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There is a growing clinical and scientific interest in catheter-directed therapy (CDT) of acute pulmonary embolism (PE). Currently, CDT should be considered for patients with high-risk PE, in whom thrombolysis is contraindicated or has failed. Also, CDT is a treatment option for initially stable patients in whom anticoagulant treatment fails, i.e., those who experience haemodynamic deterioration despite adequately dosed anticoagulation. However, the definition of treatment failure (primary reperfusion therapy or anticoagulation alone) remains an important area of uncertainty. Moreover, several techniques for CDT are available without evidence supporting one over the other, and variation in practice with regard to periprocedural anticoagulation is considerable. The aim of this position paper is to describe the currently available CDT approaches in PE patients and to standardise patient selection, the timing and technique of the procedure itself as well as anticoagulation regimens during CDT. We discuss several clinical scenarios of the clinical evaluation of the "efficacy" of thrombolysis and anticoagulation, including treatment failure with haemodynamic deterioration and treatment failure based on a lack of improvement. This clinical consensus statement serves as a practical guide for CDT, complementary to the formal guidelines.

Background In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. Methods This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. Results In the primary analysis, 587 patients were included (age: 57 [Q1–Q3: 45–68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60–1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42–0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41–1.01, p = 0.05). Conclusion Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset. (NCT04486508).

Background Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Historical epidemiological data on SVT-related mortality rate is not available to date. Methods We investigated time trends in SVT-related mortality, 2008–2019, in Veneto, an Italian high-income region of approximatively 5,000,000 inhabitants. SVT-related deaths were identified by the following ICD-10 codes: I81 (portal vein thrombosis), K75.1 (phlebitis of portal vein), K76.3 (liver infarction), K76.5 (hepatic veno-occlusive disease) or I82.0 (Budd-Chiari syndrome). Results During the study period, a total of 557,932 deaths were recorded. SVT was reported in 823 cases; 776 (94%) consisted of portal vein thrombosis. The age-standardized SVT-related mortality rate varied from 1.47 (year 2008) to 1.52 (year 2019) per 100,000 person-years. An increase in the cause-specific annual mortality rate was observed in women (0.56 in 2008 to 1.04 per 100,000 person-years in 2019; average annual percent change +5.7%, 95%CI +3.1; +8.3%). In men, the cause-specific mortality rate moved from 2.53 in 2008 to 2.03 per 100,000 person-years in 2019 (average annual percent change −1.2%, 95%CI -4.0; +1.6%). After conditioning for age and sex, the odds of having a concomitant liver disease were higher for SVT-related deaths (OR 31.6; 95%CI 17.1–37.0) compared with non-SVT-related deaths. This also applies to gastrointestinal cancers (OR 1.28; 95%CI 1.07–1.55), although to a lesser extent. Conclusions We report first epidemiological estimates of SVT-related mortality in a Western country. These values will serve as a reference to weight novel potential factors associated with SVT-related death, putting them into an epidemiological perspective. Summary box What is already known about this subject? Splanchnic vein thrombosis is a rare manifestation of venous thromboembolism, often related to liver diseases. Currently, there is no available data on its impact on the general population in terms of mortality rates. What are the new findings? Splanchnic vein thrombosis-related mortality rate was higher in men than in women and was strongly associated with the presence of liver diseases. In women, the age-standardized splanchnic vein thrombosis-related mortality rate has been increasing since 2008. How might it impact on clinical practice in the foreseeable future? We report first epidemiological estimates of splanchnic vein thrombosis-related mortality rates in a Western country. These values will serve as a reference to weight novel factors or pathologies potentially associated with splanchnic vein thrombosis and interpret them in an epidemiological perspective.

AIM OF THE STUDY Extracorporeal membrane oxygenation (ECMO) is considered a life-saving treatment option for patients in cardiogenic shock or cardiac arrest undergoing cardiopulmonary resuscitation (CPR) due to acute pulmonary embolism (PE). We sought to analyze use and outcome of ECMO with or without adjunctive treatment strategies in patients with acute PE. METHODS We retrospectively analyzed data on patient characteristics, treatments, and in-hospital outcomes for all PE patients (ICD-code I26) undergoing ECMO in Germany between 2005 and 2018. RESULTS At total of 1,172,354 patients were hospitalized with PE; of those, 2,197 (0.2%) were treated with ECMO support. Cardiac arrest requiring cardiopulmonary resuscitation was present in 77,196 (6.5%) patients. While more than one fourth of those patients were treated with systemic thrombolysis alone (n = 20,839 patients; 27.0%), a minority of patients received thrombolysis and VA-ECMO (n = 165; 0.2%), embolectomy and VA-ECMO (n = 385; 0.5%) or VA-ECMOalone (n = 588; 0.8%). A multivariable logistic regression analysis indicated the lowest risk for in-hospital death in patients who received embolectomy in combination with VA-ECMO (OR, 0.50 [95% CI, 0.41-0.61], p

BACKGROUND Although the two manifestations of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE), vary considerably, the consensus guidelines recommend similar algorithms for therapeutic anticoagulation in both conditions. Real-world data assessing contemporary management strategies in PE and DVT alone may help tailoring future recommendations towards more individualized patient care. METHODS In the present analysis, we compared demographics, comorbidities, treatment patterns, and clinical outcomes of PE versus DVT only among 2062 consecutive patients with confirmed VTE enrolled by 11 acute care hospitals between November 2012 and February 2015 in the SWIss Venous ThromboEmbolism Registry (SWIVTER). RESULTS Overall, 1246 (60 %) patients were diagnosed with PE. In comparison to DVT alone, PE patients were older (66 vs. 59 years; p

Background: Cancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty. Methods: We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media. Results: As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received. Conclusions: This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden.

Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs among survivors are receiving increasing attention. Detailing this burden would support an efficient public health resource allocation. We aimed to provide estimates for the economic and disease burden of PE also accounting for long‐term health care use and both direct and indirect costs beyond the acute phase. Methods and Results This is a cost‐of‐illness analysis with a bottom‐up approach based on data from the PREFER in VTE registry (Prevention of Thromboembolic Events—European Registry in Venous Thromboembolism). We calculated direct (clinical events and anticoagulation) and indirect costs (loss of productivity) of an acute PE event and its 12‐month follow‐up in 2020 Euros. We estimated a disability weight for the 12‐month post‐PE status and corresponding disability adjusted life years presumably owing to PE. Disease‐specific costs in the first year of follow‐up after an incident PE case ranged between 9135 Euros and 10 620 Euros. The proportion of indirect costs was 42% to 49% of total costs. Costs were lowest in patients with ongoing cancer, mainly because productivity loss was less evident in this already burdened population. The calculated disability weight for survivors who were cancer free 12 months post‐PE was 0.017, and the estimated disability adjusted life years per incident case were 1.17. Conclusions The economic burden imposed by PE to society and affected patients is considerable, and productivity loss is its main driver. The disease burden from PE is remarkable and translates to the loss of roughly 1.2 years of healthy life per incident PE case.

The International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum set of outcomes and outcome measurements for integration into clinical practice and potentially research to support clinical decision making and benchmarking of quality of care. 15 core outcomes important to patients and health-care professionals were selected and categorised into four domains: patient-reported outcomes, long term consequences of the disease, disease-specific complications, and treatment-related complications. The outcomes and outcome measures were designed to apply to all patients with venous thromboembolism aged 16 years or older. A measurement tool package was selected for inclusion in the core standard set, with a minimum number of items to be measured at predefined timepoints, which capture all core outcomes. Additional measures can be introduced to the user by a cascade opt-in system that allows for further assessment if required. This set of outcomes and measurement tools will facilitate the implementation of the use of patient-centred outcomes in daily practice.

There is a paucity of data on anticoagulation strategies and clinical outcomes after bleeding events for venous thromboembolism (VTE). In a multicenter Japanese registry enrolling 3027 patients with acute symptomatic VTE, after excluding 430 patients with thrombolysis and 207 patients without anticoagulation therapy, the current study population consisted of 2390 patients, who were divided into patients with major bleeding, clinically relevant non-major (CRNM) bleeding and no bleeding during anticoagulation therapy. All-cause death at 90 days after the bleeding events was evaluated as the primary outcome. There were 189 patients with major bleeding, 147 patients with CRNM bleeding, and 2054 patients without bleeding. Among 189 patients with major bleeding, 142 patients (75%) discontinued anticoagulants, of whom patients with temporary discontinuation and those with permanent discontinuation accounted for 63 patients (44%) and 79 patients (56%), and 58 patients (30.7%) died within 90 days after the bleeding events. The multivariable logistic regression model among patients with bleeding events revealed that active cancer and bleeding events within 90 days after VTE diagnosis were independently associated with 90-day mortality after the bleeding events (active cancer: OR 5.05, 95%CI 2.82-9.05; bleeding events within 90 days after VTE diagnosis: OR 2.23, 95%CI 1.25-3.96). In this practice-based large registry, anticoagulants were frequently discontinued in patients who experienced major bleeding events during anticoagulation therapy and nearly half of them restarted anticoagulants with mortality rate of approximately 30% within 90 days after the bleeding events, and active cancer was the most prevalent cause of death.Clinical trial registration COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000021132.

Background Despite evidence of ongoing epidemiological changes in deaths from venous thromboembolism in high-income countries, little recent information is available on the time trends in mortality related to pulmonary embolism (PE) as underlying or concomitant cause of death in Europe. Methods We accessed the regional database of death certificates of Veneto Region (Northern Italy, population 4,900,000) from 2008 to 2019. We analyzed the trends in crude and age-adjusted annual rates of mortality related to PE (reported either as underlying cause or in any position in the death certificate) using Joinpoint regression; in the contribution of PE to mortality (proportionate mortality); and, using logistic regression, in the association between PE and cancer at death. Results Between 2008 and 2019, the annual age-standardized mortality rate related to PE in Veneto decreased from 20.7 to 12.6 deaths per 100,000 population for PE in any position of the death certificate, and from 4.6 to 2.2 deaths per 100,000 population for PE as underlying cause of death. PE-related proportionate mortality remained up to twice as high in women. The age- and sex-adjusted odds ratio for cancer in deaths with versus without PE constantly increased from 1.01 (95% confidence interval [CI]: 0.88–1.16) in 2008 to 1.58 (95% CI: 1.35–1.83) in 2019. Conclusion The descending trends in PE-related mortality reported for Europe up to 2015 for both sexes continued thereafter in this high-income region of Northern Italy. However, sex differences in proportionate mortality persist. The increasing strength in the association between cancer and PE may indicate a change in risk factor distribution, calling for tailored management practices in this patient group.

Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure ≤110 mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations. ispartof: THROMBOSIS AND HAEMOSTASIS vol:122 issue:05 pages:857-866 ispartof: location:Germany status: published

Mondor disease is characterized by an acute painful thrombophlebitis occurring at specific anatomical sites. Data on its incidence, characteristics of clinical presentation, and course are unavailable to date. We studied the course of Mondor disease in patients diagnosed and followed at the University Hospital Zurich (Switzerland) between 2004 and 2020. The primary study outcomes were a diagnosis of active cancer either at the time of clinical diagnosis of Mondor disease or within 1 year, as well as 1-year all-cause death and recurrent Mondor disease. We included 45 patients and classified them into one of the three Mondor disease subgroups: thoracic ( n = 26), penile ( n = 12), or axillary ( n = 7). The median age was 39 (Q1–Q3: 30–45) years and 44% of patients were men. Surgery was the likely cause of Mondor disease in 53.8% of patients with a thoracic form, 41.7% of those with a penile location, and all of those with an axillary location. Known active cancer was present in nine (20%) of 45 patients at baseline. One-year follow-up was available for 43 patients (median 94 months), whereas 6-month data were available for the remaining two patients. During the available follow-up, no patient had a new diagnosis of cancer. In conclusion, one in five patients with Mondor disease had known cancer at the time of diagnosis. During follow-up, the rate of new cancer diagnosis and death was negligible, providing reassurance about the good prognosis of this condition. Based on these preliminary data, extended cancer screening besides what is recommended by current guidelines for the general population might not be necessary in patients with Mondor disease.

Background Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19. Methods In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up. In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist. The primary outcome was symptomatic VTE within 45 days of hospital discharge. Results Of 1529 COVID-19 patients discharged from hospital, a total of 228 (14.9%) reported potential signs or symptoms of PE or DVT and were seen for an in-hospital visit. Of these, 13 and 12 received Doppler ultrasounds or pulmonary CT angiography, respectively, of whom only one patient was diagnosed with symptomatic PE. Of 51 (3.3%) patients who died after discharge, two deaths were attributed to VTE corresponding to a 45-day cumulative rate of symptomatic VTE of 0.2% (95%CI 0.1%–0.6%; n = 3). There was no evidence of acute respiratory distress syndrome (ARDS) in these patients. Other deaths after hospital discharge included myocardial infarction (n = 13), heart failure (n = 9), and stroke (n = 9). Conclusions We did not observe a high rate of symptomatic VTE in COVID-19 patients after hospital discharge. Routine extended thromboprophylaxis after hospitalization for COVID-19 may not have a net clinical benefit. Randomized trials may be warranted., Highlights • In a large multi-center study, the incidence of venous thromboembolism in COVID-19 patients followed for 45 days after hospitalization was relatively low. • Routine extended thromboprophylaxis in COVID-19 patients who have been discharged from the hospital may not have a net clinical benefit. • Older age, history of recent cancer, and history of recent diabetes were associated with higher risk of mortality after hospital discharge

Essentials Prekallikrein (PK) deficiency is a recessive trait with isolated aPTT prolongation. KLKB1 c.451dupT is common in Nigerians (7/600 alleles) and absent in a European group (0/600). To date, all genotyped PK-deficient patients of African ancestry were homozygous for 451dupT. Diagnostics of isolated aPTT prolongation in African descendants should include PK testing. ABSTRACT: Background Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Africans according to gnomAD (allele frequency 1.43%). Patients/Methods The most common African (c.451dupT) and European (c.1643G>A, p.Cys548Tyr) PK deficiency causing KLKB1 variants were analyzed in two population-based collectives of 300 Nigerian and 300 German subjects. Genome databases were evaluated for variant frequencies and ethnicity of the subjects. The geographic origin of PK-deficient cases due to 451dupT was assessed. Results Two of five patients with PK deficiency caused by homozygous 451dupT were African, one African American, one from Oman, and one of unknown origin. The frequency of 451dupT was 1.17% in the Nigerian collective (7/600 alleles); none had Cys548Tyr. Subjects with 451dupT were found among different Nigerian ethnicities. Both variants were absent in the European collective. Database research was compatible with these findings, even though mainly data of African Americans (451dupT: 1.12%-1.78%) was accessible. A relevant number of non-American Africans are included only in the 1000Genomes collective: 451dupT frequency was 1.29% in native Africans and 1.56% in African Caribbeans. Conclusions This study underlines the higher prevalence of PK deficiency among people with African descent compared to Europeans. In order to avoid delay of necessary surgical procedures in patients of African origin, diagnostic algorithms for isolated, unexplained, activated partial thromboplastin time prolongation in these subjects should include PK deficiency screening.

Recombinant interleukin-2 (rIL-2) is indicated for metastatic renal cell carcinoma and melanoma. Over recent years low-dose rIL-2 has been studied for the treatment of autoimmune diseases and acute coronary syndrome because of its ability to expand and activate T regulatory (Treg) cells. However, several medical conditions potentially benefiting from rIL-2 administrations are characterized by an intrinsic prothrombotic risk, thus requiring concurrent anticoagulation. In our systematic review of the literature, we investigated the potential for drug interactions between oral anticoagulants and rIL-2 by assessing the influence of rIL-2 administration on transporters and cytochromes determining the pharmacokinetics of (direct) oral anticoagulants. We extracted data from 12 studies, consisting of 11 animal studies and one study in humans. Eight studies investigated the pharmacokinetics of P-glycoprotein (P-gp) substrates and reported that the intraperitoneal rIL-2 administration may inhibit intestinal P-gp. Four studies on hepatic cytochrome P450 yielded conflicting results. The only human study included in this systematic review concluded that rIL-2 suppresses the hepatic cytochrome P450, but only if given at higher doses. Based on the results from animal studies, the co-administration of rIL-2 and dabigatran etexilate, a substrate of intestinal P-gp, may lead to higher dabigatran plasma concentrations and bioavailability. Human studies should confirm whether this potential interaction is clinically relevant.

COVID-19 is a viral prothrombotic respiratory infection. Heparins exert antithrombotic and anti-inflammatory effects, and might have antiviral properties. We aimed to investigate whether thromboprophylaxis with enoxaparin would prevent untoward hospitalisation and death in symptomatic, but clinically stable outpatients with COVID-19.OVID was a randomised, open-label, parallel-group, investigator-initiated, phase 3 trial and was done at eight centres in Switzerland and Germany. Outpatients aged 50 years or older with acute COVID-19 were eligible if they presented with respiratory symptoms or body temperature higher than 37·5°C. Eligible participants underwent block-stratified randomisation (by age group 50-70 vs70 years and by study centre) in a 1:1 ratio to receive either subcutaneous enoxaparin 40 mg once daily for 14 days versus standard of care (no thromboprophylaxis). The primary outcome was a composite of any untoward hospitalisation and all-cause death within 30 days of randomisation. Analysis of the efficacy outcomes was done in the intention-to-treat population. The primary safety outcome was major bleeding. The study was registered in ClinicalTrials.gov (NCT04400799) and has been completed.At the predefined formal interim analysis for efficacy (50% of total study population), the independent Data Safety Monitoring Board recommended early termination of the trial on the basis of predefined statistical criteria having considered the very low probability of showing superiority of thromboprophylaxis with enoxaparin for the primary outcome under the initial study design assumptions. Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53-62) and 217 (46%) were women. The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 [3%] of 234 vs 8 [3%] of 238; adjusted relative risk 0·98; 95% CI 0·37-2·56; p=0·96). All hospitalisations were related to COVID-19. No deaths were reported during the study. No major bleeding events were recorded. Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group.These findings suggest thromboprophylaxis with enoxaparin does not reduce early hospitalisations and deaths among outpatients with symptomatic COVID-19. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates.SNSF (National Research Programme COVID-19 NRP78: 198352), University Hospital Zurich, University of Zurich, Dr-Ing Georg Pollert (Berlin), Johanna Dürmüller-Bol Foundation.

We aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80–4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20–3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33–3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29–5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis.

Pulmonary embolism is a known complication of coronavirus disease 2019 (COVID-19). Epidemiological population data focusing on pulmonary embolism-related mortality is limited.Veneto is a region in Northern Italy counting 4,879,133 inhabitants in 2020. All ICD-10 codes from death certificates (1st January 2018 to 31st December 2020) were examined. Comparisons were made between 2020 (COVID-19 outbreak) and the average of the two-year period 2018-2019. All-cause, COVID-19-related and the following cardiovascular deaths have been studied: pulmonary embolism, hypertensive disease, ischemic heart disease, atrial fibrillation/flutter, and cerebrovascular diseases.In 2020, a total of 56,412 deaths were recorded, corresponding to a 16% (n = 7806) increase compared to the period 2018-2019. The relative percentage increase during the so-called first and second waves was 19% and 44%, respectively. Of 7806 excess deaths, COVID-19 codes were reported in 90% of death certificates. The percentage increase in pulmonary embolism-related deaths was 27% (95%CI 19-35%), 1018 deaths during the year 2020, compared to 804 mean annual deaths in the period 2018-2019. This was more evident among men, who experience an absolute increase of 147 deaths (+45%), than in women (+67 deaths; +14%). The increase was primarily driven by deaths recorded during the second wave (+91% in October-December). An excess of deaths, particularly among men and during the second wave, was also observed for other cardiovascular diseases, notably hypertensive disease, atrial fibrillation, cerebrovascular disease, and ischemic heart disease.We observed a considerable increase of all-cause mortality during the year 2020. This was mainly driven by COVID-19 and its complications. The relative increase in the number of pulmonary embolism-related deaths was more prominent during the second wave, suggesting a possible underdiagnosis during the first wave.

The global annual incidence of venous thromboembolism (VTE) is estimated to be 0.75-2.69 per 1,000 population (1). Up to 60% of VTE events occur during or within three months after hospital admission: these are known as hospital-associated VTE and account for an estimated 10 million cases of VTE globally (2). Without preventive measures being used, hospital-associated VTE is the leading preventable cause of hospital death (2). The age-standardized pulmonary embolism (PE)-related mortality rate is similar in magnitude to respiratory infections and obstructive pulmonary disease. Although the impact of PE-related deaths is relatively high among young women (3), its global awareness by the public is low (4).

The clinical spectrum of patients with coronavirus disease 2019 (COVID-19) ranges from asymptomatic cases to severe pneumonia with acute respiratory distress syndrome. COVID-19 is associated with an increased risk of thromboembolic complications, notably pulmonary embolism and deep vein thrombosis. Arterial cardiovascular complications and myocarditis have also been described in association with COVID-19, but appear to be less prevalent. In this report of a 57-year-old man with multiple splanchnic infarctions, arterial dissections and COVID-19 as the sole potential trigger, we describe a novel type of complications and put it in the context of a growing literature on this topic.

Background Pulmonary embolism (PE) is a potentially fatal disease, but data on the incidence of fatal PE in cancer patients are scant. Objective We sought to estimate the proportion of cancer patients with PE at autopsy. Methods For this retrospective cohort study, all autopsy reports of cancer patients were retrieved from PALGA: Dutch Pathology Registry and used for data extraction. The primary outcome was PE at time of autopsy, defined as any clot obstructing a pulmonary artery. The secondary outcome was venous thromboembolism, defined as the composite of thrombotic PE, deep vein thrombosis, splanchnic vein thrombosis, or internal jugular vein thrombosis. Results A total of 9571 cancer patients were included. In 1191 (12.4%; 95% confidence interval [CI], 11.8‐13.1) patients, one or more PE events were observed at autopsy, of whom 1074 (90.2%) had a thrombotic embolism, 168 (14.1%) a tumor embolism, 9 (0.8%) a septic embolism, 7 (0.6%) a fat tissue embolism, and 3 (0.3%) a bone marrow embolism. Among patients with PE for whom the cause of death was specified in the autopsy report, death was considered PE‐related in 642 patients (66.7%), which was 6.7% of the total study population. Venous thromboembolism was observed in 1223 (12.8%; 95% CI, 12.1‐13.5) patients. Conclusion The proportion of PE in cancer patients at autopsy is substantial. Although the study population is not representative for the total cancer population, it suggests that PE is an important disease complication in cancer patients.

Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020–10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%–11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients., Highlights • COVID-19 is characterized by coagulation activation and endothelial dysfunction. Few data are available on thromboembolic complications. • We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020). • Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission. • Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications. • There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

Background: An increasing number of subjects are recovering from COVID-19, raising the need for tools to adequately assess the course of the disease and its impact on functional status. We aimed to assess the construct validity of the Post-COVID-19 Functional Status (PCFS) Scale among adult subjects with confirmed and presumed COVID-19. Methods: Adult subjects with confirmed and presumed COVID-19, who were members of an online panel and two Facebook groups for subjects with COVID-19 with persistent symptoms, completed an online survey after the onset of infection-related symptoms. The number and intensity of symptoms were evaluated with the Utrecht Symptom Diary, health-related quality of life (HrQoL) with the 5-level EQ-5D questionnaire, impairment in work and activities with the Work Productivity and Activity Impairment questionnaire and functional status with the PCFS Scale. Results: 1939 subjects were included in the analyses (85% women, 95% non-hospitalized during infection) about 3 months after the onset of infection-related symptoms. Subjects classified as experiencing ‘slight’, ‘moderate’ and ‘severe’ functional limitations presented a gradual increase in the number/intensity of symptoms, reduction of HrQoL and impairment in work and usual activities. No differences were found regarding the number and intensity of symptoms, HrQoL and impairment in work and usual activities between subjects classified as experiencing ‘negligible’ and ‘no’ functional limitations. We found weak-to-strong statistical associations between functional status and all domains of HrQoL (r: 0.233–0.661). Notably, the strongest association found was with the ‘usual activities’ domain of the 5-level EQ-5D questionnaire. Conclusion: We demonstrated the construct validity of the PCFS Scale in highly-symptomatic adult subjects with confirmed and presumed COVID-19, 3 months after the onset of symptoms. The research team acknowledges the valuable input from the patient representatives to develop the survey, and the technical support by ASolutions' Martijn Briejers and Oscar Wagemakers. We are grateful to all subjects who were willing to participate in the current study. FVCM is financially supported by ZonMW (ERACoSysMed Grant #90030355). The scientific work of YMJG is financially supported by Lung Foundation Netherlands Grant 4.1.16.085, RM is financially supported by Lung Foundation Netherlands Grant 5.1.18.232.

Introduction Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the ENDORSE multinational survey reported that only around 40% of medical patients at risk of VTE received adequate thromboprophylaxis. Methods In our systematic review and meta-analysis, we aimed at providing updated figures concerning the use of thromboprophylaxsis globally. We focused on: (i) the frequency of patients with an indication to thromboprophylaxis according with individual models; (ii) the use of adequate thromboprophylaxis; (iii) reported contraindications to thromboprophylaxis. Observational non-randomized studies or surveys focusing on medically ill patients were considered eligible. Results After screening, we included 27 studies from 20 countries for a total of 137,288 patients. Overall, 50.5% (95%CI: 41.9%-59.1%, I2 99%) of patients had an indication to thromboprophylaxis: of these, 54.5% (95%CI: 46.2%-62.6%, I2 99%) received adequate thromboprophylaxis. The use of adequate thromboprophylaxis was 66.8% in Europe (95%CI: 50.7% to 81.1%; I2 98%), 44.9% in Africa (95%CI: 31.8% to 58.4% I2 96%), 37.6% in Asia (95%CI: 25.7%-50.3%, I2 97%), 58.3% in South America (95%CI 31.1%-83.1%, I2 99%), and 68.6% in North America (95%CI 64.9%-72.6%, I2 96%). No major differences in adequate thromboprophylaxis use were found across risk assessment models. Bleeding, thrombocytopenia, and renal/hepatic failure were the most frequently reported contraindications to thromboprophylaxis. Conclusions The use of anticoagulants for VTE prevention has been proven effective and safe, but thromboprophylaxis prescriptions are still unsatisfactory among hospitalized medically ill patients around the globe with marked geographical differences.

BACKGROUND The Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and deconditioning. OBJECTIVES To assess underlying physiological determinants of PPES, and efficacy and safety of rehabilitation training in these patients. METHODS 56 consecutive PE patients with persistent dyspnea and/or functional limitations despite ≥3 months of anticoagulation underwent standardized diagnostic work-up including exercise testing as part of routine practice. All diagnostic (imaging and cardiopulmonary function) tests were interpreted by a core group of experienced clinicians. A subgroup of patients without CTEPH or other treatable conditions was referred for a 12-week personalized rehabilitation program, studying changes in physical condition and patient-reported outcome measures. RESULTS Persistent vascular occlusions were observed in 21/56 patients (38%) and CTEPH was confirmed in ten (18%). Regarding those without CTEPH, impaired cardiopulmonary responses were evident in 18/39 patients with available CPET data (46%), unrelated to chronic thrombi. Rehabilitation was completed by 27 patients after excluding 29 (patients with CTEPH or treatable comorbidities, refusal, ineligibility, or training elsewhere). Training intensity, PE-specific quality of life (PEmb-QoL) and fatigue (CIS) improved with a median difference of 20 W (p = 0.001), 3.9 points (p

The study by Z. Zhai and colleagues provides an overview of the developments observed as risk-adapted management strategies for acute pulmonary embolism have been progressively introduced and optimised in the Chinese healthcare systemhttps://bit.ly/3swGht2

BACKGROUND: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. METHODS: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555). FINDINGS: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p

Background Patients with pulmonary embolism (PE) who prematurely discontinue anticoagulant therapy ( Methods We used the data from the RIETE (Registro Informatizado de Pacientes con Enfermedad TromboEmbólica) registry to compare the prognostic ability of five machine-learning (ML) models and logistic regression to identify patients at increased risk for the composite of fatal PE or recurrent venous thromboembolism (VTE) 30 days after discontinuation. ML models included decision tree, k-nearest neighbors algorithm, support vector machine, Ensemble, and neural network [NN]. A “full” model with 70 variables and a “reduced” model with 23 were analyzed. Model performance was assessed by confusion matrix metrics on the testing data for each model and a calibration plot. Results Among 34,447 patients with PE, 1,348 (3.9%) discontinued therapy prematurely. Fifty-one (3.8%) developed fatal PE or sudden death and 24 (1.8%) had nonfatal VTE recurrences within 30 days after discontinuation. ML-NN was the best method for identification of patients experiencing the composite endpoint, predicting the composite outcome with an area under receiver operating characteristic (ROC) curve of 0.96 (95% confidence interval [CI]: 0.95–0.98), using either 70 or 23 variables captured before discontinuation. Similar numbers were obtained for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The discrimination of logistic regression was inferior (area under ROC curve, 0.76 [95% CI: 0.70–0.81]). Calibration plots showed similar deviations from the perfect line for ML-NN and logistic regression. Conclusion The ML-NN method very well predicted the composite outcome after premature discontinuation of anticoagulation and outperformed traditional logistic regression.

Lemierre Syndrome is a rare form of septic thrombophlebitis of the head and neck veins, most typically of the internal jugular vein, which affects otherwise healthy adolescents and young adults after an oropharyngitis or other local infection. It is characterized by multiple septic embolization. Despite treatment, Lemierre Syndrome displays a high rate of in-hospital complications that include thrombus progression and a new peripheral septic embolization; moreover, it can be fatal or cause disabling sequelae. The mainstay of the treatment is antibiotic therapy; anticoagulation is often used, but its role is controversial. Surgical treatment is often necessary in case of peripheral septic lesions. In the absence of prospective studies, what little guidance exists on its management is based on case series or on analogy with similar conditions, such as other forms of septic thrombophlebitis or non-septic venous thrombosis. Over the last few years, new observational evidence has improved our knowledge of the clinical epidemiology of this condition and highlighted a number of promising management strategies. We provide an overview of the treatment patterns adopted in the contemporary era, and summarize the arguments proposed so far against or in favor of alternative treatments as well as possible decision rules on the use of anticoagulation. Moreover, we outline the priorities of ongoing and future observational and interventional research.

Background and aims Women present with pulmonary embolism (PE) more often than men, while the opposite is true for proximal deep vein thrombosis (DVT). We investigated whether sex-specific differences exist in the presenting location of acute symptomatic DVT among patients without concomitant PE. Methods We tested our hypothesis in a meta-analysis of studies selected by systematically reviewing PubMed, Embase, and the grey literature. Thereafter, we analysed data of a single-center cohort including patients with first isolated acute DVT to assess the additional impact of age and provoking risk factors on the presenting location of DVT. Results We identified 7 studies for a total of 20,534 patients. The weighed pooled absolute difference in the proportion of distal DVT between women and men was +5.4% (95%CI: +0.7%; +9.5%), which corresponds to a pooled odds ratio (OR) of 1.30 (95%CI: 1.07–1.58). This difference was +6.5% (95%CI: +2.1%; +10.9%) for first distal DVT (OR 1.38; 95%CI: 1.11–1.72) and +5.3% (95%CI: +0.5%; +10.0%) for either first or recurrent distal DVT (OR 1.29; 95%CI: 1.03–1.61). In the cohort study, the larger difference in the proportion of distal DVT between women and men was observed among patients aged 51–70 (+9.5%; 95CI: +2.8%; +16.0% compared to those aged 18–50) or with unprovoked events (+8.5%; 95CI: −0.9%; +17.9%). Conclusions Among patients with first symptomatic isolated acute DVT, women presented with distal DVT more often than men, whereas men had a higher proportion of proximal DVT events. This pattern appeared to depend on age and the absence of provoking risk factors for VTE.

Aims Patients with acute pulmonary embolism (PE) classified as low risk by the Pulmonary Embolism Severity Index (PESI), its simplified version (sPESI), or the Hestia criteria may be considered for early discharge. We investigated whether the presence of right ventricular (RV) dysfunction may aggravate the early prognosis of these patients. Methods and results We did a systematic review and meta-analysis of studies including low-risk patients with acute PE to investigate the prognostic value of RV dysfunction. Diagnosis of RV dysfunction was based on echocardiography or computed tomography pulmonary angiography. In addition, we investigated the prognostic value of elevated troponin or natriuretic peptide levels. The primary outcome was all-cause mortality at 30 days or during hospitalization. We included 22 studies (N = 3295 low-risk patients) in the systematic review: 21 were selected for quantitative analysis. Early all-cause mortality rates in patients with vs. without RV dysfunction on imaging were 1.8% [95% confidence interval (CI) 0.9–3.5%] vs. 0.2% (95% CI 0.03–1.7%), respectively, [odds ratio (OR) 4.19, 95% CI 1.39–12.58]. For troponins, rates were 3.8% (95% CI 2.1–6.8%) vs. 0.5% (95% CI 0.2–1.3%), (OR 6.25, 95% CI 1.95–20.05). For natriuretic peptides, only data on early PE-related mortality were available: rates were 1.7% (95% CI 0.4–6.9%) vs. 0.4% (95% CI 0.1–1.1%), (OR 3.71, 95% CI 0.81–17.02). Conclusions In low-risk patients with acute PE, the presence of RV dysfunction on admission was associated with early mortality. Our results may have implications for the management of patients who appear at low risk based on clinical criteria alone, but present with RV dysfunction as indicated by imaging findings or laboratory markers.

PURPOSE Lemierre syndrome is a life-threatening condition characterized by head/neck bacterial infection, local suppurative thrombophlebitis and septic embolic complications in a range of sites of distant organs. No prior study focused on the course and characteristics of ophthalmic complications of Lemierre syndrome. METHODS We analysed data of 27 patients with ophthalmic complications from a large cohort of 712 cases with Lemierre syndrome reported globally between 2000 and 2017. We focused on initial manifestations, early (in-hospital) course and long-term ophthalmic deficits at the time of hospital discharge or during postdischarge follow-up. The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42016052572). RESULTS Nine (33%) patients were women; the median age was 20 (Q1-Q3: 15-33) years. Fusobacterium spp. was involved in 56% of cases. The most prevalent initial manifestations were decreased vision (35%) and periocular oedema (38%), followed by impaired eye movements/nerve palsy (28%) and proptosis (28%). Venous involvement, notably cerebral vein thrombosis (70%) and ophthalmic vein thrombosis (55%), explained the symptomatology in most cases. Septic embolism (7%), orbital abscesses (2%) and carotid stenosis (14%) were also present. Ophthalmic sequelae were reported in 9 (33%) patients, often consisting of blindness or reduced visual acuity, and nerve paralysis/paresis. CONCLUSION Ophthalmic complications represent a severe manifestation of Lemierre syndrome, often reflecting an underlying cerebral vein thrombosis. Visual acuity loss and long-term severe complications are frequent. We call for an interdisciplinary approach to the management of patients with Lemierre syndrome and the routine involvement of ophthalmologists.

Pulmonary embolism (PE)-related mortality is decreasing worldwide.Little is known about the burden imposed by pulmonary embolism for Germany, Austria and Switzerland (DACH countries).We aimed to assess pulmonary embolism-related mortality and time trends for the DACH countries based on data from the WHO Mortality Database. Deaths were considered pulmonary embolism-related if the International Classification of Disease-10 code for acute pulmonary embolism or any code for deep or superficial vein thrombosis was listed as the primary cause of death.Between 2000 and 2015, age-standardized annual pulmonary embolism-related mortality rates decreased linearly from 15.6 to 7.8 deaths per 1000 population. In the 5‑year period between 2012 and 2016, an average of 9127 pulmonary embolism-related deaths occurred annually in the DACH countries with a population of 98,273,329. Interestingly, pulmonary embolism-related mortality rates were considerably higher among women aged 15-55 years compared to age-matched men.The observed decreasing trends in pulmonary embolism-related mortality might reflect improved management of the disease including new treatment options as well as advances in imaging technologies. However, pulmonary embolism remains a substantial contributor to total mortality, especially among women aged 15-55 years. For this reason, campaigns to increase physician and public awareness are urgently required to further improve the management and treatment of this preventable thrombotic disorder, which still remains the leading preventable cause of death.HINTERGRUND: Kürzlich veröffentliche Studien zeigen eine steigende Inzidenz für die Lungenarterienembolie (LE) bei gleichzeitigem Rückgangs der LE-assoziierten Mortalität.Detaillierte Daten zur Mortalität der LE in Deutschland, Österreich und der Schweiz (DACH-Region) sind derzeit nicht vorhanden.Datensätze wurden aus der Mortalitätsdatenbank der Weltgesundheitsorganisation (WHO) ausgewertet. Hierbei analysierten wir die Häufigkeit sowohl der akuten LE als auch der tiefen/oberflächlichen Venenthrombose als primärer Todesursache.Demnach sank die jährliche altersstandardisierte Mortalität zwischen Januar 2000 und Dezember 2015 von 15,6 auf 7,8 Todesfälle pro 1000 Einwohner. Zwischen Januar 2012 und Dezember 2016 ereigneten sich in der DACH-Region (Bevölkerungsanzahl: 98.273.320 Menschen) durchschnittlich 9127 durch LE verursache Todesfälle pro Jahr. Interessanterweise ist LE–assoziierte Gesamtmortalität bei Frauen zwischen dem 15. und 55. Lebensjahr deutlich höher als bei gleichaltrigen Männern.Der Rückgang der Mortalität durch die Erkrankung LE seit dem Jahr 2000 ist vermutlich durch eine verbesserte Patientenversorgung mit Einführung neuer Antikoagulanzien und durch den vermehrten Einsatz und diagnostischen Fortschritt bei den computertomographischen Untersuchungen erklärt. Festzuhalten ist, dass die LE eine wichtige Todesursache vor allem im höheren Alter darstellt. Außerdem ist der Anteil der Frauen im gebärfähigen Alter, die nach einer akuten LE sterben, mit 3,5 % hoch. Daher sind, trotz des medizinischen Fortschritts, weitere Anstrengungen für eine Verbesserung der Prävention, Diagnostik und Therapie, aber insbesondere auch des Krankheitsbewusstseins notwendig.

Summary: A 49-year-old man was diagnosed with pre-fibrotic myelofibrosis after acute left lower-limb ischemia requiring amputation and portal vein thrombosis. After surgery he developed heparin-induced thrombocytopenia (HIT) with venous thromboembolism, successfully treated with argatroban followed by dabigatran. Our systematic review of the literature supports the use of dabigatran for suspected HIT.

Objective In patients with cancer-associated venous thromboembolism (VTE), the risk of recurrence is similar after incidental and symptomatic events. It is unknown whether the same applies to incidental VTE not associated with cancer. Methods and Results We compared baseline characteristics, anticoagulation therapy, all-cause mortality, and VTE recurrence rates at 90 days between patients with incidental (n = 131; 52% without cancer) and symptomatic (n = 1,931) VTE included in the SWIss Venous ThromboEmbolism Registry (SWIVTER). After incidental VTE, 114 (87%) patients received anticoagulation therapy for at least 3 months. The mortality rate was 9.2% after incidental and 8.4% after symptomatic VTE for hazard ratio (HR) 1.10 (95% confidence interval [CI] 0.49–2.50). After adjustment for competing risk of death, recurrence rate was 3.1 versus 2.8%, respectively, for sub-HR 1.07 (95% CI 0.39–2.93). These results were consistent among cancer (mortality: 15.9% vs. 12.6%; HR 1.32, 95% CI 0.67–2.59; recurrence: 4.8% vs. 4.7%; HR 1.02, 95% CI 0.30–3.42) and noncancer patients (mortality: 2.9% vs. 2.1%; HR 1.37, 95% CI 0.33–5.73; recurrence: 1.5% vs. 2.3%; HR 0.63, 95% CI 0.09–4.58). Patients with incidental VTE who received anticoagulation therapy for at least 3 months had lower mortality (4% vs. 41%) and recurrence rate (1% vs. 18%) compared with those who did not. Conclusion In SWIVTER, more than half of incidental VTE events occurred in noncancer patients who often received anticoagulation therapy. Among noncancer patients, early mortality and recurrence rates were similar after incidental versus symptomatic VTE. Our findings suggest that anticoagulation therapy for incidental VTE may be beneficial regardless of the presence of cancer.

It is unclear whether cardiopulmonary exercise intolerance in patients with chronic obstruction of the inferior vena cava (IVC) is reversible following endovascular IVC reconstruction.In 17 patients (mean age 45 ± 15 years, 71% men) with post-thrombotic syndrome due to IVC obstruction and preserved left ventricular ejection fraction (mean 58 ± 3%), we performed cardiopulmonary exercise testing before and 3 months after IVC reconstruction (mean 4.1 ± 1.5 implanted stents). The median time from latest episode of deep vein thrombosis to intervention was 150 (interquartile range 102-820) days.At baseline, 12 (71%) patients reported New York Heart Association (NYHA) class II or III symptoms, 76% did not achieve85% of predicted oxygen uptake at peak exercise (mean 61.8 ± 13.7%). After IVC reconstruction, the following changes were observed at anaerobic threshold: work rate increased by 14.6 W, 95%CI (-0.7; 30.0), oxygen uptake increased by 1.8 ml/kg, 95%CI (0.3; 3.3). Oxygen pulse increased by 1.95 ml per beat, 95%CI (1.12; 2.78), corresponding to a mean relative increase of 22.5%, 95%CI (12.4; 32.7) (p 0.001). The following changes were observed at peak exercise: work rate increased by 48.1 W, 95%CI (27.8; 68.4), oxygen uptake increased by 6.4 ml/kg, 95%CI (3.8; 9.1). Oxygen pulse increased by 2.68 ml per beat, 95%CI (1.60; 3.76), corresponding to a mean relative increase of 29.4%, 95%CI (17.7; 41.2) (p 0.001). At follow-up, 5 (29%) patients remained in NYHA class II.In patients with chronic IVC obstruction, cardiopulmonary exercise intolerance as a result of impaired cardiac filling is at least partially reversible following endovascular IVC reconstruction.URL: https://clinicaltrials.gov. Unique identifier: NCT02433054.

Introduction Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors. Methods PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes. Results Of 3,455 patients with acute VTE, 1,623 (47%) were women. The mean age at the time of VTE was 61 (SD 18) in women, 60 (SD 15) in men. The distribution of provoking risk factors was similar between sexes, despite a tendency for higher frequency of minor and major transient risk factors in women, and cancer or unprovoked VTE in men. At 12-month follow-up, VTE recurrence was reported in 74 (6.5%) women and 80 (6.4%) men (absolute risk difference -0.1%, 95% CI -1.9%; +2.1%). In patients with unprovoked VTE, the VTE recurrence rate was 38/612 (6.2%) in women and 53/798 (6.6%) in men (absolute risk difference -0.4, 95% CI -3.0; +2.1%). Multivariable Cox regressions confirmed the absence of sex differences. Quality of life and treatment satisfaction scores one year after VTE were lower in women than in men irrespective of the provoking risk factors (p Conclusions Despite differences in the provoking risk factors for VTE, women and men had a similar rate VTE recurrence at one year. After acute VTE, women had lower quality of life and treatment satisfaction scores.

Highlights • Acute pulmonary embolism (PE) is a frequent complication of COVID-19 infection. • The in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients. • Computed tomography angiography (CTPA) is infrequently performed., Background Acute pulmonary embolism (PE) has been described as a frequent and prognostically relevant complication of COVID-19 infection. Aim We performed a systematic review and meta-analysis of the in-hospital incidence of acute PE among COVID-19 patients based on studies published within four months of COVID-19 outbreak. Material and Methods Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to August 1, 2020 reporting the incidence of acute PE (or lung thrombosis) in COVID-19 patients. The pooled in-hospital incidence of acute PE among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. Results We analysed data from 7178 COVID-19 patients [mean age 60.4 years] included in twenty-three studies. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of PE (or lung thrombosis) was 14.7% of cases (95% CI: 9.9–21.3%, I2=95.0%, p

Summary: Background: Radiotherapy for head and neck cancer (HNC) represents a well-known predisposing factor for asymptomatic carotid artery lesions and acute cerebrovascular accidents. Our aim is to provide contemporary estimates on the prevalence, severity, and characteristics of carotid artery lesions in HNC survivors. Patients and methods: We prospectively included HNC patients who underwent radiotherapy and were free from the disease at the time of duplex ultrasound evaluation. Patients were re-contacted telephonically and those who agreed to participate were invited for an ambulatory visit when the investigators collected clinical information and performed duplex ultrasound examination based on a predefined protocol. Results: A total of 156 patients were included and underwent duplex ultrasound examination after a mean of 65.2 months from the last session of radiotherapy. A total of 36 patients (23.1%) had normal carotid arteries; mild, non-stenotic lesions were observed in 49.4% (n = 77) of patients; severe stenotic plaques were found in 27.5% (n = 43) of patients. One patient found with an asymptomatic occlusion of the left ICA. The prevalence of major cardiovascular risk factors and high radiation dose increased proportionally with plaque severity. Low echogenicity plaque was found in 59 (37.8%) patients on the right side and 57 (36.5%) on the left side; long segment plaque in 49 (31.4%) patients on the right side and in 47 (30.1%) on the left side; an atypical location of the lesions in 42 (26.9%) patients on the right side and in 48 (30.8%) on the left side. Conclusions: The prevalence of occlusion and severe stenosis after radiotherapy for HNC was very low in our study population. Low echogenicity plaque, long segment plaque, and an atypical location were common findings. Classic cardiovascular risk factors appear to have had a causative role: a routine screening of radiotherapy-treated patients might be necessary only in patients with concomitant cardiovascular risk factors or exposed to high-dose neck radiation.