5 results on '"Stefano Barco"'
Search Results
2. Severe High Molecular Weight Kininogen (HK) Deficiency: Clinical Characteristics, Deficiency-Causing KNG1 Variants in Reported and New Cases, and Estimated Prevalence
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Marion Echenagucia, Heidi Rossmann, Anke Adenaeuer, Vincenzo Rocco, Hanan F. Nazir, Stefano Barco, Sarah Krutmann, Ylenia Pancione, Friederike Häuser, Luigi Tomao, Chiara Ambaglio, Karl J. Lackner, Arlette Ruiz de Saez, Bernhard Lämmle, and Alice Trinchero
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medicine.medical_specialty ,Endocrinology ,business.industry ,High-molecular-weight kininogen ,Internal medicine ,Immunology ,medicine ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Background: Severe high molecular weight kininogen (HK) deficiency is an autosomal recessive defect of the contact system caused by mutations in KNG1. Limited scientific interest in HK deficiency due to the rarity of the seemingly asymptomatic condition may increase, as HK, the precursor of bradykinin, is now discussed as a therapeutic target e.g. in hereditary angioedema. Aims: We provide a comprehensive analysis of the diagnostic, clinical, and genetic features of HK deficiency and estimate its frequency. Methods: We identified a new case of HK deficiency, systematically review the literature, conduct new genetic studies of reported cases, and comprehensively analyze the clinical course and diagnostic criteria. Clotting activity of HK and prekallikrein (PK) (HK:C/PK:C) and antigen (HK:Ag/PK:Ag) were determined and genetic analyses of KNG1 and KLKB1 were performed by Sanger sequencing. Characteristics deduced from the known HK deficiency-causing variants were used to estimate the frequency of HK deficiency from the KNG1 variants aggregated in GnomAD. Results: 677 studies were identified by systematic review of the literature for HK deficiency. 27 of these contained individual cases of HK deficiency including 6 studies not listed in PubMed. Little-noticed cases from the gray literature account for more than one-third (16/39) of the extracted, unrelated cases. We genotyped one newly diagnosed HK-deficient case and 2 cases described in the literature and additionally evaluated all 10 studies reporting genetic data in HK-deficiency (including one case previously misdiagnosed as having PK deficiency). A total of 10 KNG1 variants causing HK deficiency (one new) were found, the most frequent being c.586C>T, p.Arg196* (4 unrelated families). Interestingly, all HK deficiency-causing variants are truncating, whereas two amino acid substitutions with presumed functional consequence, have been described as the cause of hereditary angioedema. Conservative prevalence estimates based on all known and putative HK deficiency-causing variants extracted from GnomAD (truncating variants in KNG1, including indels, nonsense and canonical splice site mutations located in that part of the gene, where relevant mutations have been described) revealed a frequency of 1 case of HK deficiency among 7,925,172 with slight differences in the analyzed ethnicities (see table). In addition, although not to the same extent as seen in PK deficiency, HK deficiency apparently is more prevalent in Africans. While it is already well known that HK deficiency causes decreased PK levels, our data indicate that factor XI levels are also frequently decreased, albeit to a lesser extent. The number of cases detected so far is too low for a more detailed analysis regarding bleeding, thrombotic, and cardiovascular events or immunological abnormalities. Conclusion: HK-deficiency is probably more frequent than previously thought. Suspected cases of contact phase defects should at least be analyzed for HK activity (besides factor XII, XI and PK activity) to facilitate conclusive evaluation of the clinical significance in the future. Figure 1 Figure 1. Disclosures Lämmle: Takeda: Membership on an entity's Board of Directors or advisory committees; Ablynx: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Baxter: Other: Travel Support, Speakers Bureau; Alexion: Other: Travel Support, Speakers Bureau; Siemens: Other: Travel Support, Speakers Bureau; Bayer: Other: Travel Support, Speakers Bureau; Roche: Other: Travel Support, Speakers Bureau; Sanofi: Other: Travel Support, Speakers Bureau.
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- 2021
3. MC-SAT: A Telemedicine Management System Utilized to Monitor Oral Vitamin K Antagonists Treatment
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Chiara Beltrametti, Picchi Chiara, Cristiani Paolo, Stefano Barco, Barone Marisa, Fabio Sabatini, Franco Piovella, and Diana Irina Iosub
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Prothrombin time ,education.field_of_study ,Telemedicine ,business.product_category ,medicine.diagnostic_test ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Phone ,INR self-monitoring ,Health care ,medicine ,Internet access ,Medical emergency ,Medical prescription ,business ,education - Abstract
Abstract 4742 The MC-SAT program is a telemedicine system developed for the management of patients under oral anticoagulant treatment (OAT). The program constitutes the natural evolution of an original research project, which assessed the capability of a telematic system in managing different chronic patients access flow to health care services. In particular, for patients on oral anticoagulation we planned a direct access to a call center server and a pre-process of the INR data obtained through self-testing with portable prothrombin time (PT) monitor. The original project performed the technology assessment of all the devices and procedures able to automatically drive international normalization ratio (INR) data from patients to specialists in a hospital anticoagulation clinic and to get patients able to read the medical answer. The ability of patients and/or general practitioners to self-determine INR without specific training and the integration of a portable PT monitor for home use into routine patient care in anticoagulation clinics was subsequently successfully evaluated. After a pilot phase of the project, during which the feasibility of the MC-SAT telemedicine service was assessed, we started the enrollment of consecutive patients. Controls matched by age (+/− 5 years), sex and therapeutic range with the cases, were selected among those who attended our anticoagulation clinic (whose population reaches 3,557 individuals) and were managed by usual care. At the beginning of the program, which is still ongoing, a portable monitor (Coagucheck®, Roche Diagnostics, Germany) has been given to 40 patients and to 10 general practitioners (GPs) provided with portable monitors and Internet access. Each GP had the task to follow 5 patients on chronic OAT. Subsequently, additional 40 patients joined, referring to the preferred community laboratory to perform the prothrombin time and subsequently send the INR results through MC-SAT. To date, the system works like this: the INR data, obtained through the portable monitor or through a local laboratory, is sent by GPRS cellular phone or by Internet computer. When an alert output is detected, an automatic message is sent to the specialist. GPRS services are implemented in order to connect the specialist to the database containing the clinical history of the patient. The specialist is able to monitor, from any location, by means of smartphone or tablet PC, all INR values recorded by the system, all the previous patient accesses to the hospital and the last weekly OAT dose. On these basis, if necessary, a change of the weekly OAT doses is made and transferred to the GP's or patients' computer. Since the start of this project in its definitive shape in june 2009, we enrolled 130 patients allocated to prolonged oral anticoagulant treatment. Of these, 80 were directly assisted by our clinic. The remaining 50 patients were assigned to the GPs. Of the 130 patients originally enrolled, 39 never provided any data. These 39 patients were among those assigned to the GPs. Even if periodically urged to do so, GPs sent data on 11 patiens only. Of the 80 patients directly assisted by our clinic, who utilized either the given portable monitor or referred to a community laboratory, 69 showed great interest to the program, did send their results and continue to do so, utilizing the system 1104 times during the period july 2010-june 2011, with a mean of 16 prescription/year/patient. No significant differences were recorded in the TTR (time in therapeutic range) between the patients enrolled and the controls. More than 80% of the answers were given before 9 hours from the request. After two years, we confirm that the use of the system represents an improvement in the management of patients under oral anticoagulant treatment, by favouring communications and, potentially, clinical outcomes. The program showed to work better when it involves the individual patient rather than GPs. Disclosures: No relevant conflicts of interest to declare.
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- 2011
4. Pregnancy and Successful Delivery in a Patient with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Previously Submitted to Pulmonary Endarterectomy (PEA)
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Marisa Barone, Chiara Picchi, Chiara Beltrametti, Franco Piovella, Diana Irina Iosub, Stefano Barco, and Montanari Laura
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medicine.medical_specialty ,Superficial vein thrombosis ,business.industry ,medicine.drug_class ,Immunology ,Low molecular weight heparin ,Cell Biology ,Hematology ,Left pulmonary artery ,medicine.disease ,Biochemistry ,Pulmonary hypertension ,Right pulmonary artery ,Thrombosis ,Surgery ,medicine.artery ,Pulmonary artery ,Medicine ,business ,Bronchial artery - Abstract
Abstract 4329 Chronic thromboembolic pulmonary hypertension (CTEPH) results from obstruction of the major pulmonary arteries by incompletely resolved or organized pulmonary emboli which have become incorporated into the pulmonary artery wall, eventually causing an increase in pulmonary vascular resistances. CTEPH is a condition that is recognised in an increased percentage of patients. Pulmonary endarterectomy (PEA) is recognized as being the only curative option for a subgroup of those patients, but anaesthesiologists and intensivists face many challenges in how they manage these patients perioperatively. Ultimately, it is the combination of skills in a multidisciplinary team that leads to a successful procedure and dramatically improves patient’s quality of life and life expectancy. Careful pre- and post-operative management is therefore essential for such a successful outcome following PEA. In 1994 in Pavia was started a program in which members of a multidisciplinary team work in close interaction with the aim of increase experience in the challenging problems these patients present in the evaluative, surgical, and post-operative phases of their care. Pregnancy in women with pulmonary hypertension (PH) is reported to carry a maternal mortality rate of 30–56%. No report is available on the management of pregnancy and delivery in patients with CTPH. We report our experience of the management of a pregnancy in a patient previously submitted to PEA in whom pressures decreased significantly but remained higher than normal due to partial intervention. EFS, 29 yrs, had first hemoptysis in 2001. Since then, she suffered effort dyspnea. A second hemoptysis occurred in 2004. She was admitted to hospital as having “Multiple foci pneumonia, with pulmonary hypertension of unclear origin”. In 2005 patient was admitted to a different hospital. A CT scan showed: “Congenital right pulmonary artery agenesia associated with bilateral multiple artero-venous malformations. NYHA Class III”. Patients was transferred to our hospital. Thrombophilic workout resulted negative. PaO2: 79.9 mmHg, pulmonary artery pressures (PAP): 130/60/13 mmHg, pulmonary vascular resistances (PVR): 1.083 dynes/sec/min−5. CT angio-scan: Severe dilation of the common pulmonary artery (34 mm). Right pulmonary artery visible only at proximal level. Bronchial artery dilation, bilaterally. V/Q scan: Absent visualization of the right pulmonary artery. Perfusion absent. Arteriography: Clearcut thrombosis of the right pulmonary artery (initial tract). Multiple typical CTPH lesions of the left pulmonary artery. Lower limb compression ultrasound (CUS): No sign of deep or superficial vein thrombosis. On 11 april, 2005 PEA was performed on the left side, with an attempt on the right side. No agenesia of the right pulmonary artery was found. Probable occlusion in early age, with evolution in fibrosis. Post surgery, PaO2: 94.3 mmHg, PAP: 53/32/15 mmHg, PVR: 453 dynes/sec/min−5. On September 16, 2005 she was pregnant, seventh week. After careful multidisciplinary counseling, patient decided to continue pregnancy. Anticoagulant treatment was switched from warfarin to low molecular weight heparin (LMWH), therapeutic dosage. Two days before elective delivery, LMWH was reduced to prophylactic dosages. On march 2, 2006 after an uncomplicated Caesarean section under general anesthesia, she delivered a healthy baby girl. During the following months, PAPs and functional parameters normalized. Patient is today in relatively good health. Is under oral vitamin K antagonists treatment. In 2007, being pregnant again, opted for therapeutic abortion. Maternal mortality in parturients with PAH or CTPH remains prohibitively high, despite lower death rates than previous decades. Early advice on pregnancy risks, including contraception, remains paramount. Women with PAH or CTPH who become pregnant warrant a multidisciplinary approach with consideration of appropriate therapies. Disclosures: No relevant conflicts of interest to declare. 06.04.2005 11.04.05PEA 18.04.2005 16.09.2005 14.02.2006 11.04.06Delivery 05.08.2010 PAP(s) (mmHg) 130/60/13(Cath) 53/32/15(Cath) 50/-/-(Us) 55/-/-(Us) 35/-/-(Us) PVR(dynes/sec/cm-5) 1083 453 – – – Syst. Pressure CO (L/min) 4.2 5.1 – – – NYHACLASS III II I Symptoms Dyspnea, Emoptysis Emoptysis Emoptysis Moderate dyspnea – Treatment none UFH/Warf Warf/UFH LMWH Warf
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- 2011
5. Efficacy of Fondaparinux in the Treatment of Heparin-Induced Thrombocytopenia with Venous Thromboembolism: Reduction of Thromboembolic Burden, Normalization of Platelet Count and Disappearance of Anti-Platelet Factor 4/Heparin Antibodies
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Marisa Barone, Federico Capra Marzani, Andrea Maria D'Armini, Mara De Amici, Vittorio Arici, Martin Langer, Gianluca Castellani, Franco Piovella, Chiara Piovella, Stefano Barco, and Chiara Beltrametti
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medicine.medical_specialty ,medicine.drug_class ,business.industry ,Immunology ,Danaparoid ,Warfarin ,Low molecular weight heparin ,Cell Biology ,Hematology ,Heparin ,Lepirudin ,Fondaparinux ,medicine.disease ,Biochemistry ,Gastroenterology ,Argatroban ,Internal medicine ,Heparin-induced thrombocytopenia ,medicine ,business ,medicine.drug - Abstract
Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) may develop during anticoagulant treatment in patients submitted to various regimens of unfractionated or low-molecular weight heparins. Several molecules have been studied as alternative anticoagulants in patients with HIT or HITT, including danaparoid, argatroban, lepirudin. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the International Normalized Ratio (INR) when co-administered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Anticoagulation of patients with HIT or HITT may be limited by antibodies cross-reactivity with danaparoid and by new generation of antibodies with lepirudin. Fondaparinux is the first of a new class of synthetic antithrombotics: the selective inhibitors of coagulation factor Xa. It is the most advanced competitor of low molecular weight heparins, which are the reference drugs in prophylaxis and treatment of venous thromboembolism. Fondaparinux does not bind to platelet factor 4 (PF4) and does not react with anti-PF4/heparin antibodies in in vitro testing. We treated 20 patients who develop HIT (3 patients) or HITT (17 patients, of whom 4 had both DVT and PE). Nine patients were previously submitted to extracorporeal circulation with unfractionated heparin (UFH) followed by low-molecular weight heparin (LMWH) for major cardiac surgery. The remaining patients had been previously treated with either UHF or LMWH at therapeutic or prophylactic dosage in internal medicine or surgery wards. In the 17 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, accordingly with their bleeding risk. To the remaining patients with HIT we gave prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Patients with HITT were treated for 4 to 25 days before starting warfarin. Fondaparinux was stopped when INR of 2.0 or more was reached. All patients showed a significant reduction of their thromboembolic burden. One episode of major bleeding was recorded in a post-surgical patient. All patients but one showed sustained normalization of the platelet number. In the remaining patient platelet count remained unchanged. Treatment was switched from fondaparinux to lepirudin and after few days her platelets reverted to close-to-normal levels. In seven patients, submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were determined using a PF4/heparin enzyme-linked immunosorbent assay (ELISA): in all cases antibody levels progressively decreased close to disappearance by 30–45 days. This series of cases provides further evidence for the safety and efficacy of fondaparinux in the treatment of both HIT or HITT.
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- 2006
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