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D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Objectives To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were receiving standard oxygen therapyIMV in patients who at randomisation were receiving non-invasive mechanical ventilationSimilar in terms of major bleeding risk Trial design Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study. Participants Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. Inclusion Criteria (all required) Age > 18 and < 80 years Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) Severe pneumonia defined by the presence of at least one of the following criteria: Respiratory Rate ≥25 breaths /minArterial oxygen saturation≤93% at rest on ambient airPaO2/FiO2 ≤300 mmHg Coagulopathy, defined by the presence of at least one of the following criteria: D-dimer >4 times the upper level of normal reference rangeSepsis-Induced Coagulopathy (SIC) score >4 No need of IMV Exclusion Criteria Age 80 years IMV Thrombocytopenia (platelet count < 80.000 mm3) Coagulopathy: INR >1.5, aPTT ratio > 1.4 Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) Known hypersensitivity to enoxaparin History of heparin induced thrombocytopenia Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) Concomitant double antiplatelet therapy Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed Pregnancy or breastfeeding or positive pregnancy test Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) Lack or withdrawal of informed consent Intervention and comparator Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants Body Weight (kg)Enoxaparin dose every 12 hours (IU)200050-69400070-89600090-1108000>11010000 The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur. Main outcomes Primary Efficacy Endpoint: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were in standard oxygen therapy by delivery interfacesNeed for IMV, in patients who at randomisation were in Cpap or NIV Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: Any of the following events occurring within the hospital stay DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were in standard oxygen therapy by delivery interfacesNeed for IMV in patients who at randomisation were in Cpap or NIVImprovement of laboratory parameters of disease severity, including: o D-dimer levelo Plasma fibrinogen levelso Mean Platelet Volumeo Lymphocyte/Neutrophil ratioo IL-6 plasma levels Mortality at 30 days Information about patients’ status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Major bleeding, defined as an acute clinically overt bleeding associated with one or more of the following: Decrease in haemoglobin of 2 g/dl or more;Transfusion of 2 or more units of packed red blood cells;Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal];Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death);Bleeding that necessitates surgical intervention Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: Clinically Relevant non-major bleeding, defined as an acute clinically overt bleeding that does not meet the criteria for major and consists of: Any bleeding compromising hemodynamicSpontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic causeIntramuscular hematoma documented by ultrasonographyEpistaxis or gingival bleeding requiring tamponade or other medical interventionBleeding from venipuncture for >5 minutesHaematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive proceduresHaemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical interventionAny other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Randomisation Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group. Numbers to be randomised (sample size) The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin. Trial Status Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Unsuccessful Desensitization in a Child with Hypersensitivity to Diazoxide

Ricostruzione paleoambientale nell'area di Firenze.

Sono state esposte le sintesi delle conoscenze scientifiche acquisite sino ad oggi sulle Antiche Vie dell'Ambra, dal Mesolitico fino all'Antica Roma e dal Mar Baltico all'Europa Meridionale, al Mar Nero ed al Medio Oriente, con riferimenti ai ritrovamenti più recenti, ai giacimenti, con particolare riguardo all'ambra baltica, e sono state avanzate contemporaneamente ipotesi o riferimenti sui tragitti relativi. Una particolare evidenza è stata data alle vie che attraverso lo scambio commerciale hanno determinato la diffusione delle diverse culture fra i popoli e quindi maggior valore assumono in questo contesto le antichissime vie di epoche in cui i contatti e la comunicazione fra i popoli erano in dipendenza soprattutto delle vie del commercio. Grande importanza hanno assunto, alla luce delle superiori considerazioni, le vie che in epoca protostorica, ed in particolare nelle età del Bronzo e del Ferro, hanno consentito e caratterizzato i commerci dell'Ambra, oltreché di altri materiali, dal Mar Baltico, all'Adriatico, all'Egeo, al Mar Nero ed al Medio Oriente, mettendo in contatto popoli e culture completamente diversi fra loro, contribuendo senza dubbio allo sviluppo delle civiltà e delle conoscenze. Le vie di pace, come quelle dell'ambra, hanno sempre generato cultura.

Made available in DSpace on 2018-11-26T16:19:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01. Added 1 bitstream(s) on 2021-07-15T14:31:45Z : No. of bitstreams: 1 S0102-09352016000100233.pdf: 352092 bytes, checksum: 840992e108b8ef878ba39db49378fff3 (MD5) The objective of this work was to evaluate the effects of adding sources of natural lipids and rumen-protected lipid source rich in polyunsaturated fatty acids to the diet of feedlot Nellore cattle on meat characteristics, blood lipoprotein concentration and fatty acid profile of subcutaneous fat of Longissimus dorsi. One hundred and twenty 24-mo-old Nellore yearling bulls were used (366.9+/-28.7kg). The experimental design was completely randomized, replicated 8 times (5 bulls/pen), with pens being considered experimental units and consisting of three treatments: (CONTR) without additional source of lipid, (GDESP) with source of natural lipid (cottonseed cake), and (GPROT) with rumen-protected lipid source rich in polyunsaturated fatty acids. Interaction (P