Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of... Show moreIntroduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome. Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting. Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795. Show less
Jeyaratnam, J.; Faraci, M.; Gennery, A.R.; Drabko, K.; Algeri, M.; Morimoto, A.; ... ; EBMT Inborn Errors Working Party 2022
Objectives Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome. Several reports have described allogeneic hematopoietic stem cell transplantation in severely affected patients,... Show moreObjectives Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome. Several reports have described allogeneic hematopoietic stem cell transplantation in severely affected patients, sometimes with promising results. In view of the scarcity of data, this study aims to analyse the efficacy and safety of allogeneic hematopoietic stem cell transplantation (HSCT) to give a more complete overview of this treatment. Methods This multicentre retrospective study on behalf of the European Society for Blood and Marrow Transplantation aimed to include all MKD patients who had undergone allogeneic HSCT. All centres related to EMBT and centres that have reported cases of allogeneic HSCT in the literature were contacted via the EBMT data office. Results We analyzed 9 patients (5 male). Treosulfan based conditioning was the most frequently used conditioning regimen. Engraftment occurred in all but one patient. Source of stem cells was cord blood (n = 2), peripheral blood stem cells (n = 4) and bone marrow (n = 5). Two patients needed a second transplantation due to an incomplete response or primary graft failure. Seven patients went into complete remission after stem cell transplantation. At final follow-up these patients reported no symptoms of MKD. Four patients suffered from grade II-IV acute graft-versus-host disease (GvHD). During follow-up two patients died due to transplantation related complications. Conclusion In conclusion, allogeneic stem cell transplantation represents an effective treatment for the most severely affected MKD patients. However, treatment-related morbidity and mortality are significant. Transplantation may be justified in patients with a severe disease course on conservative therapy. Show less
Duarte, R.F.; Labopin, M.; Bader, P.; Basak, G.W.; Bonini, C.; Chabannon, C.; ... ; European Soc Blood Marrow Transpla 2019
It is increasingly recognized that Alzheimer’s disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of... Show moreIt is increasingly recognized that Alzheimer’s disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β1−42 (Aβ1−42) may be an earlier indicator of Alzheimer’s disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual’s CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ1−42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, Aβ1−42, Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ1−42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF Aβ1−42 levels and that the resulting model also validates reasonably across PET Aβ1−42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF Aβ1−42 status, the earliest risk indicator for AD, with high accuracy. Show less
Machowcz, R.; Suarez, F.; Wiktor-Jedrzejczak, W.; Eikema, D.J.; Wreede, L. de; Blok, H.J.; ... ; Kroger, N. 2017
X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are... Show moreX-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression. (Blood. 2011;117(1):53-62) Show less
