Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

Caring for the Digital Generation: Understanding Electronic Aggression

We live in a technology-saturated world, evidenced by widespread, global use of the Internet and other forms of technology. Technology offers nearly limitless connectivity, information-sharing, and communication. Unfortunately, with these opportunities come risks, especially for children, and pediatric healthcare providers have a responsibility to be aware and informed of these risks and how to respond. This article provides a breakdown of the broad phenomenon of electronic aggression and offers practice implications for healthcare providers.     

Psychologische Aspekte des diabetischen Fußsyndroms

It is often difficult for medical professionals to understand the behaviour of people with diabetic foot syndrome. We describe the different psychological factors that play a role in the maintenance of intermittent implementation of medical recommendations. In particular we look at the consequences of neuropathy and of the recommendation to offload pressure, as well as the contradictions between the realities of the patient and the medical professionals involved in their care. We show that the solutions that patients develop are based on normal psychological processes and we encourage professionals to consider these aspects in their relationship to people with DFS and when developing individualised preventative measures.     

Intra-urban variations of neonatal and post-neonatal mortality in a developing city

Numerous surveys at the national and regional level have demonstrated that large inequalities in infant health status exist in Southern Africa. Few studies have assessed infant mortality at the intra-urban scale of geographic analysis. Comparisons between infant mortality rates from different areas are made even more meaningful if the data are divided into two primary categories based on period-of-death; these being the neonatal and post-neonatal components. This study presents the results of a survey undertaken in Metropolitan Cape Town (population 1.6 million) during 1982. The aim was to determine the spatial variation of neonatal and post-neonatal mortality at the suburb (or community) level within the city. Overall, a total of 36,789 live births and 928 infant deaths were recorded; 53.4% in the neonatal period and 46.6% in the post-neonatal period. The mean infant mortality rate was 25.2 per 1000 live births; the neonatal mortality rate and post-neonatal mortality rate being 13.5/1000 and 11.7/1000, respectively. A marked range in death rates was evident for both components. For the neonatal category it was 0.0-49.9/1000 and 0.0-40.0/1000 for the post-neonatal period. The generally low post-neonatal mortality rate among the 69 suburbs studied has made the neonatal component the dominant contributor to the infant mortality rate. However, in the lowest socio-economic areas the post-neonatal mortality rate was responsible for over 60% of infant deaths.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of a random single Doppler study of the umbilical artery for predicting perinatal outcome

A prospective blinded study was performed on 191 high-risk patients with pregnancies ranging from 25 to 42 weeks gestation to investigate the value of a single Doppler analysis of the umbilical artery blood flow waveform (systolic-to-diastolic ratio, S/D) for predicting poor perinatal outcome. This was defined as the presence of heavy meconium, delivery of a growth-retarded infant, an umbilical cord arterial pH less than 7.2, or a 5-minute Apgar score less than 7. The interval between Doppler examination and delivery ranged from 12 hours to 15 weeks. No clinical data were available to the examiner performing the Doppler study. Moreover, the Doppler measurements were unknown to the attending physicians. The sensitivity, specificity, and positive and negative predictive values of the Doppler study in predicting outcome were 30.4%, 92.9%, 36.8%, and 92.6%, respectively, with an adverse outcome prevalence of 12%. These results indicate that a single random S/D ratio from the umbilical artery is not an adequate screening test for the risk of perinatal complications.