Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Giant breast phyllodes tumor with silent thromboembolism: A case report.

BACKGROUND: Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE. CASE: A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm3 that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy. CONCLUSION: This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment.

Prescribing pattern of anticoagulants in patients with cancer associated thrombosis: Results of a survey among MITO group and AIOM society.

INTRODUCTION: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer. The aim of this survey was to better understand prescription patterns of anticoagulants, in particular of DOACs, especially in gynecological cancers (GCs). METHODS: Our survey was made up of 21 questions, the last four questions addressed to medical doctors (MDs) involved in GCs. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members. RESULTS: Overall, 113 MDs completed the questionnaire, 69 involved in GCs. Most respondents (46, 41%) were aged 30-40 years old, worked in public hospitals (59, 52.2%), were medical oncologists (86, 76.1%). LMWH was the preferred choice for the treatment of CAT (104, 92%). However, 89 respondents (78.8%) prescribed or asked to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty in verifying the therapeutic effect and the absence of antidotes in case of bleeding (37.9%). In patients with GCs, DOACs were used with niraparib, olaparib, rucaparib and immune checkpoint inhibitors (ICIs) in less than 10 patients by 23%, 20%, 9% and 10.2% of respondents, respectively. CONCLUSION: The responders are aware of the Direct-acting oral anticoagulants option and would like to use them.

Histopathological Features of Cancer-Associated Venous Thromboembolism: Presence of Intrathrombus Cancer Cells and Prothrombotic Factors.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. METHODS: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. RESULTS: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. CONCLUSIONS: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.

Venous-thromboembolism and associated health care utilization in elderly patients with diffuse large B cell lymphoma.

BACKGROUND: Patients with lymphoma have an increased risk of venous thromboembolism (VTE). The authors examined the risk of VTE and subsequent health care utilization in elderly patients with diffuse large B cell lymphoma (DLBCL). METHODS: A total of 5537 DLBCL patients ≥66 years old enrolled in Medicare from the Surveillance, Epidemiology, and End Results registry and a noncancer control group of Medicare beneficiaries (n = 5537) were identified. Cumulative incidence function to examine the risk of VTE 12 months after DLBCL diagnosis was used. Fine and Gray method was used to examine the risk factors associated with VTE risk in multivariable models. Total number of hospitalizations, outpatient visits, and Medicare spending were compared in DLBCL patients with and without VTE. RESULTS: VTE was diagnosed in 8.3% DLBCL patients and 1.5% controls, yielding an 8.6-fold higher risk of VTE in DLBCL in adjusted analysis (95% confidence interval [CI], 6.62-11.20; P < .001). Multivariable regression analysis showed that precancer VTE history was associated with an increased risk of developing VTE after a DLBCL diagnosis (hazard ratio [HR], 5.39; 95% CI, 4.39-6.63), and Asian individuals were associated with a lower risk (HR, 0.54; 95% CI, 0.29-1.00). Patients newly diagnosed with VTE after lymphoma had a 1.7-fold higher rate of hospitalization and a 1.2-fold higher rate of outpatient visits compared to those without, resulting in excess Medicare spending of $22,208 in the first year after DLBCL diagnosis. CONCLUSIONS: Elderly patients with DLBCL have an elevated risk of VTE resulting in excess health care utilization. VTE history before DLBCL was associated with increased risk of post-DLBCL VTE, and Asian individuals were associated with a lower risk of VTE.

Aspectos clínico-patológicos associados a eventos tromboembólicos venosos em pessoas diagnosticadas com neoplasias malignas não hematológicas: um estudo caso controle / Clinicopathological aspects associated with venous thromboembolic events in people diagnosed with non-hematological malignancies: a case-control study

INTRODUÇÃO: Tromboembolismo venoso (TEV) apresenta incidência elevada em pacientes oncológicos e é importante causa de morbimortalidade nesse grupo. Fatores relacionados ao paciente, ao câncer ou mesmo aos tratamentos empregados podem associar-se com um maior risco de eventos trombóticos venosos. Entretanto, o tema ainda é pouco compreendido e pouco estudado na população brasileira. OBJETIVOS: Avaliar comparativamente aspectos demográficos, histopatológicos e clínicos em pacientes com neoplasias sólidas que apresentaram ou não TEV. Avaliar possíveis fatores associados a eventos tromboembólicos venosos. Analisar as características dos eventos tromboembólicos venosos identificados. MÉTODOS: Trata-se de um estudo observacional, retrospectivo, etiológico, tipo caso controle, não pareado. Foram selecionados pacientes diagnosticados com câncer entre 2014 e 2019, acompanhados no Hospital das Clínicas da Universidade Federal de Minas Gerais, um serviço público de referência em oncologia. Casos foram definidos como pacientes com diagnóstico de TEV (desfecho) e controles aqueles sem eventos trombóticos. A exposição avaliada foi a realização de algum tratamento oncológico específico (quimioterápico, endócrino, radioterápico ou cirúrgico). Variáveis de relevância clínica foram selecionadas para análise univariada (idade, sexo, estadiamento da doença, sítios tumorais conforme escore de Khorana, realização de tratamento oncológico específico, realização de tratamentos conhecidamente trombogênicos) e potenciais fatores de confusão foram adicionados para análise multivariada. Todos os dados foram coletados por meio de revisão de prontuários médicos. RESULTADOS: Foram incluídos 91 pacientes no grupo casos e 182 no grupo controles (1:2). Ambos os grupos foram semelhantes em relação às características demográficas, histopatológicas e clínicas, porém o grupo casos apresentou maior taxa de mortalidade (30,8% versus 15,9%, p=0,04). Em análise univariada, estadiamento avançado foi associado a maior risco de TEV (OR 1,85; IC 95% 1,04-3,30; p=0,036) e tratamento com hormonioterapia foi fator protetor (OR 0,41; IC 95% 0,21-0,82; p=0,010). Após adição de fatores confundidores, análises multivariadaa mantiveram terapia endócrina associada a menor risco de TEV (OR 0,18; IC 95% 0,07-0,47; p=0,000 e OR 0,41; IC 95% 0,20-0,86; p=0,018), sem identificação de fatores de risco. Internação hospitalar (35,2%) e cirurgia (23,1%) foram os principais fatores de risco presentes nos três meses que precederam os eventos. Trombose venosa profunda (TVP) em membros inferiores ocorreu em 54,9% dos casos e tromboembolismo pulmonar (TEP) em 37,4%. Em relação ao tratamento para TEV, 52,7% dos pacientes fizeram uso de varfarina e 40,7% de novos anticoagulantes orais. CONCLUSÃO: TEV é importante causa de mortalidade em pacientes oncológicos, uma população bastante heterogênea, em que fatores associados podem se comportar de formas diferentes. No presente estudo, hormonioterapia foi fator de proteção para TEV, possivelmente porque pacientes com indicação de terapia endócrina apresentam doença inicial ou metastática controlada, com menor risco para eventos tromboembólicos venosos.

INTRODUCTION: Venous thromboembolism (VTE) has a high incidence in cancer patients, being a cause of significant morbidity and mortality in this group. Several factors are associated with a higher risk of thrombotic events, which may be related to the patient, cancer or even the treatments used. However, this topic is still poorly understood and there are few studies in the Brazilian population. OBJECTIVES: To comparatively evaluate demographic, histopathological and clinical aspects in patients with solid tumors who had or did not have VTE. To assess possible factors associated with venous thromboembolic events. To analyze the characteristics of the venous thromboembolic events. METHODS: This is an observational, retrospective, etiological, case-control, unpaired study. Were selected patients diagnosed with cancer between 2014 and 2019 and treated at the Hospital das Clínicas da Universidade Federal de Minas Gerais, a public service of reference in oncology. Cases were defined as patients diagnosed with VTE (outcome) and controls as those without thrombotic events. Exposure was defined as receiving a specific oncological treatment (chemotherapy, endocrine therapy, radiotherapy or surgery). Clinically relevant variables were selected for univariate analysis (age, sex, disease staging, tumor sites according to Khorana score, specific oncological treatment, known thrombogenic treatments) and potential confounders were added for multivariate analysis. All data were collected by reviewing medical records. RESULTS: Ninety-one patients were included in the case group and 182 in the control group (1:2). Both groups were similar in terms of demographic, histopathological and clinical characteristics, but the case group had a higher mortality rate (30.8% versus 15.9%, p=0.04). In univariate analysis, advanced staging was associated with a higher risk of VTE (OR 1,85; CI 95% 1,04-3,30; p=0,036) and treatment with hormone therapy was a protective factor (OR 0,41; CI 95% 0,21-0,82; p=0,010). After adding confounding factors, multivariate analyzes maintained endocrine therapy associated with a lower risk of VTE (OR 0.18; 95% CI 0.07-0.47; p=0.000 and OR 0.41; 95% CI 0.20- 0.86; p=0.018), without identifying risk factors. Hospitalization (35.2%) and surgery (23.1%) were the main risk factors present in the three months preceding the events. Lower extremity deep venous thrombosis (DVT) occurred in 54.9% of cases and pulmonary embolism (PE) in 37.4%. About treatment for VTE, 52.7% of the patients used warfarin and 40.7% used new oral anticoagulants. CONCLUSION: VTE is an important cause of mortality in cancer patients, a very heterogeneous population, in which associated factors can behave in different ways. In the present study, hormone therapy was a protective factor for VTE, possibly because patients with indication for endocrine therapy have initial or controlled metastatic disease, with a lower risk for venous thromboembolic events.

Platelet GPVI (Glycoprotein VI) and Thrombotic Complications in the Venous System.

The immunoglobulin receptor GPVI (glycoprotein VI) is selectively expressed on megakaryocytes and platelets and is currently recognized as a receptor for not only collagen but also a variety of plasma and vascular proteins, including fibrin, fibrinogen, laminin, fibronectin, and galectin-3. Deficiency of GPVI is protective in mouse models of experimental thrombosis, pulmonary thromboembolism as well as in thromboinflammation, suggesting a role of GPVI in arterial and venous thrombus formation. In humans, platelet GPVI deficiency is associated with a mild bleeding phenotype, whereas a common variant rs1613662 in the GP6 gene is considered a risk factor for venous thromboembolism. However, preclinical studies on the inhibition of GPVI-ligand interactions are focused on arterial thrombotic complications. In this review we discuss the emerging evidence for GPVI in venous thrombus formation and leukocyte-dependent thromboinflammation, extending to venous thromboembolism, pulmonary thromboembolism, and cancer metastasis. We also recapitulate indications for circulating soluble GPVI as a biomarker of thrombosis-related complications. Collectively, we conclude that the current evidence suggests that platelet GPVI is also a suitable cotarget in the prevention of venous thrombosis due to its role in thrombus consolidation and platelet-leukocyte complex formation.

The Application of the ThroLy Risk Assessment Model to Predict Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Patients with aggressive lymphomas are at higher risk for venous thromboembolism (VTE). ThroLy is a risk assessment model (RAM) derived to predict the occurrence of VTE in various types of lymphomas. In this study, we assess the clinical application of ThroLy RAM in a unified group of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Hospital databases were searched for patients with DLBCL and radiologically-confirmed VTE. Items in the ThroLy RAM, including prior VTE, reduced mobility, obesity, extranodal disease, mediastinal involvement, neutropenia and hemoglobin < 10.0 g/dL, were retrospectively reviewed. RESULTS: A total of 524 patients, median age 49 (range: 18-90) years were included. Patients had high disease burden; 57.3% with stage III/IV and 34.0% with bulky disease. All were treated on unified guidelines; 63 (12.0%) had primary refractory disease. Venous thromboembolic events were reported in 71 (13.5%) patients. Among 121 patients with high (> 3) ThroLy score, 22.3% developed VTE compared to 8.4% and 12.4% in those with low and intermediate risk scores, respectively (P = .014). Simplifying the ThroLy model into two risk groups; high-risk (score ≥ 3) and low risk (score < 3) can still segregate patients; VTE developed in 44 (17.2%) high-risk patients (n = 256) compared to 27 (10.1%) in the low-risk group (n = 268), P = .038. Neutropenia, a component of the ThroLy, was encountered in only 14 (2.7%) patients. CONCLUSIONS: ThroLy RAM can identify patients with DLBCL at high risk for VTE. Model can be modified by dividing patients into two, rather than three risk groups, and further simplified by omitting neutropenia.

IVC filter placement in patients undergoing surgical treatment of bone or soft-tissue tumors.

BACKGROUND AND OBJECTIVES: Patients with cancer to bone or soft tissues undergoing orthopedic procedures may be unable to receive pharmacologic prophylaxis for venous thromboembolism (VTE). Inferior vena cava (IVC) filters may be an effective method to prevent fatal pulmonary embolism (PE) in these patients. METHODS: Retrospective chart review performed for patients surgically treated for malignant disease of bone or soft tissue who had IVC filter placement. Type of surgery, anatomic region, and development of wound complications requiring repeat surgery were analyzed. RESULTS: From 2007 to 2018, 286 patients received IVC filters. Ten (3.5%) patients suffered deep vein thrombus (DVT) postoperatively. There was no acute fatal PE. Two patients suffered PE at 2 and 99 days postoperatively. Risk of DVT was comparable following surgery with endoprosthesis versus open reduction and internal fixation (p = 0.056) and with soft tissue versus bone involvement (p = 0.620). Three filter-related complications occurred. Patients disease at the femur had the highest rate of DVT. CONCLUSIONS: Following treatment of malignant disease of bone or soft-tissues, two patients with IVC filter placement experienced nonfatal PE and three patients experienced filter-related complications. No patients in this series experienced a fatal PE.

Contrasts in Glioblastoma-Venous Thromboembolism versus Bleeding Risk.

Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the course of the disease, with an incidence of up to 30% per year. Major efforts are currently being made to understand and gain novel insights into the underlying pathomechanisms of the development of VTE in patients with glioblastoma and to find appropriate biomarkers. Yet, patients with glioblastoma not only face a high thromboembolic risk but are also at risk of bleeding events. In the case of VTE, a therapeutic anticoagulation with low molecular weight heparin or, in the case of low bleeding risk, treatment with a direct oral anticoagulant, is recommended, according to recently published guidelines. With respect to an elevated bleeding risk in glioblastoma patients, therapeutic anticoagulation remains challenging in this patient group and prospective data for this vulnerable patient group are scarce, particularly with regard to direct oral anticoagulants.

Early venous thromboembolism is a strong prognostic factor in patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: There are still controversial data regarding the prognostic value of Venous ThromboEmbolism (VTE) in advanced Pancreatic Ductal AdenoCarcinoma (PDAC) and thromboprophylaxis is poorly prescribed despite international recommendations. METHODS: Medical charts of patients consecutively treated for advanced PDAC from 2010 to 2019 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Prognostic Factors were identified using a multivariate Cox's proportional hazard model. Early VTE was defined as VTE occurring within the three months following the PDAC diagnosis. RESULTS: A total of 174 patients were included (median age: 67 years; males: 55.2%; performance status (PS) 0-1: 88.5%) with metastatic disease in 74.7%. At baseline, Khorana score was high (≥ 3) in the vast majority of cases (93.7%). The cumulative incidences of VTE were 12.4% (95% CI 7.3-17.2) at 3 months, 20.4% (95% CI 13.9-26.4) at 6 months and 28.1% (95% CI 20.0-35.3) at 12 months. Patients who experienced early VTE had shorter PFS (3.8 months vs. 7.1 months; HR = 2.02; 95% CI 1.21-3.37; p = 0.006) and shorter OS (8.0 months vs. 14.1 months; HR = 2.42; 95% CI 1.37-4.30; p = 0.002) compared to the others, independently of prognostic factors such as PS, liver metastases, carcinomatosis, and chemotherapy regimen. CONCLUSION: early VTE is a strong prognostic factor in advanced PDAC and occurs in about one in 10 patients.

Oral Contraceptive Use in Obese Adolescents: A Cautionary Tale.

Venous thromboembolism (VTE) is a life-threatening complication rarely encountered with the use of combined oral contraceptives (COCs). Obesity is an additional thrombosis risk factor that has been shown to further increase the risk of VTE with the use of COCs. We present 5 cases of obese adolescents (body mass index >30 kg/m2) who encountered thrombosis complications while on COCs. Although the absolute risk of VTE events in the setting of COCs is rare, caution should be observed when choosing hormonal therapy and safer COCs alternatives discussed with adolescents who are obese.

Risk of venous thromboembolism in Asian patients with inflammatory bowel disease: a nationwide cohort study.

Routine prophylaxis for venous thromboembolism (VTE) in Asian IBD patients has been controversial. We aimed to estimate the risk of VTE of Asian patients at different phases of IBD by incorporating patient-specific risk factors. In this cohort study, we analyzed the National Health Insurance claims data between 2012 and 2016 for the entire Korean population. We calculated incidence rates and hazard ratios for VTE. The overall VTE risk was higher in patients with IBD [adjusted hazard ratio (aHR), 2.06; 95% confidence interval (CI), 1.66-2.55], than in controls. When we compare the risk of VTE by different disease phases, the risk of VTE was the highest during post-operation period after IBD-related bowel surgery (aHR, 39.7; 95% CI 9.87-159.3), followed by during hospitalized periods with flare (aHR, 27.2; 95% CI 14.9-49.65) and during hospitalized periods with non-flare (aHR, 16.23; 95% CI 10.71-24.58). The incidence rate (per 1000 person-years) was 15.26 during hospitalized periods with a flare and 9.83 during hospitalized periods with non-flare. According to age groups, the incidence rate (per 1000 person-years) during hospitalized periods with flare was 14.53 in young patients (20-39 years) and 34.58 in older patients (60-80 years). During hospitalized periods with non-flare, the incidence rate was 3.55 in young patients and 23.61 in older patients. The prophylaxis of VTE for Asian patients with IBD should be recommended in older patients admitted to hospital and be considered in young patients who are hospitalized with a flare.

Catheter-directed Thrombolysis for Neonatal IVC and Bilateral Renal Vein Thrombosis: A Case Report.

Renal vein thrombosis is the most common non-catheter-associated venous thromboembolism event in neonates, accounting for up to 20% of cases. Although mortality rates are lower than a variety of other forms of pediatric thrombosis, renal vein thrombi are associated with significant short-term and long-term sequelae. This report presents the case of a full-term neonate presenting with bilateral renal vein thrombosis with inferior vena cava involvement treated with catheter-directed thrombolysis. This case report intends to highlight the value of a multidisciplinary approach to pediatric venous thromboembolism and to outline relevant procedural details and current laboratory and imaging monitoring of catheter-directed thrombolysis.

Immunothrombosis and thromboinflammation in host defense and disease.

Platelets are increasingly being recognized for playing roles beyond thrombosis and hemostasis. Today we know that they mediate inflammation by direct interactions with innate immune cells or secretion of cytokines/chemokines. Here we review their interactions with neutrophils and monocytes/macrophages in infection and sepsis, stroke, myocardial infarction and venous thromboembolism. We discuss new roles for platelet surface receptors like GPVI or GPIb and also look at platelet contributions to the formation of neutrophil extracellular traps (NETs) as well as to deep vein thrombosis during infection, e.g. in COVID-19 patients.

Impact of contemporary regimens on the outcomes and toxicity of primary CNS lymphoma: a single-center retrospective analysis of 73 patients.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare disease with a dismal prognosis compared to its systemic large B-cell lymphoma counterpart. Real world data are limited, when considering a uniform backbone treatment. METHODS: A retrospective study of all adult patients treated sequentially with a high-dose methotrexate (HD MTX)-based regimen in a single tertiary medical center between 2003 and 2019. RESULTS: The 2015-2019 period differed from its predecessor in that most patients were treated with an HD MTX-based polychemotherapy regimen as opposed to HD MTX monotherapy (81% vs. 13%, P < .001), rituximab was given as standard of care (100% vs. 56%, P < .01), and most induction-responsive patients received consolidation treatment (70% vs. 18%, P = .01). The median progression-free and overall survival (OS) for the entire cohort (n = 73, mean age 64 years) was 9.9 and 29.8 months, respectively. Patients diagnosed between 2015 and 2019 had superior OS (P = .03) compared to those treated earlier. An interim partial response (PR) state, documented after two cycles of chemotherapy, was associated with increased incidence of progression, with only 33% of those patients achieving end-of-induction complete response. Twenty-three percent of patients developed thrombotic events and 44% developed grade 3-4 infections. HD MTX-based polychemotherapy induction was associated with both increase in thrombotic and infection incidence. CONCLUSIONS: Contemporary HD MTX-based combination therapies suggestively improved the outcomes for PCNSL, but at a cost of increased incidence of toxicity. Patients who achieve an interim PR status are at a high risk for treatment failure.

Adult Donor Blood Products as Risk Factors for Central Venous Catheter-associated Thromboembolism in Neonates: A Retrospective Case-Control Study.

This study aimed to examine whether the transfusion of donor blood products, abnormal coagulation or inflammation increase the risk of venous thromboembolism (VTE) associated with central venous catheters (CVC) in neonates. A retrospective case-control study including 25 neonates with CVC-associated VTE and tightly matched controls with CVC, but without VTE was performed. The frequency of (i) abnormal coagulation screens, (ii) increased inflammatory marker proteins before catheter insertion, or (iii) catheter-associated blood stream infection did not differ between cases and controls. No difference was found in the number or type of transfusions within the last day before VTE. However, the total number of transfusions in the time period between catheter placement and VTE diagnosis (median 6.5 d) was significantly higher (P<0.001) in cases (44 red blood cell, 61 plasma, and 18 platelet transfusions) compared with an equal median time period of 7 days postcatheter insertion in controls (26/24/11). In conclusion, intensive transfusion treatment (through a peripheral line) after CVC insertion was associated with a higher risk of VTE (odds ratio 7.58; 95% confidence interval, 0.84-68.46), suggesting that transfusion of adult donor blood products into the cellular and plasmatic hemostatic system of the neonate increases the risk for CVC-associated VTE.

Direct oral anticoagulant use in gynecologic oncology: A Society of Gynecologic Oncology Clinical Practice Statement.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in women with gynecologic malignancies. This practice statement provides clinical data and overall quality of evidence regarding the use of direct oral anticoagulants (DOACs) in this patient population. Specifically, it reviews patient selection, safety measures, and nuances of perioperative use of these medications. The scope of this document is limited to DOAC use in gynecologic oncology rather than a broad discussion of VTE prophylaxis and management in general. The following recommendations and examination of extant data are based on DOAC trials conducted primarily in mixed populations with different cancer subtypes. Many of these trials include few, or no, women with gynecologic cancer. However, because there is very limited data in gynecologic cancer-specific populations, the results of these studies represent the best available evidence to support treatment recommendations in our patients. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee believe that the results of these studies may be extrapolated, with caution, to VTE treatment and prophylaxis for patients with gynecologic cancer.