L, Zhou Q, Fu X, Jiang Z, Chen H, Fang W, Zhang X, Li Y, Tong T, Yu Z, Liu Y, Zhi X, Yan T, Zhang X, Pu Q, Che G, Lin Y, Ma L, Embun R, Aragón J, Evman S, Kocher GJ, Bertolaccini L, Brunelli A, Gonzalez-Rivas D, Dunning J, Liu HP, Swanson SJ, Borisovich RA, Sarkaria IS, Sihoe ADL, Nagayasu T, Miyazaki T, Chida M, Kohno T, Thirugnanam A, Soukiasian HJ, Onaitis MW, Liu CC, International Interest Group on Bleeding during VATS Lung Surgery

Ponatinib is associated with cardiovascular adverse events (CAEs), and its frequency in the real world is limited. In this retrospective study

Abstract

Ponatinib is associated with cardiovascular adverse events (CAEs), and its frequency in the real world is limited. In this retrospective study, we examined the survival outcomes and associated toxicities in 78 consecutive ponatinib-treated patients with chronic myeloid leukemia (CML) at the Moffitt Cancer Center from January 2011 through December 2017. The most common non-CAE was thrombocytopenia (39.7%), occurring in a dose-dependent fashion. Eighteen patients (23.1%) experienced some form of CAE, with the most common being arrhythmia (9%) and hypertension (7.7%), whereas 3 patients experienced myocardial infarction (3.8%). Before 2014, most patients were started on ponatinib 45 mg daily. There was an inverse correlation between cardio-oncology referral and the number of CAEs (P = .0440); however, a lower ponatinib starting dose, more frequent dose reduction, and increased cardio-oncology referral all were likely to have contributed to the observed decrease in CAEs after 2014. The response rate and 5-year overall survival (OS) were higher than those observed in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial (major molecular response, 58.7% vs 40% and OS, 76% vs 73%; median follow-up of 32.5 months). Ponatinib-treated patients with chronic phase-CML did not show a significant improvement with allogeneic stem cell transplantation, whereas those with accelerated phase/blast phase-CML had a much better outcome (median OS of 32.9 months vs 9.2 months; P = .01). These results demonstrate that ponatinib is highly effective. Dose adjustments and increased awareness of the cardiotoxicities associated with ponatinib may help maximize its benefits.

PMID: 32045474 [PubMed - in process]

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Longitudinal kidney function outcome in aging testicular cancer survivors.

Acta Oncol. 2020 Feb 11;:1-8

Authors: Nome RV, Småstuen MC, Bjøro T, Kiserud CE, Fosså SD

Doxorubicin (DOX) is a potent anticancer agent that binds both DNA and cardiolipin (CL). To investigate DOX binding to CL versus DNA

Abstract

Doxorubicin (DOX) is a potent anticancer agent that binds both DNA and cardiolipin (CL). To investigate DOX binding to CL versus DNA, aqueous soluble, CL-enriched nanoparticles, termed nanodisks (ND), were employed. Upon incubation with CL-ND, but not with phosphatidylcholine ND, DOX binding was detected. DOX binding to CL-ND was sensitive to buffer pH and ionic strength. To investigate if a DOX binding preference for DNA versus CL-ND exists, an agarose gel-based dye binding assay was developed. Under conditions wherein the commercial fluorescent dye, GelRed, detects a 636 bp DNA template following electrophoresis, DOX staining failed to visualize this DNA band. Incubation of the template DNA with DOX prior to electrophoresis resulted in a DOX concentration-dependent attenuation of GelRed staining intensity. When the template DNA was pre-incubated with equivalent amounts of free DOX or DOX-CL-ND, no differences in the extent of GelRed staining intensity attenuation were noted. When DOX was incubated with DNA alone, or a mixture of DNA and CL-ND, the extent of DOX-induced GelRed staining intensity attenuation was equivalent. Thus, DOX has a binding preference for DNA versus CL and, moreover, DOX-CL-ND offer a potential strategy to prevent DOX-induced cardiotoxicity while not affecting its affinity for DNA.

PMID: 32045568 [PubMed - as supplied by publisher]

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Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia.

Blood Adv. 2020 Feb 11;4(3):530-538

Authors: Chan O, Talati C, Isenalumhe L, Shams S, Nodzon L, Fradley M, Sweet K, Pinilla-Ibarz J

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombus extending into the inferior vena cava (IVC) occurs in 4%-10% of cases

Abstract

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombus extending into the inferior vena cava (IVC) occurs in 4%-10% of cases. Within this subset, pulmonary tumor embolism (PTE) appears in approximately 0.9%-2.4% of cases. We wanted to review our experience in managing patients with RCC with IVC involvement and a preoperative diagnosis of PTE.

METHODS: A total of seven patients presented at our center between January, 2005 and January, 2015 with RCC, IVC involvement, and PTE (diagnosed either by chest computerized tomography angiography or preoperative transesophageal echocardiogram). Each patient underwent a radical nephrectomy and tumor thrombectomy using an organ transplant-based approach.

RESULTS: Surgical removal of the PTE was performed in three patients (tumor embolectomy in two cases, right lower lobe resection in one case); the PTEs in four patients were considered to be too small to undergo surgical resection. PTE pathology found neoplastic cells in each patient that had surgical removal. No postoperative complications were observed in any of the seven patients. All four patients who were metastasis-free preoperatively (with 2/4 having tumor embolectomy performed) developed distant metastasis; median time-to-developing metastatic disease was 6.5 months. With a median follow-up of 19 months, three deaths because the disease have occurred.

CONCLUSION: Although RCC with IVC tumor thrombus complicated by PTE may not be catastrophic in most cases, it appears to be associated with an increased risk of developing metastatic disease. In addition, as the PTEs appear to contain neoplastic cells, pulmonary artery embolectomy at the time of nephrectomy should be performed whenever possible.

PMID: 31376225 [PubMed - indexed for MEDLINE]

12 February 2020

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

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Dye binding assay reveals doxorubicin preference for DNA versus cardiolipin.

Anal Biochem. 2020 Feb 08;:113617

Authors: Fox CA, Ryan RO

BACKGROUND: Curettage is widely used in orthopedic oncology; the defect created frequently requires filling for mechanical and functional stability

Abstract

BACKGROUND: Curettage is widely used in orthopedic oncology; the defect created frequently requires filling for mechanical and functional stability for the bones and adjacent joint. Allograft, bone graft substitute, and polymethyl methacrylate (PMMA) are the most common substances used each with their benefits and drawbacks. The aim of the study is to show that good functional result can be achieved with curettage and bone filler, regardless of type.

METHODS: A series of 267 cases were reviewed between 1994 and 2015 who received curettage treatment and placement of a bone filler. Endpoints included fracture, infection, cellulitis, pulmonary embolism, and paresthesia. Complication rates at our single institution were compared against literature values for three study cohorts: allograft, bone graft substitute, and PMMA bone fillers. Friedman test, Wilcoxon test, and Z-score for two populations were used to compare our subset against literature values and between different bone filling types.

RESULTS: Our cases included 18 autografts, 74 allografts, 121 bone graft substitute, and 54 PMMA of which the bulk of complications occurred. Our overall complication rate was 3.37%. Allograft has a complication rate of 1.35%, bone graft substitute of 4.13%, and PMMA of 5.56%. Other techniques did not yield any complications. Combination filling techniques PMMA + allograft and PMMA + bone graft substitute had sample sizes too small for statistical comparison. Statistical comparison yielded no significant difference between complications in any of the filling groups (P = 0.411).

CONCLUSIONS: Some has even argued that bone defects following curettage do not require bone filling for good outcome. However, many structural or biologic benefits that aid in earlier return to functionality can be conferred by filling large bone defects. There was no significant difference in postoperative complication rates between allograft, bone graft substitute, and PMMA when compared at our institution and with literature values. Nevertheless, one complication with a large defect filled with allograft, requiring a subsequent reconstruction using vascularized fibular graft. Taking everything into account, we see bone graft substitute as a suitable alternative to other bone filling modalities.

PMID: 31419993 [PubMed - indexed for MEDLINE]

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Pulmonary tumor embolization as early manifestation in patients with renal cell carcinoma and tumor thrombus: Perioperative management and outcomes.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Pulmonary tumor embolization as early manifestation in patients with renal cell carcinoma and tumor thrombus: Perioperative management and outcomes.

J Card Surg. 2019 Oct;34(10):1018-1023

Authors: Serena G, Gonzalez J, Gaynor JJ, Salerno T, Verzaro R, Ciancio G

BACKGROUND: Multiple myeloma is a hematologic malignancy which confers a high venous thromboembolic risk. This risk

Abstract

BACKGROUND: Multiple myeloma is a hematologic malignancy which confers a high venous thromboembolic risk. This risk is linked to patient-related factors, disease-specific mechanisms, and antimyeloma therapy, especially immunomodulatory drugs. Some studies have suggested that the thrombin generation assay may be a predictive marker of thrombosis. This study aimed to assess the hypercoagulable state in patients with multiple myeloma at diagnosis and after myeloma therapy.

METHODS: Thirty-one patients with multiple myeloma were included in a prospective study and were compared with 31 matched controls with age and gender. Thrombin generation assay was performed in patients at diagnosis prior to treatment initiation and at the end of myeloma therapy, and in controls. Parameters of lag time, peak thrombin concentration, time to peak, endogenous thrombin potential, and velocity index were analyzed.

RESULTS: Median age of patients at diagnosis was 58 years (11 men and 20 women). Twenty-three patients (74%) were classified as high vascular risk and received thromboprophylaxis. No thromboembolic events have been reported during follow-up, except a symptomatic pulmonary embolism in one patient which occurred at diagnosis. At baseline, patients with myeloma had significantly elevated velocity index as compared to controls (178 vs 128 nmol/L/min; P = .013). High-risk patients showed an elevation of plasma thrombin generation as compared to low-risk patients (endogenous thrombin potential = 1244 vs 1052 nmol/L/min; P = .043). Myeloma therapy did not significantly change the thrombin generation parameters.

CONCLUSION: Thrombin generation appears to be higher in patients with myeloma compared with controls, especially in high-risk patients, and does not change significantly after treatment completion.

PMID: 31421013 [PubMed - indexed for MEDLINE]

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Early postoperative compilations of bone filling in curettage defects.

//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

Early postoperative compilations of bone filling in curettage defects.

J Orthop Surg Res. 2019 Aug 16;14(1):261

Authors: Chen CJ, Brien EW

BACKGROUND: Pulmonary hamartoma is one of the most common benign tumors of the lung, the symptoms are often atypical, so its

Abstract

BACKGROUND: Pulmonary hamartoma is one of the most common benign tumors of the lung, the symptoms are often atypical, so its diagnosis is not so easy. We presented an elderly man with elevated D-dimer combined persistent acupuncture-like chest pain misdiagnosed as pulmonary embolism finally proved as lung hamartoma with secondary lung infection by bronchoscopy biopsy.

METHODS: Appropriate laboratory tests were carried out. The chest computed tomography (CT) scan and bronchoscopy were performed for diagnosis.

RESULTS: Laboratory tests showed D-dimer was 2,615.88 ng/mL, the chest CT scan showed the right lung portal occupying lesions accompanied by obstructive changes in the middle of the right lung and mediastinal lymphade-nopathy with partial calcification. Bronchoscopy showed the new spherical neoplasm in the middle of the right lung completely blocked the opening of the bronchus, the surface of the neoplasm was smooth and blood vessels were abundant, pathological result was lung hamartoma.

CONCLUSIONS: Elevated D-dimer is not a specific index of pulmonary embolism. When a patient's D-dimer rise combined with severe chest pain, the physician should be wary of pulmonary embolism, myocardial infarction, aortic dissection, and other emergencies, and should also take into account serious infections, tumors, and other diseases. Diagnosis needs further related examination. Chest CT scan has guidance function, and when the chest CT scan suggests the occupying lesion, the pathology examination is the key to identify the benign tumor.

PMID: 31532091 [PubMed - indexed for MEDLINE]

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The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test.

Int J Lab Hematol. 2019 Oct;41(5):684-690

Authors: Baccouche H, Hadhri M, Aissi W, Chakroun A, Bahri D, Mahjoub S, Ben Romdhane N

Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify

Abstract

Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.

PMID: 32039023 [PubMed]

16:13

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

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End of an era for erythropoiesis stimulating agents in oncology.

Int J Cancer. 2020 Feb 09;:

Authors: Schoen MW, Hoque S, Witherspoon BJ, Schooley B, Sartor O, Yang AT, Yarnold PR, Knopf KB, Hrushesky WR, Dickson M, Chen BJ, Nabhan C, Bennett CL

Abstract

Erythropoiesis stimulating agents (ESAs) are available to treat chemotherapy-induced anemia (CIA). In 2007-2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin <10

PMID: 32037527 [PubMed - as supplied by publisher]

16:13

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Elevated D-Dimer Combined with Persistent Acupuncture-like Chest Pain in An Elderly Patient Misdiagnosed as Pulmonary Embolism Finally Proved as Lung Hamartoma with Secondary Lung Infection by Bronchoscopy Biopsy: a Case Report and Literature Review.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.clin-lab-publications.com-assets-PubMed.png Related Articles

Clin Lab. 2019 Sep 01;65(9):

Authors: Chen Y, Li LQ, Wang MH, Li WQ, Zhang Q, Zhang HF, Ge YL

We report a metal-free and stereoselective four-component reaction between α-ketoamides, amines, aromatic aldehydes and β-nitroalkenes

Abstract

We report a metal-free and stereoselective four-component reaction between α-ketoamides, amines, aromatic aldehydes and β-nitroalkenes or β-pivaloxy-nitroalkanes to obtain 2,3-dihydro-4-nitropyrroles functionalized in every position. The heterocycles accessible using this reaction may have utility in the synthesis of pharmacologically active compounds.

PMID: 32039135 [PubMed]

13:03

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The Multi-Modal Effect of the Anti-fibrotic Drug Pirfenidone on NSCLC.

Front Oncol. 2019;9:1550

Authors: Marwitz S, Turkowski K, Nitschkowski D, Weigert A, Brandenburg J, Reiling N, Thomas M, Reck M, Drömann D, Seeger W, Rabe KF, Savai R, Goldmann T

Novel anticancer medicines, including targeted therapies and immune checkpoint inhibitors, have greatly improved the management of cancers

Abstract

Novel anticancer medicines, including targeted therapies and immune checkpoint inhibitors, have greatly improved the management of cancers. However, both conventional and new anticancer treatments induce cardiac adverse effects, which remain a critical issue in clinic. Cardiotoxicity induced by anti-cancer treatments compromise vasospastic and thromboembolic ischemia, dysrhythmia, hypertension, myocarditis, and cardiac dysfunction that can result in heart failure. Importantly, none of the strategies to prevent cardiotoxicity from anticancer therapies is completely safe and satisfactory. Certain clinically used cardioprotective drugs can even contribute to cancer induction. Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol. We hope to provoke further drug development studies considering these GPCRs as potential targets to be translated to treatment of human heart failure induced by anticancer drugs.

PMID: 32039239 [PubMed]

13:03

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Stereoselective Four-Component Synthesis of Functionalized 2,3-Dihydro-4-Nitropyrroles.

Front Chem. 2019;7:810

Authors: Wang D, Ma X, Dong L, Feng H, Yu P, Désaubry L

PURPOSE: To use delayed enhancement cardiac magnetic resonance (DE-CMR) as a reference standard to evaluate the prevalence and

Abstract

PURPOSE: To use delayed enhancement cardiac magnetic resonance (DE-CMR) as a reference standard to evaluate the prevalence and predictors of right atrial (RA) thrombus.

METHODS: In this retrospective study, 130 cancer patients with central venous catheters undergoing CMR from August 2012-January 2018 were included. CMR (cine-CMR and DE-CMR) and echocardiography were interpreted for RA thrombus blinded to other imaging results and clinical data. RA thrombus properties including the number of discrete masses, size, total thrombus area, and perimeter were also assessed. Cine-CMR was also used to quantify cardiac structure and function as markers of RA thrombus. Student's t-test was used to assess continuous variables; chi-square or Fisher's exact test were used to assess categorical variables.

RESULTS: 31/130 (24%) patients had RA thrombus on DE-CMR. Echocardiography (attained in 64% of the study population) demonstrated moderate sensitivity and specificity (75%, 90% respectively) in relation to DE-CMR; cine-CMR performance was higher (sensitivity 90%, specificity 98%). Patients with and without RA thrombus had similar right-sided structure/function and cancer diagnosis. Catheter depth approached significance in patients with RA thrombus (p = 0.05). 13% of patients with RA thrombus had concomitant pulmonary embolism within 60 days of CMR vs. 2% of patients without RA thrombus (p = 0.03). Embolic events were independent of RA thrombus size (p = 0.66).

CONCLUSION: Morphologic imaging by cine-CMR and echocardiography provide limited diagnostic utility for RA thrombus as established by DE-CMR tissue characterization. Catheter-associated RA thrombus occurs independently of right-sided structure or function and is associated with clinical embolic events and catheter depth.

PMID: 32036237 [PubMed - as supplied by publisher]

14:19

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Interobserver agreement of 18F-Fluorodeoxyglucose Positron-Emission Tomography combined with low-dose Computed Tomography for occult cancer screening in patients with unprovoked venous thromboembolism.

Thromb Res. 2020 Jan 30;188:25-27

Authors: Robin P, Grewal RK, Le Roux PY, Le Gal G, Salaun PY

PMID: 32036158 [PubMed - as supplied by publisher]

15:48

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

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Non-Invasive Hemodynamic Whole-Body Bioimpedance Indices for the Early Detection of Cancer Treatment-Related Cardiotoxicity: A Retrospective Observational Study.

Cardiology. 2020 Feb 07;:1-6

Authors: Schamroth Pravda N, Lev S, Itzhaki Ben Zadok O, Kornowski R, Iakobishvili Z

Abstract

INTRODUCTION: Patients undergoing chemotherapy are extremely vulnerable to cardiotoxicity. Early detection of cardiac dysfunction is of vital importance to optimize the management of these patients.

OBJECTIVE: The aim of this study was to test the effectiveness of non-invasive hemodynamic whole-body bioimpedance (WBI) technology as a modality to detect heart failure in patients undergoing chemotherapy treatment.

METHODS: This retrospective observational trial included 84 patients treated at the cardio-oncology outpatient clinic of the Rabin Medical Center. Clinical assessments were performed including biomarker testing and measurement of hemodynamic and volume status parameters as measured by WBI.

RESULTS: We included 84 patients with a median age of 64.8 years, and 40.5% were males. Clinical heart failure was detected in 43% of the whole group. Patients were divided into two groups according to baseline NT-proBNP levels with a cut-off of 900 pg/mL. Left ventricular ejection fraction did not differ between the groups. Those with NT-proBNP >900 pg/mL had lower levels of stroke index, cardiac index, and Granov-Goor index (GGI; 25.9 vs. 34.0, 2.0 vs. 2.3, 8.3 vs. 11.4, respectively, with p < 0.001 for all comparisons). The optimal cut-off value for the GGI to detect NT-proBNP >900 pg/mL was 8.3. The area under the curve of a GGI cut-off <8.3900 pg/mL was 0.81 (positive predictive value 95% and negative predictive value 72%), with a 51% sensitivity and 98% specificity.

CONCLUSION: GGI, a parameter measured by WBI, can reliably correlate to biomarker evidence of heart failure in patients after chemotherapy. Its use as a screening tool for cardiotoxicity in patients with ongoing anticancer therapy is promising.

PMID: 32036358 [PubMed - as supplied by publisher]

11 February 2020

13:03

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

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Targeting GPCRs Against Cardiotoxicity Induced by Anticancer Treatments.

Front Cardiovasc Med. 2019;6:194

Authors: Audebrand A, Désaubry L, Nebigil CG

Doxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer

Abstract

Doxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer survival rates, doxorubicin is cardiotoxic and can lead to congestive heart failure. Therapeutic options for this patient group are limited to standard heart failure medications with the only drug specific for doxorubicin cardiotoxicity to reach FDA approval being dexrazoxane, an iron-chelating agent targeting oxidative stress. However, dexrazoxane has failed to live up to its expectations from preclinical studies while also bringing up concerns about its safety. Despite decades of research, the molecular mechanisms of doxorubicin cardiotoxicity are still poorly understood and oxidative stress is no longer considered to be the sole evil. Mitochondrial impairment, increased apoptosis, dysregulated autophagy and increased fibrosis have also been shown to be crucial players in doxorubicin cardiotoxicity. These cellular processes are all linked by one highly conserved intracellular kinase: adenosine monophosphate-activated protein kinase (AMPK). AMPK regulates mitochondrial biogenesis via PGC1α signalling, increases oxidative mitochondrial metabolism, decreases apoptosis through inhibition of mTOR signalling, increases autophagy through ULK1 and decreases fibrosis through inhibition of TGFβ signalling. AMPK therefore sits at the control point of many mechanisms shown to be involved in doxorubicin cardiotoxicity and cardiac AMPK signalling itself has been shown to be impaired by doxorubicin. In this review, we introduce different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and we discuss the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity.

PMID: 32034646 [PubMed - as supplied by publisher]

10 February 2020

14:19

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

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Diagnostic utility and clinical implication of late gadolinium enhancement cardiac magnetic resonance for detection of catheter associated right atrial thrombus.

Clin Imaging. 2020 Jan 29;62:17-22

Authors: Plodkowski AJ, Chan A, Gupta D, Lakhman Y, Kukar N, Kim J, Perez-Johnston R, Ginsberg MS, Steingart RM, Weinsaft JW

Venous thromboembolism (VTE), comprising deep-vein thrombosis and pulmonary embolism, is a frequent complication in ambulatory cance

Abstract

Venous thromboembolism (VTE), comprising deep-vein thrombosis and pulmonary embolism, is a frequent complication in ambulatory cancer patients. Despite the high risk, routine thromboprophylaxis is not recommended because of the high number needed to treat and the risk of bleeding. Two recent trials demonstrated that the number needed to treat can be reduced by selecting cancer patients at high risk for VTE with prediction scores, leading the latest guidelines to suggest such an approach in clinical practice. Yet, the interpretation of these trial results and the translation of the guideline recommendations to clinical practice may be less straightforward. In this clinically-oriented review, some of the controversies are addressed by focusing on the burden of VTE in cancer patients, discussing the performance of available risk assessment scores, and summarizing the findings of recent trials. This overview can help oncologists, hematologists, and vascular medicine specialists decide about thromboprophylaxis in ambulatory cancer patients.

PMID: 32033438 [PubMed]

14:48

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

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The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity.

Cardiovasc Drugs Ther. 2020 Feb 08;:

Authors: Timm KN, Tyler DJ

OBJECTIVES: To perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying

Abstract

OBJECTIVES: To perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).

METHODS: An SLR of observational studies comparing safety outcomes of any DMARD with another intervention for the management of RA. A comparator group was required for inclusion. For treatments still without registry data (eg, sarilumab and the Janus kinase (JAK) inhibitors baricitinib, upadacitinib), randomised controlled trials (RCTs) and long-term extensions (LTEs) were used. Risk of bias (RoB) was assessed according to standard procedures.

RESULTS: Forty-two observational studies fulfilled the inclusion criteria, addressing safety outcomes with bDMARDs and sDMARDs. Nine studies showed no difference in the risk of serious infections across bDMARDs and two studies (high RoB) showed an increased risk with bDMARDs compared with conventional synthetic (cs) DMARDs (adjusted incidence rate ratio 3.1-3.9). The risk of Herpes zoster infection was similar across bDMARDs, but one study showed an increased risk with tofacitinib compared with abatacept (adjusted HR (aHR) 2.0). Five studies showed no increased risk of cancer for bDMARDs compared with csDMARDs. An increased risk of lower intestinal perforation was found for tocilizumab compared with csDMARDs (aHR 4.5) and tumour necrosis factor inhibitor (TNFi) (aHR 2.6-4.0). Sixty manuscripts reported safety data from RCTs/LTEs. Overall, no unexpected safety outcomes were found, except for the possibly increased risk of venous thromboembolism (VTE) with JAK inhibitors.

CONCLUSION: Data obtained by this SLR confirm the known safety profile of bDMARDs. The risk of VTE in RA, especially in patients on JAK inhibitors, needs further evaluation.

PMID: 32033941 [PubMed - as supplied by publisher]

13:26

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Primary Thromboprophylaxis in Ambulatory Cancer Patients: Where Do We Stand?

Cancers (Basel). 2020 Feb 05;12(2):

Authors: Mulder FI, Bosch FTM, van Es N

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune

Abstract

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.

OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.

METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death.

RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001).< 0.001).

CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

PMID: 32029128 [PubMed - in process]

9 February 2020

13:26

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

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Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis.

Ann Rheum Dis. 2020 Feb 07;:

Authors: Sepriano A, Kerschbaumer A, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, McInnes IB, Bijlsma JW, Burmester GR, de Wit M, Falzon L, Landewé R

Digoxin, a compound of the cardiac glycoside family, was originally prescribed for heart failure but has recently been rediscovered for its potent

Abstract

Digoxin, a compound of the cardiac glycoside family, was originally prescribed for heart failure but has recently been rediscovered for its potent antitumor activity. However, it has a narrow therapeutic margin due to its cardiotoxicity, limiting its safe use as an antitumor agent in clinical practice. To widen its therapeutic margin, we investigated whether the antitumor effect of digoxin is potentiated by the depletion of BCL-2-interacting cell death suppressor (BIS) in A549 lung cancer cells. BIS is a multifunctional protein that is frequently overexpressed in most human cancers including lung cancer. Our results demonstrated that the inhibitory potential of digoxin on the migratory behavior of A549 cells is significantly enhanced by BIS depletion as assessed by transwell assay and collagen-incorporated 3D spheroid culture. Western blotting revealed that combination treatment significantly reduces p-STAT3 expression. In addition, a STAT3 inhibitor substantially suppressed the aggressive phenotypes of A549 cells. Thus, our results suggest that loss of STAT3 activity is a possible molecular mechanism for the synergistic effect of digoxin and BIS depletion. Our findings suggest the sensitizing role of BIS silencing to reduce the dose of digoxin for treatment of lung cancer with a high metastatic potential.

PMID: 32029272 [PubMed - as supplied by publisher]

14:15

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Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

J Am Coll Cardiol. 2020 Feb 11;75(5):467-478

Authors: Awadalla M, Mahmood SS, Groarke JD, Hassan MZO, Nohria A, Rokicki A, Murphy SP, Mercaldo ND, Zhang L, Zlotoff DA, Reynolds KL, Alvi RM, Banerji D, Liu S, Heinzerling LM, Jones-O'Connor M, Bakar RB, Cohen JV, Kirchberger MC, Sullivan RJ, Gupta D, Mulligan CP, Shah SP, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Lawrence DP, Mahmoudi M, Devereux RB, Forrestal BJ, Mandawat A, Lyon AR, Chen CL, Barac A, Hung J, Thavendiranathan P, Picard MH, Thuny F, Ederhy S, Fradley MG, Neilan TG

BACKGROUND: Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most

Abstract

BACKGROUND: Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the cardiovascular diseases, after coronary artery disease and stroke. The advent of multi-detector computed tomographic pulmonary angiography (CTPA) has allowed better assessment of PE regarding visualisation of the peripheral pulmonary arteries, increasing its rate of diagnosis. More cases of peripheral PEs, such as isolated subsegmental PE (SSPE) and incidental PE, have thereby been identified. These two conditions are usually found in patients with few or none of the classic PE symptoms such as haemoptysis or pleuritic pain, acute dyspnoea or circulatory collapse. However, in patients with reduced cardiopulmonary reserve, classic PE symptoms can be found with isolated SSPEs. Incidental SSPE is found casually in asymptomatic patients, usually by diagnostic imaging performed for other reasons (for example routine CT for cancer staging in oncology patients). Traditionally, all PEs are anticoagulated in a similar manner independent of their location, or number and size of the thrombi. It has been suggested that many patients with SSPE may be treated without benefit, increasing adverse events by a possible unnecessary use of anticoagulants. Patients with isolated SSPE, or incidental PE, may have a more benign clinical presentation compared to those with proximal PEs. However, the clinical significance in patients, and their prognosis, needs to be studied to evaluate whether anticoagulation therapy is required. This is the second update of the Cochrane systematic review published in 2014.

OBJECTIVES: To assess the effectiveness and safety of anticoagulation therapy versus control in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE.

SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 November 2019. We also undertook reference checking to identify additional studies.

SELECTION CRITERIA: We included randomised controlled trials of anticoagulation therapy versus control in patients with SSPE or incidental SSPE.

DATA COLLECTION AND ANALYSIS: Two review authors inspected all citations identified to ensure reliable assessment. If relevant studies were identified, we planned for two review authors to independently extract data and to assess the methodological quality of identified trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions.

MAIN RESULTS: We did not identify any studies that met the inclusion criteria.

AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials to assess the effectiveness and safety of anticoagulation therapy versus control in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE. Well-conducted research is required before informed practice decisions can be made.

PMID: 32030721 [PubMed - in process]

14:15

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

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Downregulation of BIS sensitizes A549 cells for digoxin-mediated inhibition of invasion and migration by the STAT3-dependent pathway.

Biochem Biophys Res Commun. 2020 Feb 04;:

Authors: Yun HH, Kim S, Kuh HJ, Lee JH

BACKGROUND: Limited biomarkers are used for predicting risk of venous thromboembolism (VTE) associated with cancer. Circulating

Abstract

BACKGROUND: Limited biomarkers are used for predicting risk of venous thromboembolism (VTE) associated with cancer. Circulating microparticles (MPs), especially tissue factor- positive microparticles (TF+MPs), play an important role in the development of cancer-associated VTE. This study investigated the predictive value of plasma MPs and TF+MPs for VTE in lung cancer.

METHODS: A case control study was performed using the Beijing Chao-Yang Hospital Lung Cancer Registry. Cases had VTE occurring 3 months before or after a diagnosis of lung cancer. Controls were patients with lung cancer without VTE matched for age, histology, and stage. The proportion of MPs and TF+MPs was evaluated by light-scatter-based flow cytometry.

RESULTS: Between January 2012 and December 2015, 30 case with VTE and 60 controls without VTE were included. The proportion of MPs and TF+MPs was significantly more elevated in patients with VTE than in those without VTE (P <0.05<0.001)<0.001)<0.001),

CONCLUSION: The elevated proportion of MPs and TF+MPs might help predict VTE associated with lung cancer.

PMID: 32031323 [PubMed - as supplied by publisher]

12:55

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Anticoagulant treatment for subsegmental pulmonary embolism.

Cochrane Database Syst Rev. 2020 Feb 07;2:CD010222

Authors: Yoo HH, Nunes-Nogueira VS, Fortes Villas Boas PJ

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

PMID: 32026180 [PubMed - as supplied by publisher]

13:27

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An Incorrect Impression of Dose Versus the Ischemic Cardiac Toxicity Risk Profile for Breast and Chest Wall Radiation Therapy.

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

An Incorrect Impression of Dose Versus the Ischemic Cardiac Toxicity Risk Profile for Breast and Chest Wall Radiation Therapy.

Int J Radiat Oncol Biol Phys. 2020 02 01;106(2):451-452

Authors: Sarkar B

PMID: 31928645 [PubMed - indexed for MEDLINE]

8 February 2020

12:55

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

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High concentration of the plasma microparticles for venous thromboembolism associated with lung cancer.

Clin Respir J. 2020 Feb 07;:

Authors: Wang M, Huang X, Zhu M, Zhang S, Zhang Y

Over the past few decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result

Abstract

Over the past few decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, there are an increasing number of children who are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades after treatment. These problems are serious enough that all caregivers of childhood cancer survivors, including oncologists, cardiologists, and other health care personnel, must pay close attention to the short- and long-term effects of chemotherapy and radiotherapy on these children. This review discusses the effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy and the methods for preventing, screening, and treating these complications.

PMID: 32026204 [PubMed - as supplied by publisher]

13:26

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Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib.

Heart Fail Rev. 2020 Feb 05;:

Authors: Casavecchia G, Galderisi M, Novo G, Gravina M, Santoro C, Agricola E, Capalbo S, Zicchino S, Cameli M, De Gennaro L, Righini FM, Monte I, Tocchetti CG, Brunetti ND, Cadeddu C, Mercuro G

Pulmonary arterial intimal sarcoma is a rare tumour with high mortality. Due to its localisation, the symptoms can mimic pulmonary

Abstract

Pulmonary arterial intimal sarcoma is a rare tumour with high mortality. Due to its localisation, the symptoms can mimic pulmonary thromboembolism and pneumonia, therefore assessing the diagnosis and choosing the adequate therapy is never easy. Its therapy mainly consists of surgery combined with radiochemotherapy. A 46-year-old male patient with testicular seminoma, pulmonary embolism, bronchial asthma and pollen allergy in his history had a follow-up thoracic CT. On the left side of the lung, a pleura-infiltrating 7-8 cm lesion, which occluded the pulmonary artery, was described. The first biopsy specimen showed fragments of spindle cell tumour. The primary diagnosis was leiomyoma, leiomyomatous hyperplasia, yet the presence of leiomyosarcoma could not have been ruled out. Due to the arterial obstruction, the patient underwent left sided pulmonectomy. Histological examination showed a tumour mostly composed of spindle cells that were diffusely positive with SMA, focally diffuse with MDM2 immunohistochemistry together with high proliferation activity. h-Caldesmon, S-100, ERG and pancytokeratin expressions were not detected. With fluorescent in situ hybridization 10% of tumour cells showed polysomy and MDM2 amplification. According to the results, high-grade pulmonary arterial intimal sarcoma diagnosis has been made. The precise incidence of pulmonary arterial intimal sarcoma is unknown. Some literature data suggest it can be the cause of chronic pulmonary hypertension in 1-4% of the cases. Weight loss can draw attention to the malignant nature of the disease. Imaging techniques and histology are the gold standard in setting the diagnosis. The prognosis is poor. Early recognition and surgery combined with chemotherapy can prolong survival. Orv Hetil. 2020; 161(6): 232-236.

PMID: 32008347 [PubMed - indexed for MEDLINE]

13:26

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

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Cardiovascular diseases in survivors of childhood cancer.

Cancer Metastasis Rev. 2020 Feb 06;:

Authors: Bansal N, Blanco JG, Sharma UC, Pokharel S, Shisler S, Lipshultz SE

BACKGROUND: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC)

Abstract

BACKGROUND: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC) being the strongest risk factor. Current tools are not sufficient to predict VTE risk. The utility of biomarkers in predicting CVC-related VTE has been minimally explored. Our objective is to determine the utility of microparticles (MPs), factor VIII (FVIII) activity, and thrombin generation (TG) in prospectively predicting VTE occurrence in hospitalized children with CVCs.

PROCEDURE: In this nested case-control pilot study, consecutive hospitalized children needing CVC placement (1 month to 21 years) were enrolled. Venous samples were collected prior to or within 24 h of CVC placement. MPs were measured using factor Xa initiated clot-based assay. FVIII was measured using a one-stage clot-based assay. TG was measured using calibrated automated thrombogram.

RESULTS: There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07 vs 0.95 ± 0.21, P = .4), while FVIII (461 ± 120 vs 267 ± 130, P = .02), peak thrombin (418 ± 89 vs 211 ± 101, P = .001), endogenous thrombin potential (ETP) (1828 ± 485 vs 1282 ± 394, P = .03), and velocity index (VI) (182 ± 28 vs 75 ± 53, P = .001) were higher in subjects with CVC-related VTE compared to those without CVC-related VTE. Sensitivity/specificity analysis revealed optimal cutoff values for XaCT ratio (0.75), FVIII (370), ETP (1680), peak (315), and VI (130), with receiver operating characteristic area under the curve values >0.9.

CONCLUSION: MPs, FVIII, and TG can potentially predict pediatric CVC-related VTE in a prospective fashion. Stratification according to VTE risk may aid in guiding preventative efforts in future studies.

PMID: 31222954 [PubMed - indexed for MEDLINE]

7 February 2020

12:05

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

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[Intimal sarcoma of pulmonary arteries].

Orv Hetil. 2020 Feb;161(6):232-236

Authors: Sejben A, Tiszlavicz L, Furák J, Boros K, Sápi Z, Zombori T

OBJECTIVE: To examine the association between perioperative red blood cell (RBC) transfusion and postoperative venous thromboembolism (VTE

Abstract

OBJECTIVE: To examine the association between perioperative red blood cell (RBC) transfusion and postoperative venous thromboembolism (VTE) in pediatric surgical patients.

METHODS: Retrospective cohort study using the National Surgical Quality Improvement Project Pediatric, a validated registry of 118 United States children's hospitals. Patients under 19 years of age undergoing a surgical procedure between 2012 and 2017 were included, with the main exposure being RBC transfusion in the perioperative period (48 hours prior to operation to 72 hours after operation). The primary 30-day outcome of interest was a postoperative VTE requiring therapy. Risk-adjusted odds ratios (aOR) were calculated using multiple logistic regression. Subgroup analyses were performed across multiple surgical specialties. Sensitivity analyses were performed after (a) imputation for missing variables and (b) propensity score matching.

RESULTS: During the study years, 482 867 pediatric patients (56.7% male; median age, 6 years [interquartile range, 1-12 years]) underwent an operation. Of these, 30 879 (6.4%) received at least one perioperative RBC transfusion. Postoperative VTE requiring therapy occurred in 618 patients (0.13%). After adjustment for multiple risk factors, perioperative RBC transfusion was associated with an increased risk of VTE (aOR 2.4; 95% CI, 1.9-3.0). The increased VTE risk persisted after imputation of missing demographic and clinical data as well as after 1:1 propensity score matching (29 811 matched pairs, aOR 2.2; 95% CI, 1.7-2.8).

CONCLUSIONS: Perioperative RBC transfusion is associated with an increased, albeit still very low, risk of postoperative VTE in pediatric patients. Patients receiving blood in the perioperative period may benefit from additional monitoring or VTE prophylaxis.

PMID: 31298495 [PubMed - indexed for MEDLINE]

14:57

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Promising biomarkers for the prediction of catheter-related venous thromboembolism in hospitalized children: An exploratory study.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Promising biomarkers for the prediction of catheter-related venous thromboembolism in hospitalized children: An exploratory study.

Pediatr Blood Cancer. 2019 10;66(10):e27870

Authors: Nossair F, Mahajerin A, Hoang J, Diaz D, Nugent D

Venous thromboembolism is highly prevalent in lung cancer patients. Low molecular weight heparins are recommended for long term

Abstract

Venous thromboembolism is highly prevalent in lung cancer patients. Low molecular weight heparins are recommended for long term treatment of cancer associated venous thromboembolism. Direct oral anticoagulants are however an interesting alternative as they are administered orally and don't require monitoring. There are currently studies comparing both their efficacy and tolerance for cancer patients and more and more guidelines suggest considering direct oral anticoagulants for cancer associated venous thromboembolism treatment. The objective of this study was to evaluate the budgetary impact that direct oral anticoagulants use would have for lung cancer associated venous thromboembolism treatment and prevention in France. An economic model was made to evaluate the cost of venous thromboembolism treatment and prevention among patients with primary lung cancer in France by two strategies: current guidelines versus direct oral anticoagulants use. The model was fed with clinical and economic data extracted from the French national health information system. The analysis was conducted from the national mandatory Health insurance point of view. The time horizon of the study was the evaluation of the annual management cost. Lung cancer associated venous thromboembolism management's mean cost was estimated of 836€ per patient, that is a total cost of about 40 million euros per year at a national level. A 76% decrease of this cost can be expected with direct oral anticoagulants use. However, despite their benefits, these treatments raise new issues (medication interactions, bleeding management), and would likely not be recommended for all patients.

PMID: 32020515 [PubMed - as supplied by publisher]

14:57

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Association of perioperative red blood cell transfusion with postoperative venous thromboembolism in pediatric patients: A propensity score matched analysis.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Association of perioperative red blood cell transfusion with postoperative venous thromboembolism in pediatric patients: A propensity score matched analysis.

Pediatr Blood Cancer. 2019 10;66(10):e27919

Authors: Rothstein DH, Cairo SB, Schaefer BA, Lautz TB

BACKGROUND: The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic

Abstract

BACKGROUND: The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences.

DATA SOURCES: The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health.

RESULTS: We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences.

CONCLUSIONS: The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood.

PMID: 32020441 [PubMed - as supplied by publisher]

12:07

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Prevention of doxorubicin-induced Cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on Docosahexaenoic Acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial).

Trials. 2020 Feb 04;21(1):137

Authors: Carrasco R, Ramirez MC, Nes K, Schuster A, Aguayo R, Morales M, Ramos C, Hasson D, Sotomayor CG, Henriquez P, Cortés I, Erazo M, Salas C, Gormaz JG

Abstract

BACKGROUND: Anthracycline-induced cardiotoxicity (AIC), a condition associated with multiple mechanisms of damage, including oxidative stress, has been associated with poor clinical outcomes. Carvedilol, a β-blocker with unique antioxidant properties, emerged as a strategy to prevent AIC, but recent trials question its effectiveness. Some evidence suggests that the antioxidant, not the β-blocker effect, could prevent related cardiotoxicity. However, carvedilol's antioxidant effects are probably not enough to prevent cardiotoxicity manifestations in certain cases. We hypothesize that breast cancer patients taking carvedilol as well as a non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA), an enhancer of cardiac endogenous antioxidant capacity, will develop less subclinical cardiotoxicity manifestations than patients randomized to double placebo.

METHODS/DESIGN: We designed a pilot, randomized controlled, two-arm clinical trial with 32 patients to evaluate the effects of non-hypoxic cardiac preconditioning (DHA) plus carvedilol on subclinical cardiotoxicity in breast cancer patients undergoing anthracycline treatment. The trial includes four co-primary endpoints: changes in left ventricular ejection fraction (LVEF) determined by cardiac magnetic resonance (CMR); changes in global longitudinal strain (GLS) determined by two-dimensional echocardiography (ECHO); elevation in serum biomarkers (hs-cTnT and NT-ProBNP); and one electrocardiographic variable (QTc interval). Secondary endpoints include other imaging, biomarkers and the occurrence of major adverse cardiac events during follow-up. The enrollment and follow-up for clinical outcomes is ongoing.

DISCUSSION: We expect a group of anthracycline-treated breast cancer patients exposed to carvedilol and non-hypoxic myocardial preconditioning with DHA to show less subclinical cardiotoxicity manifestations than a comparable group exposed to placebo.

TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN69560410. Registered on 8 June 2016.

PMID: 32019575 [PubMed - in process]

14:57

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

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Are direct oral anticoagulants an economically attractive alternative to low molecular weight heparins in lung cancer associated venous thromboembolism management?

J Thromb Thrombolysis. 2020 Feb 04;:

Authors: Howlett J, Benzenine E, Fagnoni P, Quantin C

Adjuvant radiotherapy after breast cancer surgery is an important part of breast cancer treatment improving local control and overall

Abstract

Adjuvant radiotherapy after breast cancer surgery is an important part of breast cancer treatment improving local control and overall survival. However, a higher risk of cardiac mortality was observed when conventional radiotherapy techniques were used. Cardiac morbidity and mortality after radiation therapy have been studied in many meta-analyses. In those focused on modern radiotherapy techniques, cardiac morbidity and mortality were no longer presented. However, an extremely long follow-up period is required. Importantly, the cardiac morbidity rates vary depending not only on the dose delivered to the heart, but also on the systemic therapies administrated and the pre-existing cardiac disease. Systematic heart dose monitoring is of great importance, as are efforts to constantly decrease doses, using advanced radiotherapy techniques. Nowadays, it is essential to individualize treatment according to tumor characteristics and anatomical predispositions, and to consider the cost and benefits.

PMID: 32021574 [PubMed]

12:07

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Childhood obesity, cardiovascular and liver health: a growing epidemic with age.

World J Pediatr. 2020 Feb 04;:

Authors: Faienza MF, Chiarito M, Molina-Molina E, Shanmugam H, Lammert F, Krawczyk M, D'Amato G, Portincasa P

AIMS: Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF)

Abstract

AIMS: Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD.

METHODS AND RESULTS: We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty-nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N-terminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril-valsartan dose (low or medium/high doses).

CONCLUSIONS: Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.

PMID: 32022485 [PubMed - as supplied by publisher]

12:07

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Cardiotoxicity of breast cancer radiotherapy - overview of current results.

Rep Pract Oncol Radiother. 2020 Mar-Apr;25(2):182-186

Authors: Soumarová R, Rušinová L

The present study aimed to examine microRNA (miR)-940 expression in esophageal squamous cell carcinoma (ESCC) tissues and cells

Abstract

The present study aimed to examine microRNA (miR)-940 expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, analyze its association with the clinicopathological features and prognosis of patients, and explore the potential underlying mechanisms. miR-940 expression in ESCC cell lines and a normal esophageal cell line was detected using reverse transcription-quantitative (RT-q)PCR. Furthermore, 210 resected ESCC tissue and para-carcinoma tissue specimens were collected, and miR-940 expression in those tissues was detected by RT-qPCR. In addition, the association of miR-940 with the clinicopathological features and prognosis of patients was analyzed. In an in vitro experiment, miR-940 mimics were transduced into ESCC cells by the liposome method. An MTT assay was used to detect the effect of miR-940 on the viability of ESCC cells. The influence of miR-940 on the cell cycle and apoptotic rate of ESCC cells was detected by flow cytometry. The present results indicated that the expression levels of miR-940 in human ESCC tissues and cell lines were markedly downregulated, and that low expression of miR-940 in ESCC tissues was significantly associated with a poor degree of differentiation, positive lymph node metastasis and advanced clinical stage. Kaplan-Meier survival analysis suggested that low miR-940 expression was associated with poor prognosis. Cox regression analysis revealed that lymph node metastasis, clinical stage and miR-940 expression were independent risk factors affecting the prognosis of patients. Overexpression of miR-940 in ESCC cells markedly reduced the cell viability, blocked the cell cycle at G0/G1 phase and promoted cell apoptosis. These results suggest that miR-940 is downregulated in ESCC, which is linked to the occurrence and progression of ESCC. Conversely, overexpression of miR-940 reduced the cell viability and promoted apoptosis of ESCC cells. Therefore, miR-940 may be a promising novel prognostic marker and anti-cancer target in ESCC.

PMID: 32010243 [PubMed]

6 February 2020

12:07

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

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Effectiveness of sacubitril-valsartan in cancer patients with heart failure.

ESC Heart Fail. 2020 Feb 05;:

Authors: Martín-Garcia A, López-Fernández T, Mitroi C, Chaparro-Muñoz M, Moliner P, Martin-Garcia AC, Martinez-Monzonis A, Castro A, Lopez-Sendon JL, Sanchez PL

Dose dependent cardiotoxicity is the primary side effect of doxorubicin (DOX), but the underlying molecular mechanisms remain unclear

Abstract

Dose dependent cardiotoxicity is the primary side effect of doxorubicin (DOX), but the underlying molecular mechanisms remain unclear. An increasing amount of evidence has demonstrated that neurotrophic signaling plays a pivotal role in both neurons and the heart, but the biological association between neurotrophic signaling and DOX-induced cardiotoxicity remains unknown. The present study determined the level of neurotrophins and their receptors in the heart of rats following DOX administration. DOX was administered 7 times at a dose of 2.5 mg/kg once every 2 days via intraperitoneal injection. The present study revealed that cardiac injury parameters, such as creatine kinase (CK), creatine kinase-myocardial bound, lactate dehydrogenase, troponin T and aspartate transaminase in serum were significantly increased in the DOX group. Both the gene and protein expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the heart were markedly decreased following DOX treatment. Notably, the protein level of BDNF in the serum was inhibited in DOX-treated rats, whereas DOX induced a significant increase in the protein level of NGF in the serum. DOX induced a significant decrease in the level of tropomyosin-associated kinase A (TrkA) and the ratio of pTrkA/TrkA and pTrkB/TrkB. Furthermore, the administration of DOX suppressed downstream protein kinase B and extracellular signal regulated kinase phosphorylation. The present study first demonstrated that BDNF/TrkB signaling and NGF/TrkA signaling were altered by DOX, which indicated that neurotrophic signaling was involved in DOX-induced cardiotoxicity.

PMID: 32010279 [PubMed]

23:40

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miR-940 inhibits cell proliferation and promotes apoptosis in esophageal squamous cell carcinoma cells and is associated with post-operative prognosis.

Exp Ther Med. 2020 Feb;19(2):833-840

Authors: Wang H, Song T, Qiao Y, Sun J

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Transpulmonary driving pressure (ratio of tidal volume to respiratory system

Abstract

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Transpulmonary driving pressure (ratio of tidal volume to respiratory system compliance) increases with increased intraabdominal pressure during laparoscopic surgery. High transpulmonary driving pressure during laparoscopic surgery is associated with increased risk of postoperative pulmonary complications.Intraoperative positive end-expiratory pressure prevents atelectasis, but may also cause overdistension.

WHAT THIS ARTICLE TELLS US THAT IS NEW: This single-center study found that titrating intraoperative positive end-expiratory pressure in relation to observed intraabdominal pressure may counterbalance pneumoperitoneum-related rises in transpulmonary driving pressure during laparoscopic cholecystectomies.

BACKGROUND: Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure.

METHODS: Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. "Targeted PEEP" (2 cm H2O above intraabdominal pressure) was compared with "standard PEEP" (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure.

RESULTS: Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels.

CONCLUSIONS: Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes.

PMID: 32011334 [PubMed - as supplied by publisher]

23:39

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Involvement of neurotrophic signaling in doxorubicin-induced cardiotoxicity.

Exp Ther Med. 2020 Feb;19(2):1129-1135

Authors: Liao D, Zhang C, Liu N, Cao L, Wang C, Feng Q, Yao D, Long M, Jiang P

Enhancing tumor homing and improving the efficacy of drugs are urgent needs for cancer treatment. Herein a novel targeted, intracellularly

Abstract

Enhancing tumor homing and improving the efficacy of drugs are urgent needs for cancer treatment. Herein a novel targeted, intracellularly activatable fluorescence and cytotoxicity nanodiamond (ND) drug system (ND-PEG-HYD-FA/DOX, NPHF/D) was successfully prepared based on doxorubicin (DOX) and folate (FA) covalently bound to PEGylated NDs, in which the DOX was covalently coupled via an intracellularly hydrolyzable hydrazone bond that was stable in the physiological environment to ensure minimal drug release in circulation. Cell uptake studies demonstrated the selective internalization of NPHF/D by folate receptor (FR) mediated endocytosis in the order MCF-7 > HeLa > HepG2 ≫ CHO, using confocal laser scanning microscopy (CLSM) and flow cytometry. Interestingly, the DOX fluorescence of NPHF/D was significantly quenched, while the fluorescence recovery and cytotoxicity took place by low pH regulation in intracellular lysosomes, which made NPHF/D act as a fluorescence OFF-ON messenger for activatable imaging and cancer therapy. Of note, NPHF/D significantly inhibited the growth of tumors. Simultaneously, it was demonstrated that the introduction of FA and the cleavability of the hydrazone greatly enhanced the therapeutic performance of NPHF/D. In addition, toxicity studies in mice verified that the composites were devoid of any detected hepatotoxicity, cardiotoxicity, and nephrotoxicity using histopathology and blood biochemistry studies. Our work provides a novel strategy for cancer therapy, using ND-conjugated cancer drugs, and the exploration of theranostic drug-delivery systems.

PMID: 32011619 [PubMed - as supplied by publisher]

23:39

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Intraabdominal Pressure Targeted Positive End-expiratory Pressure during Laparoscopic Surgery: An Open-label, Nonrandomized, Crossover, Clinical Trial.

Anesthesiology. 2020 Jan 30;:

Authors: Mazzinari G, Diaz-Cambronero O, Alonso-Iñigo JM, Garcia-Gregorio N, Ayas-Montero B, Ibañez JL, Serpa Neto A, Ball L, Gama de Abreu M, Pelosi P, Maupoey J, Argente Navarro MP, Schultz MJ

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