RESUMO
DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk-benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23-2.26), major bleeding (HR 3.41, 95%CI 2.36-4.93), VTE-related mortality (HR 2.59, 95%CI 1.46-4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05-6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02-1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT.
Assuntos
Neoplasias , Trombose , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Enoxaparina/uso terapêutico , Estudos Retrospectivos , Hemorragia/induzido quimicamente , Trombose/tratamento farmacológico , Resultado do Tratamento , Neoplasias/complicações , Administração OralRESUMO
Obesity is a known risk factor for venous thromboembolism (VTE) and poses a unique set of challenges in anticoagulation management. We report a 10-year experience of VTE management in morbidly obese patients. We conducted a retrospective analysis of VTE presentations to Northern Health, Victoria, Australia, from January 2011 to December 2020, with median follow-up of 44 months. Morbidly obese patients (defined as weighing > 120 kg) were compared to those ≤ 120 kg. Patients with active malignancy were excluded. 194 VTE cases with weight > 120 kg were compared to 2168 cases weighing ≤ 120 kg. Patients > 120 kg were more likely to present with unprovoked VTE (59.3% vs. 45.2%, p < 0.001) and major VTE (74.7% vs. 67.4%, p = 0.028). Overall, patients > 120 kg were more likely to develop VTE recurrence after anticoagulation cessation (7.80 vs. 3.92 per 100-patient-years, HR 1.97, 95%CI 1.29-3.00), while there were no significant differences in major bleeding or 30-day all-cause mortality. There were no significant differences in outcomes in patients > 120 kg treated with warfarin compared to direct oral anticoagulants (DOAC), or when comparing those treated with an uncapped (1 mg/kg BD) vs. capped (< 1 mg/kg) enoxaparin dosing regimen. Morbid obesity is associated with increased clot burden at presentation and VTE recurrence following anticoagulation cessation, without significant differences in bleeding compared to those ≤ 120 kg. There were no significant differences in morbidly obese patients' outcomes when treated with warfarin or DOAC, or when treated with an uncapped or capped enoxaparin dosing strategy. Larger randomised controlled trials evaluating the safety of DOACs and different enoxaparin dosing strategies in patients > 120 kg are warranted.
Assuntos
Obesidade Mórbida , Tromboembolia Venosa , Humanos , Varfarina/uso terapêutico , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/complicações , Enoxaparina , Obesidade Mórbida/complicações , Estudos Retrospectivos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Administração OralRESUMO
BACKGROUND: The introduction of direct oral anticoagulants (DOAC) has resulted in a paradigm shift in the management of venous thromboembolism (VTE). We evaluate the impact of the transition to DOAC, over the last decade, on overall VTE clinical outcomes including in first unprovoked major VTEs. METHOD: A retrospective analysis of all VTE admissions in non-cancer patients from January 2011 to December 2020 at Northern Health, Victoria, Australia. "Warfarin era" included events that occurred between January 2011 and December 2014 and "DOAC era" from January 2016. RESULTS: There were 2687 cases involving 2508 patients (45.9 % males; median age 63 years). 98 % were symptomatic and 1261 events (47 %) were unprovoked. 1003 events occurred during the warfarin era (79 % warfarin, 6 % DOAC) and 1479 during the DOAC era (18 % warfarin, 70 % DOAC). While recurrent thrombosis during the acute phase of treatment was comparable, there were fewer recurrences during the long-term preventative phase of treatment in the DOAC era compared to warfarin era (HR 0.602, 95 % CI: 0.393-0.924, p0.020). Clinically significant bleeding events were lower in the DOAC era (HR 0.623, 95 % CI: 0.395-0.985, p = 0.043). A subanalysis of first unprovoked major VTE events (n = 602) demonstrated a significant reduction in recurrent VTE during the long-term preventative phase of treatment in the DOAC era (HR 0.296, 95 % CI: 0.097-0.901, p = 0.032) with no difference in clinically significantly bleeding rates (HR 0.529, 95 % CI 0.219-1.280, p = 0.158) between the eras. CONCLUSION: Treatment outcomes for VTE appear to have improved over time with reduced rate of thrombotic and clinically significant bleeding complications in the DOAC era.
Assuntos
Tromboembolia Venosa , Varfarina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Oral , Anticoagulantes/efeitos adversos , Hemorragia/tratamento farmacológico , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Varfarina/efeitos adversosRESUMO
Ameloblastomas are benign but locally invasive neoplasms which may grow to massive proportions and cause significant morbidity. Although some types of ameloblastoma can be treated predictably with aggressive surgical treatment, recurrent ameloblastoma and metastasising ameloblastoma are still difficult to treat. Recent studies have identified recurrent somatic and activating mutations in the mitogen-activated protein kinase (MAPK) and sonic hedgehog (SHH) signalling pathways in ameloblastoma. This development provided a possibility that molecular targeted therapies can be used as neoadjuvant treatment. In this review, we provide a summary of the latest WHO classification of ameloblastoma, the current understanding of genetic mutations and novel molecular targeted therapies arising from the recent developments.