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Background: Dissecting trends and contributing risk factors for intracranial hemorrhage (ICH) in patients treated for acute pulmonary embolism (PE) may allow for a better patient selection for existing and emerging treatment options., Methods: The German nationwide inpatient sample was screened for patients admitted due to PE 2005-2020. Hospitalizations were stratified for the occurrence of ICH; risk factors for ICH and temporal trends were investigated., Results: Overall, 816,653 hospitalizations due to acute PE in the period 2005-2020 were analyzed in the study. ICH was reported in 2516 (0.3 %) hospitalizations, and time trend analysis revealed a fluctuating but overall, largely unchanged annual incidence. There was an increase of ICH with age. Patients with ICH had a higher comorbidity burden (Charlson-Comorbidity-Index [CCI], 5.0 [4.0-7.0] vs. 4.0 [2.0-5.0]; P < 0.001), and higher CCI was associated with an OR of 1.26 (95%CI 1.24-1.27) for ICH. Further independent risk factors for ICH were age ≥ 70 years (OR 1.23 [1.12-1.34]), severe (versus low-risk) PE (OR 3.09 [2.84-3.35]), surgery (OR 1.59 [1.47-1.72]), acute kidney injury (OR 3.60 [3.09-4.18]), and ischemic stroke (OR 14.64 [12.61-17.00]). The identified risk factors for ICH varied among different reperfusion treatment groups. As expected, ICH had a substantial impact on case-fatality of PE (OR 6.16 [5.64-6.72]; P < 0.001)., Conclusions: Incidence of ICH in patients hospitalized for acute PE in Germany was overall low and depended on the patients' comorbidity burden. Identifying patients at risk for ICH allows tailored patient selection for the different reperfusion treatments and might prevent ICH., Competing Interests: Declaration of competing interest KCC, KM, TU, MJ, LV, ITF, TM, KK report no conflicts of interests. PL has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, and ReCor, honoraria from Edwards Lifesciences, Abbott Medical, Innoventric, ReCor and Boehringer Ingelheim and has stock options with Innoventric. SK reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol Myers Squibb/Pfizer. LH received lecture/consultant fees from MSD and Actelion, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pulmonary hypertension associated with left heart disease (PH-LHD) prevalence ranges significantly across studies with limited real-world evidence., Objectives: To investigate the prevalence and prognostic influence of PH-LHD in a nationwide sample., Methods: Using the 2018 US Nationwide Inpatient Sample we calculated the prevalence of PH across heart failure (HF), cardiomyopathies, aortic, and mitral valve disease. We used logistic regression to assess the impact of PH on LHD and to find significant contributors to in-hospital mortality in the PH-LHD population., Results: Among 6,270,625 hospitalizations with LHD, 801,535 (12.8 %) had a secondary PH diagnosis. PH-LHD prevalence was 17.2 % in HF with preserved ejection fraction (HFpEF), 11.8 % in HF with reduced ejection fraction (HFrEF), 16.8 % in dilated cardiomyopathy, 12.6 % in hypertrophic cardiomyopathy, 18.7 % in mitral regurgitation, 28.5 % in mitral stenosis, 13.5 % in aortic stenosis, and 13.9 % in aortic regurgitation. PH was associated with increased in-hospital mortality in HFpEF (OR 1.23; 95%CI 1.17-1.28), hypertrophic cardiomyopathy (1.42; 1.06-1.89), mitral regurgitation (1.17; 1.07-1.28), and aortic stenosis (1.14; 1.04-1.26), but not in HFrEF (1.04; 0.99-1.10), or dilated cardiomyopathy (1.13; 0.99-1.29). Among PH-LHD, in-hospital mortality was associated with age, atrial fibrillation/flutter, cancer, and acute cardiac (acute right HF, myocardial infarction, ventricular arrhythmia), or extra-cardiac (stroke, sepsis, pneumonia, acute renal failure, venous thromboembolism) diagnoses., Conclusion: In a nationwide inpatient analysis the prevalence of PH-LHD was lower than previously reported indicating reduced recognition of this disease in real world clinical practice. The diagnosis of PH-LHD was associated with worse fatality rates across all forms of LHD, except for HFrEF., Competing Interests: Declaration of competing interest LH received lecture/consultant fees from MSD and Actelion, outside the submitted work. SVB has served in unpaid trial activities for Abbott, Edwards Lifesciences, and University of Göttingen (IIT); and has served on an advisory or Speakers Bureau for Abbott Cardiovascular, Bioventrix, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, and Neochord. PL has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, and ReCor, honoraria from Edwards Lifesciences, Abbott Medical, Innoventric, ReCor, Boehringer Ingelheim, Daiichi Sankyo and has stock options with Innoventric. SR reports grants or contracts from Actelion, AstraZeneca, Bayer, Janssen, and Novartis; consulting fees from Abbott, Acceleron, Actelion, Bayer, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor; payment or honoraria from Actelion, Bayer, BMS, Ferrer, GSK, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor. SVK reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol Myers Squibb/Pfizer. GG has received speaker or consulting fees from ELPEN Pharmaceuticals, Galenica, GlaxoSmithKline, and Janssen Pharmaceutical Companies of Johnson & Johnson and MSD, outside the submitted work. The rest of the authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography diagnosing the index pulmonary embolism., Methods: We evaluated 12 new algorithms, incorporating the CTEPH prediction score, ECG reading, N‑terminal pro-brain natriuretic peptide levels and dedicated computed tomography pulmonary angiography reading, in the international InShape II cohort (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in pulmonary embolism patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index compared to the InShape II algorithm., Results: The algorithm starting with computed tomography pulmonary angiography reading of the index pulmonary embolism for six signs of CTEPH, followed by ECG/N-terminal pro-brain natriuretic peptide level assessment and echocardiography resulted in the most beneficial change compared to InShape II, with a need for echocardiography in 20% (+5%), a failure rate of 0% and a net reclassification index of +3.5%, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with a net reclassification index of +6.0%., Conclusion: Dedicated computed tomography pulmonary angiography reading of the index pulmonary embolism improved the performance of the InShape II algorithm and may improve the selection of pulmonary embolism survivors who require echocardiography to rule out CTEPH., Competing Interests: Conflict of interest: S. Barco received research support from Boston Scientific, Medtronic, Concept Medical, Sanofi and Novartis, all outside this manuscript. M. Delcroix received consulting fees from Actelion/Janssen/J&J, Acceleron/MSD, Gossamer and Ferrer; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion/Janssen/J&J, Acceleron/MSD and Ferrer, all outside the submitted work. L. Jara-Palomares reports grants from Daichii, Rovi, GlaxoSmithKline, BMS, Leo Pharma, MSD and Johnson and Johnson. H. Vliegen received grants from Johnson and Johnson; payment or honoraria for lectures, presentations, manuscript writing or educational events from Novartis and Boehringer Ingelheim; and participates on a data safety monitoring board or advisory board for Amarin and Daiichi Sankyo. S.V. Konstantinides reports grants or contacts from Daiichi Sankyo; consulting fees from Boston Scientific, Inari Medical, Bayer AG, Penumbra Inc. and Daiichi Sankyo; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boston Scientific and Penumbra Inc., all outside of the submitted work. F.A. Klok received research support from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation and the Horizon Europe Program, all outside this manuscript. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Although recurrent diverticulitis appears to be a chronic relapsing disease from a clinical standpoint, there are no sufficient data about inflammatory markers that allow monitoring recurrent diverticulitis in the quiescent phase. Our hypothesis is that serum inflammatory markers may be increased during clinical quiescent phases of diverticulitis and will drop after elective laparoscopic sigmoidectomy for uncomplicated recurrent diverticulitis. We also believe that a drop in IL-6 levels across surgery could be related to an improved quality of life., Material and Methods: This epidemiological study aims to evaluate IL-6 serum levels and quality of life preoperatively and 6 months after surgery in 30 patients undergoing elective laparoscopic sigmoidectomy for uncomplicated recurrent diverticulitis., Results: The mean preoperative IL-6 level was 9.5 +- 9.2 pg/ml (range 0-5), while at six months after surgery the mean IL-6 was 4.5 +- 3.5. (p=0.0085). Preoperative QoL measured with the GIQLI questionnaire was 98 +- 11.3 and raised significantly after surgery to 112 +- 9.8 (p=0.043)., Conclusions: We found a serum IL-6 reduction after elective laparoscopic sigmoidectomy that can be attributed to the surgical removal of the source of inflammation in patients suffering from uncomplicated recurrent diverticulitis. Similarly, the GIQLI questionnaire showed a significantly improved QoL after surgery., (Celsius.)

Objectives: To investigate the contemporary use of extracorporeal membrane oxygenation (ECMO) in conjunction with reperfusion strategies in high-risk pulmonary embolism (PE)., Design: Observational epidemiological analysis., Setting: The U.S. Nationwide Inpatient Sample (NIS) (years 2016-2020)., Patients: High-risk PE hospitalizations., Measurements and Main Results: Use of ECMO in conjunction with thrombolysis-based reperfusion (systemic thrombolysis or catheter-directed thrombolysis) or mechanical reperfusion (surgical embolectomy or catheter-based thrombectomy) with regards to in-hospital mortality and major bleeding. We identified high-risk PE hospitalizations in the NIS (years 2016-2020) and investigated the use of ECMO in conjunction with thrombolysis-based (systemic thrombolysis or catheter-directed thrombolysis) and mechanical (surgical embolectomy or catheter-based thrombectomy) reperfusion strategies with regards to in-hospital mortality and major bleeding. Among 122,735 hospitalizations for high-risk PE, ECMO was used in 2,805 (2.3%); stand-alone in 1.4%, thrombolysis-based reperfusion in 0.4%, and mechanical reperfusion in 0.5%. Compared with neither reperfusion nor ECMO, ECMO plus thrombolysis-based reperfusion was associated with reduced in-hospital mortality (adjusted odds ratio [aOR] 0.61; 95% CI, 0.38-0.98), whereas no difference was found with ECMO plus mechanical reperfusion (aOR 1.03; 95% CI, 0.67-1.60), and ECMO stand-alone was associated with increased in-hospital mortality (aOR 1.60; 95% CI, 1.22-2.10). In the cardiac arrest subgroup, ECMO was associated with reduced in-hospital mortality (aOR 0.71; 95% CI, 0.53-0.93). Among all patients on ECMO, thrombolysis-based reperfusion was significantly associated (aOR 0.55; 95% CI, 0.33-0.91), and mechanical reperfusion showed a trend (aOR 0.75; 95% CI, 0.47-1.19) toward reduced in-hospital mortality compared with no reperfusion, without increases in major bleeding., Conclusions: In patients with high-risk PE and refractory hemodynamic instability, ECMO may be a valuable supportive treatment in conjunction with reperfusion treatment but not as a stand-alone treatment especially for patients suffering from cardiac arrest., Competing Interests: Dr. Barco received lecture/consultant fees from Bayer HealthCare, Concept Medical, BTG Pharmaceuticals, INARI, Boston Scientific (BSC), and LeoPharma; institutional grants from Boston Scientific, Bentley, Bayer HealthCare, INARI, Medtronic, Concept Medical, Bard, and Sanofi; and economical support for travel/congress costs from Daiichi Sankyo, BTG Pharmaceuticals, and Bayer HealthCare, outside the submitted work. Dr. Giannakoulas reports lecture/consultant fees from Bayer HealthCare, Pfizer, and LeoPharma.Dr. Piazza has received research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation, and consulting fees from Pfizer, Boston Scientific Corporation, Janssen, Prairie Education and Research Cooperative, North American Science Associates (NAMSA), and Amgen. Dr. Konstantinides reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and BSC; institutional grants from Inari Medical; and personal lecture/advisory fees from Merck Sharp and Dohme (MSD) and Bristol-Myers Squibb (BMS)/Pfizer. Dr. Hobohm received lecture/consultant fees from MSD and Actelion, outside the submitted work. Dr. Piazza’s institution received funding from BMS/Pfizer, Janssen, Alexion, Bayer, Amgen, BSC, and Esperion (1R01HL164717-01); he disclosed he has an advisory role in BSC, Amgen, BCRI, Pulmonary Embolism (PERC), NAMSA, BMS, Janssen, and Regeneron. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Past exposure to schistosomiasis is frequent among migrants from endemic countries, and chronic untreated infection may lead to long-term morbidities., Methods: We carried out a prospective population-based cross-sectional study among migrants from endemic Sub-Saharan countries living in Barcelona, Spain. Participants had not been previously diagnosed or treated for schistosomiasis. Clinical signs and symptoms were scrutinised through a systematic revision of electronic medical records and an on-site standardised questionnaire, and blood and urine samples were screened for Schistosoma., Findings: We recruited 522 eligible participants, 74.3% males, mean age 42.7 years (SD=11.5, range 18-76), Overall, 46.4% were from Senegal and 23.6% from Gambia. They had lived in the European Union for a median of 16 years (IQR 10-21). The prevalence of a Schistosoma-positive serology was 35.8%. S. haematobium eggs were observed in urine samples in 6 (1.2%) participants. The most prevalent symptoms among Schistosoma-positive participants were chronic abdominal pain (68.8%, OR=1.79; 95%CI 1.2-2.6), eosinophilia (44.9%, OR=2.69; 95%CI 1.8-4.0) and specific symptoms associated with urinary schistosomiasis, like self-reported episodes of haematuria (37.2%; OR=2.47; 95%CI 1.6-3.8), dysuria (47.9%, OR=1.84; 95%CI=1.3-2.7) and current renal insufficiency (13.4%; OR=2.35; 95%CI=1.3-4.3). We found a significant prevalence of gender-specific genital signs and symptoms among females (mainly menstrual disorders) and males (erectile dysfunction and pelvic pain). Individuals typically presented with a multitude of interconnected symptoms, most commonly chronic abdominal pain, which are often disregarded., Conclusions: Despite the lack of urine parasite identification, the high incidence of clinical signs and symptoms strongly correlated with a positive schistosomiasis serology suggests the existence of a heavy clinical burden among long-term West African migrants living for years/decades in the study region. More research is urgently required to determine whether these symptoms are the result of long-term sequelae or a persistent active Schistosoma infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Main Aim: In July 2022, an extensive outbreak of Mpox (monkeypox) was considered by WHO as a Public Health Emergency. The objective of this study is to describe the obtained results from a Mpox case detection program in a semi-urban healthcare area where approximately 420 Primary Care physicians work., Design: An observational prospective study performed between June 01, 2022 and December 31, 2023., Setting: The Northern Metropolitan area of Barcelona, with 1400.000hab (Catalonia, Spain)., Methods: An unified Mpox management procedure was agreed, including a prior online training of Primary Care professionals, to individually assess all Mpox suspected cases from a clinical and epidemiological perspective., Participants: All patients who met clinical and/or epidemiological criteria of Mpox., Data Collection: Age, gender, risk classification (suspected/probable), cluster-linked (yes/no), high-risk sexual contact (yes/no), general symptoms, genital lesion and final diagnostic., Results: A total of 68 suspected Mpox cases were included, from which 16 (26.6%) were Mpox confirmed by PCR. Up to 13 (81.2%) were male and, among them, 12 (75%) men who have sex with men (MSM). The series, however, included two minors and three women. Among MSM, 3 (18.7%) were HIV positive and 3 had no regular access to the Public Healthcare system. Among discarded patients, any infectious disease was diagnosed in 55% of cases., Conclusions: In spite of the short series, this Primary Care community-based study identified a sub-population group showing a different profile of Mpox cases compared to other published series (lower HIV prevalence, higher representativeness of heterosexual transmission and hard to reach population)., (Copyright © 2024 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Background and Aims: Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention., Methods: After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed., Results: Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89)., Conclusions: The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Deep vein thrombosis (DVT) is a cause of considerable morbidity worldwide. It is a common clinical disease in the daily practice of several medical disciplines including general medicine, angiology, and internal medicine, as well as of interest to public health because of its preventability and its sensitivity to secular changes in the distribution of population risk factors. In this review we present a comprehensive overview of the epidemiological features of DVT, including incidence and risk factors. Additionally, we give an overview of the burden that DVT poses on modern health care systems.

Objective: Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites - chromosomal regions prone to DNA breakage during slight replication stress. Given that irradiated cells become more susceptible to genomic destabilization due to the accumulation of replication-stress-related double-strand breaks (DSBs), we explored whether RET and CCDC6 exhibit DNA breakage under replicative stress several days post-irradiation of thyroid cells., Methods: We analyzed the dynamic of DNA replication in human thyroid epithelial cells (HThy-ori-3.1) 4 days post a 5-Gy exposure using molecular DNA combing. The DNA replication schedule was evaluated through replication-timing experiments. We implemented a ChIP-qPCR assay to determine whether the RET and CCDC6 genes break following irradiation., Results: Our study indicates that replicative stress, occurring several days post-irradiation in thyroid cells, primarily causes DSBs in the RET gene. We discovered that both the RET and CCDC6 genes undergo late replication in thyroid cells. However, only RET's replication rate is notably delayed after irradiation., Conclusion: The findings suggest that post-irradiation in the RET gene causes a breakage in the replication fork, which could potentially invade another genomic area, including CCDC6. As a result, this could greatly contribute to the high prevalence of chromosomal RET/PTC rearrangements seen in patients exposed to external radiation.

Background and Aims: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis., Methods: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model., Results: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]., Conclusions: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Pulmonary embolism (PE) is a potentially life-threatening condition. Admission and treatment in the intensive care unit (ICU) is an important element in critically ill PE patients., Objectives: We aimed to identify risk factors for ICU admission and differences in patient profiles regarding risk factors and comorbidities between PE patients who had to be admitted to an ICU and those who were treated in a normal ward without ICU., Methods: We used the German nationwide inpatient sample to analyze all hospitalizations of PE patients in Germany from 2016 to 2020 stratified for ICU admission., Results: Overall, 484,859 hospitalized PE patients were treated in German hospitals from 2016 to 2020. Among these, 92,313 (19.0%) were admitted to ICU. Patients treated in ICU were younger (69.0 [IQR, 58.0-78.0] vs 72.0 [IQR, 60.0-80.0] years; P  < .001) and had higher prevalence of cardiovascular risk factors and comorbidities. In-hospital case fatality rate was elevated in PE patients treated in ICU (22.7% vs 10.7%; P  < .001), and ICU admission was independently associated with increased in-hospital case fatality (odds ratio [OR], 2.54; 95% CI, 2.49-2.59; P  < .001). Independent risk factors for ICU admission comprised PE with imminent or present decompensation (OR, 3.30; 95% CI, 3.25-3.35; P  < .001), hemodynamic instability (OR, 4.49; 95% CI, 4.39-4.59; P  < .001), arterial hypertension (OR, 1.20; 95% CI, 1.18-1.22; P  < .001), diabetes mellitus (OR, 1.16; 95% CI, 1.14-1.18; P  < .001), obesity (OR, 1.300; 95% CI, 1.27-1.33; P  < .001), surgery (OR, 2.55; 95% CI, 2.50-2.59; P  < .001), stroke (OR, 2.86; 95% CI, 2.76-2.96; P  < .001), pregnancy (OR, 1.45; 95% CI, 1.21-1.74; P  < .001), heart failure (OR, 1.74; 95% CI, 1.71-1.77; P  < .001), atrial fibrillation/flutter (OR, 1.69; 95% CI, 1.66-1.73; P  < .001), chronic obstructive pulmonary disease (OR, 1.21; 95% CI, 1.18-1.24; P  < .001), and renal failure (OR, 1.92; 95% CI, 1.88-1.95; P  < .001)., Conclusion: ICU treatment is an important element in the treatment of PE patients. Besides hemodynamic compromise, cardiovascular risk factors, stroke, pregnancy, and cardiopulmonary as well as renal comorbidities were independent predictors of ICU admission. Necessity of ICU admission was afflicted by increased case fatality., (© 2024 The Author(s).)

Objective: The aim of this study was to assess the clinical impact of hand-foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a large group of patients with advanced thyroid cancer. Moreover, we looked for possible associations between HFS occurrence and clinical and pathological features., Methods: We retrospectively evaluated 239 patients with advanced thyroid cancer: 165 treated with lenvatinib and 74 with sorafenib. Statistical analyses were performed to verify which features could be correlated with HFS development., Results: HFS was observed in 35/74 (47.4%) and in 43/165 (26.7%) patients treated with sorafenib or lenvatinib, respectively. The median latency from the drug beginning and HFS appearance was 27 days for sorafenib and 2.9 months for lenvatinib. G3/G4 toxicity was observed in 16/35 (45.7%) patients treated with sorafenib and only in 3/43 (7%) treated with lenvatinib. Drug dose reduction due to HFS was required in 19/74 (25.7%) and 3/165 (1.8%) patients treated with sorafenib and lenvatinib, respectively. HFS occurrence was significantly associated with a longer duration of therapy in both groups., Conclusion: HFS was a frequent adverse event during both lenvatinib and sorafenib therapy, with a higher frequency and toxicity grade during sorafenib treatment. HFS was the most frequent reason for drug reduction or discontinuation in patient treated with sorafenib. Early diagnosis of HFS is important to allow early intervention, possibly in a multidisciplinary setting, and to avoid treatment discontinuation, which is highly relevant to obtain the maximum effectiveness of systemic therapy.

Objectives: This ex vivo study aimed to evaluate the influence of different filling techniques on the filling removal from oval root canals filled with bioceramic sealer., Methods: Thirty-six mandibular incisors with single oval canals were filled with bioceramic sealer following the techniques (n = 12): single-cone, modified McSpadden, or continuous wave of condensation, and scanned by micro-computed tomography (micro-CT). The filling was removed using the Clearsonic ultrasound tip and Reciproc system up to the R40 instrument, and the working time was recorded. The teeth were scanned again by micro-CT. Percentage of remnant volume (mm³) of the filling material, dentin thickness, and root canal transportation were measured. The data was analyzed using parametric and non-parametric tests with a significance level of 5%., Results: It took more time to remove the filling material using the continuous wave of condensation technique (p < 0.05), followed by the modified McSpadden and single-cone techniques. There was no difference (p > 0.05) when comparing the percentage of remaining filling material among the three groups, nor did it among the segments of each tooth. There was also no difference in the analysis of dentin thickness and transportation when comparing the groups (p > 0.05)., Conclusions: The filling technique did not influence the amount of remaining filling material, dentin thickness, and transportation. The working time was longer with thermoplastic filling techniques., Clinical Relevance: Endodontic retreatment in teeth filled with bioceramic sealers increases with their use. Several techniques are used to fill the root canals, thus, it is important to know whether the filling technique influences the non-surgical endodontic retreatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available., Objectives: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach., Methods: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored., Results: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% received education at the time of VTE diagnosis only, leading to 63.5% receiving no or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One-third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history., Conclusion: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management., Competing Interests: Declaration of competing interests N.P. reports a training fellowship from the International Society on Thrombosis and Haemostasis and research funding from International Network of VENous Thromboembolism Clinical Research Networks (INVENT) outside of the submitted work. I.M. reports research funding from Leo Pharma and BMS-Pfizer outside of the submitted work, and advisory board/honoraria from Bayer, BMS-Pfizer, Leo, and Sanofi. P.A. reports research funding from Novo Nordisk, Sanofi, and Spark Therapeutics outside of the submitted work. G.C.M. reports personal fees from Bayer and BMS-Pfizer outside the submitted work. N.V.E. received, outside of the submitted work, advisory board honoraria from Daiichi-Sankyo, Bayer, and Leo Pharma paid to his institution. A.L. reports lecture fees from Leo Pharma outside the submitted work. E.O. reports funding from Novo Nordisk outside the submitted work and Pfizer advisory board/honoraria. F.N.A. reports grant funding (IIS paid to university) from Daiichi-Sankyo, Leo Pharma, Sanofi, and Actelion, and consultancy for Boston Scientific, outside of the submitted work. H.C.O. received a training fellowship from the International Society on Thrombosis and Haemostasis. D.M. reports speaker fees from Leo Pharma, BMS, and Pfizer. C.A. reports personal fees from Bayer, BMS/Pfizer, Daiichi-Sankyo, and Sanofi outside the submitted work. L.A.C. reports that her research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, Leo Pharma, Sanofi, Valeo Pharma, and Servier. S.B. received consultancy and speaker fees from Bayer, Concept Medical, Boston Scientific, and Inari outside of the submitted work. M.D.N. reports personal fees from Bayer, Daiichi-Sankyo, BMS-Pfizer, Leo Pharma, and Viatris outside the submitted work. The remaining authors report no relevant conflicts of interest to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objective: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined., Methods and Results: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis)., Conclusions: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Age-sex specific trend analyses of ischemic heart disease (IHD)-related mortality and prevalent risk factors can improve our understanding and approach to the disease., Methods: We performed a 15-year retrospective epidemiological analysis of acute and chronic IHD-related mortality and prevalent cardiovascular risk factors using administrative data from Veneto, a socio-economically homogeneous Italian region. Standard mortality statistics using the underlying cause of death (UCOD) and deaths with any mention of IHD in death certificates (MCOD) from ICD-10 codes I20-I25 was performed between 2008 and 2022., Results: A total of 134,327 death certificates reported IHD-related deaths, representing 18.6% of all deaths. Proportional mortality decreased from 14.6% in 2008 to 7.8% in 2022 for deaths with IHD as the UCOD and from 23.5% to 14.6% for deaths with IHD among the MCOD. A more pronounced decline of proportionate and case-specific mortality rate was seen in women. The decline in mortality over the whole study period was larger for acute (vs. chronic) IHD. The COVID-19 pandemic led to a marked increase in mortality in 2020 (+12.2%) with a subsequent further decline. IHD-related deaths displayed a typical seasonal pattern with more deaths during winter. The prevalence of cardiovascular risk factors was higher in IHD (vs. no IHD) deaths: this association appeared more pronounced in younger adults., Conclusions: We provided an analysis of epidemiological trends in IHD-related mortality and prevalence of risk factors. Our findings indicate a change in the pattern of cardiovascular deaths and may suggest a switch in death from acute to chronic conditions., Competing Interests: Declaration of competing interest We declare that we have no competing interests related to this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the USA in the past decade, but the potential economic impact on European healthcare systems remains unknown., Methods and Results: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the USA. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-20 and the model reflecting increasing access to advanced treatment from the PERT™ national quality assurance database registry 2018-21. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-30. The NIS-based model yielded a slow increase, reaching 3.1% (95% confidence interval 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay., Conclusion: Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions., Competing Interests: Conflict of interest: K.M, Kl.K., Ka.K., H.B., T.N., C.A., I.T.F., T.M.T., K.C., M.L., J.R., and L.V.: no disclosures; B.K.: AngioDynamics, Penumbra, Viz.ai, and Dexcom (consultant); R.P.R.: BMS and Janssen (institutional research support); Abbott, Dova, Inari, Janssen, and Penumbra (advisory/consultant); STORM-PE National Lead Investigator, Penumbra; The PERT Consortium™ President; J.M.M.: AngioDynamics, Penumbra, Argon Medical, Pavmed, Auxetics, Innova Vascular, Inquis Medical, Retriever Medical, and Boston Scientific (consultant); K.R.: Abbott Vascular, AngioDynamics, Auxetics, Becton Dickinson, Boston Scientific, Contego, Imperative Care/TRUVIC, Johnson and Johnson Biosense Webster, Medtronic, Neptune Medical, Philips, SurModics, and Terumo (consultant/advisory board); Access Vascular, Aerami, Althea Medical, Auxetics, Contego, Endospan, Imperative Care/TRUVIC, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, ProSomnus, Sealonix, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Valcare, Vantis Vascular, Vasorum, and VuMedi (equity or stock options); NIH, Abiomed, Boston Scientific, Novo Nordisk, Penumbra, and Gettinge-Atrium (research grants via institution); The National PERT Consortium™, Board of Directors; S.B. Boston Scientific, Medtronic, Bayer, and Sanofi (institutional research support by Board); Boston Scientific, Penumbra, and Viatris (personal fees/honoraria); R.N.C.: Penumbra, Steering Committee; J.S.G.: advisor and research fees to the institution from Boston Scientific and Inari Medical; equity in Endovascular Engineering; R.A.L.: Boston Scientific and Medtronic (advisory board); Penumbra, Abbott Vascular, Neptune Medical, Bard Vascular, Cordis, Biosense Webster, Becton Dickinson, SurModics, and Abbott Vascular (speakers bureau); Philips Healthcare, Spectranetics, Terumo, Boston Scientific, Inari, Penumbra, Ethicon, Vesper, and Black Swan (research support); Imperative Vascular, Summa Vascular, Innova Vascular, and Thrombolex (equity shareholder); L.H.: MSD and Janssen (personal lecture/consultant fees); S.V.K.: Bayer AG, Boston Scientific, Daiichi-Sankyo, LumiraDx, and Penumbra (personal lecture/advisory fees and research grants to institution); MSD, Pfizer, and Bristol-Myers Squibb (personal lecture/advisory fees); E.A.S.: NIH/NHLBI K23HL150290, Food & Drug Administration, and SCAI (funding); Abbott, BD, Boston Scientific, Cook, Medtronic, and Philips (grants to institution); Abbott, BD, Boston Scientific, Cagent, Conavi, Cook, Cordis, InfraRedx, Medtronic, Philips, Recor, Shockwave, and VentureMed (speaking/consulting)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: It was demonstrated that differentiated thyroid cancer (DTC) patients may develop multiple primary tumors (MPT) during follow-up. Many studies showed an association between reduced telomere length and cancer phenotype; in particular, the short telomeres were associated with the development of a primary tumor. However, the role of altered telomere length in MPT development has not yet been demonstrated. The aim of this study was to evaluate the possible correlation between a short telomere length in blood leukocytes and the risk of developing MPT in DTC patients., Patients and Methods: We retrospectively evaluated 167 DTC patients followed up for a median of 13.6 years. Our control group was represented by 105 healthy subjects without any thyroid disease or present or past history of tumors. Our study groups, age-matched, were evaluated for the relative telomere length measured in leukocytes of peripheral venous blood., Results: The relative telomere length (RTL) was significantly different in healthy subjects compared to the total group of differentiated thyroid cancer patients [ p < 0.0001]. Shorter telomeres length was observed in DTC patients with ( n = 32) and without ( n = 135) MPT compared to healthy subjects ( p < 0.0001 and p = 0.0002, respectively). At multivariate analysis, the parameters independently associated with the presence of MPT were RTL [OR: 0.466 (0.226-0.817), p = 0.018] and the familial DTC [OR: 2.949 (1.142-8.466), p = 0.032]., Conclusions: The results of this study suggest a role of the relative telomere length in predicting MPT development in DTC patients. Our results contribute to increasing the knowledge of the genetic mechanisms underlying MPT development in DTC patients, considering relative telomere length as a possible prognostic marker.

Background and Aims: The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany., Methods and Results: We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0 days)., Conclusions: We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE., (© 2024. The Author(s).)

Background: Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test., Methods: We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain. Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire., Results: We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18-76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11-21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive for Schistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positive Schistosoma serology results: pelvic pain (45.2%; OR = 1.57, 95% CI: 1.0-2.4), pain on ejaculation (14.5%; OR = 1.85, 95% CI: 1.0-3.5), dyspareunia (12.4%; OR = 2.45, 95% CI: 1.2-5.2), erectile dysfunction (9.5%; OR = 3.10, 95% CI: 1.3-7.6), self-reported episodes of infertility (32.1%; OR = 1.69, 95% CI: 1.0-2.8), haematuria (55.2%; OR = 2.37, 95% CI: 1.5-3.6), dysuria (52.1%; OR = 2.01, 95% CI: 1.3-3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%; OR = 1.81, 95% CI: 1.0-3.1). Clinical signs tended to cluster., Conclusions: Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positive Schistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis., (© 2024. The Author(s).)

Context: American Thyroid Association (ATA) guidelines do not consider age at diagnosis as a prognostic factor on the estimation of the risk of persistent/recurrent disease in differentiated thyroid carcinoma (DTC) patients. While age at diagnosis has already been assessed in high-risk patients, it remains to be established in low- and intermediate-risk patients., Objective: The aim of our study was to investigate the role of age as a prognostic factor in the short- and long-term outcome of DTC patients classified at low and intermediate risk according to the ATA stratification risk system., Methods: We retrospectively evaluated 863 DTC patients (mean follow-up: 10 ± 6.2 years) 52% classified as low (449/863) and 48% as intermediate risk (414/863). For each ATA-risk class patients were divided into subgroups based on age at diagnosis (<55 or ≥55 years)., Results: In the intermediate-risk group, patients aged 55 years or older had a higher rate of structural disease (11.6% vs 8.9%), recurrent disease (4.1% vs 0.7%), and death (4.1% vs 1%) when compared with younger patients (<55 years) (P = .007). Multivariate analysis confirmed that older age at diagnosis (odds ratio [OR] = 3.9; 95% CI, 1.9-8.6; P < .001) was an independent risk factor for worse long-term outcome together with response to initial therapy (OR = 13.0; 95% CI, 6.3-27.9; P < .001), and T (OR = 32; 95% CI, 1.4-7.1; P = .005) and N category (OR = 2.3; 95% CI, 1.1-5.0; P = .03). Nevertheless, a negative effect of older age was documented only in the subgroup of intermediate DTC patients with persistent structural disease after initial therapy. Indeed, the rate of worse long-term outcome rose from 13.3% in the whole population of intermediate DTC patients to 47.8% in patients with persistent structural disease after initial therapy (P < .001) and to 80% in patients older than 55 years and persistent structural disease after initial therapy (P = .02)., Conclusion: Our results suggest that age at diagnosis further predict individual outcomes in Intermediate-Risk DTC allowing ongoing management to be tailored accordingly., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pulmonary embolism (PE) and its sequelae impact healthcare systems globally. Low-risk PE patients can be managed with early discharge strategies leading to cost savings, but post-discharge costs are undetermined., Purpose: To define healthcare resource utilisation and overall costs during follow-up of low-risk PE., Methods: We used an incidence-based, bottom-up approach and calculated direct and indirect costs over 3-month follow-up after low-risk PE, with data from the Home Treatment of Patients with Low-Risk Pulmonary Embolism (HoT-PE) cohort study., Results: Average 3-month costs per patient having suffered low-risk PE were 7029.62 €; of this amount, 4872.93 € were associated with PE, accounting to 69.3% of total costs. Specifically, direct costs totalled 3019.33 €, and of those, 862.64 € (28.6%) were associated with PE. Anticoagulation (279.00 €), rehospitalisations (296.83 €), and ambulatory visits (194.95 €) comprised the majority of the 3-month direct costs. The remaining costs amounting to 4010.29 € were indirect costs due to loss of productivity., Conclusion: In a patient cohort with acute low-risk PE followed over 3 months, the majority of costs were indirect costs related to productivity loss, whereas direct, PE-specific post-discharge costs were low. Effective interventions are needed to reduce the burden of PE and associated costs, especially those related to productivity loss., (© 2023. The Author(s).)

Background: Dissecting the determinants of functional capacity during long-term follow-up after acute pulmonary embolism (PE) can help to better characterize a patient population with persisting limitation., Methods: In a prospective cohort study, consecutive unselected survivors of acute PE underwent 3- and 12-month follow-up, including six-minute walking distance (6MWD) and dyspnea assessment with the modified Medical Research Council (mMRC) scale. We used reference equations adjusting for age, sex, and anthropometric measurements to define abnormal 6MWD., Results: Overall, 323 of 363 (89.0%) patients had at least one recorded 6MWD value at one year. At 3 months, the prevalence of abnormal 6MWD was 21.9% and at 12 months it was 18.3%. At 3 and 12 months, 58.8% and 52.1% with abnormal 6MWD did not report dyspnea, respectively. On average and during follow-up, 6MWD significantly improved with time, while the mMRC dyspnea scale did not. Abnormal 6MWD was associated with younger age (odds ratio per decade, 0.91; 95% CI, 0.88-0.94), higher body mass index (1.10; 1.03-1.17), smoking (3.53; 1.34-9.31), intermediate- or high-risk PE (3.21; 1.21-8.56), and higher mMRC grading (2.28; 1.59-3.27). Abnormal 6MWD at 3 months was associated with the prospectively defined endpoint of post-PE impairment (3.72; 1.50-9.28) and with poor disease-specific and generic health-related quality of life., Conclusion: Three months after PE, 37% of patients reported dyspnea and 22% had abnormal 6MWD. After a year, 20% still had abnormal 6MWD. Dyspnea correlated with abnormal 6MWD, but over 50% of patients with abnormal 6MWD did not report dyspnea. Abnormal 6MWD predicted subsequent post-pulmonary embolism impairment and worse long-term quality of life., Clinical Trial Registration: German Clinical Trials Register Identifier DRKS00005939., Competing Interests: Declaration of competing interests I.T.F. reports no conflicts of interest. L.V. reports no conflicts of interest. S.B. reports grants or contracts from Bayer, INARI, Boston Scientific, Medtronic, Bard, SANOFI, and Concept Medical; consulting fees from INARI; payment or honoraria from INARI, Boston Scientific, and Concept Medical; and support for attending meetings and/or travel from Bayer and Daiichi Sankyo. K.C.C. reports no conflicts of interest. R.E. reports lecture fees from Boehringer Ingelheim, OMT, Novartis, Janssen-Cilag, United Therapeutics, AstraZeneca, Berlin Chemie, research funding from Boehringer Ingelheim, OMT, Janssen-Cilag, and consulting fees from BetaPharm, OMT, Lungpacer Medical. G.G. reports personal lecture/advisory fees from Bayer HealthCare, Pfizer and LeoPharma. M.H. reports honoraria for lectures and advisory board activities from Astra Zeneca, Bayer HealthCare, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Daichi Sankyo, Janssen, MSD, OMT, Pfizer, Santis. L.H. reports consulting fees from MSD and Janssen. K.K. reports no conflicts of interest. H.W. reports lecture and consulting fees from Actelion/Janssen, GSK, Bayer HealthCare, Daiichi Sanchyo, Biotest, Boehringer Ingelheim, MSD and Roche. S.R. reports grants or contracts from Actelion, AstraZeneca, Bayer, Janssen, and Novartis; consulting fees from Abbott, Acceleron, Actelion, Bayer, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor; payment or honoraria from Actelion, Bayer, BMS, Ferrer, GSK, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor. S.V.K. reports grants or contracts from Bayer AG; consulting fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; and payment or honoraria from Bayer AG, MSD, Pfizer, and Bristol-Myers Squibb., (Copyright © 2023. Published by Elsevier Inc.)