Iris Reconstruction: A Surgeon's Guide.

Objectives: The aim of this review paper is to summarise surgical options available for repairing iris defects at the iris-lens plane, focusing on suturing techniques, iridodialysis repair, and prosthetic iris devices. Methods: A thorough literature search was conducted using multiple databases, including Medline, PubMed, Web of Science Core Collection, and the Cochrane Library, from inception to February 2024. Relevant studies were screened based on predefined criteria, and primary references cited in selected articles were also reviewed. Results: Various surgical techniques were identified for iris defect repair. Suturing methods such as interrupted full-thickness sutures and the McCannel technique offer solutions for smaller defects, while iridodialysis repair techniques address detachment of the iris from the ciliary body. Prosthetic iris devices, including iris-lens diaphragm devices, endocapsular capsular tension ring-based devices, and customizable artificial iris implants, provide options for larger defects, each with its own advantages and limitations. Conclusions: Successful iris reconstruction requires a personalised approach considering factors like defect size, ocular comorbidities, and patient preference. Surgeons must possess a thorough understanding of available techniques and prosthetic devices to achieve optimal outcomes in terms of both visual function and, nonetheless, cosmetic appearance.

Investigational drugs inhibiting complement for the treatment of geographic atrophy.

INTRODUCTION: Geographic atrophy (GA) is a progressive form of age-related macular degeneration (AMD) that leads to severe visual impairment and central vision loss. Traditional treatment options for GA are limited, highlighting the need for new therapeutic approaches. In recent years, targeting the complement system has emerged as a promising strategy for the treatment of GA. AREAS COVERED: This expert opinion article reviews the investigational drugs inhibiting the complement cascade for the treatment of GA. Specifically, it focuses on the recent FDA approved pegcetacoplan, a C3 complement inhibitor, and avacincaptad pegol, a C5 complement inhibitor, highlighting their potential efficacy and safety profiles based on clinical trial data. EXPERT OPINION: FDA approval of intravitreal pegcetacoplan and avacincaptad pegol marks significant progress in the landscape of GA treatment. However, variable results from trials underscore the complex nature of GA and the importance of patient selection. Complement inhibition holds promise, but ongoing research is vital to refine treatment strategies and offer improved outcomes for GA patients.

Corrigendum: Diagnostic and therapeutic management of the thoracic outlet syndrome. Review of the literature and report of an Italian experience.

[This corrects the article DOI: 10.3389/fcvm.2022.802183.].

Transesophageal Echocardiography Guidance to Prevent and Manage Pitfalls from Abdominal Normothermic Regional Perfusion and Optimize Timing during Organ Retrieval from a Donor after Circulatory Death.

An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of life support. One of the challenges of A-NRP is ensuring the correct vascular devices' positionings, specifically extracorporeal membrane oxygenation cannulae and aortic balloons, typically achieved through fluoroscopy with or without contrast agents. Here, we present a case report in which transesophageal echocardiography (TEE) helped the transplant team to effectively procure viable abdominal organs from a cDCD donor in the shortest time frame, as minimizing time is one of the most crucial factors in maintaining organ viability. TEE use leads to a more effective and efficient A-NRP procedure with limited complications. In addition, it allows us to observe the circulation of both the thoracic and part of the abdominal organs using one fast exam. This case is the first report describing TEE as a primary guide and useful tool for DCD donors. However, prospective studies are needed to confirm that TEE could be used as standard practice during all DCD organ retrieval procedures.

Efficacy and safety of combined Xen Gel Stent-45 implantation and 25-gauge Pars Plana Vitrectomy: a case series.

Purpose: To report outcomes in terms of efficacy and safety of patients affected with Primary Open Angle Glaucoma (POAG) and Vitreoretinal Disease, who have undergone Pars Plana Vitrectomy (PPV) and ab-interno XEN gel 45 (Abbvie) implantations. Methods: This is a retrospective, observational, case series on five patients who underwent combined Pars Plana Vitrectomy and XEN gel Stent 45 implantation at "Careggi Hospital" Eye Clinic of Florence. Best-corrected visual acuity (BCVA) evaluation, intraocular pressure (IOP) measurements with Goldmann applanation tonometer (GAT), and several glaucoma medications were evaluated at the baseline and at one, three, six, and twelve months after surgery. Complications were recorded up to 1 year after surgery. Results: 5 eyes in five patients were enrolled. IOP dropped from an average of 21,2 ± 3,3 mmHg preoperatively to 14,6 ± 1,1 mmHg at the end of the follow-up period (month 12), with a mean percentage reduction of 58%. One patient needed a needling procedure (20%). None needed reintervention. We did not register any case of hypotony (IOP < 6,5 mmHg), hypotony maculopathy and choroidal detachment. The postoperative number of anti-glaucomatous molecules was on average 0,2 ± 0,4. Conclusion: Our results suggested that combined Pars Plana Vitrectomy and XEN gel stent 45 implantation is safe and effective for patients affected by visually significant vitreoretinal diseases and POAG. Abbreviations: AC = anterior chamber, BCVA = Best-corrected visual acuity, ERM = epiretinal membrane, FTMH = full-thickness macular holes, FU = fluorouracil, GAT = Goldmann applanation tonometer, IOP = intraocular pressure, MIGS = minimally invasive glaucoma surgery, MMC = mitomycin C, NVG = neovascular glaucoma, OCT = optical coherence tomography, POAG = Primary Open Angle Glaucoma, PPV = Pars Plana Vitrectomy, SD = standard deviation, TB = Trabeculectomy, VF = visual field, VMI = Vitreomacular Interface, VMA = vitreomacular adhesion, VMT = vitreomacular traction.

Safety and Efficacy of Rivaroxaban as Extended-Phase Anticoagulation in Patients with Cancer and Venous Thromboembolism: A Preliminary Data Analysis from the Mac Project.

Extended-phase anticoagulation with direct oral Xa inhibitors (OAXI) is suggested in patients with cancer-associated venous thromboembolism (CAT). We report on patients enrolled in the MAC (Monitoring AntiCoagulants) Project, given rivaroxaban as extended-phase anticoagulation after CAT. The primary efficacy outcome was the incidence of symptomatic recurrent VTE; the primary safety outcomes were incidence of major and non-major clinically relevant bleeding, adverse events, and all-cause mortality. The mean patients' follow-up was 19 months (SD 16); 64/604 (11%) had CAT. Recurrent VTE occurred in 9.3% and in 8.1% of patients with and without CAT (OR 1.2, 95% CI 0.5 to 2.9; p = 0.6). Major bleeding occurred in 4.7% and in 2.6%, respectively (OR = 1.8, 95% CI 0.5 to 6.6, p = 0.4), and non-major clinically-relevant bleeding in 4.7% and in 4.1% (OR = 1.2, 95% CI 0.3 to 3.9, p = 0.7). The relative figures for fatal haemorrhage and all-cause death were 1.6% versus 0%, and 1.6% versus 0.4%. Rivaroxaban appears to be effective and safe as extended-phase anticoagulation in patients with CAT. The mean treatment period was 3-times the standard 6-month course.

Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project.

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes.

Correction: Di Micco et al. Clinical Differences between COVID-19 and a COVID-like Syndrome. J. Clin. Med. 2021, 10, 2519.

Incorrect Affiliation [...].

Diagnostic and Therapeutic Management of the Thoracic Outlet Syndrome. Review of the Literature and Report of an Italian Experience.

The Thoracic Outlet Syndrome is a clinical potentially disabling condition characterized by a group of upper extremity signs and symptoms due to the compression of the neurovascular bundle passing through the thoracic outlet region. Because of the non-specific nature of signs and symptoms, to the lack of a consensus for the objective diagnosis, and to the wide range of etiologies, the actual figure is still a matter of debate among experts. We aimed to summarize the current evidence about the pathophysiology, the diagnosis and the treatment of the thoracic outlet syndrome, and to report a retrospective analysis on 324 patients followed for 5 years at the Padua University Hospital and at the Naples Fatebenefratelli Hospital in Italy, to verify the effectiveness of a specific rehabilitation program for the syndrome and to evaluate if physical therapy could relieve symptoms in these patients.

First and second transscleral cyclophotocoagulation treatments provide similar intraocular pressure-lowering efficacy in patients with refractory glaucoma.

PURPOSE: The aim of this study is to address the safety and effectiveness of a second continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) treatment by comparing its outcome against a first CW-TSCPC treatment in the same patients with refractory glaucoma. METHODS: Twenty-one eyes with either primary or secondary glaucoma received a second CW-TSCPC laser session ≥ 3 months after the first treatment. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of topical or oral ophthalmic pressure-reducing medications were registered at every time point up to the last follow-up at 3 months. A complete slit-lamp examination was conducted to record for complications or other abnormal ocular findings. Success was defined as IOP between 6 and 21 mmHg and > 20% reduction in IOP with or without anti-glaucoma medications. RESULTS: At 3 months follow-up of the first CW-TSCPC treatment, a 24.8% decrease in IOP was observed, whereas a 45.6% IOP decrease was observed 3 months post the second CW-TSCPC treatment. Visual acuity did not decrease, and no major complications were observed post either treatment within the follow-up period. Time to failure was 79.5 ± 24.6 and 77.1 ± 29.4, respectively (P = 0.955). No serious complications were observed. CONCLUSION: A second CW-TSCPC treatment proved to be a safe and effective treatment option when the first CW-TSCPC treatment was insufficient in maintaining the desired IOP level for a prolonged time (mean time between both sessions 6.4 ± 8.0 months).

MicroPulse Transscleral Laser Therapy Demonstrates Similar Efficacy with a Superior and More Favorable Safety Profile Compared to Continuous-Wave Transscleral Cyclophotocoagulation.

PURPOSE: The aim of this study was to compare effectiveness and safety of MicroPulse transscleral laser therapy (MP-TLT) using the original MicroPulse P3® device and continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) using the G-Probe® device in glaucoma. METHODS: Spherical equivalent, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of topical or oral ophthalmic pressure-reducing medications were registered at every time point, up to the last follow-up at 12 months. A complete slit-lamp examination was conducted to record the following complications: corneal edema, persistent ocular hypotony (IOP ≤5 mmHg) on two consecutive follow-up visits, choroidal detachment, phthisis bulbi, sympathetic ophthalmia, cystoid macular edema, or other abnormal ocular findings. Success was defined as IOP between 6 and 21 mmHg and >20% reduction in IOP with or without antiglaucoma medications. RESULTS: 47 eyes underwent MP-TLT and 150 CW-TSCPC. At 12 months, success was achieved in 88.6% in the CW-TSCPC group and 87.5% in the MP-TLT group (p = 0.883). In the CW-TSCPC group, eyes achieved a 42.4% IOP reduction (from 28.3 ± 12.3 mmHg to 15.3 ± 6.0 mmHg) and a 31.1% reduction (from 22.0 ± 7.2 mmHg to 15.7 ± 4.8 mmHg) in the MP-TLT group. Visual acuity remained primarily unaltered in both groups. CONCLUSION: MP-TLT was as effective in lowering IOP as CW-TSCPC and achieved comparable success. Additionally, MP-TLT demonstrated consistent and effective outcomes at every time point. The improved safety profile of MP-TLT allows the therapeutic spectrum to be broadened, granting ophthalmologists' treatment of glaucoma in earlier stages of glaucoma than those typically treated with CW-TSCPC, i.e., early to moderate and to patients with good central-vision.

Clinical Differences between COVID-19 and a COVID-Like Syndrome.

COVID-19 is an infection due to SARS-CoV-2; this virus has been identified as the cause of the present pandemic. Several typical characteristics are present in this infection, in particular pneumonia with possible lung failure, but atypical clinical presentations are being described daily by physicians around the world. Ground-glass opacities with pneumonia are the most common and dangerous presentations of the COVID-19 disease, and they are usually associated with positive nasopharyngeal swab (NPS) tests with detectable SARS-CoV-2 viral RNA. Compared to the general population, hospital workers have been at a greater risk of infection ever since the first patients were hospitalized. However, hospital workers have also been reported as having COVID-like symptoms despite repeated negative swab tests but having tested positive for SARS-CoV-2 antibodies with serological tests. We can postulate that a COVID-like syndrome is possible, in particular in hospital workers, that is characterized by symptoms similar to those of COVID-19, but with repeated negative nasopharyngeal swabs. These repeated negative NSPs make the difference in daily clinical management with people that experienced a single false negative nasopharyngeal swab; furthermore, a clear clinical differentiation of these situations is still lacking in the literature. For this reason, here, we report our main findings from a cohort of patients with a COVID-like syndrome compared to a similar group affected by typical COVID-19.

Favorable long-term results of endovenous laser ablation of great and small saphenous vein incompetence with a 1470-nm laser and radial fiber.

OBJECTIVE: Scarce information is available on the long-term results of endovenous laser ablation (EVLA) for great saphenous vein (GSV) or small saphenous vein (SSV) insufficiency. We sought to provide data on the status of patients at least 9 years after EVLA. METHODS: In 2018, we undertook a cross-sectional survey of ambulatory patients who had undergone EVLA in our tertiary care center in 2008-2009. Of 240 eligible patients, 5 died of causes not related to EVLA, 20 refused to participate, and 12 were lost to follow-up. Thus, 203 patients were re-evaluated; of them, 161 (79%) had GSV insufficiency and 42 (21%) had SSV insufficiency. The mean follow-up was 114 months (standard deviation, 11 months). All included patients underwent an echocardiography-color Doppler (ECD) evaluation, a clinical visit, and a standardized medical history. We assessed the competence of the junction and of the treated and untreated saphenous trunk and the presence of recurrent varicose veins. The trunk was considered ablated if it was nonvisible on B-mode or, when visible, if it was noncompressible or without flow or reflux on color flow Doppler analysis. Any recurrent varicose vein with the leakage point located in the treated saphenous vein was considered a failure. We asked patients about the effect of EVLA on their preoperative complaints and about any new or recurrent symptoms. We also recorded any complication or additional subsequent treatment and all data necessary to calculate the clinical class (C of the Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] classification) and the Venous Clinical Severity Score (VCSS). Finally, we investigated potential associations between the study outcomes and variables by multiple logistic regression techniques. RESULTS: Some 10 years after EVLA, we performed a single clinical and ECD evaluation in 203 patients. Only one recanalization (0.5%; 95% confidence interval, 0.0-2.7) of the treated GSV trunk was observed in an otherwise asymptomatic patient. Up to 98% of patients were asymptomatic or significantly improved after EVLA. Additional subsequent treatments occurred in 21% of patients with GSV insufficiency and 5% of patients with SSV insufficiency. Three complications were observed, two in the GSV group (varicophlebitis, saphenous nerve damage) and one (varicophlebitis) in the SSV group. The mean C class of CEAP and the mean VCSS were significantly lower at the end of follow-up, both in patients with GSV insufficiency (C class, 3.2 vs 1.5 [P = .00001]; VCSS, 6.3 vs 1.6 [P = .001]) and in patients with SSV insufficiency (C class, 2.9 vs 1.1 [P = .00001]; VCSS, 5.4 vs 0.7 [P = .001]). Only the maximum diameter of the GSV at the junction independently correlated with ECD-confirmed reflux in the treated saphenous trunk or in the anterior accessory saphenous vein (odds ratio, 1.10; 95% confidence interval, 1.01-1.21). CONCLUSIONS: EVLA using a 1470-nm diode laser with radial fibers provides stable and valuable long-term results in patients with either GSV or SSV insufficiency.

Survival and quality of life after early discharge in low-risk pulmonary embolism.

INTRODUCTION: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes. METHODS: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism. RESULTS: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001). CONCLUSIONS: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.

COVID-19 and Venous Thromboembolism in Intensive Care or Medical Ward.

Despite thromboprophylaxis, patients with coronavirus disease 2019 (COVID-19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with COVID-19 admitted to both intensive care units (ICUs) and medical wards (MWs). Consecutive patients admitted for COVID-19 to the MW and the ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of the internal jugular, and the upper and lower limbs veins every 7 days (± 1 day) after the admission; and, if negative, once-weekly until discharge or death. In case of suspected pulmonary embolism, a multidetector computed tomographic angiography was performed. The primary outcome was the proportion of any deep-vein thrombosis (DVT) and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020, a total of 85 patients were investigated, 44 (52%) in MWs and 41 (48%) in the ICU. Despite thromboprophylaxis, VTE occurred in 12 patients in the MWs (27.3%) and 31 patients in the ICU (75.6%) with an odds ratio of 9.3 (95% confidence interval (CI) 3.5-24.5; P < 0.001). Multiple-site DVT occurred in 55.6% of patients (95% CI 39.6-70.5). Increased D-dimer levels significantly correlated with VTE (P = 0.001) and death (P = 0.015). Summarizing, patients with COVID-19 admitted to the MW or ICU showed a high frequency of venous thromboembolism, despite standard-dose or high-dose thromboprophylaxis. Whether thrombosis, particularly asymptomatic events, may play a role in the morbidity and mortality of patients with COVID-19 remain to be clarified.

Use of RAAS Inhibitors and Risk of Clinical Deterioration in COVID-19: Results From an Italian Cohort of 133 Hypertensives.

BACKGROUND: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients. METHODS: A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09-0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17-1.83, P = 0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality.

MAC Project-Monitoring Anticoagulant Therapy Observational Study: Rationale and Protocol.

Real-life studies complement data from registrative trials. Because of the delayed registration of direct oral anticoagulants in Italy, scarce real-life data on such treatments is available for the Italian population. The aim of the MAC project is to collect real-life clinical information in unselected patients given oral anticoagulants for venous thromboembolism, during a 5-year follow-up period. This is a prospective-cohort, multi-center, observational study performed in four Italian centers. The estimated samples size is 4,000 patients. The efficacy outcomes are: incidence of symptomatic recurrent venous thromboembolism and of post-thrombotic syndrome. The safety outcomes are: incidence of major bleeding, clinically relevant non-major bleeding, minor bleeding, serious adverse events, and mortality. The MAC project has the potential to improve our understanding of the epidemiology and of the therapeutic strategies adopted in Italian patients with venous thromboembolism. Clinical Trial Registration: WWW.ClinicalTrials.Gov, identifier: NCT0432939.

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.