Laboratory validation and field usability assessment of a point-of-care test for serum bilirubin levels in neonates in a tropical setting [version 1; referees: 2 approved]

Background: Screening and monitoring serum bilirubin (SBR) in neonates is crucial to prevent neonatal hyperbilirubinemia (NH)-associated morbidity and mortality worldwide. A lack of resources is often a barrier for measuring SBR in developing countries. Reliable, cost-effective, easy to use point-of-care (POC) SBR tests are needed. This study aimed to evaluate the technical accuracy and usability of the Bilistick System (BS), a new bilirubin POC test, in a tropical setting. Methods: This was a mixed-methods study, including laboratory validation of the BS, direct observation of technical procedures as performed by the midwives and midwives’ assessment of the device’s easiness of use through focus group discussions (FGD) and a self-administered questionnaire. The study was conducted in a field clinic of the Shoklo Malaria Research Unit along the Thailand-Myanmar border between January and December 2017. Results: A total of 173 samples were tested at a median age of 4 days. BS generated an error message—providing no SBR readout—in 48.6% of the tests performed. For the tests that yielded a result, the correlation coefficient (95% CI) between BS and routine laboratory bilirubinometer SBR was 0.87 (0.77-0.93). The accuracy decreased with increasing haematocrit and at higher humidity (≥75%). Direct observation of the operators using the device and analysis of the focus group discussions and questionnaires indicated that the BS was considered easy to use and required limited training. Conclusions: This evaluation showed that the BS, in its current formulation, does not provide reliable results for measuring SBR in a tropical, low-resource setting  but has acceptable usability features

Consensus recommendations on the use of 18F-FDG PET/CT in lung disease

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and monitor disease progression and treatment outcomes in lung diseases, disorders that interfere with gas exchange through alterations of the pulmonary parenchyma, airways and/or vasculature. To date, however, there are no widely accepted standard acquisition protocols and imaging data analysis methods for pulmonary 18F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging. To help harmonize the acquisition and analysis and promote reproducibility, acquisition protocol and analysis method details were collated from seven PET centers. Based on this information and discussions among the authors, the consensus recommendations reported here on patient preparation, choice of dynamic versus static imaging, image reconstruction, and image analysis reporting were reached.                   </p

Neonatal hyperbilirubinemia in a low resource setting

This thesis is divided in 3 parts. Neonatal jaundice and NH are defined and physiology and physiopathology described in Part 1. Chapter 1 presents the main causes of neonatal jaundice and NH, in particular G6PD deficiency; the consequences of severe NH and its resulting burden. In Chapter 2 the Shoklo Malaria Research Unit (SMRU) is portrayed including details on the Special Care Baby Unit (SCBU), the unit dedicated to unwell neonates. An overview of the population seeking care at SMRU is presented.The rationale of the studies presented in this thesis introduces Part 2. Then the burden of the disease on the Thai-Myanmar border is explored in two retrospective analysis: Chapter 3 describes the prevalence of NH and factors associated with severity among neonates admitted in the SCBU between 2009 and 2014 1 and Chapter 4 describes the immediate and long term consequences of extreme NH in the same setting where exchange transfusion is not available. Findings from those two studies led to the development of a protocol to further detail the epidemiology of NH using a prospective birth cohort design presented in Chapter 52. In Chapter 6, timing of NH occurrence and risk factors associated with NH in the first week of life and by gestational age categories are explored. Factors influencing the SBR response to phototherapy (PT) and the risk of recurrence after initially successful PT are explained in Chapter 7. Chapters 8 & 9 focus on a new POC tool for SBR measurements and on the challenges to diagnose G6PD-deficiency with a fluorescent spot test in newborns 3,4. In Part 3, the challenges encountered by the health staff while managing neonates with NH are presented and solutions suggested in Chapter 10. In Chapter 11, the barriers to care for NH in a low resource setting are discussed and recommendations proposed. The main results that have emerged from this thesis, as well as their strengths and limitations are summarized in Chapter 12 and recommendations for future work proposed.Doctorat en Sciences médicales (Médecine)info:eu-repo/semantics/nonPublishe

Interleukin-12-activated natural killer cells recognize B7 costimulatory molecules on tumor cells and autologous dendritic cells.

Activation of natural killer (NK) cells in the presence of interleukin-12 (IL-12) augments the capacity of these effector cells to recognize B7-1- and B7-2-expressing target cells. These effector cells also efficiently lyse autologous B7-positive progenitor or organ-derived dendritic cells, suggesting a physiologic regulatory pathway between IL-12, NK cells, and B7-expressing antigen-presenting cells. Although IL-12-activated NK cells secreted higher levels of interferon-gamma, this cytokine did not play a role in synergistic effects of IL-12 and B7 on NK activation. The B7-counterreceptor was found to be selectively upregulated on IL-2/IL-12 as compared with IL-2-activated NK cells. CD28 is functionally involved in the recognition of B7 on target cells since IL-2/IL-12-activated NK cells derived from CD28 knockout mice were strongly reduced in their capacity to lyse syngeneic B7-positive tumor cells as well as antigen-presenting cells. However, recognition of B7 on allogeneic targets did not require the expression of CD28 on the IL-2/IL-12-activated NK cells. Hence, IL-12 triggers the expression of both CD28-dependent and CD28-independent mechanisms that allow NK cells to eliminate B7-positive target cells including autologous dendritic cells.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Enhancement of a Spontaneous Immune Response against a B-Cell Lymphoma by Dendritic Cells Leads to Protection against the Tumor

Journal ArticleFLWNAinfo:eu-repo/semantics/publishedSpecific Immunotherapy of Cancer with Vaccine

Enhancement of a spontaneous immune response against a B-cell lymphoma by dendritic cells leads to protection against the tumor

Journal ArticleFLWNAinfo:eu-repo/semantics/publishedSpecific Immunotherapy of Cancer with Vaccine

Laboratory validation and field usability assessment of a point-of-care test for serum bilirubin levels in neonates in a tropical setting [version 2; referees: 2 approved, 1 approved with reservations]

Background: Screening and monitoring serum bilirubin (SBR) in neonates is crucial to prevent neonatal hyperbilirubinemia (NH)-associated morbidity and mortality worldwide. A lack of resources is often a barrier for measuring SBR in developing countries. Reliable, cost-effective, easy to use point-of-care (POC) SBR tests are needed. This study aimed to evaluate the technical accuracy and usability of the Bilistick System (BS), a new bilirubin POC test, in a tropical setting. Methods: This was a mixed-methods study, including laboratory validation of the BS, direct observation of technical procedures as performed by the midwives and midwives’ assessment of the device’s easiness of use through focus group discussions (FGD) and a self-administered questionnaire. The study was conducted in a field clinic of the Shoklo Malaria Research Unit along the Thailand-Myanmar border between January and December 2017. Results: A total of 173 samples were tested at a median age of 4 days. BS generated an error message—providing no SBR readout—in 48.6% of the tests performed. For the tests that yielded a result, the correlation coefficient (95% CI) between BS and routine laboratory bilirubinometer SBR was 0.87 (0.77-0.93). The accuracy decreased with increasing haematocrit and at higher humidity (≥75%). Direct observation of the operators using the device and analysis of the focus group discussions and questionnaires indicated that the BS was considered easy to use and required limited training. Conclusions: This evaluation showed that the BS, in its current formulation, does not provide reliable results for measuring SBR in a tropical, low-resource setting  but has acceptable usability features

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study [version 1; referees: 2 approved]

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated