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.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Tubercular pseudoaneurysm of aorta: a rare association with vertebral tuberculosis.

BACKGROUND CONTEXT: Pseudoaneurysm of the aorta in association with vertebral tuberculosis is a rare phenomenon. With the resurgence of human immunodeficiency virus (HIV) and associated resistant tuberculosis, this life-threatening complication requires greater awareness. PURPOSE: Our purpose is to report the rare presentation and successful management of tubercular pseudoaneurysm of the aorta in association with vertebral tuberculosis, and to highlight the clinicoradiological features for early and prompt diagnosis of this potentially fatal, but treatable, disease. STUDY DESIGN: A single case report and overview of the disease comprises the design of this study. PATIENT SAMPLE: The patient, already surgically intervened, is a 27-year-old male with increasing abdominal and back pain, upper motor neuron signs, and constitutional signs and symptoms. OUTCOME MEASURES: At 33 months follow-up, there is complete resolution of the signs and symptoms, and the patient is back to his previous vocation. METHODS: The diagnosis was confirmed by magnetic resonance imaging and contrast computed tomography. Endoaneurysmorrhaphy of the pseudoaneurysm along with a complete course of antitubercular treatment was given to the patient, and he has presently been followed up for 33 months. RESULTS: The patient's signs and symptoms have been completely resolved without any recurrence. CONCLUSION: Despite the use of modern chemotherapy and imaging techniques, this disastrous complication still occurs and reinforces the need for early suspicion, diagnosis, surgical resection, and antitubercular therapy along with close postoperative follow-up to prevent recurrence. With the resurgence of HIV (and other immunocompromised states) associated and resistant tuberculosis, we should be more alert than ever to this life-threatening complication.     

Mebendazole retention enema for severe Trichuris trichiura (whipworm) infection: a case report

The authors report a case of massive Trichuris trichiura infection, resulting in severe anaemia and congestive cardiac failure in a 9-year-old Iban boy, who was resistant to the usual oral anthelmintic treatment, but promptly responded to mebendazole retention enema. This patient also had an associated Entamoeba histolytica infection.