Common risk factors for gastrointestinal bleeding (GIB) are advanced age and the use of antiplatelet or anticoagulants drugs for the prevention of cardiovascular diseases.
In this prospective ...real-world observational study, oral anticoagulated patients were recruited and followed between June 2013 and December 2019. The primary end-point was to evaluate a possible relationship between bleeding events and patients' clinical history of gastrointestinal disease prior to the start of the therapy. The secondary end-points were time of GIB appearance and the percentage of idiopathic or provoked events, i.e., bleeding due to a gastrointestinal disease. In case of GIB event all the patients were studied by means of endoscopic procedures. Cox regression was used to calculate the relative hazard ratios (HRs) of GIB for each considered clinical variable.
734 patients on both VKAs or DOACs were studied. Overall, 46 hemorrhagic events were recorded: 6 were major bleeding (0.42/100 patient-years) while 43 were clinically relevant non major bleeding (2.8/100 patient-years). The Cox regression analysis did not show any relationships among GIB and the variables considered.
The patients' clinical history is neither a predictor for GIB bleeding nor a guide to the choice of the oral anticoagulant to be administered. Routinely applying bleeding risk screening, such as occult blood in the stool, should be added to the periodic laboratory checks for early recognition of patients at higher risk of GIB.
•The history of gastrointestinal disease is neither a predictor for GIB nor a guide to the choice of the oral anticoagulant.•GIB during oral anticoagulation is mostly secondary to an underlying gastrointestinal pathologic condition.•Bleedings are more frequent in the lower gastrointestinal tract. Occult blood stool should be periodically checked.
•Trace metals have a close relationship with the Haemostatic System.•They can allow to stabilize blood clots.•They can also activate blood coagulation.
In this narrative review we report the main ...relationships between trace metals and the hemostatic system since this aspect has seldom attracted the attention of the scientific community.
A basic aspect to be considered is the importance of maintaining the fine control of all trace metals’ levels since they have an important impact on the pathophysiology of the hemostatic system.
It is worth noting that poor diet habits are responsible for most trace metal deficiencies, while pollution is responsible for dangerous exposure to them with a consequent negative impact on the general population. This appears of paramount importance in planning the implementation of food and nutrient support to ameliorate the hidden hunger and the quality of life of people especially in developing countries and limiting poisons both in the air and food. As it often happens, when damage to certain mechanisms takes a very long time to appear, no attention is paid to the importance of a systematic prevention to avoid late negative outcomes.
The characteristics and the clinical course of antiphospholipid syndrome (APS) in high-risk patients that are positive for all three recommended tests that detect the presence of antiphospholipid ...(aPL) antibodies have not been described.
This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein I (beta2GPI) antibodies. Laboratory data were confirmed in a central reference laboratory.
One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow-up period was 12.2% (95% CI, 9.6-14.8) after 1 year, 26.1% (95% CI, 22.3-29.9) after 5 years and 44.2% (95% CI, 38.6-49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95% CI 1.3-4.1; P<0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths).
Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.
Thanks to the availability of the MEDITS survey data, a standardized picture of the occurrence and abundance of demersal Chondrichthyes in the northern Mediterranean has been obtained. During the ...spring-summer period between 2012 and 2015, 41 Chondrichthyes, including 18 sharks (5 orders and 11 families), 22 batoids (3 orders and 4 families) and 1 chimaera, were detected from several geographical sub-areas (GSAs) established by the General Fisheries Commission for the Mediterranean. Batoids had a preferential distribution on the continental shelf (10-200 m depth), while shark species were more frequent on the slope (200-800 m depth). Only three species, the Carcharhiniformes Galeus melastomus and Scyliorhinus canicula and the Torpediniformes Torpedo marmorata were caught in all GSAs studied. On the continental shelf, the Rajidae family was the most abundant, being represented in primis by Raja clavata and then by R. miraletus, R. polystigma and R. asterias. The slope was characterized by the prevalence of G. melastomus in all GSAs, followed by S. canicula, E. spinax and Squalus blainville. Areas under higher fishing pressure, such as the Adriatic Sea and the Spanish coast (with the exception of the Balearic Islands), show a low abundance of chondrichthyans, but other areas with a high level of fishing pressure, such as southwestern Sicily, show a high abundance, suggesting that other environmental drivers work together with fishing pressure to shape their distribution. Results of generalized additive models highlighted that depth is one of the most important environmental drivers influencing the distribution of both batoid and shark species, although temperature also showed a significant influence on their distribution. The approach explored in this work shows the possibility of producing maps modelling the distribution of demersal chondrichthyans in the Mediterranean that are useful for the management and conservation of these species at a regional scale. However, because of the vulnerability of these species to fishing exploitation, fishing pressure should be further incorporated in these models in addition to these environmental drivers.
Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a ...possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered.
From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment.
A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0–19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes.
The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin.
•Over-anticoagulation episodes are more frequent in females than in males and this finding can justify the lower TTR in females.•In almost all the patients, over-anticoagulation is not associated with bleeding events so stopping VKAs is enough to reverse an excess of anticoagulation.•Recovery of INR performs better with acenocoumarol that could be used in patients who present several over-anticoagulation episodes during their anticoagulant therapy.•Recovery of INR values does not differ in males and females treated with both warfarin and acenocoumarol.
Introduction
T cell reactivity against pancreatic autoantigens is considered one of the main contributors to the destruction of insulin-producing cells in type 1 diabetes (T1D). Over the years, ...peptide epitopes derived from these autoantigens have been described in NOD mice and in both HLA class II transgenic mice and humans. However, which ones are involved in the early onset or in the progressive phases of the disease is still unclear.
Methods
In this work we have investigated, in early-onset T1D pediatric patients and HLA-matched controls from Sardinia, the potential of preproinsulin (PPI) and glutamate decarboxylase 65 (GAD65)-derived peptides to induce spontaneous T cell proliferation responses of peripheral blood mononuclear cells (PBMCs).
Results
Significant T cell responses against PPI1-18, PPI7-19 and PPI31-49, the first two belonging to the leader sequence of PPI, and GAD65271-285 and GAD65431-450, were found in HLA-DR4, -DQ8 and -DR3, -DQ2 T1D children.
Conclusions
These data show that cryptic epitopes from the leader sequence of the PPI and GAD65271-285 and GAD65431-450 peptides might be among the critical antigenic epitopes eliciting the primary autoreactive responses in the early phases of the disease. These results may have implications in the design of immunogenic PPI and GAD65 peptides for peptide-based immunotherapy.
In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with ...COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease.
PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm.
The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed.
The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.
Summary
Introduction
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are abnormal but unreliable in cirrhotic patients to express their risk of bleeding. However, these ...patients may also suffer from thrombotic episodes. In order to investigate the dynamics of the formation of fibrin, the clot waveform analysis (CWA) of aPTT was studied together with a score for the evaluation of the thromboembolic risk.
Methods
CWA in terms of velocity (1st derivative), acceleration (2nd derivatives) and density (Delta) of aPTT and the Padua Prediction Score (PPS) for venous thromboembolism were studied in 191 cirrhotic patients.
Results
CWA values were lower in the cirrhotic patients when compared to the control groups. However, Delta, 1st and 2nd derivatives were higher in cirrhotic patients with elevated PPS in comparison to those with a low PPS. The 1st derivative was significantly associated with a high PPS score (>4): OR: 2.66, CI: 95% 1.23–5.78.
Conclusions
Two opposing tendencies seem to be present in cirrhotic disease: the first shows a weakness of clot formation while the second a predisposition towards thrombosis, identified by the PPS.
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