The role of self-expanding vascular stent in superior vena cava syndrome for advanced tumours.

INTRODUCTION: Superior vena cava (SVC) syndrome (SVCS) is a life-threatening occurrence that necessitates prompt treatment. At present, endovascular stenting is proposed as a first-line treatment to relieve symptoms. We assessed the effectiveness, safety and outcome of SVC stent positioning in patients affected with advanced cancer. METHODS: Forty-two patients undergoing stent positioning in the SVC for neoplasms from January 2002 to December 2018 form the basis of this retrospective study. Demographic data, risk factors, associated diseases, symptoms at presentation according to the score proposed by Kishi and the type of SVCS according to Sanford and Doty were collected. Minor and major complications were recorded. Suspected stent occlusion was confirmed by means of recurrence of symptoms followed by a confirmatory computed tomography (CT). RESULTS: Thirty-four (81%) patients had a nonresectable lung tumour invading or compressing the SVC. Five (12%) patients had a non-Hodgkin's lymphoma, and three (7%) had metastatic lymphadenopathies. Nitinol stents (Memotherm®) were employed in 19 (45%) patients, and steel stents (Wallstent™) in the remaining 23 (55%) patients. Thirty-five (85%) patients died during follow up for disease progression and the overall survival rate at 24 months was 11% (standard error (SE)=0.058). Thirteen patients (32%) had a recurrence of SVCS because of stent thrombosis in three (23%) and extrinsic compression from uncontrolled cancer progression in ten (77%). The overall symptom-free interval at 24 months was 57% (SE=0.095). CONCLUSIONS: We recommend the use of the endovascular procedure as a first-line treatment in locally advanced or metastatic tumour in the presence of SVCS.

Histopathology of salivary glands.

Salivary gland (SG) biopsy is a technique broadly applied for the diagnosis of primary Sjögren's syndrome (pSS), lymphoma accompanying SS, sarcoidosis, amyloidosis, and IgG4-related disease The most peculiar feature of pSS on biopsy is focal lymphocytic sialadenitis. In the past, several histological scores have been reported in the literature to describe glandular involvement during pSS. However, the variability among centres in reporting glandular scores is one of the rationales behind the development of standardised consensus guidance. SGs as well as lacrimal glands are involved in up to 50% of patients with IgG4-related disease with 3 histopathological hallmarks such as dense lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis. SGs can be also affected by amyloidosis with MSG biopsy being more sensitive than that of rectal mucosa or subcutaneous fat. SG involvement is a rare manifestation during sarcoidosis, and the presence of non-caseating granulomas needs to be differentiated from granulomas of other etiology. This review article provides an overview of normal and pathological SGs in the context of rheumatic diseases, identifying key elements in the tissue as diagnostic and prognostic biomarkers, useful in the current clinical practice.

Association between anti-citrullinated alpha enolase antibodies and clinical features in a cohort of patients with rheumatoid arthritis: a pilot study.

In recent years several antibodies against citrullinated peptides (ACPAs) have been identified in patients with rheumatoid arthritis (RA) and their pathogenic, diagnostic and prognostic significance is under intense investigation. Among ACPAs, those targeting citrullinated alpha enolase (anti-CEP1) have been identified in RA but data about their ability to predict the development of erosive disease are conflicting. Furthermore, no data are currently available concerning their possible association with extra-articular manifestations (EAMs) in RA. The aim of this study was to investigate the prevalence and significance of anti-CEP1 from a prognostic point of view. In this pilot study we confirmed that anti-CEP1 Abs are associated with higher prevalence of bone erosions, but we also provided the first evidence of an association between anti-CEP1 Abs and RA interstitial lung disease (ILD). These results provide the basis to investigate the association between anti-CEP1 Abs and EAMs in larger cohorts of RA patients to possibly confirm its role as biomarker for RA-ILD.

Cardiovascular disease risk burden in primary Sjögren's syndrome: results of a population-based multicentre cohort study.

OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of patients with 1343 pSS. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events.

Clinical and biological differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome: results of a large multicentre study.

OBJECTIVES: To determine the clinical and laboratory differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome (pSS), in a large Italian multicentre cohort. METHOD: Patients were selected according to the following criteria: fulfilling the American-European classification criteria for pSS, serum cryoglobulin and gammaglobulin levels evaluated, and lack of hepatitis C virus (HCV) infection. Multinomial analyses were performed by distinguishing three groups of pSS: (i) purpura associated with cryoglobulinaemic vasculitis (CV), (ii) purpura associated with hypergammaglobulinaemic vasculitis (HGV), and (iii) pSS patients without purpura (pSS controls). Patients with purpura but without cryoglobulins or hypergammaglobulinaemia were excluded. RESULTS: A total of 652 patients were enrolled in this study. Group 1/CV comprised 23/652 patients (3.53%), group 2/HGV 40/652 patients (6.13%), and group 3/pSS controls 589/652 (90.34%). The three groups were found to be significantly different from each other (post-estimation test: group 1/CV vs. group 3/pSS controls: p < 0.0001; group 1/CV vs. group 2/HGV: p = 0.0001; group 2/HGV vs. group 3/pSS controls: p = 0.0003), thus confirming the different phenotypes of purpura in pSS.Multivariate analyses revealed that peripheral neuropathy (p < 0.001), low C4 (p < 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.02), and the presence of anti-SSB/La antibodies (p = 0.02) characterized CV whereas rheumatoid factor (p = 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.01), and anti-SSA/Ro antibodies (p = 0.049) were significantly associated with HGV. Lymphoma was associated only with CV. CONCLUSIONS: HGV is a cutaneous vasculitis, related to a benign B-cell proliferation, whereas CV is a systemic immune complex-mediated vasculitis with complement activation and a higher risk of lymphoma, thus confirming CV but not HGV as a prelymphomatous condition in pSS.

A retrospective, multicenter study evaluating the prognostic value of minor salivary gland histology in a large cohort of patients with primary Sjögren's syndrome.

OBJECTIVE: The objective of this report is to investigate the prognostic value of minor salivary glands (MSG) assessment, routinely performed with hematoxilin-eosin (H&E) staining, for the diagnosis of primary Sjögren's syndrome (pSS). METHODS: We retrospectively evaluated clinical, serological and histological features of 794 pSS patients. H&E-stained sections were assessed using the Chisholm and Mason grading system and/or the focus score (FS). RESULTS: FS allowed the identification of a number of differences in the disease spectrum, and its prognostic role was further confirmed by quantifying the association between FS value and clinical/serological variables with binary logistic regression. Moreover, hypocomplementemia and FS resulted the only variables associated with lymphoma at univariate analysis, and FS appeared to be associated with lymphoma independently on complement fraction concentrations. Conversely, when patients were divided according to the Chisholm and Mason grading system, we failed to observe any significant difference between subgroups. CONCLUSION: In addition to its diagnostic role, our data seem to support that the routine assessment of MSG-FS with H&E staining is useful to predict at the time of diagnosis the adverse outcomes, such as lymphoma and extraglandular manifestations, that complicate the pSS course. On this basis, it should be recommended that an MSG biopsy be performed even in those patients displaying clinical and serological criteria, allowing the diagnosis of pSS independent of histological status.

Expansion of CD4+CD25-GITR+ regulatory T-cell subset in the peripheral blood of patients with primary Sjögren's syndrome: correlation with disease activity.

OBJECTIVES: CD4+CD25high regulatory T cells (TREG) represent a suppressive T cell subset deeply involved in the modulation of immune responses and eventually in the prevention of autoimmunity. Growing evidence demonstrated that patients with autoimmune and inflammatory chronic diseases display an impairment of TREG cells or activated effector T cells unresponsive to TREG. Glucocorticoid-induced TNFR-related protein (GITR) is a widely accepted marker of murine TREG cells, but little is known in humans. Aim of the present study was to investigate the characteristics of different subsets of TREG cells in Sjögren's syndrome and the potential role of GITR as marker of human TREG cells. METHODS: Fifteen patients with primary Sjogren's syndrome (SS) and 10 sex- and age-matched normal controls (NC) were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies. Disease activity was assessed using the EULAR Sjögren's syndrome disease activity index (ESSDAI). RESULTS: Although the proportion of circulating CD25highGITRhigh subset was similar in SS patients and NC, an expansion of the CD25-GITRhigh cell population was observed in the peripheral blood of SS patients. Interestingly, this expansion was more relevant in patients with inactive rather than active disease. CONCLUSIONS: The number of CD4+CD25-GITRhigh cells is increased in SS as compared to NC. Moreover, the fact that the expansion of this cell subset is prevalently observed in patients with inactive disease suggests that these cells may play a role in counteracting inflammatory response.

CEA versus CAS: short-term and mid-term results.

AIM: Ischemic stroke represents a major health problem and it is an important cause of long-term disability. The aim of this study was to compare short-term and mid-term results of carotid endarterectomy and stenting. METHODS: During a three-year period, we enrolled 300 patients with carotid stenosis that fit with Stroke Prevention and Educational Awareness Diffusion (SPREAD) guidelines and we performed 150 carotid endarterectomy operations (CEA) and 150 carotid artery stenting procedures (CAS) with distal protection devices. All patients underwent preoperative and postoperative: neurological examination, ultrasound imaging, magnetic resonance imaging (MRI) and cognitive tests; moreover all patients were submitted to preoperative, intraoperative and postoperative Transcranial Doppler (TCD) monitoring, in order to detect microembolic signals (MES). RESULTS: Mortality was zero; two patients developed myocardial infarction in the CEA group during follow-up. The main post-operative results after endarterectomy versus CAS were respectively: neurological deficit: 1.3% vs. 3.3%, embolic lesions at postoperative MRI: 4% vs. 34% and worsening of cognitive tests: 4% vs. 25.3%. CONCLUSION: CEA seems to be the treatment of choice for carotid stenosis, due to its low rate of mortality and morbidity, especially in asymptomatic patients; CAS should be carried out only in particular subgroup of cases, such as: restenosis, previous neck surgery or radian therapy, anatomical high bifurcation or extended lesions. Ongoing multicenter randomized trials may give a definitive answer to this matter.

[Glucocorticoid induced TNFR-related protein (GITR) as marker of human regulatory T cells: expansion of the GITR(+)CD25⁻ cell subset in patients with systemic lupus erythematosus]. / Glucocorticoid-induced TNFR-related protein (GITR) come marker di cellule T regolatorie umane: espansione della sottopopolazione cellulare GITR(+)CD25⁻ in pazienti affetti da lupus eritematoso sistemico.

OBJECTIVES: Regulatory T cells (T(REG)) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR) is a well known marker of murine T(REG) cells, but little is known in humans. The aim of this study was to investigate the characteristics of T(REG) cells in systemic lupus erythematosus (SLE) and the potential role of GITR as marker of human T(REG). METHODS: Nineteen SLE patients and 15 sex- and age-matched normal controls (NC) were enrolled. CD4(+) T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR) using TaqMan probes. RESULTS: The CD25(high)GITR(high) subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05). On the opposite, the CD25⁻GITR(high) cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01). Interestingly, FoxP3 at mRNA level was expressed in both CD25⁻GITR(high) and CD25(high)GITR(high) cells, suggesting that both cell subsets have regulatory activity. CONCLUSIONS: CD4(+)CD25⁻GITR(high) cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.

Classic and endovascular surgical management of isolated iliac artery aneurysms.

AIM: Isolated iliac artery aneurysm is a rare pathology that is often asymptomatic for long periods; this late diagnosis exposes patients to a high risk of death following aneurysm rupture. The aim of this study was to establish the most suitable diagnostic approach, the correct indications for treatment, and the most appropriate tactics and surgical technique. METHODS: Twenty-eight patients were observed over 13 years. Aneurysmal involvement was unilateral in 22 cases and bilateral in the remaining 6 patients. Preoperative diagnostic tests included eco-colour Doppler (ECD) and angio-CT in all cases, with angio-MR and angiography as more selective procedures. Seventeen patients underwent conventional open surgery with prosthetic replacement of the aneurysmatic tract, 7 patients were treated using endovascular exclusion, and lastly 4 were monitored over time. RESULTS: There was no perioperative mortality for either treatment. During the postoperative period following conventional open surgery, complications included one case of severe respiratory failure, one microembolism of the lower limb, and 2 periprosthetic hematoma. During the follow-up, we observed one pseudo-aneurysm, 3 cases of retrograde ejaculation and one patient with erectile dysfunction after traditional surgery; there was one minor endoleak after endovascular exclusion. CONCLUSIONS: Our experience suggests that ECD is a useful method for arriving at an early diagnosis, while angio-CT imaging is essential for a correct preoperative study. Aneurysms with a diameter equal or greater than 3 cm or that present annual increases in excess of 5 mm represent a correct indication for treatment. Conventional open surgery is the treatment of choice for young patients in good general conditions. Endovascular exclusion is indicated when the patient's clinical conditions contraindicate open surgery and the morphology of the aneurysmal arterial district allows the endoprosthesis to be safely implanted.