Supportive Care Needs of Newly Diagnosed Cancer Patients in a Comprehensive Cancer Center: Identifying Care Profiles and Future Perspectives.

The prompt introduction of supportive care for patients with cancer leads to a better quality of life, potential survival benefits, and improvements in treatment safety. Considering that patients' needs vary, descriptive assessments could serve as a compass for an efficient and prompt healthcare response. The aim of this study was to identify supportive care needs in newly diagnosed patients according to cancer type. A retrospective study was conducted by collecting data from the case consultation and medical records of a comprehensive cancer center in France. Patients' needs were divided into twelve domains: nutrition, psychological support, psychiatric support, social care, physiotherapy, addictology, pain management, palliative care, pharmacology, complementary and alternative practice (CAM), sexual health, and speech therapy. Out of 6217 newly diagnosed patients of various cancer types who sought medical care at Gustave Roussy in 2021, 2541 (41%) required supportive cancer care (SCC), and of them, 1331 patients (52%) required two or more different SCC specialist interventions. The top five interventions were dietary (for 60% of patients), physiotherapy (33%), psychology (29%), social care (28%), and pain management (16%). Subgroup analysis according to cancer department highlighted additional specific needs: CAM for breast cancer patients (11%), speech specialist (27%) and addictologist (22%) interventions for ENT patients, psychiatry consultations for neurological patients (16%), and palliative care for dermatology patients (23%). The aforementioned data suggest that an early, multidisciplinary supportive care intervention should be required. Assembling human resources at the time of diagnosis within a dedicated day unit would be the next appropriate step in developing personalized care pathways related to the highlighted needs.

Comparison of the DOAC Dipstick Test on Urine Samples With Chromogenic Substrate Methods on Plasma Samples in Outpatients Treated With Direct Oral Anticoagulants.

Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at plasma thresholds of about 30 ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma concentration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4 + 16.1 years, female n = 63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129 ± 118 ng/mL for rivaroxaban, and 163 ± 130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30 ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants.

Benefice and pitfall of direct oral anticoagulants in very high-risk myeloproliferative neoplasms.

INTRODUCTION: Direct oral anticoagulants (DOACs) have recently proven their efficacy and safety, as primary and secondary prevention agents for thrombosis in cancer patients. We aimed to determine if DOACs might be a suitable choice to reduce the thrombotic risk in myeloproliferative neoplasm (MPN) patients. MATERIALS AND METHODS: We analysed a large multicentric cohort of MPN patients treated with rivaroxaban or apixaban after atrial fibrillation (AF) or thrombotic events. RESULTS: We included 135 MPN patients with a median follow-up of 23.8 months since DOAC initiation. Twenty patients (14.8 %) developed 30 thrombotic events (28 arterial thromboses in 19 patients) for a global incidence of 6.5 % patient-years. No difference was highlighted between apixaban and rivaroxaban in terms of thrombosis risk, but the incidence of arterial thrombosis was significantly higher on low-dose DOACs (11.9 vs. 4.5 % patient-years, p = 0.04). Bleeding events were more frequent in the full-dose group (41.2 vs. 15.2 %, p = 0.006). However, major and clinically relevant non major (CRNM) bleeding events occurred in 18 patients (13.3 %), with no difference between the groups. Age was the only identified thrombotic risk factor, whereas risk factors for major or CRNM bleeding were a full-dose treatment regimen and a combination of DOAC/low-dose aspirin. CONCLUSIONS: DOACs seem effective in preventing venous thrombosis in MPN patients with AF or VTE. For these high-risk patients, low-dose DOACs exposed patients to more arterial thrombosis but fewer bleeding events. Prospective studies are needed to evaluate and compare DOACs to the currently recommended antithrombotic drugs for high-risk MPN patients.

Thrombotic and Hemorrhagic Issues Associated with Myeloproliferative Neoplasms.

Thrombotic and hemorrhagic complications are related to a significant rate of morbidity and mortality in patients with myeloproliferative neoplasms (MPNs), they are therefore called "thrombohemorrhagic" syndromes. Several clinical factors, such as age and presence of cardiovascular comorbidities are responsible for thrombotic complications. High blood counts, platelet alterations, presence of JAK2 mutation and possibly of other CHIP mutations such as TET2, DNMT3A, and ASXL1, procoagulant microparticles, NETs formation, endothelial activation and neo-angiogenesis are some of the parameters accounting for hypercoagulability in patients with myeloproliferative neoplasms. Bleeding complications emerge as a result of platelet exhaustion. They can be also linked to a functional deficiency of von Willebrand factor, when platelet counts rise above 1000G/L. The mainstay of management consists on preventing hemostatic complications, by antiplatelet and/or anticoagulant treatment and myelosuppressive agents in high-risk patients.Circumstances related to a high thrombohemorrhagic risk, such as pregnancy and the perioperative period, prompt for specific management with regards to anticoagulation and myelosuppression treatment type. In order to apply a patient-specific treatment strategy, there is a need for a risk score assessment tool encompassing clinical parameters and hemostasis biomarkers.

Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19.

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 (n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation (n = 310) and validation (n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening.

Modelization of Blood-Borne Hypercoagulability in Myeloma: A Tissue-Factor-Bearing Microparticle-Driven Process.

Introduction Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma. The identification of the procoagulant potential of cancer cells, which is principally related to tissue factor (TF) expression, attracts particular interest. The mechanisms by which myeloma plasma cells (MPCs) activate blood coagulation have been poorly investigated. Aim To identify the principal actors related with MPCs that boost thrombin generation (TG). Methods TF and annexin V expression by MPCs and MPC-derived microparticles (MPC-dMPs) was analyzed by flow cytometry. TF activity (TFa) and TF gene expression were also determined. TG in the presence of MPCs or MPC-dMPs was assessed with the calibrated automated thrombogram assay (CAT) in normal human PPP and in plasma depleted of factor VII or XII. TG was also assessed in plasma spiked with MPCs and MPC-dMPs. Results MPC-dMPs expressed approximately twofold higher levels of TF as compared with MPCs. The TFa expressed by MPC-dMPs was significantly higher compared with that expressed by MPCs. MPCs and MPC-dMPs enhanced TG of human plasma. TG was significantly higher with MPC-dMPs compared with MPCs. Conclusion MPCs indirectly induce blood-borne hypercoagulability through the release of MPC-dMPs rich in TF. Since MPCs, expressing low TFa, represent a weak procoagulant stimulus, the hypercoagulability at the microenvironment could be the resultant of MPC-dMPs rich in TF.

Longer procoagulant phospholipid-dependent clotting time, lower endogenous thrombin potential and higher tissue factor pathway inhibitor concentrations are associated with increased VTE occurrence in patients with newly diagnosed multiple myeloma: results of the prospective ROADMAP-MM-CAT study.

Venous thromboembolism (VTE) is a common complication in newly diagnosed symptomatic multiple myeloma (NDMM) patients. We explored cellular and plasma hypercoagulability in NDMM patients to identify relevant biomarkers that can be used in combination with clinical factors in the development of a risk assessment model (RAM) for VTE. Untreated patients (n = 144) with NDMM were prospectively enrolled, baseline biomarkers prior to anti-myeloma treatment and thromboprophylaxis initiation were obtained. These were compared against values in a group of healthy individuals with similar age and sex distribution. The primary study end point was symptomatic VTE occurrence. At 12-month follow-up cumulative VTE rate was 10.4%. NDMM patients showed biological signs of cellular and plasma hypercoagulability and endothelial cell activation. Procoagulant phospholipid clotting time (Procoagulant-PPL) was shorter, P-selectin levels lower and thrombin generation attenuated overall compared to healthy subjects. Longer Procoag-PPL®, lower endogenous thrombin potential (ETP), and higher levels of tissue factor pathway inhibitor (TFPI) were associated with VTE occurrence. Multivariate analysis showed that Procoag-PPL® and ETP were independent risk factors for VTE. We conclude that Procoag-PPL® and ETP can be prospectively incorporated into a RAM for VTE in MM in combination with clinical and disease risk factors.

Comparison of antithrombin-dependent and direct inhibitors of factor Xa or thrombin on the kinetics and qualitative characteristics of blood clots.

BACKGROUND: Venous thromboembolism (VTE) is associated with significant morbidity and mortality. OBJECTIVES: We investigated the impact of direct and AT-dependent FXa or thrombin inhibitors on thrombus formation. METHODS: Whole blood thromboelastometry and thrombin generation were assessed after triggering the TF pathway. Clinically relevant concentrations of rivaroxaban, fondaparinux, dabigatran or tinzaparin and an association of rivaroxaban and dabigatran were examined. RESULTS: All agents delayed thrombus formation in a concentration-dependent manner, as documented by the prolongation of the clotting time (CT) and clot formation time (CFT). Rivaroxaban did not significantly alter the α-angle or maximum clot firmness (MCF). In contrast, dabigatran and fondaparinux altered the process of clot structure by decreasing the α-angle, but did not modify clot firmness. The later property was significantly affected only by tinzaparin that also reduced the MCF. The association of rivaroxaban and dabigatran did not affect the MCF, although it amplified the effect on CFT and α-angle. CONCLUSIONS: All agents delayed thrombus formation. However, the compounds differed substantially with respect to fibrin polymerization rate and clot firmness. Comparison of the data obtained by thrombin generation assessment with those obtained by the thromboelastometric study shows that the delay in clot formation is principally associated with prolongation of the initiation phase of thrombin formation as well as a reduction of the propagation phase. Tinzaparin was much more potent than the other agents both with regard to suppression of thrombin generation and by delay in clot formation.

Updated clinical models for VTE prediction in hospitalized medical patients.

Venous thromboembolism (VTE) occurring in hospitalized medical patients is associated with increased length of hospitalization, high rate of acute care hospital transfer, longer inpatient rehabilitation and multiplication of health-care costs. Identification of acutely ill hospitalized medical patients eligible for thromboprophylaxis is a sophisticated process. Global VTE risk stems from the combination of predictors related with the acute medical illness, comorbidities, associated treatments and patients' intrinsic risk factors. Emerging clinical risk factors related to underlying pathologies should be considered when VTE risk is assessed. The Padua Prediction Score (PPS), the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-RAM) and the Geneva Risk Score are three robust risk assessment models (RAM) which underwent extensive external validation in cohorts of acutely ill hospitalized medical patients. The development of the IMPROVE bleeding risk assessment model and the identification of D-Dimer increase as a biomarker-predictor of VTE are some steps forward for personalized thromboprophylaxis. The beneficial impact of the RAMs in VTE prevention is already seen by the decrease of in-hospital VTE rates when RAMs are incorporated in electronic alert systems.

Prognostic Implication of the Absolute Lymphocyte to Absolute Monocyte Count Ratio in Patients With Classical Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine or Equivalent Regimens.

Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 × 10(9)/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 × 10(9)/L). Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages ΙΑ/ΙΙΑ and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker.

Pure red cell aplasia complicating the course of long-standing mantle cell lymphoma.

Pure red cell aplasia (PRCA) is a rare cause of severe hypoplastic anemia characterized by profound depletion of erythroid precursors. Although PRCA may be associated with lymphoproliferative diseases, it has never been described in mantle cell lymphoma (MCL). We report what to our knowledge is the first case of a patient with indolent, non-nodal MCL complicated by PRCA. The patient presented with severe hypoproliferative anemia in the setting of a long-standing diagnosis of B-cell chronic lymphocytic leukemia. Bone marrow studies revealed the complete absence of erythroid progenitors. Cyclin D1 positivity on immunohistochemistry, confirmed by a positive FISH for t(11;14) (q13;q32), established the final diagnosis of MCL in conjunction with PRCA. Rituximab monotherapy led to rapid remission of splenomegaly and the leukemic picture, but the patient achieved transfusion independency only with subsequent administration of cyclosporine-A, and remained so during the subsequent 15 months despite the gradual disease recurrence.

The presence of CD55- and/or CD59-deficient erythrocytic populations in patients with rheumatic diseases reflects an immune-mediated bone-marrow derived phenomenon.

BACKGROUND: Complement has the potential to provoke severe impairment to host tissues, as shown in autoimmune diseases where complement activation has been associated with diminished CD55 and/or CD59 expression on peripheral blood cell membranes. The aim of this study was to evaluate the presence of CD55- and/or CD59-deficient erythrocytic populations in patients with different rheumatic diseases and to investigate possible correlations with clinical or laboratory parameters. MATERIAL AND METHODS: CD55 and CD59 expression was evaluated in erythrocytes of 113 patients with rheumatic diseases, 121 normal individuals, and 10 patients with paroxysmal nocturnal hemoglobinuria (PNH) using the Sephacryl gel microtyping system. Ham and sucrose tests were also performed. RESULTS: Interestingly, the majority of patients (104/113, 92%) demonstrated CD55- and/or CD59-deficient erythrocytes: 47 (41.6%) with concomitant deficiency of CD55 and CD59, 50 (44.2%) with isolated deficiency of CD55, and 6 (6.2%) with isolated deficiency of CD59. In normal individuals, only 2 (1%) had concomitant CD55/CD59 negativity and 3 (2%) had isolated CD55 or CD59 deficiency. All PNH patients exhibited simultaneous CD55/CD59 deficiency. Positive Ham and sucrose tests were found only in PNH patients. There was no association between the CD55- and/or CD59-deficient erythrocytes and hemocytopenias or undergoing treatment. However, CD55 expression significantly influenced hemoglobin values (F=6.092, p=0.015). CONCLUSIONS: This study provides evidence supporting the presence of erythrocytes with CD55 and/or CD59 deficiency in patients with rheumatic diseases. Moreover, CD55 deficiency on red cells influences hemoglobin concentration. Further studies using molecular techniques will clarify the exact pathophysiological mechanisms of this deficiency.