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It has been suggested that anti-neutrophil cytoplasmic antibody (ANCA) specificity, rather than clinical diagnosis influences the phenotype and course of ANCA-associated vasculitis (AAV). However, preliminary evidence suggests that further combined levels of categorisation might be of clinical relevance. The aim of this study was to investigate differences in clinical presentation at disease onset and outcomes based on clinical diagnosis and ANCA specificity.Newly diagnosed patients with GPA or MPA assessed in three referral centres between 2000 and 2016 were included. Patients were grouped as MPO-ANCA-positive granulomatosis with polyangiitis (MPO-GPA), PR3-ANCA-positive-GPA (PR3-GPA), and MPO-ANCA-positive microscopic polyangiitis (MPO-MPA).Of the 143 AAV patients included (female 52%), 87 were categorised as PR3-GPA, 23 as MPO-GPA, and 33 as MPO-MPA. Patients with MPO-GPA were significantly younger than MPA patients (age 49±15 versus 63±10; p0.001). MPO-GPA had significantly more frequent subglottic stenosis compared to PR3-GPA. Ear, nose, throat involvement was significantly more frequent in both GPA groups compared to MPA. Type of pulmonary involvement differed between both GPA groups and MPA with diffuse pulmonary haemorrhage being significantly more frequent in the latter (7% in PR3-GPA, 0% in MPO-GPA, 27% in MPOMPA; p0.001). Renal involvement was more frequent in MPO-MPA compared to both MPO-GPA and PR3-GPA (impaired renal function in 84%, 39%, and 36%, respectively; p0.001). PR3-GPA relapsed significantly more than the other two groups. After adjusting for age, MPO-GPA was a significant risk factor for mortality [HR 4.44 (95%CI 1.46-13.52), p=0.009].ANCA specificity identifies specific subsets of disease characterised by different clinical presentation and outcome within the clinical diagnosis of GPA.

Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: Results A total of 1338 patients with AAV were included: 66% had disease onset at Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.

OBJECTIVE: Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. METHODS: We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ���4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. RESULTS: Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). CONCLUSION: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

To evaluate the importance of Doppler ultrasonography in fetuses in the management of fetal growth restriction (FGR).Sixty-five pregnant women, aged between 23 to 39 years and from 27 to 37 weeks of pregnancy were selected; they all carried a single fetus showing a diminished growth curve in respect to the previous echographic examinations. Women affected with diabetes types I and II, renal pathologies and/or past endocrinopathies were excluded. All the patients with fetal growth restriction underwent accurate flussimetric mapping of some fetal districts such as umbilical artery and ductus venosus. Modalities of birth and the neonatal outcome were also considered.The patients selected were divided into 4 groups according to the velocimetrical data. The neonatal outcome was positive when the end diastolic flow was present in the umbilical artery associated with a normal flow in the ductus venosus. In cases where the end diastolic flow was absent in the umbilical artery, the management and neonatal outcome varied in relation to the morphology of the flow in the ductus venosus: the absence or reverse A phase of the mentioned flow is often indicative of acute fetal distress and unfavourable prognosis. Reverse end diastolic flow in the umbilical artery was always associated with the intrauterine death of the fetus.Our results confirm the validity of Doppler ultrasonography in the management and in the choice of timing for birth in cases of fetal growth restriction.

The aim of this study was to evaluate the clinical significance of borderline fetal pyelectasis, whether it is associated with chromosomal aberration or is the expression of a structural defect of the urinary tracts.We carried out echographies on 2900 pregnant women in the 2nd trimester of their pregnancies between January 1998 and March 2002 at the Department of Obstetrics, Gynaecology and Neonatology. Any patient with fetuses affected by borderline pyelectasis in association with other echographic markers of aneuploidy and in women 35 years of age and older with fetuses presenting isolated pyelectasis underwent amniocentesis for karyotyping.We discovered 2.1% (62 cases) of borderline pyelectasis in the general population. The karyotype was normal in all cases of isolated pyelectasis; 3/5 of the fetuses with borderline renal pyelectasts associated with other risk factors showed a chromosomal aberration.In accordance with existing documentation, the results of our research confirmed that isolated borderline pyelectasis does not increase the risk of chromosomopathies; this latter is significantly more frequent when pyelectasis is present in older pregnant women (35 years of age) or is associated with other sonographic markers of chromosomal anomalies (choroids plexus cysts, cystic hygroma etc.). Prenatal cytogenetic tests of the fetal karyotype are to be recommended in older mothers and/or in presence of associated echographic anomalies. In this study we propose an early diagnosis of mild forms of pyelectasis which are misdiagnosed by superficial echographies, but which can be associated with chromosomopathy.

Introduction Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results One-hundred and six patients were included (median age at onset of 55 years [IQR 42–67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13–77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4–9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51–13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.

The aim of this paper was to establish the physiologic changes in the coagulation and fibrinolytic systems during normal pregnancy.One-hundred and twenty normal pregnant women were investigated in a longitudinal study involving 3 measurements: blood samples were collected at 12, 24 and 36 weeks of gestation and were assayed for prothrombin time, antithrombin III (ATIII) activity, protein C activity, protein S (PS) activity, prothrombin fragments 1+2, type 1 plasminogen activator inhibitor activity, tissue plasminogen activator antigen, plasminogen, activated protein C resistance, factors VII and VIII levels and D dimer. Student t-test, one way analysis of variance (ANOVA) and Fisher test were used for statistical analysis.Factor VII and factor VIII were always increased with respect to controls. Variance analysis showed a statistically significant reduction for anticoagulants (PS) and a rise for F1+2 and D dimer. With regard to fibrinolysis, there was an increase both for t-PA and PA1-1 during pregnancy. Moreover, the increased activity of factors of haemostasis was accompanied by an increase of activity and concentration of ATIII and acquired activated protein C resistance.These findings suggest that normal pregnancy is associated with an hypercoagulable state, resulting into a moderate risk for thrombosis during the different trimesters of pregnancy. Also broad spectrum assays which measure a range of trombin/fibrin formation in serum have become an established mean to identify activation of blood coagulation and/or fibrinolysis. There is a considerable interest in the application of these assays to the diagnosis of other acquired hypercoagulable states; such as thrombophilia during pregnancy. From the viewpoint of coagulation/fibrinolysis changes, the follow-up of thrombophilia markers could be recommended when levels of coagulation parameters exceed the normal values during pregnancy.

Obiettivo. Lo scopo di questo studio era verificare l’incidenza delle complicanze conseguenti alla diagnosi prenatale invasiva effettuata mediante amniocentesi presso il centro di Diagnosi Prenatale del Secondo Ateneo di Napoli. Metodi. Sono state intervistate telefonicamente 1.580 pazienti circa le complicanze conseguenti ad amniocentesi effettuate nel periodo compreso tra gennaio 2001 e dicembre 2003. Risultati. Delle intervistate hanno risposto correttamente al questionario soltanto 1.416 pazienti. Le complicanze verificatesi nelle prime 24 h dall’intervento (complicanze precoci) sono state costituite da lievi contrazioni e lipotimie da riflesso vagale rispettivamente nell’8,3% e nel 6,7% dei casi; perdite di liquido amniotico si sono avute nell’l,06% mentre sanguinamenti si sono avuti nello 0,85% dei casi. L’incidenza di aborti nella settimana successiva all’intervento è risultata essere pari allo 0,78%. Parti prematuri si sono verificati solo nel 6% delle pazienti sottoposte ad amniocentesi; parti spontanei a termine nel 43% e mediante taglio cesareo nel 51% dei casi. L’indice di Apgar è risultato normale nel 95,7% dei nati. Nel restante 4,3% si sono avute patologie quali ipoglicemia o distress respiratorio prontamente regrediti. Le complicanze precoci e l’incidenza di aborti sono risultati significativamente correlati con il traumatismo uterino conseguente alla seconda infissione dell’ago, ma non con l’età della paziente o con il prelievo transplacentare. Conclusioni. L’ortodossia della tecnica associata allo scrupoloso rispetto del protocollo e alla rigorosa selezione delle pazienti sono presupposti necessari per una riduzione sempre maggiore delle complicanze relative all’amniocentesi.

The aim of this study is to implement the use of biochemical parameters in the analysis of fetal urine to assist with decision making for surgical intervention for fetal obstructive uropathy. Three patients were selected over a 6 month period following ultrasound diagnosis of megabladder and oligohydramnios. Amniocentesis and cystocentesis were performed for karyotyping and biochemical urinary electrolyte evaluation, respectively. Fetal urine biochemistry assisted in decision making with regard to patient and fetal well being. In each of the cases the parameter cutoffs were diagnostic of fetal condition. While the long term benefits of fetal intervention for obstructive uropathy are still debated, we feel that the use of urine biochemical criterIa provide the best current method to select the subjects to be submitted to vesicoamniotic shunt centres.