p sivasothy | University College London (original) (raw)
Papers by p sivasothy
Autoimmunity Reviews, 2017
To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiit... more To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis 51 (EGPA) based on phenotype and presence or absence of ANCA. 52 Methods: Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of 53 predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least 54 one systemic organ manifestation attributable to systemic disease. 55 Results: The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. 56 Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glo-57 merulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall 58 on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong 59 surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic 60 vasculitis (p = 0.005) and with the presence of ANCA (p b 0.001). Overall, 59% of patients had polyangiitis as de-61 fined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one 62 systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifesta-63 tions including arthralgias (p = 0.02) and renal disease (p = 0.024), had higher peripheral eosinophilia (p = 64 0.027), and a trend towards less myocarditis (p = 0.057). Using predefined criteria of vasculitis and surrogates 65 of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. 66 Conclusion: We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as 67 hypereosinophilic asthma with systemic (non vasculitic) manifestations.
The Journal of Heart and Lung Transplantation, 2009
Burkholderia gladioli is an unusual organism that has become increasingly responsible for infecti... more Burkholderia gladioli is an unusual organism that has become increasingly responsible for infections in patients who are immunosuppressed, including patients who have undergone solid organ transplantation. This article presents a patient in whom a mediastinal mass due to Burkholderia gladioli developed after lung transplantation. A review of the literature is also presented.
The New England journal of medicine, Apr 5, 2018
Malignant pleural effusion affects more than 750,000 persons each year across Europe and the Unit... more Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through ...
Presse médicale (Paris, France : 1983), 2013
ABSTRACT Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss), is a rare necrotiz... more ABSTRACT Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss), is a rare necrotizing vasculitis of small-sized vessels, associated to antimyeloperoxydase ANCA in 40% of patients. EGPA occurs in patients with asthma. Asthma is sever, associated with eosinophilia and extrapulmonary symptoms. Among them, mononeuritis multiplex is the most frequent symptom. When cardiac involvement is present, prognosis is poor. Despite a good overall prognosis, deaths are caused by vasculitis activity, gastrointestinal and cardiac involvement. Treatment is well codified based on steroids, which are quickly effective. Immunosuppressants combined with corticosteroids are compulsory to treat the most sever forms, mainly when cardiac and gastrointestinal or renal symptoms are present.
BMJ open respiratory research, 2018
Physicians face considerable challenges in ensuring safe and effective care for patients admitted... more Physicians face considerable challenges in ensuring safe and effective care for patients admitted to hospital with pleural disease. While subspecialty development has driven up standards of care, this has been tempered by the resulting loss of procedural experience in general medical teams tasked with managing acute pleural disease. This review aims to define a framework though which a minimum standard of care might be implemented. This review has been written by pleural clinicians from across the UK representing all types of secondary care hospital. Its content has been formed on the basis of literature review, national guidelines, National Health Service England policy and consensus opinion following a round table discussion. Recommendations have been provided in the broad themes of procedural training, out-of-hours management and pleural service specification. Procedural competences have been defined into descriptive categories: emergency, basic, intermediate and advanced. Provis...
Cet article decrit la realisation de remblais experimentaux par le reemploi des argiles tres plas... more Cet article decrit la realisation de remblais experimentaux par le reemploi des argiles tres plastiques en remblai. Dans un premier temps, une presentation des resultats des etudes geotechniques effectuees sur les differents materiaux plastiques rencontres sur l'aire d'etude sera effectuee. Puis, le programme du chantier experimental et les resultats obtenus seront exposes et discutes : les resultats de suivi dans le temps de ces remblais ont fait l'objet d'un rapport de recherche et ne seront pas presentes dans ce document. Enfin, des suggestions de methodologie d'etude et de conditions de reutilisation seront proposees pour les sols A4.
Pulmonary Circulation, 2011
Journal of Cardiothoracic and Vascular Anesthesia, 2006
Journal of Biological Chemistry, 2000
Journal of Biological Chemistry, 1999
Clinical Radiology, 1998
To describe the computed tomography (CT) appearances of tracheal stenosis in Wegener's granulomat... more To describe the computed tomography (CT) appearances of tracheal stenosis in Wegener's granulomatosis (WG) and to assess the additional value of reformatted images. Patients and Methods: Ten patients with tracheal involvement by WG were assessed with spiral CT and both coronal and three-dimensional surface shaded images were generated. Fibreoptic bronchoscopy was also performed in all patients. Results: Ninety per cent of lesions were situated in the subglottic region. In all cases there was circumferential mucosal thickening, in nine cases extending over a relatively short distance (mean 2.4 cm). The degree of narrowing of the axial luminal diameter ranged from 23% to 100%. In three patients there was contiguous involvement of the vocal cords evident on CT, two further cases with mild vocal cord inflammation were identified bronchoscopically. Other CT findings included mucosal irregularity and ulceration (50 %), and involvement of the tracheal cartilages (20%). Conclusion: Wegener's granulomatosis may involve the trachea with resultant stenosis. Spiral CT is an easily performed, non-invasive technique which provides accurate assessment of tracheal lesions and is complementary to bronchoscopy. The main additional advantage of coronal reformatted images was our added confidence in defining the upper and lower limits of lesions and in the evaluation of vocal cord involvement. Screaton, N. J.,
Clinical Otolaryngology, 2009
Objectives: This study aimed to evaluate the response of refractory Wegener's granulomatosis affe... more Objectives: This study aimed to evaluate the response of refractory Wegener's granulomatosis affecting the ear, nose and throat and granulomatous eye disease to B-cell depletion with rituximab. Design: A retrospective case note review. Setting: Tertiary Centre. Participants: All patients who received rituximab for refractory Wegener's granulomatosis affecting the head and neck were included. Main outcome measures: Demographic and follow-up data at five time points were recorded. Response was measured using change in the Birmingham Vasculitis Activity Score and prednisolone dose. Secondary outcomes included changes in additional immunomodulators and anti-neutrophil cytoplasm antibodies serology. Adverse events were recorded for the duration of follow-up. Results: Thirty-four patients were included in the analysis. The median age was 47, the male to female ratio was 3 : 2 and the overall median follow-up was 25.5 months. At six months, nine (26%) patients had a partial response, twenty-one (62%) were in remission and four (12%) did not respond. All four non-responders went into remission after a second course of rituximab. Total Birmingham Vasculitis Assessment score decreased after rituximab at all time points (P < 0.001). Four of five patients with retro-orbital involvement responded well to treatment. Two patients were considered secondary failures requiring alternative therapy after an initial response. Adverse events included four major chest infections, two cancers and six infusion reactions. Conclusions: Our cohort derived considerable benefit from rituximab permitting a reduction in immunosuppressive exposure and prednisolone dose with few major adverse effects. There was an 80% (4 ⁄ 5) response in patients with retro-orbital granulomas. The effect of rituximab was most noticeable in the first 6 months (88% response).
Best Practice & Research Clinical Rheumatology, 2009
The pulmonary vasculitides are a heterogeneous group of rare disorders that result from an inflam... more The pulmonary vasculitides are a heterogeneous group of rare disorders that result from an inflammatory process damaging the vessel wall and consequent impaired blood flow, ischaemia and tissue necrosis. The clinical manifestation of these vasculitides depends on the site, size, type and severity of the inflammatory process. Vasculitis involving the airways is a common feature of the anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitides (AASVs) and can predate the diagnosis by years. Secondary causes of vasculitis associated with connective tissue disorders are also capable of presenting with pulmonary features. Recognition of involvement, investigation and treatment are important to ameliorate symptoms for patients. This article concentrates on the assessment and specific management of upper and lower airway problems of AASV.
Background: EGPA is a small vessel vasculitis characterised by the presence of tissue eosinophili... more Background: EGPA is a small vessel vasculitis characterised by the presence of tissue eosinophilia, necrotising vasculitis and granulomatous inflammation1. Typically, a prodromal asthmatic phase, leads to an eosinophilic stage, which can evolve to include the presence of vasculitis with renal manifestations. In the recent randomised, placebo-controlled MIRRA trial for relapsing and refractory EGPA, adjuvant therapy with anti-IL5 mAB Mepolizumab [MEPO] at 300mg s/c monthly, accrued longer times in remission, reduced steroid exposure and reduced relapse rates2. Objectives: The aim of our study was to analyse the response and outcome for EGPA patients who received 100mg s/c of MEPO monthly for a minimum of 52 weeks, with particular focus on the steroid minimisation benefits. Methods: This retrospective, descriptive study analysed 13 patients with EGPA, who received 100mg s/m monthly MEPO therapy under the eosinophilic asthma care-pathway. Time points of assessment included MEPO commenc...
Autoimmunity Reviews, 2017
To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiit... more To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis 51 (EGPA) based on phenotype and presence or absence of ANCA. 52 Methods: Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of 53 predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least 54 one systemic organ manifestation attributable to systemic disease. 55 Results: The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. 56 Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glo-57 merulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall 58 on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong 59 surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic 60 vasculitis (p = 0.005) and with the presence of ANCA (p b 0.001). Overall, 59% of patients had polyangiitis as de-61 fined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one 62 systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifesta-63 tions including arthralgias (p = 0.02) and renal disease (p = 0.024), had higher peripheral eosinophilia (p = 64 0.027), and a trend towards less myocarditis (p = 0.057). Using predefined criteria of vasculitis and surrogates 65 of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. 66 Conclusion: We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as 67 hypereosinophilic asthma with systemic (non vasculitic) manifestations.
The Journal of Heart and Lung Transplantation, 2009
Burkholderia gladioli is an unusual organism that has become increasingly responsible for infecti... more Burkholderia gladioli is an unusual organism that has become increasingly responsible for infections in patients who are immunosuppressed, including patients who have undergone solid organ transplantation. This article presents a patient in whom a mediastinal mass due to Burkholderia gladioli developed after lung transplantation. A review of the literature is also presented.
The New England journal of medicine, Apr 5, 2018
Malignant pleural effusion affects more than 750,000 persons each year across Europe and the Unit... more Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through ...
Presse médicale (Paris, France : 1983), 2013
ABSTRACT Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss), is a rare necrotiz... more ABSTRACT Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss), is a rare necrotizing vasculitis of small-sized vessels, associated to antimyeloperoxydase ANCA in 40% of patients. EGPA occurs in patients with asthma. Asthma is sever, associated with eosinophilia and extrapulmonary symptoms. Among them, mononeuritis multiplex is the most frequent symptom. When cardiac involvement is present, prognosis is poor. Despite a good overall prognosis, deaths are caused by vasculitis activity, gastrointestinal and cardiac involvement. Treatment is well codified based on steroids, which are quickly effective. Immunosuppressants combined with corticosteroids are compulsory to treat the most sever forms, mainly when cardiac and gastrointestinal or renal symptoms are present.
BMJ open respiratory research, 2018
Physicians face considerable challenges in ensuring safe and effective care for patients admitted... more Physicians face considerable challenges in ensuring safe and effective care for patients admitted to hospital with pleural disease. While subspecialty development has driven up standards of care, this has been tempered by the resulting loss of procedural experience in general medical teams tasked with managing acute pleural disease. This review aims to define a framework though which a minimum standard of care might be implemented. This review has been written by pleural clinicians from across the UK representing all types of secondary care hospital. Its content has been formed on the basis of literature review, national guidelines, National Health Service England policy and consensus opinion following a round table discussion. Recommendations have been provided in the broad themes of procedural training, out-of-hours management and pleural service specification. Procedural competences have been defined into descriptive categories: emergency, basic, intermediate and advanced. Provis...
Cet article decrit la realisation de remblais experimentaux par le reemploi des argiles tres plas... more Cet article decrit la realisation de remblais experimentaux par le reemploi des argiles tres plastiques en remblai. Dans un premier temps, une presentation des resultats des etudes geotechniques effectuees sur les differents materiaux plastiques rencontres sur l'aire d'etude sera effectuee. Puis, le programme du chantier experimental et les resultats obtenus seront exposes et discutes : les resultats de suivi dans le temps de ces remblais ont fait l'objet d'un rapport de recherche et ne seront pas presentes dans ce document. Enfin, des suggestions de methodologie d'etude et de conditions de reutilisation seront proposees pour les sols A4.
Pulmonary Circulation, 2011
Journal of Cardiothoracic and Vascular Anesthesia, 2006
Journal of Biological Chemistry, 2000
Journal of Biological Chemistry, 1999
Clinical Radiology, 1998
To describe the computed tomography (CT) appearances of tracheal stenosis in Wegener's granulomat... more To describe the computed tomography (CT) appearances of tracheal stenosis in Wegener's granulomatosis (WG) and to assess the additional value of reformatted images. Patients and Methods: Ten patients with tracheal involvement by WG were assessed with spiral CT and both coronal and three-dimensional surface shaded images were generated. Fibreoptic bronchoscopy was also performed in all patients. Results: Ninety per cent of lesions were situated in the subglottic region. In all cases there was circumferential mucosal thickening, in nine cases extending over a relatively short distance (mean 2.4 cm). The degree of narrowing of the axial luminal diameter ranged from 23% to 100%. In three patients there was contiguous involvement of the vocal cords evident on CT, two further cases with mild vocal cord inflammation were identified bronchoscopically. Other CT findings included mucosal irregularity and ulceration (50 %), and involvement of the tracheal cartilages (20%). Conclusion: Wegener's granulomatosis may involve the trachea with resultant stenosis. Spiral CT is an easily performed, non-invasive technique which provides accurate assessment of tracheal lesions and is complementary to bronchoscopy. The main additional advantage of coronal reformatted images was our added confidence in defining the upper and lower limits of lesions and in the evaluation of vocal cord involvement. Screaton, N. J.,
Clinical Otolaryngology, 2009
Objectives: This study aimed to evaluate the response of refractory Wegener's granulomatosis affe... more Objectives: This study aimed to evaluate the response of refractory Wegener's granulomatosis affecting the ear, nose and throat and granulomatous eye disease to B-cell depletion with rituximab. Design: A retrospective case note review. Setting: Tertiary Centre. Participants: All patients who received rituximab for refractory Wegener's granulomatosis affecting the head and neck were included. Main outcome measures: Demographic and follow-up data at five time points were recorded. Response was measured using change in the Birmingham Vasculitis Activity Score and prednisolone dose. Secondary outcomes included changes in additional immunomodulators and anti-neutrophil cytoplasm antibodies serology. Adverse events were recorded for the duration of follow-up. Results: Thirty-four patients were included in the analysis. The median age was 47, the male to female ratio was 3 : 2 and the overall median follow-up was 25.5 months. At six months, nine (26%) patients had a partial response, twenty-one (62%) were in remission and four (12%) did not respond. All four non-responders went into remission after a second course of rituximab. Total Birmingham Vasculitis Assessment score decreased after rituximab at all time points (P < 0.001). Four of five patients with retro-orbital involvement responded well to treatment. Two patients were considered secondary failures requiring alternative therapy after an initial response. Adverse events included four major chest infections, two cancers and six infusion reactions. Conclusions: Our cohort derived considerable benefit from rituximab permitting a reduction in immunosuppressive exposure and prednisolone dose with few major adverse effects. There was an 80% (4 ⁄ 5) response in patients with retro-orbital granulomas. The effect of rituximab was most noticeable in the first 6 months (88% response).
Best Practice & Research Clinical Rheumatology, 2009
The pulmonary vasculitides are a heterogeneous group of rare disorders that result from an inflam... more The pulmonary vasculitides are a heterogeneous group of rare disorders that result from an inflammatory process damaging the vessel wall and consequent impaired blood flow, ischaemia and tissue necrosis. The clinical manifestation of these vasculitides depends on the site, size, type and severity of the inflammatory process. Vasculitis involving the airways is a common feature of the anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitides (AASVs) and can predate the diagnosis by years. Secondary causes of vasculitis associated with connective tissue disorders are also capable of presenting with pulmonary features. Recognition of involvement, investigation and treatment are important to ameliorate symptoms for patients. This article concentrates on the assessment and specific management of upper and lower airway problems of AASV.
Background: EGPA is a small vessel vasculitis characterised by the presence of tissue eosinophili... more Background: EGPA is a small vessel vasculitis characterised by the presence of tissue eosinophilia, necrotising vasculitis and granulomatous inflammation1. Typically, a prodromal asthmatic phase, leads to an eosinophilic stage, which can evolve to include the presence of vasculitis with renal manifestations. In the recent randomised, placebo-controlled MIRRA trial for relapsing and refractory EGPA, adjuvant therapy with anti-IL5 mAB Mepolizumab [MEPO] at 300mg s/c monthly, accrued longer times in remission, reduced steroid exposure and reduced relapse rates2. Objectives: The aim of our study was to analyse the response and outcome for EGPA patients who received 100mg s/c of MEPO monthly for a minimum of 52 weeks, with particular focus on the steroid minimisation benefits. Methods: This retrospective, descriptive study analysed 13 patients with EGPA, who received 100mg s/m monthly MEPO therapy under the eosinophilic asthma care-pathway. Time points of assessment included MEPO commenc...