The Vienna Prediction Model for identifying patients at low risk of recurrent venous thromboembolism: a prospective cohort study.

BACKGROUND AND AIMS: Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and guidelines suggest extended-phase anticoagulation. Many patients never experience recurrence but are exposed to bleeding. The aim of this study was to assess the performance of the Vienna Prediction Model (VPM) and to evaluate if the VPM accurately identifies these patients. METHODS: In patients with unprovoked VTE, the VPM was performed 3 weeks after anticoagulation withdrawal. Those with a predicted 1-year recurrence risk of ≤5.5% were prospectively followed. Study endpoint was recurrent VTE over 2 years. RESULTS: A total of 818 patients received anticoagulation for a median of 3.9 months. 520 patients (65%) had a predicted annual recurrence risk of ≤5.5%. During a median time of 23.9 months, 52 patients had non-fatal recurrence. The recurrence risk was 5.2% [95% confidence interval (CI) 3.2-7.2] at 1 year and 11.2% (95% CI 8.3-14) at 2 years. Model calibration was adequate after 1 year. The VPM underestimated the recurrence risk of patients with a 2-year recurrence rate of >5%. In a post-hoc analysis, the VPM's baseline hazard was recalibrated. Bootstrap validation confirmed an ideal ratio of observed and expected recurrence events. The recurrence risk was highest in men with proximal deep-vein thrombosis or pulmonary embolism and lower in women regardless of the site of incident VTE. CONCLUSIONS: In this prospective evaluation of the performance of the VPM, the 1-year rate of recurrence in patients with unprovoked VTE was 5.2%. Recalibration improved identification of patients at low recurrence risk and stratification into distinct low-risk categories.

Lipoprotein(a) and Pulmonary Embolism Severity-A Retrospective Data Analysis.

AIM: We aimed to investigate a correlation between PE severity and Lp(a) levels. METHODS: We performed a retrospective data analysis from our medical records of PE patients admitted to the University Hospital Graz, Austria. Patients with an Lp(a) reading within a 1-year interval before and after PE diagnosis were included. In accordance with the 2019 ESC guidelines for the diagnosis and management of acute PE, severity assessment was carried out classifying patients into four groups: low risk (LR), intermediate low risk (IML), intermediate high risk (IMH) and high risk (HR). The study period of interest was between January 1, 2002 and August 1, 2020. RESULTS: We analyzed 811 patients with PE, of whom 323 (40%) had low-risk PE, 343 (42%) had intermediate-low-risk PE, 64 (8%) had intermediate-high-risk PE, and 81 (10%) had high-risk PE, respectively. We did not observe an association between PE severity and Lp(a) concentrations. In detail, median Lp(a) concentrations were 17 mg/dL [25-75th percentile: 10-37] in low-risk PE patients, 16 mg/dL [10-37] in intermediate-low-risk PE patients, 15mg/dL [10-48] in intermediate-high-risk PE patients, and 13mg/dL [10-27] in high-risk PE patients, respectively (Kruskal-Wallis p = 0.658, p for linear trend = 0.358). CONCLUSION: The current findings suggest no correlation between PE severity and Lp(a) levels.

Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel.

INTRODUCTION: Recent advances in prophylactic anticoagulation and antineoplastic treatment for advanced pancreatic cancer (aPC) warrant an updated reassessment of thromboembolic risk in this population. This multicenter retrospective cohort study aims to comprehensively characterize incidence, risk factors, and outcomes of venous (VTE) and arterial thromboembolism (ATE) in homogenously treated patients with aPC. METHODS: Four hundred and fifty-five patients with aPC undergoing palliative first-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE. RESULTS: Over a median follow-up of 26 months, 86 VTE (cumulative incidence: 20.0%; 95% confidence interval [CI]: 16.3-24.0) and 11 ATE events (cumulative incidence: 2.8%; 95% CI: 1.5-4.9) were observed. VTE diagnosis was associated with increased mortality (transition hazard ratio [THR]: 1.59 [95% CI: 1.21-2.09]) and increased risk of cancer progression (THR: 1.47 [95% CI: 1.08-2.01]), while the impact of ATE on mortality was numerically but not statistically significant (THR: 1.85 [95% CI: 0.87-3.94]). The strongest predictor of increased VTE risk was history of cancer-associated VTE (subdistribution hazard ratio [SHR]: 3.29 [95% CI: 2.09-5.18]), while the Khorana score (SHR: 0.78 [0.57-1.06]) failed to predict VTE risk. A history of cerebrovascular disease was associated with markedly increased ATE risk (SHR: 22.05 [95% CI: 6.83-71.22], p < 0.001), especially ischemic stroke. Risk of VTE/ATE did not significantly differ according to type of first-line chemotherapy. CONCLUSION: Patients with aPC undergoing palliative first-line chemotherapy with FOLFIRINOX or GN face a high risk for VTE/ATE and its diagnosis is linked to worse clinical outcomes. VTE-risk prediction models have limited ability to sub-stratify thrombotic events in this high-risk scenario.

Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection-A Cross-Sectional Study.

Background: Rising data suggest that COVID-19 affects vascular endothelium while the underlying mechanisms promoting COVID-19-associated endothelial dysfunction and inflammatory vasculopathy are largely unknown. The aim was to evaluate the contribution of COVID-19 to persisting vascular injury and to identify parameters linked to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy. Methods: In a cross-sectional design, flow-mediated dilation (FMD), nitroglycerine-related dilation (NMD), pulse-wave velocity (PWV), augmentation index, intima-media thickness (IMT), compounds of the arginine and kynurenine metabolism, homocysteine, von Willebrand factor (vWF), endothelial microparticles (EMP), antiendothelial cell antibodies, inflammatory, and immunological parameters, as well as nailfold capillary morphology were measured in post-COVID-19 patients, patients with atherosclerotic cardiovascular diseases (ASCVD) and healthy controls without prior or recent SARS-CoV-2 infection. Results: Post-COVID-19 patients had higher values of PWV, augmentation index, IMT, asymmetric and symmetric dimethylarginine, vWF, homocysteine, CD31+/CD42b- EMP, C-reactive protein, erythrocyte sedimentation rate, interleukin-6, and ß-2-glycoprotein antibodies as well as lower levels of homoarginine and tryptophan compared to healthy controls (all with p < 0.05). A higher total number of pathologically altered inflammatory conditions and higher rates of capillary ramifications, loss, caliber variability, elongations and bushy capillaries with an overall higher microangiopathy evolution score were also observed in post-COVID-19 patients (all with p < 0.05). Most parameters of endothelial dysfunction and inflammation were comparably altered in post-COVID-19 patients and patients with ASCVD, including FMD and NMD. Conclusion: COVID-19 may affect arterial stiffness, capillary morphology, EMP and selected parameters of arginine, kynurenine and homocysteine metabolism as well as of inflammation contributing to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy.

Rituximab as a Treatment Option after Autologous Hematopoietic Stem Cell Transplantation in a Patient with Systemic Sclerosis.

Systemic sclerosis (SSc) is an intractable autoimmune disease characterized by vasculopathy and organ fibrosis. Autologous hematopoietic stem cell transplantation (AHSCT) should be considered for the treatment of selected patients with rapid progressive SSc at high risk of organ failure. It, however, remains elusive whether immunosuppressive therapies such as rituximab (RTX) are still necessary for such patients after AHSCT, especially in those with bad outcomes. In the present report, a 43-year-old man with diffuse cutaneous SSc received AHSCT. Despite AHSCT, SSc further progressed with progressive symptomatic heart failure with newly developed concomitant mitral and tricuspid valve insufficiency, thus the patient started on RTX 8 months after AHSCT. Shortly after initiation of RTX, clinical symptoms and organ functions ameliorated subsequently. Heart valve regurgitations were reversible after initiation of RTX treatment. Currently, the patient remains in a stable condition with significant improvement of clinical symptoms and organ functions. Reporting about therapies after AHSCT in SSc is a very important issue, as randomized controlled trials are lacking, and therefore this report adds to evidence that RTX can be considered as a treatment option in patients with SSc that do not respond to AHSCT.

Effect of short-interval rituximab and high-dose corticosteroids on kidney function in systemic sclerosis: Long-term experience of a single centre.

INTRODUCTION: Scleroderma renal crisis (SRC) is a rare but one of the most recognised complications of systemic sclerosis (SSc). Corticosteroid (CS) use has been considered as a major risk factor for SRC. Several studies reported the efficacy of rituximab (RTX) with an acceptable safety profile in SSc. However, data on the long-term effect of high-dose CS concomitant to RTX on kidney function are lacking. METHODS: We retrospectively analysed SSc patients (n = 35) treated with a lower dosage and short-interval RTX and concomitant high-dose CS at the Department of Internal Medicine at the Medical University of Graz between 2010 and 2019. The kidney function was assessed using the estimated glomerular filtration rate (eGFR) at every RTX admission. The annual decline of kidney function was evaluated by linear mixed model analysis. RESULTS: At the RTX initiation, one patient had a decreased kidney function indicated by eGFR < 60 mL/min/1.73 m2 (median: 96 mL/min/1.73 m2 ; interquartile range (IQR): 43-136). Patients received RTX and complementary high-dose CS for a median follow-up time of 3.4 years (range 0.6-9.5). A linear mixed model analysis with the patient as random effect and time from first RTX as fixed effect estimated an annual decline of 1.98 mL/min/1.73 m2 of the eGFR (95% confidence interval: [-2.24, -1.72]; P <.001). During the follow-up period, no patient experienced SRC or a significant drop in kidney function. CONCLUSIONS: A regular, high-dose CS given contemporary to RTX seems to be a safe option for kidney function in patients with SSc. Our findings provide additional knowledge in risk evaluation and planning of individualised therapies or designing clinical studies using RTX.

Prevalence and prognostic factors for aortic dilatation in giant cell arteritis - a longitudinal study.

OBJECTIVES: Predictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD. METHODS: GCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review. RESULTS: 144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p < 0.05). During follow-up, no GCA patient required surgical aortic repair or suffered aortic rupture/dissection. CONCLUSIONS: Thoracic but not abdominal ADs occur more commonly in GCA patients, however, the subsequent risk for aortic repair, rupture or dissection is low. Changes of T-cell subsets, presence of polymyalgia rheumatica and increased carotid IMT at disease onset are associated with AD development.

Platelet-rich Plasma for Androgenetic Alopecia Treatment: A Randomized Placebo-controlled Pilot Study.

Platelet-rich plasma injections have been presented as an effective treatment for androgenetic alopecia; however, reliable study data concerning this therapy are lacking. The current randomized, placebo-controlled pilot study explored this novel therapy in 30 healthy male subjects with androgenetic alopecia. Five platelet-rich plasma treatments, at intervals of 4-6 weeks, and 2 follow-up examinations were performed. Twenty subjects were injected intracutaneously with platelet-rich plasma and 10 with physiological saline. Treatment efficacy was assessed by changes in hair number and diameter, measured with the TrichoScan system. A secondary objective was to assess clinical improvement, which was evaluated by an independent reviewer using patient photographs and a 5-point Likert scale. In addition, subject satisfaction was assessed by survey. No improvements were seen over the course of the trial, using TrichoScan measurements or visual assessment. In conclusion, these results suggest that treatment with platelet-rich plasma as a monotherapy does not improve hair growth in men with androgenetic alopecia.

The White Blood Cell Count to Mean Platelet Volume Ratio for the Prediction of Chronic Limb-Threatening Ischemia in Lower Extremity Artery Disease.

: Background: The white blood cell count to mean platelet volume ratio (WMR) is increasingly gaining importance as a promising prognostic marker in atherosclerotic disease, but data on lower extremity artery disease (LEAD) are not yet available. The principle aim of this study was to assess the association of the WMR with the occurrence of CLTI (chronic limb-threatening ischemia) as the most advanced stage of disease. METHODS: This study was performed as a retrospective analysis on 2121 patients with a diagnosis of LEAD. Patients were admitted to the hospital for the reason of LEAD and received conservative or endovascular treatment. Blood sampling, in order to obtain the required values for this analysis, was implemented at admission. Statistical analysis was conducted by univariate regression in a first step and, in case of significance, by multivariate regression additionally. RESULTS: Multivariate regression revealed an increased WMR (p < 0.001, OR (95%CI) 2.258 (1.460-3.492)), but also advanced age (p < 0.001, OR (95%CI) 1.050 (1.040-1.061)), increased CRP (p < 0.001, OR (95%CI) 1.010 (1.007-1.014)), and diabetes (p < 0.001, OR (95%CI) 2.386 (1.933-2.946)) as independent predictors for CLTI. CONCLUSIONS: The WMR presents an easily obtainable and cost-effective parameter to identify LEAD patients at high risk for CLTI.

Increased Bleeding Risk in a Patient with Oral Anticoagulant Therapy and Concomitant Herbal Intake - A Case Report.

We report the case of a 36-year old male, under stable rivaroxaban therapy for 18 months, who was admitted to our emergency room with sudden onset of hemoptysis. Anticoagulant therapy was given after recurrent spontaneous deep vein thrombosis (DVT) and a heterozygous Factor-V-Leiden mutation was present. There was no co-medication reported, however, the patient reported a constant intake of three liters of home-brewn ginger tea per day in the last month. The patient was hospitalized to further investigate the reason of hemoptysis.

Reversal strategies in patients treated with direct oral anticoagulants.

Administration of direct oral anticoagulants (DOACs) for the treatment of venous thrombotic events (VTE) or non-valvular atrial fibrillation (AF) is now standard of care and has demonstrated clinical efficacy and safety in numerous clinical studies. Usually these substances have lower overall mortality and less risk of cerebral hemorrhage, but depending on the substance and study, they are more likely to cause gastrointestinal bleeding than vitamin K antagonists (VKA), the medication that used to be standard for VTE and AF. Since DOACs have very short plasma elimination half-lives compared to VKA, for most bleeding events, expert opinions suggest that withdrawal of DOACs and supportive care will likely suffice to stop a bleeding episode. Because there is a bleeding risk associated with DOACs, reversal strategies may be needed if a patient receiving DOAC therapy bleeds during surgery or an invasive procedure. So far, idarucizumab has been the only available antidote that binds specifically to dabigatran and safely and quickly reverses its anticoagulant effects. Idarucizumab has no effects on anti Xa inhibitors or other anticoagulants. To date, treatment of serious, life-threatening bleeds in patients with anti-Xa-inhibitor has involved 4 factor prothrombin complex concentrates (PCC). PCC restores normal hemostasis laboratory values in most patients with major bleeding events after anti Xa inhibitor intake. Recently, the US Food and Drug Administration (FDA) approved andexanet alfa as the first specific antidote for the anti-Xa inhibitors apixaban and rivaroxaban. So far clinical experience with this substance and data comparing it with PCC are lacking. Currently ciraparantag is under investigation as a universal reversal agent for all DOACs and low molecular weight heparin as well. Because it is so broadly applicable, ciraparantag might be a good future option for the management of most bleeding complications under anticoagulant treatment. The aim of this review is to summarize recent study data and recommendations on nonspecific and specific DOAC reversal strategies and to present the current evidence.