A novel RASA1 mutation causing capillary malformation-arteriovenous malformation (CM-AVM) presenting during pregnancy.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized clinical entity caused by mutation of the RASA1 gene, which encodes p120-RasGAP. Here we describe, for the first time, a patient with CM-AVM presenting during the late stages of pregnancy with pulmonary "capillary level" microvascular shunt, worsening cutaneous capillary malformations, and gross fluid overload. Sequencing revealed a novel mutation of the RASA1 gene involving a frameshift mutation in the RASGAP domain of RASA1.

Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear.

Patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) requiring dialysis at diagnosis are at risk for developing end-stage renal disease (ESRD) or dying. Short-term results of a trial comparing plasma exchange (PLEX) to intravenous methylprednisolone (IV MeP) suggested PLEX improved renal recovery. Here we conducted long-term follow-up to see if this trend persisted.

B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design.

B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints.

Perineal rectosigmoidectomy: quality of life.

Aim: For any surgical treatment of full-thickness rectal prolapse, little attention has been given to quality of life (QoL). This study prospectively evaluated continence, constipation and QoL after perineal rectosigmoidectomy for full-thickness rectal prolapse in young and elderly patients in the long term.

Method: From May 2003 to May 2010, consecutive patients suffering from full-thickness rectal prolapse and treated with perineal rectosigmoidectomy were prospectively studied.

Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial.

Background: Granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses are associated with severe infections in patients with AAV.

Current modalities in the diagnosis of pulmonary vasculitis.

Introduction: This review addresses the pulmonary manifestations of the vasculitides, with a focus on diagnostic modalities. Haemorrhagic presentations (usually associated with nephritis: the pulmonary-renal syndrome) are the most common vasculitic cause of early death.

Areas Covered: The diagnostic modalities in the pulmonary vasculitides are reviewed, with a focus on primary systemic vasculitis.

Antineutrophil cytoplasm antibody-associated vasculitis: recent developments.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small-to-medium-sized blood vessel vasculitis and the presence of ANCA. Although our understanding of the causes of AAV remains limited, new information supporting an autoimmune basis is emerging. This review highlights recent progresses in etiology, pathogenesis, classification, and treatment.

Review of sacral neuromodulation for management of constipation.

Background: Sacral neuromodulation (SN) is an emerging treatment for constipation. This review evaluates the mechanism of action, techniques, efficacy, and adverse effects of SN in the management of constipation.

Methods: Electronic searches for studies describing the use of SN were performed in PubMed, MEDLINE and Embase.

Changes in proteinase 3 anti-neutrophil cytoplasm autoantibody levels in early systemic granulomatosis with polyangiitis (Wegener's) may reflect treatment rather than disease activity.

Objectives: To investigate the nature of the relationship between proteinase 3 anti-neutrophil cytoplasm autoantibody (PR3-ANCA) and relapse in patients with early systemic granulomatosis with polyangiitis (Wegener's) (GPA).

Methods: Clinical data from 16 relapsing and 12 non-relapsing patients with early systemic GPA from a randomised clinical trial were correlated to monthly PR3-ANCA values over 18 months. Each sample was examined using 9 different enzyme-linked immunosorbent assays (ELISAs) to ensure reliability of ANCA results.

Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis with poor kidney function: a subgroup analysis of the Aspreva Lupus Management Study.

Background: Mycophenolate mofetil (MMF) frequently is used as an alternative to intravenous cyclophosphamide to treat lupus nephritis. Whether MMF is adequate for patients with severely decreased kidney function at the time of treatment is uncertain.

Study Design: We conducted a post hoc subgroup analysis of patients with low estimated glomerular filtration rates (eGFRs) from a large trial of MMF compared to cyclophosphamide in lupus nephritis.

Long-term outcome of severe alveolar haemorrhage in ANCA-associated vasculitis: a retrospective cohort study.

Objectives: Alveolar haemorrhage (AH) is a major cause of early death in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There is a paucity of information regarding the outcomes of AAV patients presenting with severe AH.

Method: A retrospective cohort study.

The characterisation and determinants of quality of life in ANCA associated vasculitis.

Objectives: To contextualise and identify the determinants of poor health related quality of life (QOL) among patients with antineutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV).

Methods: A multicentre AAV case-control study was conducted using two matched groups of population and chronic disease controls. Measures of physical and mental QOL as well as putative bio-psychosocial determinants of QOL impairment were collected.

Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting.

Background: Colorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-α (FRα) and Epithelial growth factor receptor (EGFR).

Methods: Marker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0-15).

Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial.

Background: Membranous nephropathy leads to end-stage renal disease in more than 20% of patients. Although immunosuppressive therapy benefits some patients, trial evidence for the subset of patients with declining renal function is not available. We aimed to assess whether immunosuppression preserves renal function in patients with idiopathic membranous nephropathy with declining renal function.

A disease activity score for ENT involvement in granulomatosis with polyangiitis (Wegener's).

Objectives/hypothesis: Accurate assessment of disease activity in patients with otorhinolaryngological manifestations of granulomatosis with polyangiitis (Wegener's) (ENT/GPA) is necessary for treatment decisions and clinical trials. We have designed a disease activity score (ENT/GPA DAS) for this purpose.

Study Design: A prospective cross-sectional study.

Population-based study of laparoscopic colorectal cancer surgery 2006-2008.

Background: Clinical guidelines recommend that, where clinically appropriate, laparoscopic tumour resections should be available for patients with colorectal cancer. This study aimed to examine the introduction of laparoscopic surgery in the English National Health Service.

Methods: Data were extracted from the National Cancer Data Repository on all patients who underwent major resection for a primary colorectal cancer diagnosed between 2006 and 2008.

Rituximab for ANCA-associated vasculitis in the setting of severe infection.

Objectives: The combination of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and severe infection presents a challenge because current therapies with high-dose glucocorticoids and cyclophosphamide (CYC) are immunosuppressive and increase the risk of infection. Thus, coincident infection delays and complicates the introduction of treatment. Rituximab (RTX) is an alternative to CYC in AAV and may be preferable in the setting of severe infection.

Autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: data from the European Group for Blood and Marrow Transplantation registry.

Objectives: Patients with systemic lupus erythematosus (SLE) refractory to conventional immunosuppression suffer substantial morbidity and mortality due to active disease and treatment toxicity. Immunoablation followed by autologous stem cell transplantation (ASCT) is a novel therapeutic strategy that potentially offers new hope to these patients.

Methods: This retrospective survey reviews the efficacy and safety of ASCT in 28 SLE patients from eight centres reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 2001 and 2008.

Treating vasculitis with conventional immunosuppressive agents.

Standard therapy for granulomatosis with polyangiitis and other vasculitides is a combination of cyclophosphamide and glucocorticoids. Although most patients achieve remission, relapses and treatment-related morbidities are common. Clinical trials have yielded a wealth of data about less toxic alternatives to standard therapy, including new agents and methods of delivery.

Long-term follow-up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer.

Background: Laparoscopic resection is used widely in the management of colorectal cancer; however, the data on long-term outcomes, particularly those related to rectal cancer, are limited. The results of long-term follow-up of the UK Medical Research Council trial of laparoscopically assisted versus open surgery for colorectal cancer are presented.

Methods: A total of 794 patients from 27 UK centres were randomized to laparoscopic or open surgery in a 2:1 ratio between 1996 and 2002.

Retinoic acid-induced protein 3: identification and characterisation of a novel prognostic colon cancer biomarker.

Aim Of The Study: Validated molecular biomarkers are urgently required in colon cancer (CC) to accurately define prognosis and, ideally, to predict response to therapeutic modalities such as adjuvant chemotherapy. We aimed to identify and characterise a novel membrane-associated protein in CC tissues which may offer diagnostic and, potentially, therapeutic targeting opportunities.

Methods: Label-free mass spectrometric (MS) quantitation was employed to profile matched colon tissues for malignancy-associated proteins.