Disease Extent Index Research Articles

P891 Comparative Effectiveness and Safety of Infliximab and Tacrolimus in the Treatment of Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects approximately 20% of patients with ulcerative colitis (UC). Patients failing initial corticosteroid therapy receive salvage therapy with either infliximab (IFX) or calcineurin inhibitors, cyclosporine (CYS) or tacrolimus (TAC). We aimed to compare the effectiveness and safety of IFX and the oral calcineurin inhibitor, TAC, in this setting. Methods This retrospective cohort study included consecutive patients with ASUC, based on the Truelove and Witts criteria, admitted to Tel Aviv Medical Center between 2017 and 2022 and treated with salvage therapy. Demographic, clinical, and laboratory data were retrieved. The primary endpoint was successful salvage therapy defined as clinical response resulting in discharge without colectomy. Secondary endpoints included the colectomy rates at 90 days and the safety profile of the treatments. Results During the study period 96 patients with ASUC were admitted to our center. Of these, 40 patients received salvage therapy – 21 patients received IFX and 16 received TAC and were included in the analysis; 3 patients received CYS and were excluded from the study. Demographic data are detailed in Table 1. Disease duration was significantly longer in patients receiving TAC (mean (±SD) 9.7 years (±7.1) vs 4.5 (±5.9), p=0.04). In addition, patients receiving TAC had significantly greater prior exposure to advanced therapies (14 (87.5%) vs 6 (28.6%), p<0.001) and 12 (75%) patients had previous exposure to IFX. Baseline markers of disease severity including disease extent, hemoglobin, C-reactive protein (CRP), albumin and body mass index (BMI) were similar between the treatment groups (Table 1). Therapeutic success was similar between treatment groups (IFX: 18 (86%) vs TAC: 15 (94%), p=0.62). The 90-day colectomy rate (IFX: 4 (19%) vs TAC: 2 (12.5%), p=0.68), CRP upon discharge (median (IQR) IFX: 15 mg/L (3.3-27) vs TAC: 11 mg/L (5.4-25, p=0.64) and length of hospitalization (mean (±SD) IFX: 23.5 days (±19.46) vs TAC: 17.56 days (±5), p=0.19) were similar between the groups. Safety profiles were similar between the treatment groups with mild electrolyte disturbances treated conservatively in both groups and no observed infections, deaths or other adverse events. Conclusion This real world, retrospective study shows that IFX and TAC have similar effectiveness and safety in the setting of ASUC. In this study, patients receiving TAC had significantly longer disease duration and advanced therapy exposure than those receiving IFX and still maintained excellent effectiveness highlighting TAC’s value in this setting.

Characteristics of Older Patients with Takayasu's Arteritis: A Two-Center, Cross-Sectional, Retrospective Cohort Study.

Few studies have assessed elderly patients with Takayasu's arteritis (TAK). To evaluate the progression of TAK in different age groups and its possible effects on drug treatment and disease activity. This cross-sectional and retrospective cohort study included 66 TAK patients. Patients were interviewed and data of the 12 preceding months were collected from electronic medical records. The patients were divided into four quartiles according to current age and compared for clinical and laboratory data, treatment, comorbidities, disease status, and functional status. Statistical significance was set at p<0.05. The groups were Q1(22-36 years, n=16), Q2(37-42 years, n=18), Q3(43-49 years, n=17), and Q4(51-66 years, n=15). The frequency of patients with disease activity, fatigue, comorbidities and vascular impairments, and the TAK disease extent index were also comparable between the groups. With age, disease duration was longer (p=0.001), fewer patients used prednisone (Q1:43.8%, Q2:33.3%, Q3:11.8%, and Q4:6.7%; p=0.049) and immunosuppressive drugs [Q1:100.0%, Q2:66.7%, Q3:58.8%, and Q4:46.7%; Q1 versus Q3 (p=0.043), and Q1 versus Q4 (p=0.005) in post-hoc analyses], and patients had greater functional status impairment (Q2 versus Q3, p=0.003). In addition, the levels of disease damage, new TAK symptoms, and complications in the preceding 12 months were not different between the groups. Older patients with TAK require minimal drug treatment, and have greater impairment of functional status, which may be attributed to aging-related factors.

Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis.

Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries is difficult to access except during open surgical procedures. Assessment of disease activity in TAK, therefore, relies on surrogate measures. Clinical disease activity measures such as the National Institutes of Health (NIH) score, the Disease Extent Index in TAK (DEI.TAK) and the Indian TAK Clinical Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization of stenosis, dilatation, and vessel wall characteristics. Vascular wall uptake of 18-fluorodeoxyglucose or other ligands using positron emission tomography computerized tomography (PET-CT) helps assess metabolic activity, which reflects disease activity well in a subset of TAK with normal APRs. Angiographic scoring systems to quantitate the extent of vascular involvement in TAK have been developed recently. Erythrocyte sedimentation rate and C-reactive protein have a moderate performance in distinguishing active TAK. Numerous novel biomarkers are under evaluation in TAK. Limited literature suggests a better assessment of active disease by combining APRs, PET-CT, and circulating biomarkers. Validated damage indices and patient-reported outcome measures specific to TAK are lacking. Few biomarkers have been evaluated to reflect vascular damage in TAK and constitute important research agenda.

Increased modified DUBLIN scores are associated with serious ulcerative colitis and treatment failure

Grading of endoscopic lesions is important for determining the severity of ulcerative colitis and developing treatment strategies, but the commonly used methods are not sufficient. This study aimed to investigate whether new endoscopic scoring systems incorporating lesions and disease extent are associated with clinical disease severity and maintainable remission. This was a retrospective study. In all, 110 patients with ulcerative colitis were included and 87 completed 12-month follow-up. Colonoscopy was performed within 1 week before blood samples were taken. Degree of ulcerative colitis burden of luminal inflammation (DUBLIN) scores were calculated as the product of Mayo endoscopic score (MES) by disease extent and ulcerative colitis endoscopic index of severity was used to replace MES when calculating modified DUBLIN scores. DUBLIN and modified DUBLIN scores were increased in the moderate and severe groups significantly (p < 0.05). Both of increased scores contributed to the detection of serious diseases, and the clinical cutoff values of DUBLIN and modified DUBLIN were 3[area under the curve (AUC) = 0.809, p = 0.001) and 7(AUC = 0.815, p = 0.001), respectively. They were with high sensitivity, but the specificity of DUBLIN was lower. Both scores were correlated to partial Mayo scores, C-reactive protein and erythrocyte sedimentation rate positively, and they were correlated to the albumin negatively (p < 0.05). Higher modified DUBLIN scores (>7) were associated with an increased risk of treatment failure (hazard ratio = 4.96, 95% confidence interval: 1.17-21.00, p = 0.03), but there were no association between DUBLIN scores and long-term remission (p > 0.05). Increased DUBLIN and modified DUBLIN scores were conducive to screening serious disease, but only modified DUBLIN scores had the potential to assist in making an upgraded therapeutic schedule.

Clinical course of 602 patients with Takayasu's arteritis: comparison between Childhood-onset versus adult onset disease.

To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK). Data related to clinical features and response to treatment of patients with cTAK (age of onset <16 years) and aTAK from a large observational cohort in our tertiary care teaching hospital were noted and compared. Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P < 0.01), but subsequent relapses were equally common (30% vs 27%; P = 0.63). Independent associations of disease duration at presentation with disease extent [Disease Extent Index in TAK (DEI.Tak)] and damage [TAK Damage Score (TADS)] were observed (P ≤ 0.01). Moreover, 54% of patients with symptom duration of >5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression. Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK.

Poor obstetric outcomes in Indian women with Takayasu arteritis

IntroductionTakayasu’s arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset.MethodsWomen aged more than 18 years with Takayasu’s arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI.TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR.ResultsOf the 64 women interviewed, aged 29 (24–38) years and disease duration 5 (4–10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18–30) years. Type 5 disease was the most common (n = 32, 59.3%), and an equal number of patients had Ishikawa’s class I and II disease (n = 26, 40.6%). Median ITAS (n = 44) was 13 (7–16), DEI.Tak 12.5 (9–16.75) and TADS 8 (6.5–10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8–8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2–3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong’s score greater than or equal to 4 predicted lower birth weight (p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak (r = 0.78) and TADS (r = 0.58).ConclusionWomen with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong’s scoring can be useful to predict birth weight.

Childhood-onset Takayasu arteritis: A 15-year experience from a tertiary referral center.

To describe clinical manifestations, angiographic findings, treatment, activity and damage of our Takayasu arteritis patients. The patients who met European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society classification criteria for childhood-onset Takayasu arteritis were reviewed in a retrospective longitudinal manner from 2002 to 2017. Extent of the disease was assessed by Disease Extent Index for Takayasu Arteritis (DEI.Tak), activity by Pediatric Vasculitis Activity Score and Indian Takayasu's Arteritis Activity Score (ITAS 2010) and damage by Pediatric Vasculitis Damage Index and Takayasu Arteritis Damage Score (TADS). Sixteen subjects (75% female) with a median disease duration of 3.1years were enrolled in this study. While the median age at disease onset was 12.1years, there was only a 2.5months diagnostic delay. Treatment regime included corticosteroids (100%), which were combined with azathioprine or methotrexate in 93.8% and 37.5% of the subjects, respectively. Severe and refractory cases were treated with cyclophosphamide (62.5%) and subsequently with tocilizumab (37.5%). Seven patients (43.8%) required either percutaneous endovascular intervention or bypass for severe disease refractory to medications. The correlation of the activity and damage scores with each other was fairly good. Damage was found to be associated only with high disease activity and extensive disease at disease onset, but not with other parameters. Despite high usage rates of aggressive immunosuppressive therapy and biologic agents, almost half of the patients underwent interventional procedures. When medications failed, endovascular and surgical interventions were of great importance to avoid end-organ ischemia. The performance of the new activity (DEI.Tak and ITAS2010) and damage indices (TADS) seems satisfactory.

Peripheral Arterial Tonometry in Pulmonary Vasculitis.

Vascular wall inflammation in primary vasculitides results in diminished vessel dilation and finally impaired blood flow, causing multiple organs dysfunction and ultimate damage. In granulomatosis with polyangiitis (GPA), the inflammatory process concerns small and medium sized vessels and its pulmonary location is often predominant. The pivotal role in the development of that pathology plays vascular endothelium. Endothelial vasodilatory function strongly depends on the instant production and release of nitrogen oxide (NO), a potent local factor controlling vascular tonus. NO output is triggered by a variety of stimuli, especially by ischemia. The endothelial vasodilatory ability can be measured indirectly by a few of methods, one of them is peripheral arterial tonometry (PAT). The method assesses reactive hyperemia, mediated mostly by NO release, as a response to vessel occlusion. The vasodilatory reaction depends on the quality of the endothelium which deteriorates with time of GPA disease progression. The aim of the present study was to estimate a correlation between the clinical status, reflected by the disease extent index (DEI), and the vasodilatory endothelial function reflected by the index of arterial reactive hyperemia (RHI), measured by PAT in 27 patients with GPA, having a significant pulmonary involvement. We found a moderate inverse correlation between DEI and log-transformed RHI (r=-0.46, p<0.05). The conclusion is that impaired endothelial function, as assessed by RHI-PAT, might predict the GPA progression.

Long-term outcome of patients with ANCA-associated vasculitis treated with plasma exchange: a retrospective, single-centre study.

BackgroundPlasma exchange (PLEX) has been used routinely for treatment of severe renal vasculitis and/or alveolar haemorrhage (AH) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the long-term benefit of PLEX in AAV remains unclear. We aimed to describe the characteristics and outcomes of patients treated with PLEX in a single centre.MethodsPatients with AAV were identified by performing a case review of medical records of 705 patients who received PLEX in a single tertiary referral centre between 2000 and 2010. Patient characteristics and outcomes were recorded. The Kaplan-Meier method, log-rank tests and Cox regression analysis were used for survival analyses.ResultsA total of 94 patients with AAV were identified (44 men, 50 women; median age 60 years, range 21–90 years; 52 proteinase 3-ANCA, 41 myeloperoxidase-ANCA and 1 ANCA-negative; 8 double-positive for ANCA and anti-glomerular basement membrane; 93 newly diagnosed/1 relapse; 55 [58.5 %] required dialysis). The reasons for initiating PLEX therapy were severe renal involvement alone in 52 %, AH in 10 %, both renal involvement and AH in 35 %, and “other” in 3 %. The patients had 3–27 (median 7) PLEX sessions. At 3 months, 81 (86 %) of 94 were alive and 62 (66 %) of 94 were alive and dialysis-independent. The median follow-up was 41 months (minimum-maximum 0.5–137 months), when 56 (59.6 %) of 94 patients were alive and 47 (50 %) were dialysis-independent. The estimated overall survival rates were 75.3 % at 1 year and 61.1 % at 5 years. Patient survival decreased with increasing age at presentation (5-year survival 85 % for age <50 years, 64.4 % for ages 50–65 years, and 41 % for >65 years; p < 0.01 for comparison between all groups). Estimated renal survival rates were 65.5 % at 1 year and 43 % at 5 years. Renal survival was worse in patients aged >65 years than in the younger patients (5-year survival 25.1 % in patients >65 years vs. 50.8 % for those ≤65 years, p < 0.01). The estimated renal survival was better in patients with higher Disease Extent Index (DEI) >6 than in patients with DEI ≤6 (5-year survival 52.1 % vs. 39.4 %, p = 0.04), even though this was not confirmed in multivariate analysis.ConclusionsThe mortality of patients presenting with severe manifestations of AAV remains high despite the use of PLEX. Older age at presentation is associated with worse overall and renal prognosis.

AB0682 Severe disease course of pediatric granulomatosis with polyangiitis as compared to adult patients: a long-term, single center, follow up study

BackgroundGranulomatosis with polyangiitis (GPA) is a rare disease in childhood. Treatment strategies and clinical approach are still mostly derived from adult GPA studies.ObjectivesThe present study was aimed to compare disease...

Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010)

There are no valid instruments to measure disease activity in Takayasu arteritis (TA). We aim to provide a valid measure to assess clinical disease activity with or without incorporating acute phase reactants. The Indian Takayasu Clinical Activity Score (ITAS) was initially derived from disease manifestations scored in the Disease Extent Index (DEI.Tak). The ITAS was validated by a group of physicians scoring both live and paper cases for inter-rater reliability (IRR), convergence with BVAS, correlation with the Physician's Global Assessment (PGA) and ESR/CRP. It was further validated at a single centre in 177 patients for its ability to discriminate between active and inactive disease state at first visit and sensitivity to change in 132 active patients measured serially at two follow-up visits. ITAS-A also included graded scores for ESR/CRP. The final ITAS2010 contains 44 items with 33 features arising from the cardiovascular system. Seven key items are weighted to score 2 and all others score 1 only. Inter-observer variability was highly satisfactory (IRR 0.97). The ITAS showed superior inter-rater agreement compared with the BVAS (IRR 0.9) and PGA (IRR 0.82). In the single-centre study, median ITAS scores at first visit were significantly higher in active disease (5.62 ± 3.14) compared with grumbling (3.36 ± 1.96) and inactive disease (1.27 ± 1.26, P < 0.0001). The therapy induced a significant decrease in the ITAS2010 but the higher ITAS-A scores remained elevated. The ITAS2010, validated in over 300 TA patients and sensitive to change, is a useful measure of clinical disease activity for patient monitoring. Higher ITAS-A scores suggest poor control of active disease by current therapy.

A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg–Strauss, EGPA): monocentric experiences in 150 patients

ObjectiveTo evaluate a vasculitis centre based management strategy for eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA).MethodsA retrospective cohort study at a vasculitis referral centre was performed. All EGPA patients admitted from...

Vasculitis assessment and Takayasu aorto-arteritis

Assessment of disease activity using clinical instruments like Birmingham Vasculitis Activity Score and Vasculitis Damage index has been extensively used both in trial and clinic setting. It has revolutionised outcome assessment for small size vasculitis as evidenced from studies carried out by the European vasculitis group. There is a need for clinical assessment tools for large vessel disease like Takayasu arteritis, which is seen more frequently in India. An attempt has been made by the Indian Rheumatology Association Vasculitis core group to validate instruments, like Disease Extent Index for Takayasu Arteritis (DEI.Tak), Indian Takayasu Activity Score (ITAS) and Takayasu Arteritis Damage Scores. Both DEI.Tak and ITAS have received interests from international investigators. Widespread usage of these instruments will pave the way to controlled clinical trials for TA.

Two‐Dimensional Speckle‐Tracking Echocardiography Reveals Systolic Abnormalities in Granulomatosis with Polyangiitis (Wegener’s)

Two-dimensional speckle-tracking echocardiography (STE) is a novel technique providing accurate assessment of myocardial function. However, its value in granulomatosis with polyangiitis (Wegener's) (WG) has not been studied. To assess the presence and frequency of systolic left ventricular (LV) dysfunction using STE and to determine incremental value of STE over standard echocardiography to detect myocardial abnormalities in WG. Twenty-two WG patients (11 males, 11 females, mean age 46.8 ± 12.3 years) and 22 sex- and age-matched healthy subjects underwent standard and STE. Global longitudinal, circumferential, and rotational deformation parameters were calculated. All patients had LV ejection fraction (EF) >50%. LVEF was 65.0 ± 7.5% and LV end-diastolic volume index 44.8 ± 11.8 mL/m(2) . Regional LV wall motion abnormalities were found in 7 (32%), while abnormal global STE determined systolic dysfunction in 16 (73%) subjects (P = 0.008). Global longitudinal, circumferential and radial peak-systolic deformational parameters (strain or strain rate) were decreased in 11 (50%), 9 (41%), and 3 (14%) patients (P = 0.02), respectively. Comparing patients with abnormal and normal STE derived global systolic function, the former had higher cumulative disease extent index (10.6 ± 3.0 vs 7.5 ± 1.8; P = 0.03) and vasculitis damage index (7.9 ± 1.9 vs 6.0 ± 1.7; P = 0.04). Despite normal LVEF the global systolic LV abnormalities detected by STE are common in WG. They correspond to the extent and severity of WG and are more frequent than regional wall motion abnormalities in standard echocardiography.

Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations

ObjectiveFirst, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in...

Time to focus on outcome assessment tools for childhood vasculitis

Childhood systemic vasculitides are a group of rare diseases with multi-organ involvement and potentially devastating consequences. After establishment of new classification criteria (Ankara consensus conference in 2008), it is now time to establish measures for proper definition of activity and damage in childhood primary vasculitis. By comparison to adult vasculitis, there is no consensus for indices of activity and damage assessment in childhood vasculitis. Assessment of disease activity is likely to become a major area of interest in pediatric rheumatology in the near future. After defining the classification criteria for primary systemic childhood vasculitis, the next step was to perform a validation study using the original Birmingham vasculitis activity score as well as the disease extent index to measure disease activity in childhood vasculitis. Presently, there are efforts in place to develop a pediatric vasculitis activity score. This paper reviews the current understanding about the assessment tools (i.e., clinical features, laboratory tests, radiologic assessments, etc.) widely used for evaluation of the disease activity and damage status of the children with vasculitis.

An Exploratory Study of Endorectal Magnetic Resonance Imaging and Spectroscopy of the Prostate as Preoperative Predictive Biomarkers of Biochemical Relapse After Radical Prostatectomy

Radical prostatectomy has significant side effects. Preoperative information predicting its long-term outcome would be valuable to patients and physicians. We determined whether pretreatment endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging predicts biochemical recurrence after radical prostatectomy. Of 202 patients who underwent endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging from January 2000 to December 2002 before radical prostatectomy 130 satisfied study inclusion criteria and were included in analysis. We compared imaging factors with potential predictive capability to biochemical recurrence data, including magnetic resonance imaging risk score based on local disease extent and magnetic resonance spectroscopic imaging index lesion characteristics, such as the number of voxels and degree of metabolic abnormality (magnetic resonance spectroscopic imaging grade). We evaluated associations of these imaging variables with time to biochemical recurrence by Cox proportional hazards regression adjusted for known predictors of biochemical recurrence, such as stage, grade and prostate specific antigen. At a median 68-month followup there were 26 biochemical failures. Risk score, lesion volume and high grade voxels each correlated with time to biochemical recurrence. In a model combining clinical parameters risk score, lesion volume and at least 1 high grade voxel the magnetic resonance spectroscopic imaging variables remained significant but the magnetic resonance imaging score dropped out. Index lesion volume on magnetic resonance spectroscopic imaging and high grade magnetic resonance spectroscopic imaging voxels correlate with time to biochemical recurrence after radical prostatectomy even when adjusted for clinical data. Results suggest the preoperative predictive usefulness of endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging in patients considering radical prostatectomy.

Long-term follow-up of microscopic polyangiitis, 17-year experience at a single center

Background Long-term prognoses of Wegener granulomatosis (WG) and Churg–Strauss syndrome (CSS) are known; however, few data exist on long-term prognoses for microscopic polyangiitis (MPA). Our aim was to analyse the prognoses of MPA. Methods Cohort study with retrospective selection of patients. Twenty-two patients admitted to our Hospital (1990–2006) with biopsy-proven MPA were studied. The start date for entry into the study was the date of diagnosis. Statistical analysis was performed to look for prognostic factors for survival. Results MPA patients were followed-up for a median of 78 (5–131) months. MPA patients were treated with cyclophosphamide (Cy) plus corticosteroid (Cs) (59%) or Cs alone (41%). Seven MPA patients died. Cumulative MPA patient survival at 1, 5, and 10 years were 85% (75–95%), 85% (75–95%), and 74% (60–88%) in those treated with Cy plus Cs and 50% (32–68%), 36% (14–58%), and 0% (0–30%) in those treated with Cs alone, respectively ( P = 0.04). Disease extent index < 5 ( P = 0.02) and age < 65 years ( P = 0.02) were associated with improved survival rates in MPA patients treated with Cy. Five MPA (23%) patients relapsed after a median of 54 months (35–93). No variables were related to relapses. Despite treatment, 11 MPA (50%) patients developed end-stage renal disease after a median of 9 months (0–53). Conclusions Most MPA patients had life-threatening renal or lung involvement at diagnosis. Patients not treated with immunosuppressants had a poorer prognosis. The long-term prognosis of MPA patients who survived 6 months post diagnosis was good, although renal survival rates are low.

B-lymphocyte activating factor levels are increased in patients with Wegener’s granulomatosis and inversely correlated with ANCA titer

Circulating autoantibodies against neutrophils (ANCA) are a distinctive finding in patients with Wegener's granulomatosis (WG). B-lymphocyte activating factor (BAFF) promotes autoantibody production by increasing B cell survival and proliferation. We investigated serum BAFF levels (s-BAFF) in a WG patient cohort in relation to ANCA titers and disease activity. Baseline data were obtained in twenty-two WG patients (55% female, age 44 years, disease duration 1 year). S-BAFF was determined by capture ELISA and associations between s-BAFF, clinical (Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI) and Disease Extent Index (DEI)) and biochemical (C-reactive protein (CRP), IgG and ANCA) disease measures were analysed in a cross sectional as well as longitudinal analysis. S-BAFF was increased in WG patients compared to healthy controls (1.8 vs. 0.55 ng/ml, p < 0.01). S-BAFF was higher in ANCA negative than ANCA-positive WG sera (2.16 vs. 1.29 ng/ml, p < 0.01), correlated independently and inversely with ANCA levels (Rs -0.48, p < 0.01) but did not correlate with CRP, BVAS, DEI or VDI scores. Individual s-BAFF profiles were stable over time in 68% of patients. The finding of a negative correlation between ANCA levels and s-BAFF that is independent of steroid treatment indicates that BAFF does not directly drive ANCA production in WG.

Mammographic Density, Estrogen Receptor Status and Other Breast Cancer Tumor Characteristics

The aim of this study was to examine the relationship between mammographic density and histological characteristics of breast tumors within a case-control study population. This study was an expansion of a large size case-control study examining the relationship between breast density and breast cancer risk. Percent and area of breast density was assessed in 370 invasive breast cancer cases and 1904 age-matched controls, using a computer-assisted method. Associations between breast density and estrogen receptor (ER) status, histological grade, histological size, lymph node status, vascular invasion, disease extent, and Nottingham Prognostic Index were evaluated, using logistic regression. Women with 50% or greater mammographic density have a 2.63-fold risk (95% confidence interval [95% CI] = 1.78-3.87; p < 0.001) of developing breast cancer compared to women with less than 10% density. Increase in every category of percentage of breast density is also associated with a 1.45-fold risk in developing ER positive tumors relative to ER negative tumors (odds ratio [OR] = 1.02; 95% CI = 1.00-1.04; p = 0.048), and increase in every quartile of absolute area of density is associated with a 1.48-fold ER positive breast cancer risk [95% CI = 1.06-2.07; p = 0.020]. Furthermore, breast density was found to be associated with specifically ER positivity, invasion as well as invasion with in situ, histological grades 1 and 2, tumor size larger than 1.1 cm, lack of vascular invasion, lymph node positivity and negativity, and NPI less than 4.0. After stratifying the data according to mode of diagnosis, the relationship became slightly stronger in the interval cancer group. Similar results were in observed using percent density and absolute density readings. Mammographic density was a stronger risk factor for ER positive [OR = 2.94; 95% CI = 1.94-4.43; p < 0.001] than ER negative cancers when comparing breasts with greater than 50% dense region to those with less than 10% density. No other tumor characteristic had a significant correlation with breast density. These results suggest that mammographic percent density may be more strongly related to ER positive than ER negative breast cancer, but otherwise is a risk factor for breast cancer independent of other tumor characteristics.