41 results on '"De Malmanche T"'
Search Results
2. Adult encephalitis surveillance : experiences from an Australian prospective sentinel site study
- Author
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EASTWOOD, K., PATERSON, B. J., LEVI, C., GIVNEY, R., LOEWENTHAL, M., DE MALMANCHE, T., LAI, K., GRANEROD, J., and DURRHEIM, D. N.
- Published
- 2015
3. Management dilemmas in a case of angioedema with normal C1 inhibitor function during pregnancy
- Author
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Tran, Y. D. and de Malmanche, T.
- Published
- 2013
- Full Text
- View/download PDF
4. ATYPICAL HAEMOLYTIC URAEMIC SYNDROME WITH A NOVEL COMPLEMENT FACTOR H MUTATION: 219
- Author
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SMYTH, B, ROXBURGH, S, WARD, C, and DE MALMANCHE, T
- Published
- 2013
5. Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis
- Author
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Hiles, S. A., Baker, A. L., de Malmanche, T., and Attia, J.
- Published
- 2012
6. Prevalence of Helicobacter pylori positivity in patients undergoing percutaneous coronary intervention
- Author
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Hiew, C., Duggan, A., de Malmanche, T., Hatton, R., Baker, F., Attia, J., and Collins, N.
- Published
- 2012
- Full Text
- View/download PDF
7. Prevalence and predictors for helicobacter pylori infection in patients undergoing percutaneous coronary intervention
- Author
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HIEW, C, DUGGAN, A, DE MALMANCHE, T, HATTON, R, HADDAD, R, ABED, H, and COLLINS, N
- Published
- 2009
8. Serum Midkine Rapidly Increases by Three Hundred-fold Following Heparin Administration During Coronary Angiography
- Author
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Sugito, S., primary, Hall, S., additional, Al-Omary, M., additional, De Malmanche, T., additional, Robertson, G., additional, and Boyle, A., additional
- Published
- 2019
- Full Text
- View/download PDF
9. Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.
- Author
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Barbour T.D., Isbel N.M., de Malmanche T., Durkan A., Hissaria P., Blombery P., Fox L.C., Cohney S.J., Kausman J.Y., Shortt J., Hughes P.D., Wood E.M., Barbour T.D., Isbel N.M., de Malmanche T., Durkan A., Hissaria P., Blombery P., Fox L.C., Cohney S.J., Kausman J.Y., Shortt J., Hughes P.D., and Wood E.M.
- Abstract
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.Copyright © 2018 Asian Pacific Society of Nephrology
- Published
- 2018
10. Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand
- Author
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Fox, LC, Cohney, SJ, Kausman, JY, Shortt, J, Hughes, PD, Wood, EM, Isbel, NM, de Malmanche, T, Durkan, A, Hissaria, P, Blombery, P, Barbour, TD, Fox, LC, Cohney, SJ, Kausman, JY, Shortt, J, Hughes, PD, Wood, EM, Isbel, NM, de Malmanche, T, Durkan, A, Hissaria, P, Blombery, P, and Barbour, TD
- Abstract
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.
- Published
- 2018
11. TNFRSF13B Variants in SLE and Immunodeficiency
- Author
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David A. Fulcher, Stephen Adelstein, D'Alfonso S, Matthew C. Cook, Carola G. Vinuesa, Martyn A. French, Paul A. Gatenby, Rúa Figueroa I, Alarcón Riquelme M, De Malmanche T, Chew Gyj, Cervera R, Vasconcelos C, D S Riminton, Doria A, Scorza R, Roger Garsia, Martins B, Pravin Hissaria, and Mercan S
- Subjects
Severe combined immunodeficiency ,Common variable immunodeficiency ,Selective IgA deficiency ,Biology ,medicine.disease_cause ,medicine.disease ,Penetrance ,Virology ,Autoimmunity ,Immunology ,Genotype ,medicine ,Allele ,Immunodeficiency - Abstract
Background: The co-existence of autoimmunity and primary antibody deficiency in some individiuals is intriguing. The transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) gene (TNFRSF13B) has been implicated in both autoimmunity and primary antibody deficiency to varying extents in mice and humans. However, the phenotype described in mice with TNFRSF13B polymorphisms has not been entirely consistent with patients with similar orthologous polymorphisms.Objective: To further understand the relationship between TNFRSF13B variants and PAD and autoimmunity, we set out to determine the association of the two most common TNFRSF13B polymorphisms with autoimmunity and immunodeficiency, in patients with primary antibody deficiency and SLE.Method: We genotyped the C104R and A181E polymorphisms of TNFRSF13B in193 individuals and 144 controls from the Australian and New Zealand Antibody Deficiency Allele (ANZADA) Study, 107 patients from the Australian Point Mutation in Systemic Lupus Erythematosus (APOSLE) study, 169 patients with SLE from a European population, and 263 European controls. We were also able to determine TNFRSF13B genotypes for family members for nine of twelve pedigrees with primary antibody deficiency identified with TNFRSF13B variants.Results: The total number of TNFRSF13B variants in the primary antibody deficiency cohort was significantly higher than in the control group (p=0.0089; OR 9.481 [95% CI 1.218−73.81]). Similar results were obtained when patients with systemic lupus erythematosus were analysed. TNFRSF13B variants were strongly associated with SLE (p=0.0161, OR 3.316 [95% CI 1.245-8.836]). Familial analysis revealed incomplete penetrance of the TNFRSF13B variants.Conclusion: Taken together, the two most common TNFRSF13B variants are associated with primary antibody deficiency and systemic lupus erythematosus.
- Published
- 2014
12. TNFRSF13B Variants in SLE and Immunodeficiency
- Author
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Chew, Gary, Gatenby, Paul, Mercan, S, De Malmanche, T, Adelstein, Stephen, Garsia, R, Hissaria, Pravin, French, Martyn A., Riminton , D. Sean, Fulcher, David, Scorza, R, D'Alfonso, D, Doria, A, Garcia De Vinuesa, Maria Carola, Cook, Matthew, Chew, Gary, Gatenby, Paul, Mercan, S, De Malmanche, T, Adelstein, Stephen, Garsia, R, Hissaria, Pravin, French, Martyn A., Riminton , D. Sean, Fulcher, David, Scorza, R, D'Alfonso, D, Doria, A, Garcia De Vinuesa, Maria Carola, and Cook, Matthew
- Published
- 2014
13. TNFRSF13B variants in SLE and immunodeficiency
- Author
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Chew, Gary Y. J, Gatenby, Paul A, Mercan, S, De Malmanche, T, Adelstein, Stephen, Garsia, Roger, Hissaria, Pravin, French, Martyn, Riminton, D. Sean, Fulcher, David A, Scorza, R, D'Alfonso, S, Doria, A, Rua Figueroa, I, Cervera, R, Vasconcelos, C, Martins, B, Alarcon Riquelme, M, Vinuesa, Carola, Cook, Matthew C, Chew, Gary Y. J, Gatenby, Paul A, Mercan, S, De Malmanche, T, Adelstein, Stephen, Garsia, Roger, Hissaria, Pravin, French, Martyn, Riminton, D. Sean, Fulcher, David A, Scorza, R, D'Alfonso, S, Doria, A, Rua Figueroa, I, Cervera, R, Vasconcelos, C, Martins, B, Alarcon Riquelme, M, Vinuesa, Carola, and Cook, Matthew C
- Abstract
Background: The co-existence of autoimmunity and primary antibody deficiency in some individiuals is intriguing. The transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) gene (TNFRSF13B) has been implicated in both autoimmunity and primary antibody deficiency to varying extents in mice and humans. However, the phenotype described in mice with TNFRSF13B polymorphisms has not been entirely consistent with patients with similar orthologous polymorphisms. Objective: To further understand the relationship between TNFRSF13B variants and PAD and autoimmunity, we set out to determine the association of the two most common TNFRSF13B polymorphisms with autoimmunity and immunodeficiency, in patients with primary antibody deficiency and SLE. Method: We genotyped the C104R and A181E polymorphisms of TNFRSF13B in193 individuals and 144 controls from the Australian and New Zealand Antibody Deficiency Allele (ANZADA) Study, 107 patients from the Australian Point Mutation in Systemic Lupus Erythematosus (APOSLE) study, 169 patients with SLE from a European population, and 263 European controls. We were also able to determine TNFRSF13B genotypes for family members for nine of twelve pedigrees with primary antibody deficiency identified with TNFRSF13B variants. Results: The total number of TNFRSF13B variants in the primary antibody deficiency cohort was significantly higher than in the control group (p=0.0089; OR 9.481 [95% CI 1.218−73.81]). Similar results were obtained when patients with systemic lupus erythematosus were analysed. TNFRSF13B variants were strongly associated with SLE (p=0.0161, OR 3.316 [95% CI 1.245-8.836]). Familial analysis revealed incomplete penetrance of the TNFRSF13B variants. Conclusion: Taken together, the two most common TNFRSF13B variants are associated with primary antibody deficiency and systemic lupus erythematosus.
- Published
- 2014
14. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude
- Author
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UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lechner-Scott, J, Spencer, B, de Malmanche, T, Attia, J, Fitzgerald, M, Trojano, M, Grand'Maison, F, Gomez, J Antonio C, Izquierdo, G, Duquette, P, Girard, M, Grammond, P, Oreja-Guevara, C, Hupperts, R, Bergamaschi, R, Boz, C, Giuliani, G, Van Pesch, Vincent, Iuliano, G, Fiol, M, Cristiano, E, Verheul, F, Saladino, M Laura, Slee, M, Barnett, M, Deri, N, Flechter, S, Vella, N, Shaw, C, Herbert, J, Moore, F, Petkovska-Boskova, T, Jokubaitis, V, Butzkueven, H, MSBase study group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lechner-Scott, J, Spencer, B, de Malmanche, T, Attia, J, Fitzgerald, M, Trojano, M, Grand'Maison, F, Gomez, J Antonio C, Izquierdo, G, Duquette, P, Girard, M, Grammond, P, Oreja-Guevara, C, Hupperts, R, Bergamaschi, R, Boz, C, Giuliani, G, Van Pesch, Vincent, Iuliano, G, Fiol, M, Cristiano, E, Verheul, F, Saladino, M Laura, Slee, M, Barnett, M, Deri, N, Flechter, S, Vella, N, Shaw, C, Herbert, J, Moore, F, Petkovska-Boskova, T, Jokubaitis, V, Butzkueven, H, and MSBase study group
- Abstract
Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) statusfor the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. Methods: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. Results: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). Conclusions: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis
- Published
- 2012
15. Frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude
- Author
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Lechner-Scott, J., Spencer, B., de Malmanche, T., Attia, J., Fitzgerald, M., Trojano, M., Grand'Maison, F., Gomez, J. Antonio C., Izquierdo, G., Duquette, P., Girard, M., Grammond, P., Oreja-Guevara, C., Hupperts, R., Bergamaschi, P., Boz, C., Giuliani, G., van Pesch, V., Iuliano, G., Fiol, M., Cristiano, E., Verheul, F., Laura Saladino, M., Slee, M., Barnett, M., Deri, N., Flechter, S., Vella, N., Shaw, C., Herbert, J., Moore, F., Petkovska-Boskova, T., Jokubaitis, V., Butzkueven, H., Lechner-Scott, J., Spencer, B., de Malmanche, T., Attia, J., Fitzgerald, M., Trojano, M., Grand'Maison, F., Gomez, J. Antonio C., Izquierdo, G., Duquette, P., Girard, M., Grammond, P., Oreja-Guevara, C., Hupperts, R., Bergamaschi, P., Boz, C., Giuliani, G., van Pesch, V., Iuliano, G., Fiol, M., Cristiano, E., Verheul, F., Laura Saladino, M., Slee, M., Barnett, M., Deri, N., Flechter, S., Vella, N., Shaw, C., Herbert, J., Moore, F., Petkovska-Boskova, T., Jokubaitis, V., and Butzkueven, H.
- Abstract
With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.
- Published
- 2011
16. 103. Statins, depression and the inflammatory hypothesis of depression: A meta-analysis of randomized controlled trials
- Author
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Hiles, S.A., primary, Baker, A.L., additional, Handley, T., additional, de Malmanche, T., additional, and Attia, J., additional
- Published
- 2013
- Full Text
- View/download PDF
17. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude
- Author
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Lechner-Scott, J, primary, Spencer, B, additional, de Malmanche, T, additional, Attia, J, additional, Fitzgerald, M, additional, Trojano, M, additional, Grand’Maison, F, additional, Gomez, J Antonio C, additional, Izquierdo, G, additional, Duquette, P, additional, Girard, M, additional, Grammond, P, additional, Oreja-Guevara, C, additional, Hupperts, R, additional, Bergamaschi, R, additional, Boz, C, additional, Giuliani, G, additional, van Pesch, V, additional, Iuliano, G, additional, Fiol, M, additional, Cristiano, E, additional, Verheul, F, additional, Saladino, M Laura, additional, Slee, M, additional, Barnett, M, additional, Deri, N, additional, Flechter, S, additional, Vella, N, additional, Shaw, C, additional, Herbert, J, additional, Moore, F, additional, Petkovska-Boskova, T, additional, Jokubaitis, V, additional, and Butzkueven, H, additional
- Published
- 2011
- Full Text
- View/download PDF
18. Prevalence ofHelicobacter pyloripositivity in patients undergoing percutaneous coronary intervention
- Author
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Hiew, C., primary, Duggan, A., additional, de Malmanche, T., additional, Hatton, R., additional, Baker, F., additional, Attia, J., additional, and Collins, N., additional
- Published
- 2010
- Full Text
- View/download PDF
19. Prevalence and predictors for Helicobacter pylori infection in patients undergoing percutaneous coronary intervention
- Author
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Hiew, C., primary, Duggan, A., additional, de malmanche, T., additional, Hatton, R., additional, Haddad, R., additional, Abed, H., additional, and Collins, N., additional
- Published
- 2009
- Full Text
- View/download PDF
20. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.
- Author
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Lechner-Scott, J, Spencer, B, de Malmanche, T, Attia, J, Fitzgerald, M, Trojano, M, Grand’Maison, F, Gomez, J Antonio C, Izquierdo, G, Duquette, P, Girard, M, Grammond, P, Oreja-Guevara, C, Hupperts, R, Bergamaschi, R, Boz, C, Giuliani, G, van Pesch, V, Iuliano, G, and Fiol, M
- Subjects
CEREBROSPINAL fluid ,MULTIPLE sclerosis ,HEALTH outcome assessment ,PROGNOSIS ,LATITUDE variation ,PATIENTS - Abstract
The article presents a study on the frequency of cerebrospinal fluid (CSF) oligoclonal banding in patients with multiple sclerosis (MS). It states the use of the MSBase, a web-based collaborative MS outcome registry, to find out the OCB positivity in patients with MS and its effect to disability outcome. It concludes that OCB in patients with MS contribute to worse prognosis with latitude variation.
- Published
- 2012
- Full Text
- View/download PDF
21. Complement-mediated thrombotic microangiopathy on a background of Alport syndrome: A case report.
- Author
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Coorey CP, de Malmanche T, Chou A, and Feddersen M
- Subjects
- Humans, Biopsy, Male, Kidney pathology, Adult, Complement Activation, Treatment Outcome, Nephritis, Hereditary complications, Nephritis, Hereditary diagnosis, Thrombotic Microangiopathies etiology, Thrombotic Microangiopathies diagnosis
- Abstract
Here we present a case of complement-mediated thrombotic microangiopathy (TMA) in a patient who has a background of Stage 5 chronic kidney disease secondary to Alport syndrome. We explain our approach to the diagnosis of TMA, especially the reliance on non-renal manifestations of TMA and the role of kidney biopsy given there was a background of advanced kidney impairment at baseline., (© 2024 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)
- Published
- 2024
- Full Text
- View/download PDF
22. Diagnostic accuracy of ANCA serology in ANCA-associated vasculitis with renal involvement.
- Author
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Cohen A, Weerasinghe N, Lemmert K, de Malmanche T, and Myint T
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Adult, Glomerulonephritis blood, Glomerulonephritis diagnosis, Glomerulonephritis immunology, Biopsy, Kidney pathology, Sensitivity and Specificity, Peroxidase immunology, Peroxidase blood, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis blood, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis diagnosis, Antibodies, Antineutrophil Cytoplasmic blood
- Abstract
Background: Pauci-immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end-stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well-established., Aim: We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement., Methods: We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay., Results: Eight hundred and forty-eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci-immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci-immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89-0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%-87.6%) and a specificity of 94.0% (95% CI: 91.6%-96.0%)., Conclusions: ANCA titres are highly predictive of pauci-immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life-threatening disease., (© 2024 Royal Australasian College of Physicians.)
- Published
- 2024
- Full Text
- View/download PDF
23. Does an electronic pathology ordering system change the volume and pattern of routine testing in hospital? An interrupted time series analysis.
- Author
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de Carle M, Macnab B, Utainrat J, Herkes-Deane J, Attia J, de Malmanche T, Teber E, Palazzi K, Scowen C, and Hure A
- Subjects
- Humans, Diagnostic Tests, Routine, Australia, Practice Patterns, Physicians' statistics & numerical data, Tertiary Care Centers, Interrupted Time Series Analysis, Medical Order Entry Systems statistics & numerical data
- Abstract
Aims: Identifying and reducing low-value care is a vital issue in Australia, with pathology test ordering a common focus in this field. This study builds on previous research and aimed to quantify the impact of the implementation of an electronic ordering (e-ordering) system on the volume of pathology testing, compared with manual (paper based) ordering., Methods: An audit and analysis of pathology test data were conducted, using an interrupted time series design to investigate the impact of the e-ordering system on pathology ordering patterns. All medical and surgical adult inpatients at a tertiary referral hospital in Newcastle, Australia, were included over a 3-year period., Results: Overall, there were no statistically significant differences in the volume of orders due to the implementation of the e-ordering system. There was a slight increase in the aggregated volume (tests per admission and tests per bed day) of tests ordered across the entire study period, reflecting a secular trend., Conclusions: Despite providing greater visibility and tracking of orders, we conclude that the implementation of an e-ordering system does not, in and of itself, reduce ordering volume. Efforts to identify and reduce low-value care will require intentional effort and specifically designed educational programmes or hard-wired algorithms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
24. Morphine-specific IgE testing in the assessment of neuromuscular blocking agent allergy: a single centre experience.
- Author
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Chow KL, Patchett K, Reeves G, de Malmanche T, Gillies D, and Boyle M
- Subjects
- Humans, Morphine, Codeine, Immunoglobulin E, Skin Tests, Hypersensitivity, Neuromuscular Blocking Agents adverse effects, Anaphylaxis, Drug Hypersensitivity diagnosis
- Published
- 2024
- Full Text
- View/download PDF
25. Measurement of Complement Activation via Plasma-Soluble C5b-9 Comparison with Terminal Complement Complex Staining in a Series of Kidney Biopsies.
- Author
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Wijaya C, Burns C, Hall S, Farmer M, Jones D, Rowlandson M, Choi P, Formby M, and de Malmanche T
- Subjects
- Humans, Pilot Projects, Complement System Proteins, Complement Activation, Kidney pathology, Biopsy, Hemoglobins, Complement Membrane Attack Complex, Kidney Diseases pathology
- Abstract
Introduction: With the emergence of therapeutic complement inhibitors, there is a need to identify patients with complement-driven inflammation. C5b-9 is the terminal product of the three complement pathways and therefore a marker of total complement activation. We present a pilot study which aims to assess whether plasma soluble C5b-9 (sC5b-9) correlates with terminal complement complex (TCC) staining in kidney tissue. The secondary aim was to assess the utility of plasma sC5b-9 as part of routine workup in kidney patients undergoing kidney biopsy., Methods: Thirty-seven patients undergoing kidney biopsy had plasma sC5b-9 and TCC staining on kidney tissue performed. Additional blood markers including creatinine, haemoglobin, CRP, factor H, factor I, and midkine levels were also taken. These parameters were correlated with the histological diagnoses. Patients were divided into a diseased group (n = 31) and a control group (n = 6) consisting of transplanted kidneys with minor or no changes. Of the biopsies in the control group, 50% were performed as per protocol, and the other 50% were performed due to clinical need., Results: There was no correlation found between plasma sC5b-9 and TCC kidney staining. Elevated sC5b-9 levels were found in a heterogeneous group of patients but were associated with higher CRP and lower haemoglobin levels. Overall, there was more TCC kidney staining in the diseased group compared with the control group, and a trend was observed of diabetic, primary membranous nephropathy, and amyloidosis patients having more intense glomerular and peritubular/interstitial staining., Conclusion: Plasma sC5b-9 as a marker of total complement activation does not correlate with TCC kidney staining. This discordance suggests that plasma sC5b-9 and TCC staining are distinct markers of disease. TCC staining reflects chronicity and tissue deposition of complement over time. Conversely, plasma sC5b-9 concentrations change rapidly and reflect systemic complement activation. Complement activation was present in a heterogeneous group of kidney disease, indicating the underlying role of complement in many disorders., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
- Full Text
- View/download PDF
26. Anti-tissue transglutaminase (tTG) screening using relative light units to identify IgA deficiency.
- Author
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Wijaya C, Lemmert K, and De Malmanche T
- Subjects
- Autoantibodies analysis, Humans, Immunoglobulin A, Protein Glutamine gamma Glutamyltransferase 2, Sensitivity and Specificity, Transglutaminases, Celiac Disease diagnosis, IgA Deficiency diagnosis
- Abstract
IgA deficiency is more common in patients with coeliac disease (CD). Total IgA levels are often recommended as part of first line coeliac testing along with anti-tissue transglutaminase (tTG) IgA, to identify these patients and reduce falsely negative results. This study aimed to identify patients with complete IgA deficiency by determining a cut-off threshold on chemiluminescent tTG IgA testing. A chemiluminescent assay QUANTA Flash h-tTG was reviewed using the BIO-FLASH automated platform. tTG relative light units (RLU) were analysed in relation to total IgA levels. Correlation analysis was performed and distributions of tTG RLU were compared between the IgA deficient and IgA detectable groups, and ROC analysis was performed to identify a suitable threshold. A total of 203 samples were reviewed in our initial cohort. There was a strong correlation between IgA and tTG RLU levels (Pearson correlation coefficient 0.495, p<0.001). There was a statistically significant difference of 170.57 RLU between the means of the IgA deficient and IgA detectable group (p<0.001, 156.50-184.64). A receiver operating characteristic (ROC) curve was generated with area under the curve of 0.997. A cut-off of less than 300 tTG RLU for identification of IgA deficiency was chosen, which had a sensitivity and specificity of 100% and 98.9%, respectively. A prospective validation cohort was conducted which confirmed the initial results. Our study has validated an algorithm to identify complete IgA deficiency by implementing a threshold of 300 RLU during tTG IgA testing by chemiluminescent immunoassay. This approach resulted in a sensitivity of 100% to detect patients with complete IgA deficiency. Widespread uptake would result in improved workflow, workload and turnaround time, and reduce the need for unnecessary blanket testing of total IgA in the screening for coeliac disease., (Copyright © 2022 Royal College of Pathologists of Australasia. All rights reserved.)
- Published
- 2022
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27. Biomarkers to Guide the Timing of Surgery: Neutrophil and Monocyte L-Selectin Predict Postoperative Sepsis in Orthopaedic Trauma Patients.
- Author
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Briggs GD, Lemmert K, Lott NJ, de Malmanche T, and Balogh ZJ
- Abstract
Deciding whether to delay non-lifesaving orthopaedic trauma surgery to prevent multiple organ failure (MOF) or sepsis is frequently disputed and largely based on expert opinion. We hypothesise that neutrophils and monocytes differentially express activation markers prior to patients developing these complications. Peripheral blood from 20 healthy controls and 162 patients requiring major orthopaedic intervention was collected perioperatively. Neutrophil and monocyte L-selectin, CD64, CD11, CD18, and CXCR1 expression were measured using flow cytometry. The predictive ability for MOF and sepsis was assessed using the Receiver Operating Characteristic (ROC) comparing to C-reactive protein (CRP). Neutrophil and monocyte L-selectin were significantly higher in patients who developed sepsis. Neutrophil L-selectin (AUC 0.692 [95%CI 0.574-0.810]) and monocyte L-selectin (AUC 0.761 [95%CI 0.632-0.891]) were significant predictors of sepsis and were not significantly different to CRP (AUC 0.772 [95%CI 0.650-0.853]). Monocyte L-selectin was predictive of MOF preoperatively and postoperatively (preop AUC 0.790 [95%CI 0.622-0.958]). CD64 and CRP were predictive of MOF at one-day postop (AUC 0.808 [95%CI 0.643-0.974] and AUC 0.809 [95%CI 0.662-0.956], respectively). In the perioperative period, elevated neutrophil and monocyte L-selectin are predictors of postoperative sepsis. Larger validation studies should focus on these biomarkers for deciding the timing of long bone/pelvic fracture fixation.
- Published
- 2021
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- View/download PDF
28. Report of the Survey Conducted by RCPAQAP on Current Practices for Beta-Migrating Paraprotein Reporting.
- Author
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Smith JD, Wijeratne N, Schneider HG, de Malmanche T, Hissaria P, Toit SD, Chiu W, Boyder C, Morison IM, Tseng A, Glegg K, Wienholt L, and Mollee P
- Abstract
Competing Interests: Competing Interests: None declared.
- Published
- 2021
- Full Text
- View/download PDF
29. Heparin Administration, but Not Myocardial Ischemia or Necrosis, Leads to Midkine Elevation.
- Author
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Sugito S, Hall S, Al-Omary MS, De Malmanche T, Robertson G, Collins N, and Boyle A
- Subjects
- Anticoagulants adverse effects, Biomarkers blood, Coronary Artery Disease blood, Coronary Artery Disease diagnostic imaging, Dose-Response Relationship, Drug, Heparin adverse effects, Humans, Non-ST Elevated Myocardial Infarction blood, Non-ST Elevated Myocardial Infarction diagnostic imaging, Prospective Studies, ST Elevation Myocardial Infarction blood, ST Elevation Myocardial Infarction diagnostic imaging, Time Factors, Treatment Outcome, Up-Regulation, Anticoagulants administration & dosage, Coronary Artery Disease therapy, Heparin administration & dosage, Midkine blood, Non-ST Elevated Myocardial Infarction therapy, Percutaneous Coronary Intervention adverse effects, ST Elevation Myocardial Infarction therapy
- Abstract
Midkine (MK) is a heparin-binding growth factor, whose role as a biomarker of coronary artery disease, myocardial ischaemia and necrosis has not been well measured. This study quantified serial MK levels in patients undergoing coronary angiography (CA) and identified factors associated with MK. In this single-centre, parallel cohort study, forty patients undergoing CA had arterial samples collected prior, 10 and 20 min after heparin administration. Four groups were examined: 1-stable coronary artery disease (CAD) without percutaneous coronary intervention (PCI); 2-stable CAD for elective PCI; 3-non-ST elevation myocardial infarction (NSTEMI) with or without PCI; 4-ST elevation myocardial infarction (STEMI) with primary PCI. Groups 1, 2 and 4 were heparin naïve, allowing assessment of the effects of myocardial necrosis between baseline levels; group 3 had received low-molecular-weight heparin. MK levels were analysed by ELISA. Median MK at baseline did not differ between groups, demonstrating that myocardial ischaemia or necrosis does not affect MK levels. Heparin administration had an immediate effect on median MK at 10 min, showing an average 500-fold increase that is dose-dependent (R
2 = 0.35, p = 0.001). Median MK levels remained elevated at 20 min following heparin administration. Multivariate analysis showed that the estimated glomerular filtration rate (eGFR) was the only predictor of elevated baseline MK (p = 0.02). Baseline MK did not correlate with high-sensitivity troponin-I (HsTnI) taken just before CA (p = 0.97), or peak HsTnI during admission (p = 0.74). MK is not a reliable marker of myocardial ischaemia or necrosis. MK increased significantly in all patients following heparin administration in a dose-dependent manner.- Published
- 2020
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30. Genomic investigation of inherited thrombotic microangiopathy-aHUS and TTP.
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Enjeti AK, de Malmanche T, Chapman K, and Ziolkowski A
- Subjects
- Antibodies, Monoclonal therapeutic use, Complement System Proteins genetics, Complement System Proteins metabolism, Erythrocytes metabolism, Humans, Plasma Exchange, Thrombotic Microangiopathies blood, Thrombotic Microangiopathies therapy, Genetic Testing, Genomics, Thrombotic Microangiopathies genetics
- Abstract
Thrombotic microangiopathies (TMA) are a heterogeneous group of red cell fragmentation syndromes characterized by a tendency for thrombosis and pathognomonic red cell fragments in peripheral blood, which results in thrombosis in the microvasculature due to endothelial damage. Genomic investigations into inherited TMAs are of diagnostic, prognostic and therapeutic value. Here, we present two cases that capture the importance of performing genomic testing in rare disorders. Treatment options for these conditions, such as plasma exchange and monoclonal antibodies against complement factors, are intensive and expensive health care interventions. The results of genomic investigation into rare TMAs can better inform the clinicians and their patients of prognosis and suitable personalized treatment options., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
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31. An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis.
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Turner KA, Frinack JL, Ettore MW, Tate JR, Graziani MS, Jacobs JFM, Booth RA, McCudden CR, Keren DF, Delgado JC, Zemtsovskaja G, Fullinfaw RO, Caldini A, de Malmanche T, Katakouzinos K, Burke M, Palladini G, Altinier S, Zaninotto M, Righetti G, Melki MT, Bell S, and Willrich MAV
- Subjects
- Antibodies, Monoclonal chemistry, Antibodies, Monoclonal, Humanized chemistry, Humans, Immunoglobulin Isotypes chemistry, Limit of Detection, Paraproteinemias diagnosis, Reproducibility of Results, Blood Protein Electrophoresis methods, Laboratories, Hospital standards, Myeloma Proteins analysis
- Abstract
Background Serum protein electrophoresis (SPEP) is used to quantify the serum monoclonal component or M-protein, for diagnosis and monitoring of monoclonal gammopathies. Significant imprecision and inaccuracy pose challenges in reporting small M-proteins. Using therapeutic monoclonal antibody-spiked sera and a pooled beta-migrating M-protein, we aimed to assess SPEP limitations and variability across 16 laboratories in three continents. Methods Sera with normal, hypo- or hypergammaglobulinemia were spiked with daratumumab, Dara (cathodal migrating), or elotuzumab, Elo (central-gamma migrating), with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Provided with total protein (reverse biuret, Siemens), laboratories blindly analyzed samples according to their SPEP and immunofixation (IFE) or immunosubtraction (ISUB) standard operating procedures. Sixteen laboratories reported the perpendicular drop (PD) method of gating the M-protein, while 10 used tangent skimming (TS). A mean percent recovery range of 80%-120% was set as acceptable. The inter-laboratory %CV was calculated. Results Gamma globulin background, migration pattern and concentration all affect the precision and accuracy of quantifying M-proteins by SPEP. As the background increases, imprecision increases and accuracy decreases leading to overestimation of M-protein quantitation especially evident in hypergamma samples, and more prominent with PD. Cathodal migrating M-proteins were associated with less imprecision and higher accuracy compared to central-gamma migrating M-proteins, which is attributed to the increased gamma background contribution in M-proteins migrating in the middle of the gamma fraction. There is greater imprecision and loss of accuracy at lower M-protein concentrations. Conclusions This study suggests that quantifying exceedingly low concentrations of M-proteins, although possible, may not yield adequate accuracy and precision between laboratories.
- Published
- 2020
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- View/download PDF
32. An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part II: limit of detection and follow-up of patients with small M-proteins.
- Author
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Jacobs JFM, Turner KA, Graziani MS, Frinack JL, Ettore MW, Tate JR, Booth RA, McCudden CR, Keren DF, Delgado JC, Zemtsovskaja G, Fullinfaw RO, Caldini A, de Malmanche T, Katakouzinos K, Burke M, Palladini G, Altinier S, Zaninotto M, Righetti G, Melki MT, Bell S, and Willrich MAV
- Subjects
- Antibodies, Monoclonal chemistry, Antibodies, Monoclonal, Humanized chemistry, Follow-Up Studies, Humans, Immunoglobulin Isotypes chemistry, Limit of Detection, Paraproteinemias diagnosis, Blood Protein Electrophoresis methods, Laboratories, Hospital standards, Myeloma Proteins analysis
- Abstract
Background Electrophoretic methods to detect, characterize and quantify M-proteins play an important role in the management of patients with monoclonal gammopathies (MGs). Significant uncertainty in the quantification and limit of detection (LOD) is documented when M-proteins are <10 g/L. Using spiked sera, we aimed to assess the variability in intact M-protein quantification and LOD across 16 laboratories. Methods Sera with normal, hypo- or hyper-gammaglobulinemia were spiked with daratumumab or elotuzumab, with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Laboratories blindly analyzed samples according to their serum protein electrophoresis (SPEP)/isotyping standard operating procedures. LOD and intra-laboratory percent coefficient of variation (%CV) were calculated and further specified with regard to the method (gel/capillary electrophoresis [CZE]), gating strategy (perpendicular drop [PD]/tangent skimming [TS]), isotyping (immunofixation/immunosubtraction [ISUB]) and manufacturer (Helena/Sebia). Results All M-proteins ≥1 g/L were detected by SPEP. With isotyping the LOD was moderately more sensitive than with SPEP. The intensity of polyclonal background had the biggest negative impact on LOD. Independent of the method used, the intra-laboratory imprecision of M-protein quantification was small (mean CV = 5.0%). Low M-protein concentration and high polyclonal background had the strongest negative impact on intra-laboratory precision. All laboratories were able to follow trend of M-protein concentrations down to 1 g/L. Conclusions In this study, we describe a large variation in the reported LOD for both SPEP and isotyping; overall LOD is most affected by the polyclonal immunoglobulin background. Satisfactory intra-laboratory precision was demonstrated. This indicates that the quantification of small M-proteins to monitor patients over time is appropriate, when subsequent testing is performed within the same laboratory.
- Published
- 2020
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- View/download PDF
33. Identifying low value pathology test ordering in hospitalised patients: a retrospective cohort study across two hospitals.
- Author
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Hure A, Palazzi K, Peel R, Geraghty D, Collard P, De Malmanche T, Tran H, Reeves P, Searles A, Jorm L, and Attia J
- Subjects
- Hospitals, Humans, Medical Order Entry Systems, Retrospective Studies, Diagnostic Tests, Routine economics, Health Care Costs, Practice Patterns, Physicians' economics
- Abstract
The push to identify low value care has led to scrutiny of pathology test re-ordering. The objective of this study was to identify the patterns of ordering pathology tests among inpatients in teaching hospitals and model strategies to reduce unnecessary testing. This was a retrospective cohort study of all adult medical and surgical inpatients admitted to one major teaching hospital and one rural hospital in the same health district over 2 years. Obstetric, gynaecological, intensive care, elective/day procedures and dialysis admissions were excluded. Orders for electrolytes, urea and creatinine (EUC), full blood count (FBC), thyroid stimulating hormone (TSH), glycated haemoglobin (HbA1c), vitamin D, and troponin, date of order, and value of the resulting test, were obtained from a health district data warehouse. Pathology results were mapped to each inpatient day. EUC and FBC constituted over 90% of all inpatient pathology requests for these six tests. Between 40-45% of inpatients had EUC and/or FBC performed daily. After the first couple of tests, the retest interval was consistently around 24 hours, regardless of the previous value of the test, consistent with a culture of routine ordering. This was less pronounced in the rural hospital compared to the urban teaching hospital. Lockouts (applied when previous tests normal) or minimum retest intervals (applied to previously normal and abnormal tests) of various lengths were tested on the data to find optimal combinations that reduced unnecessary tests without missing too many very abnormal tests. A lockout of 48 hours for EUC and 48 hour lockout combined with a 12 hour minimum retest interval for FBC appear optimal to reduce over ordering and could save approximately AU$400/inpatient bed per year at a single teaching hospital. There is evidence of low value re-ordering of EUC and FBC pathology tests. Implementation of a computerised physician order entry system with inbuilt prompts to restrict unnecessary re-ordering of pathology tests may be a practical solution., (Copyright © 2019 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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34. Routine complement blood tests are insensitive for alternative complement activation.
- Author
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de Malmanche T
- Subjects
- Complement Activation, Hematologic Tests, Humans, Interferon-beta, Multiple Sclerosis, Thrombotic Microangiopathies
- Published
- 2019
- Full Text
- View/download PDF
35. Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.
- Author
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Fox LC, Cohney SJ, Kausman JY, Shortt J, Hughes PD, Wood EM, Isbel NM, de Malmanche T, Durkan A, Hissaria P, Blombery P, and Barbour TD
- Subjects
- ADAMTS13 Protein blood, ADAMTS13 Protein immunology, Australia, Autoantibodies blood, Biomarkers blood, Complement Factor H immunology, Consensus, Hemolytic-Uremic Syndrome blood, Hemolytic-Uremic Syndrome diagnosis, Hemolytic-Uremic Syndrome therapy, Humans, Immunologic Factors therapeutic use, New Zealand, Predictive Value of Tests, Purpura, Thrombotic Thrombocytopenic blood, Purpura, Thrombotic Thrombocytopenic diagnosis, Purpura, Thrombotic Thrombocytopenic therapy, Risk Factors, Rituximab therapeutic use, Shiga-Toxigenic Escherichia coli isolation & purification, Steroids therapeutic use, Thrombotic Microangiopathies blood, Treatment Outcome, Antibodies, Monoclonal, Humanized therapeutic use, Complement Inactivating Agents therapeutic use, Plasma Exchange standards, Thrombotic Microangiopathies diagnosis, Thrombotic Microangiopathies therapy
- Abstract
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA., (© 2018 Asian Pacific Society of Nephrology.)
- Published
- 2018
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36. Primary thyroid T-cell lymphoma arising in a middle-aged Caucasian male.
- Author
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Reeders J, Thant A, de Malmanche T, and Pasupathy A
- Subjects
- CD4-Positive T-Lymphocytes pathology, Humans, Lymphoma, T-Cell pathology, Male, Middle Aged, Thyroid Gland pathology, Thyroid Neoplasms pathology, White People, Lymphoma, T-Cell diagnosis, Thyroid Neoplasms diagnosis
- Published
- 2017
- Full Text
- View/download PDF
37. The role of inflammatory markers in explaining the association between depression and cardiovascular hospitalisations.
- Author
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Hiles SA, Baker AL, de Malmanche T, McEvoy M, Boyle M, and Attia J
- Subjects
- Aged, Aged, 80 and over, Biomarkers blood, Body Mass Index, Cardiovascular Diseases complications, Cardiovascular Diseases psychology, Depression complications, Depression psychology, Depressive Disorder blood, Depressive Disorder complications, Depressive Disorder psychology, Female, Humans, Inflammation complications, Inflammation psychology, Male, Middle Aged, Risk Factors, Waist-Hip Ratio, C-Reactive Protein metabolism, Cardiovascular Diseases blood, Depression blood, Hospitalization, Inflammation blood, Interleukin-6 blood
- Abstract
This study investigated whether inflammation may explain the relationship between depression and incident cardiovascular hospitalisations. Participants (55-85 years) completed baseline depression and physical assessment. Those without self-reported cardiovascular events were followed prospectively for hospital admissions for angina, myocardial infarction and cerebral infarction (median 937 days). Across 5140 person-years of risk (N = 1692), there were 47 incident cardiovascular hospitalisations (2.8 %). Controlling for age and gender, interleukin (IL)-6, C-reactive protein (CRP), body mass index (BMI) and waist-to-hip ratio were associated with future cardiovascular events. Mediation analysis showed that CRP accounted for 8.1 % and IL-6 10.9 % of the effect of depression on cardiovascular events, and including the indirect effect in the model substantially reduced the direct relationship between depression and cardiovascular hospitalisations. BMI and waist-to-hip ratio accounted for indirect effects of 7.7 and 10.4 %, respectively. Inflammatory markers partly explain the association between depression and cardiovascular events, although other shared factors also likely contribute.
- Published
- 2015
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38. Chronic granulomatous disease presenting as refractory pneumonia in late adulthood.
- Author
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Sarwar G, de Malmanche T, Rassam L, Grainge C, Williams A, and Arnold D
- Abstract
We present a case of refractory pneumonia in an adult patient with underlying chronic granulomatous disease (CGD). Her lobectomy tissue grew B urkholderia cepacia and histopathology revealed diffuse severe pneumonic consolidation with suppurative/necrotizing granulomata. An initial attempt to find an underlying immune deficiency was unsuccessful. Following recurrent invasive infections, repeat immunological assessment revealed reduced neutrophil function, demonstrating skewed carrier status (lyonization) for X-linked CGD (only 3% normal cells). A pathogenic mutation in the CYBB gene was found on sequencing. CYBB gene encodes the gp91phox, a catalytic subunit of nicotinamide adenine dinucleotide phosphate-oxidase that produces reactive oxygen species in phagocytes. Lyonization increases with age, explaining the delayed clinical CGD. CGD is a rare neutrophil disorder that usually presents in early life with recurrent infections due to bacteria and fungi primarily involving lungs and skin. It is secondary to a defective NADPH oxidase system needed to kill intracellular organisms and activate the formation of neutrophil extracellular traps.
- Published
- 2015
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39. Unhealthy lifestyle may increase later depression via inflammation in older women but not men.
- Author
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Hiles SA, Baker AL, de Malmanche T, McEvoy M, Boyle M, and Attia J
- Subjects
- Aged, Australia epidemiology, C-Reactive Protein metabolism, Cross-Sectional Studies, Depression blood, Disease Progression, Female, Follow-Up Studies, Humans, Inflammation blood, Interleukin-6 blood, Male, Middle Aged, Quality of Life psychology, Residence Characteristics, Retrospective Studies, Self Report, Depression epidemiology, Depression psychology, Inflammation epidemiology, Life Style, Sex Characteristics
- Abstract
Depression and inflammatory markers have a reliable cross-sectional association although less is known about the prospective relationship. The current study investigated whether pro-inflammatory markers are prospectively associated with depression, and whether indicators of unhealthy lifestyle, physical health and psychosocial functioning may drive this association. Participants were drawn from the Hunter Community Study, a community-dwelling cohort of individuals aged 55-85 years (N = 1410). Participants completed baseline physiological assessment, health-related questionnaires, and blood sampling for the analysis of inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6. Participants completed the same depressive symptom questionnaire again after 3.5-5.5 years. Depression outcomes at follow-up were analysed dichotomously using established scale cut-off scores and continuously as a "residual score", representing the variation in follow-up depressive symptoms not explained by baseline symptoms and age. Analyses were conducted on males and females separately. At baseline, indicators of unhealthy lifestyle, physical health and psychosocial functioning were associated with depressive symptoms and inflammatory markers. For males, there were no relationships between inflammatory markers and follow-up depression outcomes. In females, IL-6 was significantly associated with depression outcomes in univariate, but not multivariate analyses. However, IL-6 significantly mediated the association between the predictors of waist-to-hip ratio, smoking and psychological coping at baseline, and follow-up depression outcomes. The results support the inflammatory hypothesis of depression, although females may be more vulnerable to effects. The findings raise the possibility that unhealthy lifestyle and psychosocial stress may drive inflammation and subsequent depressive symptoms., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
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40. A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity.
- Author
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Hiles SA, Baker AL, de Malmanche T, and Attia J
- Subjects
- Comorbidity, Cross-Sectional Studies, Data Interpretation, Statistical, Depression epidemiology, Depressive Disorder, Major metabolism, Humans, Inflammation metabolism, Inflammation psychology, Inpatients, Life Style, Outpatients, Depression metabolism, Interleukin-10 metabolism, Interleukin-6 metabolism
- Abstract
Epidemiological evidence for the inflammatory hypothesis of depression is largely cross-sectional; people with depression have elevated levels of circulating pro-inflammatory markers compared to people without depression. The limitation of cross sectional research is the potential for extraneous factors to influence observed effects. The purpose of this meta-analysis of cross-sectional studies of interleukin(IL)-6 and IL-10 in people with and without depression is to provide a targeted analysis of potential moderator factors relating to the diagnosis of depression and to physical and psychiatric comorbidity. Electronic searches of Embase and Medline databases were conducted using subject headings "interleukin-6" or "interleukin-10" and those relating to depression. Studies were included if they measured circulating marker levels in serum or plasma in a group of people with and without depressive symptoms (99 studies for IL-6, 19 studies for IL-10). IL-6 was elevated in depressed compared to non-depressed groups (d = 0.46, 99% CI 0.34 to 0.58, I(2) = 85.9%). This effect was larger in subgroups where depressive disorders were diagnosed compared to those with only depressive symptoms via standardized inventory, and subgroups where participants were recruited from inpatient or outpatient settings compared to the general community. The effect was also larger in those who were not selected for a particular comorbidity compared to those selected for cardiovascular disease. IL-10 effect size was not significant (d = -0.31, 99% CI -0.95 to 0.32, I(2) = 94.1%) which was not accounted for in subgroup analyses or meta-regression, indicating there is not a global elevation in cytokines. These data highlight that comorbidity and behavioral aspects of depression need to be measured and controlled in future prospective and experimental research testing the inflammatory hypothesis of depression., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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41. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.
- Author
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Lechner-Scott J, Spencer B, de Malmanche T, Attia J, Fitzgerald M, Trojano M, Grand'Maison F, Gomez JA, Izquierdo G, Duquette P, Girard M, Grammond P, Oreja-Guevara C, Hupperts R, Bergamaschi R, Boz C, Giuliani G, van Pesch V, Iuliano G, Fiol M, Cristiano E, Verheul F, Saladino ML, Slee M, Barnett M, Deri N, Flechter S, Vella N, Shaw C, Herbert J, Moore F, Petkovska-Boskova T, Jokubaitis V, and Butzkueven H
- Subjects
- Adult, Cross-Sectional Studies, Female, Humans, Incidence, Male, Registries, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis epidemiology, Oligoclonal Bands cerebrospinal fluid
- Abstract
Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power., Methods: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome., Results: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001)., Conclusions: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.
- Published
- 2012
- Full Text
- View/download PDF
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