RESUMO
AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.
Assuntos
Obesidade , Sobrepeso , Humanos , Obesidade/terapia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/terapia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Itália/epidemiologia , Comorbidade , Terapia Comportamental/métodos , Terapia Comportamental/normas , Guias de Prática Clínica como Assunto/normas , Gerenciamento Clínico , Cirurgia Bariátrica/métodosRESUMO
Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.
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Anafilaxia , COVID-19 , Hipersensibilidade Imediata , Humanos , Polissorbatos/efeitos adversos , Polietilenoglicóis/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Excipientes/efeitos adversos , Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Estudos Retrospectivos , Programas de Imunização , Testes Cutâneos , Itália/epidemiologiaRESUMO
BACKGROUND: Migrants from developing to Western countries tend to become more sensitised to host than to origin country allergens, although substantial changes in migration patterns have occurred in recent decades. METHODS: We investigated adult immigrants with respiratory allergy, first tested for allergic sensitisation between 1985 and 2012 in a highly industrialised area in Italy. A comparison was made of the sensitisation pattern between immigrants and a random sample of native-born subjects affected by a respiratory allergy, and among immigrants according to macro-region of origin and time period. RESULTS: Between 1985 and 2012, 480 immigrants with respiratory allergy had a first positive allergy test. Immigrants were sensitised mainly to grass (67.1%), house dust mites (HDM) (38.5%) and birch (27.5%), with a pattern of sensitisation very similar to that observed in Italians (native-born). An increase in the proportion of subjects with asthma and of subjects with polysensitisation was observed from the first (1985-2002) to the middle (2003-2007) and the most recent period (2008-2012). In recent years, the proportion of subjects with polysensitisation in immigrants is higher than in Italians (native-born) (53.3% vs. 40.1%). Among immigrants, the risk of sensitisation to grass was higher in those from Sub-Saharan Africa (odds ratio, OR=2.76) and Latin America (OR=2.49), whereas risk of sensitisation to HDM was higher among immigrants from South Asia (OR=2.71), compared to immigrants from Eastern Europe. CONCLUSIONS: Immigrants develop multiple sensitisations more frequently than native-born people, and are especially sensitised to local allergens; the country of origin seems to play a role.
Assuntos
Emigrantes e Imigrantes , Hipersensibilidade Respiratória/etnologia , Saúde da População Urbana/etnologia , Adulto , África Subsaariana/etnologia , Ásia/etnologia , Países Desenvolvidos , Países em Desenvolvimento , Europa Oriental/etnologia , Feminino , Humanos , Desenvolvimento Industrial , Itália/epidemiologia , América Latina/etnologia , Masculino , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/imunologia , Saúde da População Urbana/estatística & dados numéricosRESUMO
BACKGROUND: The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC. MATERIALS AND METHODS: A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed. RESULTS: Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months). CONCLUSIONS: ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse.
Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Recidiva Local de Neoplasia , Humanos , DNA Tumoral Circulante/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Prognóstico , Biomarcadores Tumorais/sangue , Terapia Neoadjuvante/métodos , Intervalo Livre de DoençaRESUMO
Cutaneous squamous cell carcinoma (CSCC) accounts for â¼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.
Assuntos
Carcinoma de Células Escamosas , Oncologia , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico , Itália , Oncologia/normas , Guias de Prática Clínica como AssuntoRESUMO
Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.
Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/tratamento farmacológico , Abordagem GRADE , Proteínas Hedgehog/uso terapêutico , Carcinoma Basocelular/terapia , Carcinoma Basocelular/tratamento farmacológico , Oncologia , Itália/epidemiologiaRESUMO
BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by a difficult diagnosis, different types of presentation, variable course and poor prognosis. MATERIALS AND METHODS: Eighty-one patients with MPM observed in 14 Italian oncology institutions from 1982 to 2007 have been examined with the aim of delineating the history of MPM. RESULTS: Presentation symptoms were ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting in various associations. Computed tomography scan and echotomography signs were ascites, abdominal mass and peritoneal thickening. Peritoneal fluid cytology (61 cases) was positive for mesothelioma in 31 and for malignancy, not mesothelioma, in 13. Laparoscopy was carried out in 40 cases and laparotomy in 36. Thrombocytosis was present in 59 cases. Associated tumors diagnosed during the lifetime were colorectal cancer in two cases and cheek carcinoma, thyroid carcinoma, tongue carcinoma, bladder carcinoma and testicular seminoma. Thirty patients were treated with surgery and 45 with chemotherapy. The median survival time from diagnosis is 13 months. Ascites, fever and vomiting were significative variables at presentation; only vomiting holds significance in a multivariate analysis. CONCLUSIONS: MPM is a disease with various types of presentation, frequently associated with thrombocytosis, sometimes with other tumors. Survival and diagnosis time can differ in various types of MPM. Prognosis is poor.
Assuntos
Mesotelioma/diagnóstico , Mesotelioma/etiologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amianto/efeitos adversos , Comorbidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/epidemiologia , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Urticarial vasculitis (UV) is an uncommon type of chronic urticaria (CU), which exhibits leucocytoclastic vasculitis. Painful and long-lasting (> 24 h) weals associated with purpura or bruising are considered indicative of UV. It is often responsive to oral corticosteroids and poorly to oral antihistamines. Hypocomplementaemia and systemic involvement are also commonly reported. AIMS: To diagnose patients with UV histologically and then compare their clinical features and response to various treatment regimens. METHODS: Biopsies were taken from 312 subjects with CU unresponsive to oral antihistamines; of these, 47 were histologically diagnosed as having UV. Biopsies were taken irrespective of the clinical features of weal eruption. Other diseases known to be associated with small-vessel vasculitis had previously been excluded. Results. Individual weals lasted < 24 h in 57.4% of patients, and pain or tenderness was reported only by 8.6%. Extracutaneous features were present in 81%, hypocomplementaemia in 11% and abnormalities of other laboratory parameters (i.e. raised erythrocyte sedimentation rate, microscopic haematuria) in 76.6%. Hydroxyzine was effective in only one patient. Both oral corticosteroids and cinnarizine were effective in a high percentage of the patients. CONCLUSION: This diagnostic approach allowed us to identify a large group (47 patients) with UV. Most did not present the clinical (prolonged duration of weals and bruising) and laboratory features that have previously been described as characteristic of UV. Cinnarizine was found to be a valuable treatment option.
Assuntos
Autoanticorpos/imunologia , Pele/patologia , Urticária/patologia , Vasculite/patologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Artralgia/complicações , Biópsia , Vasos Sanguíneos/patologia , Criança , Resistência a Medicamentos , Feminino , Febre/complicações , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Urticária/tratamento farmacológico , Urticária/imunologia , Vasculite/tratamento farmacológico , Vasculite/imunologiaRESUMO
AIMS AND BACKGROUND: The present work assessed the impact of two decrees on ethics committees in Italy, aimed at bringing the national laws on the conduct of clinical trials into line with the rest of the EC, and regulating and facilitating not-for-profit research. MATERIAL AND METHODS: Prospectively collected data from an Italian multicentre study were examined with respect to the ethics review process. Administrative and time elements of the review process were audited. Main outcome measures were time between the application submission and the ethics committee definitive opinion, type and number of application submission forms, number of ethics committees that refused fee exemption, and time between the ethics committee approval and the administrative authorisation. RESULTS: A total of 134 local research ethics committees (LRECs) were approached. Application submission procedures and application forms varied greatly; paper submission was mandatory. The median time from submission to approval was 72 days. Only two LRECs refused the fee exemption. The median time from LREC approval to administrative agreement was 50 days and only 9.6% of local authorities came to a verbal agreement with the sponsor. CONCLUSIONS: Italian LRECs are still not sufficiently efficient in complying with the Directive 2001/20/EC requirement (60 days). Better coordination of LRECs work is needed although the optimal level of coordination between them is still not known. In the meantime, national guidelines are needed concerning the application of Directive 2001/20/EC. The behaviour of Italian LRECs towards not-for-profit research was excellent although only the fee exemption was requested.
Assuntos
Pesquisa Biomédica/legislação & jurisprudência , Comissão de Ética/legislação & jurisprudência , Pesquisa Biomédica/ética , Pesquisa Biomédica/normas , Comissão de Ética/ética , Comissão de Ética/normas , Regulamentação Governamental , Guias como Assunto/normas , ItáliaRESUMO
We describe a diagnostic and therapeutic protocol for the management of chronic urticaria. It is derived from an extensive review of current literature, with a cost-effective evaluation of laboratory investigations and therapeutic approaches. Our protocol may not represent a cornerstone for chronic urticaria: much has in fact to be clarified on pathogenetic mechanisms and aetiological factors. Nevertheless, its application should be able, in our opinion, to identify what is useful or not in the everyday management of chronic urticaria patients.
Assuntos
Protocolos Clínicos , Urticária/diagnóstico , Urticária/terapia , Doença Crônica , Humanos , Pele/patologia , Testes Cutâneos , Urticária/dietoterapia , Urticária/patologia , Vasculite/etiologia , Vasculite/patologiaRESUMO
Despite the widely recognized practical importance of anticardiolipin (aCL) ELISA, the reliability of this test has been recently discussed. In order to investigate this area on European scale, we sent to 30 experienced centers a questionnaire focusing on the diagnostic procedures applied to patients with antiphospholipid syndrome (APS) and on the detailed protocols used to perform aCL. Anticardiolipin ELISA was found to be the most frequently performed test in patients with suspected APS, but significant difference was shown among the various protocols. The cross-laboratory multiple examination of ten serum samples evaluated independently by the 24 centers pointed out the difficulty in getting comparable results. Therefore a "consensus" protocol was derived from the aCL methods giving the best performance. The materials and reagents necessary to perform the "consensus" method, including, as putative standards, one IgG and one IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The results of one IgG and one IgM aCL high positive sera measured in serial dilutions were compared. A progressive decrease in the variability of the values obtained for a given sample appeared evident when all the laboratories used the same standard, in their own in-house ELISA and even more in the "consensus" ELISA. Our data show that aCL ELISA standardization is necessary in order to obtain comparable results in different laboratories.
Assuntos
Anticorpos Anticardiolipina/sangue , Adulto , Anticorpos Monoclonais , Síndrome Antifosfolipídica/diagnóstico , Coleta de Dados , Tomada de Decisões , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Humanos , Imunoglobulina G , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
A modified poly(ethylene glycol) (PEG) has been developed for the soluble-polymer-supported synthesis of beta-lactams. The monomethylether of PEG (MeOPEG) with an average M(W) of 5000 was used as the support, a 4-(3-propyl)phenyl residue as the spacer, and a 4-oxyphenylamino group as the moiety with the reactive functionality. From this modified PEG representative aromatic, heteroaromatic, unsaturated, and aliphatic imines were obtained in high yields by different procedures. The polymer-supported imines were then employed to prepare several beta-lactams by enolate/imine condensation and ketene/imine cycloaddition. Examples of the control of the absolute stereochemistry during the azetidinone ring formation are also reported. The reactions carried out on the polymer-bound imines showed a remarkable similarity to those performed on nonimmobilized imines, both in terms of yields and stereoselectivities. Removal of the beta-lactams from the polymer has also been accomplished to directly deliver the N-unsubstituted azetidinones.
RESUMO
Autoantibodies directed to phospholipids or to phospholipid binding proteins are now studied using a growing number of laboratory tests. However, the history of the interest in this area goes back to the identification of the so-called false positive reactions in the non-treponemal serological test for syphilis (STS) and to the subsequent description of an in vitro coagulation defect called lupus anticoagulant (LAC). In the 1980s the introduction of the anticardiolipin antibody (aCL) immunoassay was a determining factor in the definition of the antiphospholipid syndrome (APS). In addition, lupus prone mice spontaneously producing aCL antibodies and normal mice passively infused with these antibodies provided useful models for the study of the pathogenic role of aPL. When in 1990 a phospholipid binding protein (beta 2glycoprotein I, beta 2GPI) was identified as the cofactor required for aCL antibody binding, the true antigenic target of the antibodies was first discussed. Soon afterwards an anti-beta 2GPI ELISA was developed that has proved to be of great clinical significance. We will discuss here the similarities and differences between these various assays (LAC, aCL, and anti-beta 2GPI), focusing on their specificity, sensitivity and practical applications.
Assuntos
Anticorpos Anticardiolipina , Síndrome Antifosfolipídica/diagnóstico , Glicoproteínas/imunologia , Glicoproteínas de Membrana/imunologia , Animais , Síndrome Antifosfolipídica/imunologia , Autoanticorpos , Ensaio de Imunoadsorção Enzimática , Reações Falso-Positivas , Humanos , Camundongos , Sensibilidade e Especificidade , beta 2-Glicoproteína IRESUMO
The BF3.OEt2 or LiClO4 catalyzed hetero Diels-Alder reaction of 1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky's diene) with enantiomerically pure 4-formylazetidin-2-ones affords the corresponding cycloadducts in fair to good yields and in diastereoisomeric ratios of up to 98:2.
Assuntos
Antibacterianos/síntese química , Azetidinas/química , Butadienos/química , Estereoisomerismo , beta-LactamasRESUMO
We studied 99 patients with systemic autoimmune disease (5 males, 94 women; mean age 37 year, range 16-72): 28 Primary Antiphospholipid Syndrome, 67 Systemic lupus Erythematosus, 1 Mixed Connective Tissue Disease, 2 Undifferentiated Connective Tissue Disease and 1 Discoid Lupus. Based on the observation that native PT shows conformational changes in presence of Ca++ ions and discloses new epitopes available for binding with phospholipids, we performed 3 different methods for the detection of aPT in presence and absence of Ca++, finding a different incidence of specific autoantibodies, associated with clinical features of APS (aPT in presence of Ca++) or non associated (aPT in absence of Ca++). The presence of aPT was significantly associated also with the presence of Lupus Anticoagulant (LAC). The detection of aPT (in presence of Ca++) significantly enhances diagnostic sensibility of APS allowing the identification of a subset of patients (6/99) with clinical features of APS, but with negative LAC, aCL and a beta2-GPI; in fact (limited to thrombotic episodes) the sensibility rises from 56.2% with one test (LAC) to 81.1% with the application of LAC, aCL, a(beta)2GPI and aPT.
Assuntos
Síndrome Antifosfolipídica/imunologia , Autoanticorpos/imunologia , Protrombina/imunologia , Trombofilia/imunologia , Adolescente , Adulto , Idoso , Especificidade de Anticorpos , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos/sangue , Cálcio/farmacologia , Quelantes/farmacologia , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/imunologia , Ácido Edético/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Glicoproteínas/imunologia , Humanos , Imunoglobulina G/imunologia , Inibidor de Coagulação do Lúpus/análise , Lúpus Eritematoso Discoide/complicações , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/imunologia , Valor Preditivo dos Testes , Tempo de Protrombina , Trombofilia/etiologia , beta 2-Glicoproteína IRESUMO
Alterations of elastic properties may contribute to the accelerated atherosclerosis in patients with T2D. Little is known, however, about radial artery distensibility in this patient group. A total of 19 patients with T2D and 19 controls were investigated.An echotracking system coupled to a plethysmograph was used to assess the morphologic and elastic properties of radial artery. Distensibility and compliance were evaluated using Langewouters' equations. Distensibility and compliance did not differ significantly in patients with diabetes compared with controls. In contrast, radial IMT and WCSA were significantly higher in patients with T2D than in controls. Multiple regression analyses revealed a significant association between SBP and IMT (r(2) = 0.40, p<0.001) as well as WCSA (r = 0.54; r(2) = 0.30; p<0.001 ) in individuals with diabetes. In conclusion, distensibility and compliance of the radial artery are not reduced in patients with T2D. In contrast, radial IMT and WCSA are significantly higher in patients with T2D than in controls.These modifications are chiefly and positively related to SBP.
Assuntos
Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/patologia , Artéria Radial/patologia , Túnica Íntima/patologia , Túnica Média/patologia , Idoso , Pressão Sanguínea , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Complacência (Medida de Distensibilidade) , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/fisiopatologia , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pletismografia , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Esfigmomanômetros , Sístole , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , UltrassonografiaRESUMO
OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos/sangue , Citrulina/imunologia , Fator Reumatoide/sangue , Adulto , Idoso , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Humanos , Infliximab , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Two chiral bisoxazolines (box) supported on a modified poly(ethylene glycol) (PEG) have been prepared by a reaction sequence that involved formation of the properly functionalized box and their attachment to the polymer matrix by means of a spacer and a linker. The solubility properties of PEG allowed use of the supported box as ligands in some catalytic asymmetric transformations carried out under homogeneous conditions and to recover the ligands as if bound to an insoluble support. When the supported box were employed in combination with Cu(II) salts in the Diels-Alder cycloaddition between cyclopentadiene and N-acryloyloxazolidinone, low levels of enantioselectivity were observed (up to 45% ee). Much better results were obtained in the cyclopropanation of styrenes carried out in the presence of CuOTf (up to 93% ee) and in the ene-reaction between alpha-methylstyrene or methylenecyclohexane and ethylglyoxalate (up to 95% ee). One of the ligands, readily recovered by precipitation and filtration, was recycled two times in the ene-reaction with marginal loss in the catalytic activity and very limited erosion of the enantioselectivity.
RESUMO
A short stereoselective synthesis of the acetoxy azetidinone (1), an important precursor of several biologically active beta-lactam antibiotics, has been accomplished in seven steps and 32.8% overall yield from the easily available and inexpensive (R) ethyl 3-hydroxybutanoate.
Assuntos
Carbapenêmicos/síntese química , Lactamas/síntese química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Espectrofotometria Infravermelho , EstereoisomerismoRESUMO
The introduction of anticardiolipin antibody (aCL) assay, described in 1983, was able to focus much attention on the study of patients suffering from thrombosis, repeated fetal loss and thrombocytopenia, and allowing the identification of the so called antiphospholipid syndrome (APS). The identification of beta2 glycoprotein I (beta2GPI) as an essential component of the antigenic complex recognized by aCL suggested that this molecule could be a direct target of the antibody response. Since then, different groups have described ELISAs for the detection of anti beta2GPI antibodies, applied to the clinical evaluation of patients with APS, and showing an overall better specificity. Recently, anti beta2GPI were also shown to bind apoptotic bodies resulting in an alteration of their physiological clearance with the triggering of TNFalpha release. This observation suggests that anti beta2GPI may also modify the immunogenicity of apoptotic bodies and of the autoantigens that they contain.