The cross-talk between thrombosis and inflammatory storm in acute and long-covid-19: Therapeutic targets and clinical cases

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state

A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI = Rate of Events/Rate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM

Development of a combined micro-macro mechanics analytical approach to design shape memory alloy spring-based actuators and its experimental validation

In this work, an analytical procedure for the preliminary design of shape memory alloy spring-based actuators is investigated. Two static analytical models are considered and interconnected in the frame of the proposed procedure. The first model, based on the works from An, is able to determine the material properties of the SMA components by means of experimental test data and is able to size the SMA component based on the requirements of the system. The second model, based on a work from Spaggiari, helps to design and size an antagonist spring system that allows one to obtain the geometric characteristics of springs (SMA and bias) and the mechanical characteristics of the entire actuator. The combined use of these models allows one to define and size a complex SMA actuator based on the actuation load requirements. To validate the design procedure, static experimental tests have been performed with the entire SMA actuator

Prophylactic arterial catheterization in the management of high risk patients for obstetric haemorrhage

OBJECTIVES: Post-partum haemorrhage still remains one of the major causes of maternal morbidity and mortality. In case of abnormal placentation it is possible to carry out preventive and therapeutic actions. To maintain fertility in reproductive-aged women and to avoid a more radical surgery, embolization has been introduced in patients at high risk for haemorrhage. To describe a new option in the management of patients with abnormal placentation by an elective, preventive arterial catheterization and selective embolization of pelvic arteries. PATIENTS AND METHODS: A retrospective study including thirty six patients with abnormal placental invasion. All patients were prepared in the angiographic room and preventive arterial catheterization was performed before elective caesarean delivery. Materials for interventional angiography were transferred to the operating room. During surgery, selective embolization of pelvic arteries was realized in case of uncontrolled bleeding. RESULTS: Thirty-six elective arterial catheterizations were performed: 4 cases (11.1%) required embolization, haemorrhage was stopped in 2 patients. Hysterectomy was performed in two cases (5.5%). No death was reported. Two humeral thrombosis (5.5%) were registered. CONCLUSIONS: Prophylactic arterial catheterization appears to be safe. The main advantage is the reduction of the interval between the onset of bleeding and the embolization. This new option of management may contribute to reduce the risk of hysterectomy and maternal death

Il contributo degli esuli italiani alla riflessione sui caratteri dei totalitarismi: alcuni casi di studio

Il saggio esami la riflessione sviluppata da alcuni grandi esuli italiani sui caratteri dei totalitarism

Aging Skin: Nourishing from the Inside Out, Effects of Good Versus Poor Nitrogen Intake on Skin Health and Healing

Skin is the outermost defense organ which protects us from the environment, constituting around 8 % of an adult’s body weight. Healthy skin contains one-eighth of the body’s total proteins. The balance of turnover and synthesis of skin proteins is primarily dependent on the availability of sufficient nitrogen-containing substrates, namely, amino acids, essential for protein metabolism in any other tissue and body organs. The turnover of skin proteins has been shown to be rapid, and the mobilization of amino acids at the expense of skin proteins is relevant in experimental models of protein malnutrition. As a result, alterations in nutritional status should be suspected, diagnosed, and eventually treated for any skin lesions. Protein malnutrition has a dramatic prevalence in patients aged >70 or more, independent of the reason for hospitalization. The quality of nutrition and content of essential amino acids are strictly connected to skin health and integrity of its protein components. Collagen fiber deposition is highly and rapidly influenced by alterations in the essential to nonessential amino acid ratios. The most relevant nutritional factor of skin health is the prevalence of essential amino acids

Homocysteinylated Albumin Promotes Increased Monocyte-Endothelial Cell Adhesion and Up-Regulation of MCP1, Hsp60 and ADAM17

RATIONALE:The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE:Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS:Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS:Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling

Neprilysin inhibitor-angiotensin II receptor blocker combination (sacubitril/valsartan): rationale for adoption in SARS-CoV-2 patients

On 11 March 2020, the World Health Organization (WHO) declared the corona virus disease 2019 (COVID-19) outbreak as a ‘pandemic’.1 No valid therapy for COVID-19 is actually available. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is empirically treated with antivirals, antimalarics,tocilizumab, etc.2 Production of a vaccine for COVID-19 has been attempted, although approval needs time. We describe a possible, alternative approach for treating COVID-19. Lymphocyte count hasbeen associated with increased disease severityrisk.3 Patients who died from COVID-19 showed a significantly lower lymphocyte count than survivors, therefore this should be closelymonitored.3 Repletion of lymphocytes couldprobably have beneficial effects on recovery. A recent hypothesis suggests that the inhibition of the angiotensin 1 receptor (AT1R) may provide benefits to COVID-19 patients.4 Thishypothesis is based on the observation that the SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor to bind thevirus to the bronchial cell membrane. Theenzymes ACE and ACE2 belong to the samepeptidase family but have two very different physiological functions. ACE cleaves angiotensin I to generate angiotensin II (Ang II), whichbinds to and activates AT1R, and thus promoting vasoconstriction. ACE2 cleaves Ang II and generates angiotensin 1-7, a powerful vasodilator acting through Mas receptors. AT1R antagonists are widely used in hypertensive patientsbut they increase the ACE2 cardiac expressionin rats5 and the urinary concentration of ACE2.6 It has been demonstrated that the binding ofvirus to ACE2 leads to ACE2 down-regulation

The smart detection of ship severe roll motions and decision-making for evasive actions

This paper presents a numerical model for the smart detection of synchronous and parametric roll resonance of a ship. The model implements manoeuvring equations superimposed onto ship dynamics in waves. It also features suited autopilot and rudder actuator models, aiming at a fair depiction of the control delay. The developed method is able to identify and distinguish between synchronous and parametric roll resonance, based on the estimation of encounter wave period from ship motions. Therefore, it could be useful as a smart tool for manned vessels and, also, in the perspective of unmanned and autonomous vessels (in the paper it is assumed a hypothetical remote crew). Once the resonance threat is identified, different evasive actions are simulated and compared, based on course and speed change. Calculations are carried out on a ro-ro pax vessel vulnerable to parametric roll. We conclude that, in roll resonance situations, and in the absence of roll stabilisation systems on-board, course change could be the most effective countermeasure