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.

Gender-specific differences in haemostatic parameters and their influence on blood loss in bimaxillary surgery.

OBJECTIVE: The objectives of this prospective cohort study were to establish gender-related differences in blood loss and haemostatic profiles associated with bimaxillary surgery. In addition, we aimed to identify if any gender differences could be established which might help predict blood loss volume. MATERIALS AND METHODS: Fifty-four patients (22 males; 32 females) undergoing bimaxillary surgery for skeletal dentofacial deformities were eligible for inclusion. Blood samples were taken 1 day preoperatively and 48 h postoperatively for detailed gender-specific coagulation analysis incorporating global coagulation assays (endogenous thrombin potential) and specific coagulation parameters. Blood loss was measured at two different time points: (1) the end of surgery, visible intraoperative blood loss (IOB) using 'subtraction method'; and (2) 48 h postoperatively perioperative bleeding volume (CBL-48 h) using 'haemoglobin-balance method' and Nadler's formula. Correlation and regression analyses were performed to identify relevant parameters affecting the amount of blood loss. RESULTS: Significant differences in IOB and CBL-48 h were observed (p < 0.001). Men had higher IOB versus women, lacking statistical significance (p = 0.056). In contrast, men had significantly higher CLB-48 h (p = 0.019). Reduced CBL-48 h was shown to be most closely associated with the level of Antithrombin-III being decreased in females. CONCLUSIONS: Male gender is associated with higher IOB and CBL-48 compared with females. Gender does not affect IOB regarding haemostatic profile but does correlate strongly with procedure length. Conversely, CBL-48 is closely associated with gender-specific imbalances in the anticoagulant system. CLINICAL RELEVANCE: Knowledge of gender-related differences will help clinicians establish predictive factors regarding excessive blood loss in orthognathic surgery and identify at-risk patients.

VA-ECMO and thrombus aspiration in a pulmonary embolism patient with cardiac arrest and contraindications to thrombolytic therapy.

A 57-year-old male patient with a history of proximal deep vein thrombosis on vitamin K antagonist therapy, suffered a recent hypertensive intracranial hemorrhage without significant neurological deficit. Three weeks later he presented with bilateral central pulmonary embolism. He had witnessed cardiac arrest and was put on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Endovascular thrombectomy with an Aspirex device led to a significant improvement of hemodynamics. VA-ECMO was terminated after one day, an IVC filter was inserted, and he was discharged from ICU after 15 days. In conclusion, VA-ECMO and endovascular therapy are rescue strategies in patients with contraindications for thrombolysis.

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.

Preserved Left Atrial Mechanics Following a 5-h Laboratory Triathlon in Euhydrated Athletes.

The purpose of this study was to investigate echocardiographic changes in left ventricular (LV) diastolic filling and left atrial (LA) strain mechanics following prolonged exercise. Ten male triathletes completed a 60-min swim, 180-min bike exercise, and a 60-min all-out run in a laboratory environment. Special attention was paid to prevent dehydration and energy deficit during the exercise protocol. All participants underwent comprehensive echocardiographic analyses of Doppler- and volumetric-derived LV diastolic filling indices and novel speckle-tracking echocardiography (STE)-derived LA strain indices. LV stroke volume (pre: 108.0±15.9 vs. post: 88.8±19.0 mL; p=0.03) and LA passive emptying volume (pre: 31.2±7.5 vs. post: 22.4±9.8 mL; p=0.05) were significantly reduced following the exercise protocol. Of the STE-derived indices of LA function, reservoir and conduit strain did not change significantly, while there was a trend towards enhanced contraction strain (pre: 15.1±3.8 vs. post: 19.4±4.8%; p=0.07). Resting heart rate was significantly higher post-exercise (53.1±5.0 vs. 81.9±16.9 bpm; p<0.001) and its change correlated strongly with depression of Doppler-derived ratio of early to late ventricular filling velocities (r=0.74, p=0.01) and reduction of LA passive emptying volume (r=0.86, p=0.01). Following prolonged exercise, LV stroke volume was reduced due to heart rate related reduction in LA passive emptying volume whereas global LA strain mechanics were not compromised in this study.

Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study.

The aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96-692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87-5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

Age-dependent effects of homocysteine and dimethylarginines on cardiovascular mortality in claudicant patients with lower extremity arterial disease.

The association among serum homocysteine (HCY), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial dysfunction, although the underlying pathology is not fully elucidated. We investigated the relationship of HCY with SDMA and ADMA regarding their long-time outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant patients with lower extremity arterial disease. 120 patients were included in a prospective observational study (observation time 7.96 ± 1.3 years) with cardiovascular mortality as the main outcome parameter. Patients with intermittent claudication prior to their first endovascular procedure were included. HCY, SDMA, and ADMA were measured by high-performance liquid chromatography. Cutoff values for HCY (≤/>15 µmol/l), SDMA (≤/>0.75 µmol/l), and ADMA (≤/>0.8 µmol/l) differed significantly regarding cardiovascular mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In multivariable linear regression, age was the only significant independent risk factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007-0.028; p = 0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age was an independent predictor for cardiovascular death. Older patients have higher values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff values of HCY and SDMA due to strong age dependency.

[Edoxaban for stroke prevention in atrial fibrillation and treatment of venous thromboembolism: an expert position paper]. / Edoxaban zur Schlaganfallprophylaxe bei Patienten mit nicht-valvulärem Vorhofflimmern und zur Behandlung venöser Thromboembolien: ein interdisziplinäres Positionspapier.

Edoxaban is the most recent available representative of the Non-Vitamin K antagonist oral anticoagulants (NOAC). The approval was based on the largest phase III trials of NOACs for stroke prevention in patients with non-valvular atrial fibrillation (AF, ENGAGE-AF), and for the treatment of venous thromboembolism (VTE, HOKUSAI-VTE). In both trials, edoxaban was associated with similar efficacy and a significant reduction in bleeding events with respect to the pre-defined primary safety endpoints, as compared to warfarin.Additionally, the once daily dosing of edoxaban, the clinically investigated strategy for dose-reduction based on clearly defined criteria and the favorable pharmacokinetic profile might further support the clinical applicability of the substance.In the light of recent data, this expert consensus document aims to summarize the latest clinical trial results while providing a concise overview of current guideline recommendations on the management of patients with non-valvular AF and VTE.

Blood Platelet Volume Represents a Novel Prognostic Factor in Patients with Nonmetastatic Renal Cell Carcinoma and Improves the Predictive Ability of Established Prognostic Scores.

PURPOSE: The average size of blood platelets determined by mean platelet volume might represent a biologically meaningful parameter in carcinogenesis and potentially serve as a novel prognostic biomarker in renal cell carcinoma. MATERIALS AND METHODS: In this retrospective analysis of the records of 652 patients we evaluated the potential prognostic value of mean platelet volume and its ability to improve existing risk assessment tools used in adjuvant clinical trials in nonmetastatic renal cell carcinoma cases. Associations of mean platelet volume with baseline covariates and clinical outcomes (recurrence, and death from renal cell carcinoma and other causes) were assessed with the competing risk estimators of Kaplan-Meier, and Marubini and Valsecchi, respectively. Univariable and multivariable Cox proportional hazard models were constructed. The Harrell c-index was applied to test improvements in the predictive accuracy of the established Leibovich prognosis score. RESULTS: Small platelet volume was associated with large tumors (p = 0.043), high Fuhrman grade (p = 0.001), sarcomatoid components (p <0.0001), histological tumor necrosis (p = 0.044) and vascular invasion (p = 0.022). On univariable and multivariable analyses small platelet volume accurately predicted recurrent renal cell carcinoma (continuously and binary coded) and cancer specific survival. Adding mean platelet volume to the Leibovich prognosis score improved its discriminative performance (c-index = 0.83, p = 0.004). CONCLUSIONS: Mean platelet volume represented a highly significant predictor of recurrence and cancer specific death in patients with renal cell carcinoma. This parameter improved the accuracy of the Leibovich prognosis score to better predict long-term outcomes in localized renal cell carcinoma cases after curative surgical resection.

Intra-arterial thrombolysis of digital artery occlusions in a patient with polycythemia vera.

There are limited therapeutic options for the resolution of digital artery occlusions. Intra-arterial thrombolysis with anticoagulative and thrombolytic drugs successfully restored the blood flow in the affected digital arteries.

NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients.

BACKGROUND: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. METHODS: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. RESULTS: Five-year OS and PFS were 50.4% (95% CI: 39.2-60.6) and 44.0% (33.4-54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl-1), and 66.2% (60.4-71.5) and 59.6% (53.7-65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10-1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16-2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17-9.23, P<0.0001). CONCLUSIONS: We demonstrate that elevated uric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index.

Uric acid levels in blood are associated with clinical outcome in soft-tissue sarcoma patients.

BACKGROUND: Recent evidence indicates toward a role of uric acid (UA) as a potential antioxidant. Elevated UA levels were shown to be associated with better survival in various malignancies. The aim of the present study was to evaluate the prognostic relevance of pre-operative UA levels on cancer-specific survival (CSS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection. METHODS: Three hundred and fifty-seven patients with STS were included in the study. Pre-operative serum UA level was measured using an enzymatic colorimetric assay. The effect of UA levels on CSS was analyzed using Kaplan-Meier curves. To further evaluate the prognostic impact of UA levels, univariate and multivariate Cox proportional models were calculated. RESULTS: Among the 357 STS patients, cancer-related deaths occurred in 20 (24.7%) of 81 patients with a serum UA level <279.6 µmol/L and in 36 (13%) of 276 patients with a UA level ≥279.6 µmol/L. In univariate analysis, elevated UA levels were significantly associated with increased CSS in STS patients [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.26-0.77, p=0.004]. Furthermore, elevated UA levels remain a significant factor for better CCS in multivariate analysis (HR 0.42, 95% CI 0.23-0.75, p=0.003). CONCLUSIONS: Our study is the first one to demonstrate that higher UA levels are associated with positive clinical outcome in STS patients. UA levels are a simple and cost-effective test for the assessment of the prognosis of STS patients.

Endothelial function and carotid intima-media thickness in giant-cell arteritis.

BACKGROUND: Vascular endothelial dysfunction and intima-media thickness are characteristic aspects of several vasculitides. We investigated retrospectively the impact of steroid treatment on endothelial dysfunction and intima-media thickness in giant-cell arteritis. METHODS: Forty-one patients with giant-cell arteritis (28 female and 13 male) underwent flow-mediated dilatation, a marker of endothelial function, and carotid intima-media thickness within 24 h after diagnosis and 6 months thereafter. Both parameters were investigated in 41 patients of an age- and gender-matched control group. RESULTS: Brachial flow-mediated dilatation response at baseline was 3.4% (0.2, 8.0) and 1.7% (0.2, 4.8) in giant-cell arteritis patients and control group, respectively. After 6 months treatment, flow-mediated dilatation response was 2.8% (0.4, 4.8) in patients with giant-cell arteritis (P = 0.066) and 1.4% (0.1, 5.5) in the control group (P = 0.741). In contrast, mean carotid intima-media thickness of giant-cell arteritis patients improved significantly between baseline [1.0 mm (0.79, 1.2)] and 6-month follow-up [0.82 mm (0.7, 1.04), P < 0.001]. Subjects with additional symptoms of polymyalgia rheumatica had a notable enlargement of carotid intima-media thickness [1.23 mm (1.14, 2.09)] compared to giant-cell arteritis patients without polymyalgia rheumatica at baseline [0.91 mm (0.76, 1.04), P = 0.001] and 6-month follow-up [1.16 mm (0.80, 1.26) vs. 0.77 mm (0.68, 0.88), P = 0.009]. CONCLUSION: Steroid therapy has no influence on endothelial function but does significantly improve carotid intima-media thickness in giant-cell arteritis. This divergence of endothelial function and intima-media thickness reflects the specifity of giant-cell arteritis for cerebrovascular arteries thereby sparing the brachial arteries.

Changes in lipid metabolism and extension of venous thromboembolism.

BACKGROUND/AIMS: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common diseases with a vast number of acquired and congenital risk factors. Disorders of the lipid metabolism are not established risk factors for venous thromboembolism (VTE) so far. However, in recent literature, associations between VTE and the metabolic syndrome, especially with elevated lipid parameters, have been described. The aim of our study was to investigate the association between the extension of VTE and changes in the lipid profile. METHODS: We included 178 VTE patients in our study; 59 patients had isolated PE, 39 patients had isolated DVT of the leg and 80 patients had both (DVT and PE). Concerning PE, we distinguished between massive and submassive PE. We evaluated plasma lipids and lipoproteins in PE and DVT patients as well as in massive and submassive PE patients. RESULTS: PE patients had higher levels of plasma triglycerides [median (interquartile range): 162 (109-254) vs. 136.5 (96.5-162) mg/dl, p = 0.047] and lower levels of high-density lipoprotein cholesterol (HDL-C; 52.1 ± 17.2 vs. 63.9 ± 22.7 mg/dl, p = 0.004) than DVT patients. Furthermore, PE patients were significantly older than DVT patients (59.6 ± 16.9 vs. 52.2 ± 15.5 years, p = 0.02). We were not able to find differences in lipid parameters in patients with massive PE compared to those with submassive PE. However, patients with massive PE were more obese than patients with submassive PE (body mass index 29.1 ± 4.6 vs. 26.9 ± 4.9, p = 0.012). CONCLUSIONS: Lipid parameters and lipoproteins differ between DVT and PE patients. PE patients had higher triglyceride and lower HDL-C levels compared with DVT patients.

Cancer related venous thromboembolism - prophylaxis and therapy.

Cancer is a highly thrombophilic entity leading to a high rate of symptomatic and even asymptomatic venous thromboembolic (VTE) events in patients suffering from malignant disease. As VTE events have impact on survival and can be reduced significantly by anticoagulant treatment, guidelines on prophylaxis of these events by means of anticoagulation exist from various societies. Purpose of this review is to give a concise overview of current possibilities for prophylaxis and also for the therapy of VTE events in cancer patients.

Incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a U.S. population: a retrospective population-based study.

BACKGROUND: Skin and soft tissue infections (SSTIs) are commonly occurring infections with wide-ranging clinical manifestations, from mild to life-threatening. There are few population-based studies of SSTIs in the period after the rapid increase in community-acquired methicillin-resistant Staphyloccus aureus (MRSA). METHODS: We used electronic databases to describe the incidence, microbiology, and patient characteristics of clinically-diagnosed skin and soft tissue infections (SSTIs) among members of a Northern California integrated health plan. We identified demographic risk factors associated with SSTIs and MRSA infection. RESULTS: During the three-year study period from 2009 to 2011, 376,262 individuals experienced 471,550 SSTI episodes, of which 23% were cultured. Among cultured episodes, 54% were pathogen-positive. Staphylococcus aureus (S. aureus) was isolated in 81% of pathogen-positive specimens, of which nearly half (46%) were MRSA. The rate of clinically-diagnosed SSTIs in this population was 496 per 10,000 person-years. After adjusting for age group, gender, race/ethnicity and diabetes, Asians and Hispanics were at reduced risk of SSTIs compared to whites, while diabetics were at substantially higher risk compared to non-diabetics. There were strong age group by race/ethnicity interactions, with African Americans aged 18 to <50 years being disproportionately at risk for SSTIs compared to persons in that age group belonging to other race/ethnicity groups. Compared to Whites, S. aureus isolates of African-Americans and Hispanics were more likely to be MRSA (Odds Ratio (OR): 1.79, Confidence Interval (CI): 1.67 to 1.92, and, OR: 1.24, CI: 1.18 to 1.31, respectively), while isolates from Asians were less likely to be MRSA (OR: 0.73, CI: 0.68 to 0.78). CONCLUSIONS: SSTIs represent a significant burden to the health care system. The majority of culture-positive SSTIs were caused by S. aureus, and almost half of the S. aureus SSTIs were methicillin-resistant. The reasons for African-Americans having a higher likelihood, and Asians a lower likelihood, for their S. aureus isolates to be methicillin-resistant, should be further investigated.