ABSTRACT

AIMS: Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies.

METHODS: We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed.

RESULTS: Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95%CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95%CI: 0.62-0.82, p<0.0001),<0.0001),<0.0001),

CONCLUSIONS: This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.

PMID:37257759 | DOI:10.1016/j.diabres.2023.110734

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PubMed articles on: Cardio-Oncology

Natriuretic Peptides, Cardio-Oncology

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

NO ABSTRACT

PMID:37257014 | DOI:10.14744/AnatolJCardiol.2023.6

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PubMed articles on: Cancer & VTE/PE

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

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

NO ABSTRACT

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

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PubMed articles on: Cancer & VTE/PE

D-dimer testing: A narrative review

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

ABSTRACT

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

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

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PubMed articles on: Cancer & VTE/PE

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

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

ABSTRACT

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

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

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

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

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

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

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

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02744092.

PMID:37266947 | DOI:10.1001/jama.2023.7843

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PubMed articles on: Cancer & VTE/PE

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

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

ABSTRACT

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

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

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

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

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

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

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

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PubMed articles on: Cancer & VTE/PE

Body Mass Index (BMI) Related Morbidity with Thyroid Surgery

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

ABSTRACT

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

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

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

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

LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2023.

PMID:37265205 | DOI:10.1002/lary.30789

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PubMed articles on: Cancer & VTE/PE

Prevention of venous thromboembolism in patients with cancer

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

ABSTRACT

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

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

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PubMed articles on: Cancer & VTE/PE

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

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

ABSTRACT

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

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

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

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

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

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

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PubMed articles on: Cancer & VTE/PE

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

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

ABSTRACT

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

PMID:37268064 | PMC:PMC10232718 | DOI:10.1016/j.jtha.2023.05.020

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PubMed articles on: Cancer & VTE/PE

Current status and hotspots evolution in myeloproliferative neoplasm: a bibliometric analysis from 2001 to 2022

Eur Rev Med Pharmacol Sci. 2023 May;27(10):4510-4519. doi: 10.26355/eurrev_202305_32457.

ABSTRACT

OBJECTIVE: In the last 20 years, the field of myeloproliferative neoplasm (MPN) has changed dramatically. This study aims to provide new ideas for the scientific research of MPN by systematically combing the literature.

MATERIALS AND METHODS: CiteSpace and VOSviewer were used to carry out a bibliometric analysis of MPN papers to visualize the development process, research hotspots, and cutting-edge trends in clinical practice, mechanisms, and management strategies related to MPN.

RESULTS: 1,099 authors from 736 institutions in 113 countries/regions published 11,922 papers in 1,807 academic journals. The United States and Italy were in the leading positions in this research field. Mayo Clinic is the institution with the largest number of publications. Only a few countries and institutions have shown active cooperation. Ayalew Tefferi and Ruben A. Mesa are outstanding contributors to the field. Blood and Leukemia are considered influential journals based on publications and citations. In this field, the research of MPN mainly focuses on the occurrence and progress mechanism of MPN, the clinical significance of non-driving gene mutation, optimization of primary and secondary thromboprophylaxis, clinical research of long-acting interferon and JAK2 inhibitors, and exploration of better therapies for myelofibrosis (primary and secondary) and post-MPN acute myeloid leukemia (AML).

CONCLUSIONS: The research is in a stage of rapid development. The collaboration between different institutions or countries (regions) still has room to grow. The hotspot analysis shows that the research of MPN mainly focuses on gene mutation, thrombosis, new drug applications, disease progression, etc.

PMID:37259732 | DOI:10.26355/eurrev_202305_32457

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PubMed articles on: Cancer & VTE/PE

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor

Thromb Haemost. 2023 May 31. doi: 10.1055/s-0043-1769609. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancers. The risk factors and pathophysiological mechanisms of venous thromboembolic events (VTEs) of this new therapeutic class are still to be specified.

METHODS: The included patients had to have cancer and should be treated with ICI. Data analyzed included demographic data, biological data, and immune-related adverse events (IRAEs). We studied the prevalence of VTEs and the factors associated with VTEs.

RESULTS: Of 374 patients on ICI, over a median follow-up period of 15.2 months, the number of VTE was 50 (13.4%). The majority of patients were treated for metastatic melanoma or nonsmall cell lung cancer. There was no difference in prevalence or survival between cancer types. Patients with combined therapy composed of nivolumab and ipilimumab had higher 1-year cumulative VTE occurrence (29.3% [95% confidence interval [CI]: 9.7; 44.6]) than patients with pembrolizumab (14.9%, [95%CI: 2.5; 25.8], p= 0.03) or nivolumab (9.1%, [95% CI: 5.0; 12.9], p< 0.01). The presence of IRAE was associated with a higher risk of VTE occurrence compared with patients without any IRAE (1-year VTE cumulative incidence: 17.42% [95% CI: 9.5; 24.65] vs. 9.46% [95% CI: 5.18; 13.55], p= 0.04). There was a higher risk of VTE in patients treated with the combination of nivolumab and ipilimumab (adjusted subdistribution hazard ratio [SHR]: 3.71 [95% CI: 1.74; 7.90], p< 0.001) and in patients with IRAE (adjusted SHR: 2.14 [95% CI: 1.22; 3.75], p< 0.01).

CONCLUSION: The prevalence of VTE was 14.2% under ICIs. IRAE and combine treatment of nivolumab and ipilimumab were associated with VTE. The pathophysiological mechanisms are multiple and complex with a possible link to aberrant activation of the immune system.

PMID:37257835 | DOI:10.1055/s-0043-1769609

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PubMed articles on: Cancer & VTE/PE

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study

Pediatr Blood Cancer. 2023 May 17:e30425. doi: 10.1002/pbc.30425. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients.

PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined.

RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%.

CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

PMID:37194482 | DOI:10.1002/pbc.30425

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PubMed articles on: Cardio-Oncology

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

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

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

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PubMed articles on: Cardio-Oncology

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

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