Background: Flow cytometric analysis of the TCR-Vb repertoire can help to determine T cell clonal... more Background: Flow cytometric analysis of the TCR-Vb repertoire can help to determine T cell clonality. The most useful application is in the early diagnosis of T cell neoplasms. Methods: All TCR Vb assays performed between 2010-2019 at John Hunter Hospital Laboratory were included. 24 Vb families were tested, gated on CD4 or CD8 cells. Results: 37 Vb assays were performed on 36 patients. 35 tests were performed on blood, with 2 on tissue. 3 cases were paediatric. The distribution of results were: 20 monoclonal, 5 suspected and 12 polyclonal. The final clinical diagnoses will be presented. Discussion: In the monoclonal and suspicious groups, abnormalities in Vb4, Vb14 and Vb17 were most frequently found. If screening using only these specificities, a total percentage of <3% or >58% was suspicious of clonality and should prompt full TCR-Vb testing. Based on the samples audited, this screening method has a sensitivity of 96% and specificity of 91%. Conclusion: TCR-Vb analysis by flow cytometry is a rapid quantitative method to determine T cell clonality. We propose the use of a screening method using 3 Vb antibodies in one tube, with further characterisation if warranted. Further studies are needed.
Background Electrophoretic methods to detect, characterize and quantify M-proteins play an import... more 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 (immunofi...
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential... more 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. Whilst 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 hours 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 haemolyt...
Please cite this article in press as: Lumsdaine W, et al. Neutrophil oxidative burst capacity for... more Please cite this article in press as: Lumsdaine W, et al. Neutrophil oxidative burst capacity for peri-operative immune monitoring in trauma patients. Injury (2014),
Post injury immune dysfunction can result in serious complications. Measurement of biomarkers may... more Post injury immune dysfunction can result in serious complications. Measurement of biomarkers may guide the optimal timing of surgery in clinically borderline patients and therefore prevent complications. peri-operative measurement of neutrophil oxidative burst capacity as an indicator of the immune response to major orthopaedic surgical procedures. Prospective cohort study of trauma patients aged ≥16 yrs with pelvic, acetabular, femoral shaft or tibial shaft fractures requiring surgical intervention. Blood samples were taken immediately pre-op and at 30 min, 7, 24 and 72-9 6 h post-operatively. Neutrophil oxidative burst capacity was measured both with and without stimulation by formyl-methionyl-leucyl-phenylalanine (fMLP, a chemotactic factor). Clinical outcomes measured were mortality, length of stay, MOF, pneumonia, acute respiratory distress syndrome (ARDS) and sepsis. 100 consecutive orthopaedic trauma patients were enrolled over a 16 month period. 78% were male, with a mean a...
We present a case of refractory pneumonia in an adult patient with underlying chronic granulomato... more 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.
Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiolo... more Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiology of this condition has value for clinical management, detecting novel and emerging pathogens, and guiding timely public health interventions. When this study was conducted there was no standardized diagnostic algorithm to aid identification of encephalitis or systematic surveillance for adult encephalitis. In July 2012 we tested three pragmatic surveillance options aimed at identifying possible adult encephalitis cases admitted to a major Australian hospital: hospital admissions searches, clinician notifications and laboratory test alerts (CSF herpes simplex virus requests). Eligible cases underwent structured laboratory investigation and a specialist panel arbitrated on the final diagnosis. One hundred and thirteen patients were initially recruited into the 10-month study; 20/113 (18%) met the study case definition, seven were diagnosed with infectious or immune-mediated encephalitis ...
This study investigated whether inflammation may explain the relationship between depression and ... more 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...
Depression and inflammatory markers have a reliable cross-sectional association although less is ... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;residual score&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, 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.
Cross-sectional studies support an association between depression and inflammatory markers. Howev... more Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression. A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change. Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=-0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=-0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=-0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities. The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.
We present a case of an unsensitized patient with end-stage kidney disease secondary to atypical ... more We present a case of an unsensitized patient with end-stage kidney disease secondary to atypical haemolytic uremic syndrome (aHUS) with mutations in CD46/MCP and CFH who developed severe, intractable antibody-mediated rejection (ABMR) unresponsive to therapy post kidney transplantation. There were no haematological features of thrombotic microangiopathy. The patient received standard induction therapy and after an initial fall in serum creatinine, severe ABMR developed in the setting of urosepsis. Despite maximal therapy with thymoglobulin, plasma exchange and methylprednisolone, rapid graft loss resulted and transplant nephrectomy was performed. Luminex at 4 weeks showed a new DSA and when repeated after nephrectomy showed antibodies to each of the 5 mismatched antigens with high MFI. The rate of recurrence of disease in patients with aHUS referred for transplantation is 50% and is associated with a high rate of graft loss. It is dependent in part on the nature of the mutation with circulating factors CFH and CFI more likely to cause recurrent disease than MCP which is highly expressed in the kidney. There is increasing interest in the role of complement in the development and propagation of ABMR via terminal complement activation. This case suggesting that dysregulation of the alternative complement pathway within the transplant kidney may have contributed to the severe AMR. Very little is known about the impact of complement dysregulation and the development of anti HLA antibodies however the strength of HLA antibody formation was prominent in this case.
Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal b... more 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 Lechner-Scott et al.
The adverse effect of haemorrhagic complications after percutaneous coronary intervention (PCI) o... more The adverse effect of haemorrhagic complications after percutaneous coronary intervention (PCI) on outcome is well established with Helicobacter pylori infection known to be an important precipitant of peptic ulcer disease in patients receiving non-steroidal anti-inflammatory drug therapy. The prevalence of H. pylori positivity in patients undergoing PCI and receiving subsequent antiplatelet therapy is unknown. We sought to determine the prevalence and features associated with H. pylori positivity in patients undergoing PCI. All patients undergoing PCI between August 2008 and April 2009 were identified and assessed for H. pylori positivity with serological status determined by using a commercially supplied enzyme-linked immunosorbent assay. A total of 245 patients undergoing PCI during the study period had samples obtained for H. pylori serology. Of these, 91 were positive for H. pylori serology (37%) and 148 were negative (60%) with six samples being equivocal (3%). Of those patients positive for H. pylori, 75% were on agents at admission known to promote or precipitate gastrointestinal haemorrhage. Patients positive for H. pylori tended to be older, with increased creatinine and more likely to be receiving proton pump inhibitor therapy. In an unselected cohort of patients undergoing PCI in a single centre, we detected a prevalence of H. pylori positivity in 37% of patients; this denotes a potentially treatable precipitant of haemorrhage in a considerable portion of patients receiving dual antiplatelet therapy after PCI. Further prospective study is required to determine if the presence of H. pylori positivity is associated with adverse events in terms of gastrointestinal and cardiac outcomes.
Background: Flow cytometric analysis of the TCR-Vb repertoire can help to determine T cell clonal... more Background: Flow cytometric analysis of the TCR-Vb repertoire can help to determine T cell clonality. The most useful application is in the early diagnosis of T cell neoplasms. Methods: All TCR Vb assays performed between 2010-2019 at John Hunter Hospital Laboratory were included. 24 Vb families were tested, gated on CD4 or CD8 cells. Results: 37 Vb assays were performed on 36 patients. 35 tests were performed on blood, with 2 on tissue. 3 cases were paediatric. The distribution of results were: 20 monoclonal, 5 suspected and 12 polyclonal. The final clinical diagnoses will be presented. Discussion: In the monoclonal and suspicious groups, abnormalities in Vb4, Vb14 and Vb17 were most frequently found. If screening using only these specificities, a total percentage of <3% or >58% was suspicious of clonality and should prompt full TCR-Vb testing. Based on the samples audited, this screening method has a sensitivity of 96% and specificity of 91%. Conclusion: TCR-Vb analysis by flow cytometry is a rapid quantitative method to determine T cell clonality. We propose the use of a screening method using 3 Vb antibodies in one tube, with further characterisation if warranted. Further studies are needed.
Background Electrophoretic methods to detect, characterize and quantify M-proteins play an import... more 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 (immunofi...
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential... more 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. Whilst 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 hours 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 haemolyt...
Please cite this article in press as: Lumsdaine W, et al. Neutrophil oxidative burst capacity for... more Please cite this article in press as: Lumsdaine W, et al. Neutrophil oxidative burst capacity for peri-operative immune monitoring in trauma patients. Injury (2014),
Post injury immune dysfunction can result in serious complications. Measurement of biomarkers may... more Post injury immune dysfunction can result in serious complications. Measurement of biomarkers may guide the optimal timing of surgery in clinically borderline patients and therefore prevent complications. peri-operative measurement of neutrophil oxidative burst capacity as an indicator of the immune response to major orthopaedic surgical procedures. Prospective cohort study of trauma patients aged ≥16 yrs with pelvic, acetabular, femoral shaft or tibial shaft fractures requiring surgical intervention. Blood samples were taken immediately pre-op and at 30 min, 7, 24 and 72-9 6 h post-operatively. Neutrophil oxidative burst capacity was measured both with and without stimulation by formyl-methionyl-leucyl-phenylalanine (fMLP, a chemotactic factor). Clinical outcomes measured were mortality, length of stay, MOF, pneumonia, acute respiratory distress syndrome (ARDS) and sepsis. 100 consecutive orthopaedic trauma patients were enrolled over a 16 month period. 78% were male, with a mean a...
We present a case of refractory pneumonia in an adult patient with underlying chronic granulomato... more 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.
Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiolo... more Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiology of this condition has value for clinical management, detecting novel and emerging pathogens, and guiding timely public health interventions. When this study was conducted there was no standardized diagnostic algorithm to aid identification of encephalitis or systematic surveillance for adult encephalitis. In July 2012 we tested three pragmatic surveillance options aimed at identifying possible adult encephalitis cases admitted to a major Australian hospital: hospital admissions searches, clinician notifications and laboratory test alerts (CSF herpes simplex virus requests). Eligible cases underwent structured laboratory investigation and a specialist panel arbitrated on the final diagnosis. One hundred and thirteen patients were initially recruited into the 10-month study; 20/113 (18%) met the study case definition, seven were diagnosed with infectious or immune-mediated encephalitis ...
This study investigated whether inflammation may explain the relationship between depression and ... more 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...
Depression and inflammatory markers have a reliable cross-sectional association although less is ... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;residual score&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, 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.
Cross-sectional studies support an association between depression and inflammatory markers. Howev... more Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression. A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change. Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=-0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=-0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=-0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities. The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.
We present a case of an unsensitized patient with end-stage kidney disease secondary to atypical ... more We present a case of an unsensitized patient with end-stage kidney disease secondary to atypical haemolytic uremic syndrome (aHUS) with mutations in CD46/MCP and CFH who developed severe, intractable antibody-mediated rejection (ABMR) unresponsive to therapy post kidney transplantation. There were no haematological features of thrombotic microangiopathy. The patient received standard induction therapy and after an initial fall in serum creatinine, severe ABMR developed in the setting of urosepsis. Despite maximal therapy with thymoglobulin, plasma exchange and methylprednisolone, rapid graft loss resulted and transplant nephrectomy was performed. Luminex at 4 weeks showed a new DSA and when repeated after nephrectomy showed antibodies to each of the 5 mismatched antigens with high MFI. The rate of recurrence of disease in patients with aHUS referred for transplantation is 50% and is associated with a high rate of graft loss. It is dependent in part on the nature of the mutation with circulating factors CFH and CFI more likely to cause recurrent disease than MCP which is highly expressed in the kidney. There is increasing interest in the role of complement in the development and propagation of ABMR via terminal complement activation. This case suggesting that dysregulation of the alternative complement pathway within the transplant kidney may have contributed to the severe AMR. Very little is known about the impact of complement dysregulation and the development of anti HLA antibodies however the strength of HLA antibody formation was prominent in this case.
Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal b... more 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 Lechner-Scott et al.
The adverse effect of haemorrhagic complications after percutaneous coronary intervention (PCI) o... more The adverse effect of haemorrhagic complications after percutaneous coronary intervention (PCI) on outcome is well established with Helicobacter pylori infection known to be an important precipitant of peptic ulcer disease in patients receiving non-steroidal anti-inflammatory drug therapy. The prevalence of H. pylori positivity in patients undergoing PCI and receiving subsequent antiplatelet therapy is unknown. We sought to determine the prevalence and features associated with H. pylori positivity in patients undergoing PCI. All patients undergoing PCI between August 2008 and April 2009 were identified and assessed for H. pylori positivity with serological status determined by using a commercially supplied enzyme-linked immunosorbent assay. A total of 245 patients undergoing PCI during the study period had samples obtained for H. pylori serology. Of these, 91 were positive for H. pylori serology (37%) and 148 were negative (60%) with six samples being equivocal (3%). Of those patients positive for H. pylori, 75% were on agents at admission known to promote or precipitate gastrointestinal haemorrhage. Patients positive for H. pylori tended to be older, with increased creatinine and more likely to be receiving proton pump inhibitor therapy. In an unselected cohort of patients undergoing PCI in a single centre, we detected a prevalence of H. pylori positivity in 37% of patients; this denotes a potentially treatable precipitant of haemorrhage in a considerable portion of patients receiving dual antiplatelet therapy after PCI. Further prospective study is required to determine if the presence of H. pylori positivity is associated with adverse events in terms of gastrointestinal and cardiac outcomes.
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