Venous thromboembolism in COVID-19 patients

We read with interest the study published by Tang and coll.1 in a recent issue of the Journal of Thrombosis and Haemostasis. In this retrospective analysis, conducted at the Tongji Hospital of Wuhan, China, it is reported that heparin treatment reduces mortality in subjects affected by severe COVID-19 who have \u201csepsis-induced coagulopathy\u201d. The definition of severe COVID-19 was the presence of at least one of following: respiratory rate 6530 breaths /min; arterial oxygen saturation 6493% at rest; PaO2/FiO2 64300 mmHg. The Authors of this study also reported that, among subjects not treated with heparin, mortality raised according with D-dimer levels. Of note, patients that received heparin in this study were mostly treated with enoxaparin, at the thromboprophylactic dose of 40-60 mg/day, for at least 7 days

The BIM-based Integrated Design of the SHiP Project Decay Volume

The Search for Hidden Particles (SHiP) experiment is a new general-purpose fixed target facility proposed at the CERN Super Proton Synchrotron accelerator to search for longlived exotic particles associated with Hidden Sectors and Dark Matter. This paper reports on the BIM integrated design of SHiP’s decay volume, a conical steel vessel under vacuum that should host several large particle physics detector systems. The use of BIM characterized the design of the decay volume, both in the modeling and structural design phase, and in the process definition phase for the realization and implementation in the facility of the device. This procedure helps to minimize the risks of incorrect design and construction of the device during the whole process. With the automation of the virtual model and the use of interoperable software, in addition to speeding up the exchange of information, it is possible also to export the detailed information of the structural design directly to the numerical control machines for the prefabrication of the various steel modules. Then, the BIM approach to support the integrated design of the SHiP project decay volume from the conceptual planning to the construction phase is shown in this work

Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis

Background: Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19). Objectives: To evaluate the incidence of VTE in patients with COVID-19. Methods: MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19. Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis. Results: 3487 patients from 30 studies were included. Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%–66%). PE with or without DVT occurred in 12% of patients (95% PI, 2%–46%) and DVT alone in 14% (95% PI, 1%–75%). Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%–57%) and DVT in 6% (95% PI, 0%–60%), compared to 11% (95% PI, 2%–46%) and 24% (95% PI, 2%–85%) in studies using other diagnostic strategies or patient sampling. In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%–66%), PE in 19% (95% PI, 6%–47%), and DVT alone in 7% (95% PI, 0%–69%). Corresponding values in general wards were respectively 9% (95% PI, 0%–94%), 4% (95% PI, 0%–100%), and 7% (95% CI, 1%–49%). Conclusions: VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE. The threshold for clinical suspicion should be low to trigger prompt diagnostic testing

Pulmonary Embolism in COVID-19 Patients: Which Diagnostic Algorithm Should We Use?

Introduction: Although pulmonary embolism (PE) is a frequent complication of the clinical course of COVID-19, there is a lack of explicit indications regarding the best algorithm for diagnosing PE in these patients. In particular, it is not clear how to identify subjects who should undergo computed tomography pulmonary angiography (CTPA), rather than simply X-ray and/or high resolution computed tomography (HRCT) of the chest. Methods: We retrospectively analyzed COVID-19 patients who presented to the Emergency Department (ED) of our University hospital with acute respiratory failure, or that developed acute respiratory failure during hospital stay, to determine how many of them had a theoretical indication to undergo CTPA for suspected PE according to current guidelines. Next, we looked for differences between patients who underwent CTPA and those who only underwent X-ray and/or HRCT of the chest. Finally, we determined whether patients with a confirmed diagnosis of PE had specific characteristics that made them different from those with a CTPA negative for PE. Results: Out of 93 subjects with COVID-19 and acute respiratory failure, 73 (78.4%) had an indication to undergo CTPA according to the revised Geneva and Wells scores and the PERC rule-out criteria, and 54 (58%) according to the YEARS algorithm. However, in contrast with these indications, only 28 patients (30.1%) underwent CTPA. Of note, they were not clinically different from those who underwent X-ray and/or HRCT of the chest. Among the 28 subjects who underwent CTPA, there were 10 cases of PE (35.7%). They were not clinically different from those with CTPA negative for PE. Conclusions: COVID-19 patients with acute respiratory failure undergo CTPA, X-ray of the chest, or HRCT without an established criterion. Nonetheless, when CTPA is performed, the diagnosis of PE is anything but rare. Validated tools for identifying COVID-19 patients who require CTPA for suspected PE are urgently needed

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients

Background: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. Methods: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). Results: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50–69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156–484), the incidence of VTE recurrences was 3.8% (95%CI 1.0–9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1–10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6–8.1). Conclusions: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings

Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs\u2014produced either by endothelial cells, platelets, leukocytes, and erythrocytes\u2014was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs\u2014which was measured in MP-depleted plasma\u2014was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications

Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo

Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker \u3b1SMA, with direct connections between \u3b1SMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans

Metabolic Syndrome (MetS), Systemic Inflammatory Response Syndrome (SIRS), and Frailty: Is There any Room for Good Outcome in the Elderly Undergoing Emergency Surgery?

Background: Patients with MetS or SIRS experience higher rates of mortality and morbidity, across both cardiac and noncardiac surgery. Frailty assessment has acquired increasing importance in recent years as it predisposes elderly patients to a worse outcome. The aim of our study was to investigate the influence of MetS, SIRS, and with or without frailty on elderly patients undergoing emergency surgical procedures. Methods: We analyzed data of all patients with nonmalignant diseases requiring an emergency surgical procedure from January 2017 to December 2020. The occurrence of MetS was identified using modified definition criteria used by the NCEP-ATP III Expert Panel: obesity, hypertension, diabetes, or if medication for high triglycerides or for low HDL cholesterol was taken. Systemic inflammatory response syndrome (SIRS) was evaluated according to the original consensus study (Sepsis-1). The frailty profile was investigated by the 5-modified Frailty Index (5-mFI) and the Emergency Surgery Frailty Index (EmSFI). Postoperative complications have been reported and categorized according to the Clavien–Dindo (C–D) classification system. Morbidity and mortality have been mainly considered as the 30-day standard period definition. Results: Of the 2,318 patients included in this study, 1,010 (43.6%) fulfilled the criteria for MetS (MetsG group). Both 5-Items score and EmsFI showed greater fragility in patients with MetS. All patients with MetS showed more frequently a CACI index greater than 6. The occurrence of SIRS was higher in MetSG. LOS was longer in patients with MetS (MetSG 11.4 ± 12 days vs. n-MetSG 10.5 ± 10.2 days, p = 0.046). MetSG has a significantly higher rate of morbidity (353 (35.%) vs. 385 (29.4%), p = 0.005). The mortality rate in patients with MetS (98/1010, 10%) was similar to that in patients without it (129/1308, 10%). Considering patients with MetS who developed SIRS and those who had frailty or both, the occurrence of these conditions was associated with a higher rate of morbidity and mortality. Conclusion: Impact of MetS and SIRS on elderly surgical patient outcomes has yet to be fully elucidated. The present study showed a 43.6% incidence of MetS in the elderly population. In conclusion, age per se should be not considered anymore as the main variable to estimate patient outcomes, while MetS and Frailty should have always a pivotal role