Tuberculosis (TB) epidemiology is changing in Western and Central Europe due to the rise in immigration and refugees fleeing high-TB-burden areas of war and devastation. The change in local demography and the lack of sensitive and specific TB diagnostic and monitoring tools, especially for cases of childhood TB, leads to either missed cases or over-treatment of this group. Here we present a promising new diagnostic approach, the T cell activation marker (TAM)-TB assay, and its performance in a case of extra-pulmonary TB occurring in a 16 year old refugee from Afghanistan. This assay is based on the characterization of 3 activation markers (CD38, HLA-DR, and Ki67) and one maturation marker (CD27) on M. tuberculosis-specific CD4 T cells. It was performed at time-points T0 (10 days), T1 (1 month), T2 (6 months), and T3 (12 months) post-treatment initiation. All markers were able to detect active tuberculosis (aTB) within this patient at T0 and reverted to a healthy/LTBI phenotype at the end of treatment. Tantalizingly, there was a clear trend toward the healthy/LTBI phenotype for the markers at T1 and T2, indicating a potential role in monitoring anti-TB treatment in the future. This assay may therefore contribute to improved TB diagnostic algorithms and TB treatment monitoring, potentially allowing for individualization of TB treatment duration in the future.
Context Several studies have highlighted the importance of the 11oxygenated 19carbon (11oxC19) adrenalderived steroids as potential biomarkers for monitoring patients with 21hydroxylase deficiency (21OHD). Objective To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD. Design, Setting, and Participants Cross-sectional single center study including 59 patients with classic 21OHD (men=30; women=29) and 49 BMI- and agematched controls (men=19; women=30). Outcome Measures Salivary concentrations of the following steroids were analyzed by LCMS/MS: 17hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11βhydroxyandrostenedione (11OHA4) and 11ketotestosterone (11KT). Results Similar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: mean reduction of hormone concentrations between timepoint one and five (Δmean) in male patients = 66 %; male controls Δmean = 83 %; female patients Δmean = 47 %; female controls Δmean = 86 %; 11KT: male patients Δmean = 57 %; male controls Δmean = 63 %; female patients Δmean = 50 %; female controls Δmean = 76 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r pmale = 0.773 <0.0001; r pfemale = 0.737 <0.0001), and 11OHA4 (r pmale = 0.633 0.0002; r pfemale = 0.564 0.0014) were observed in patients but not present or reduced in controls. Conclusions Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.
Objectives Children with salt-wasting congenital adrenal hyperplasia (CAH) have an impaired function of steroid synthesis pathways. They require therapy with glucocorticoid (GC) and mineralocorticoid hormones to avoid salt-wasting crisis and other complications. Most commonly, children receive hydrocortisone thrice daily with the highest dose in the morning, mimicking the regular physiology. However, reverse circadian treatment (RCT) had been suggested previously. In this study, we aimed to determine the efficacy of RCT in prepubertal children with CAH by comparing the salivary 17-hydroxyprogesterone (s17-OHP) levels individually. Methods In this retrospective study, we analyzed the records of children with classical CAH and RCT who were monitored by s17-OHP levels. The study included 23 patients. We identified nine prepubertal children with RCT schemes (three boys and six girls) and compared the s17-OHP levels in the morning, afternoon, and evening. The objective of this study was to demonstrate the non-effectiveness of RCT in terms of lowering the morning s17-OHP concentration. In addition, we compared s17-OHP day profiles in six patients on RCT and non-RCT therapy (intraindividually). Results Eight of nine children with RCT showed higher s17-OHP levels in the morning compared to the evening. In addition, none of the children showed a significant deviation of development. Three children were overweight. No adrenal crisis or pubertal development occurred. Comparison of RCT and non-RCT regimens showed no difference in 17-OHP profiles. Conclusions Our data do not support the use of RCT schemes for GC replacement in children with CAH due to lack of benefits and unknown long-term risks.
Context: Several studies have highlighted the importance of the 11 oxygenated 19 carbon (11oxC19) adrenal derived steroids as potential biomarkers for monitoring patients with 21 hydroxylase deficiency (21OHD). Objective: To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD. Design, Setting, and Participants: Cross-sectional single center study including 34 patients with classic 21OHD (men=14; women=20) and 32 BMI- and age matched controls (men=15; women=17). Outcome Measures: Salivary concentrations of the following steroids were analyzed by LC MS/MS: 17 hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11β hydroxyandrostenedione (11OHA4) and 11 ketotestosterone (11KT). Results: Similar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: male patients Δmean = 79 %; male controls Δmean = 81%; female patients Δmean = 33 %; female controls Δmean = 91 %; 11KT: male patients Δmean = 64 %; male controls Δmean = 60 %; female patients Δmean = 49 %; female controls Δmean = 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p)male = 0.741**; r(p)female = 0.842****), and 11OHA4 (r(p)male = 0.385n.s.; r(p)female = 0.527*) were observed in patients but not in controls. Conclusions: Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.
Idiopathic hyperammonemia (IHA) is a severe condition, which has been reported in intensive chemotherapy and bone marrow transplantation. This case elucidates the diagnostic dilemma in children undergoing initiation of chemotherapy and developing severe disorders of qualitative and quantitative consciousness in the presence of hyperammonemia (HA) and lactic acidosis. The role of mitoxantrone as a causative agent for IHA in children is elusive. Children undergoing chemotherapy are often in a poor general condition, and the clinical presentation of HA is heterogeneous. This case should be a reminder for clinicians to check for HA in children with tumor lysis syndrome and acute neurological deterioration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.