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.     

Novel KIR genotypes and gene copy number variations in northeastern Thais

KIR (Killer Immunoglobulin‐like Receptor) variants influence immune responses and are genetic factors in disease susceptibility. Using sequence‐specific priming PCR, we have previously described the diversity of KIR genes in term of presence/absence in northeastern Thais (NETs). To provide additional resolution beyond conventional methods, quantitative PCR was applied to determine KIR copy number profiles. Novel expanded and contracted KIR copy number profiles were identified at cumulatively high frequencies. These all comprise haplotypes with duplication (6·9%) or deletion (2·7%) of KIR3DL1/S1 along with adjacent genes. Five expanded KIR profiles comprised haplotypes with duplications of KIR2DP1, 2DL1, 3DP1, 2DL4, 3DL1/S1 and 2DS1/4, whereas two contracted profiles contained only a single copy of KIR3DP1, 3DL1/S1 and 2DL4. Using a KIR haplotype prediction program (KIR Haplotype Identifier), 14% of NET haplotypes carried atypical haplotypes based on the gene copy number data.     

Sclerotic osseous metastases from renal cell carcinoma

This case series describes and illustrates three cases of sclerotic osseous metastases from untreated renal cell carcinoma (RCC). RCC is commonly metastatic to the skeleton but almost always produces lytic metastases, with only three prior reports of sclerotic metastases identified in the literature. Sclerotic metastasis causing low back pain was the initial disease presentation in two of the three patients in this case series and the first manifestation of metastatic disease in one. The most common metastatic sites of RCC, i.e., retroperitoneal lymph nodes, lung, and liver, were not identified in any of the cases, and skeletal involvement with epidural extension was the only site of metastasis in two. Pathologic specimens from all three cases revealed RCC of high nuclear grade.     

Uterine sarcomas: then and now

OBJECTIVE: The purpose of this article is to provide an updated review of uterine sarcomas. The traditionally described neoplasms are reviewed as well as several recently characterized entities in terms of their imaging and clinical aspects. We attempt to provide a longitudinal imaging overview, from initial presentation to follow-up. Imaging features are also described of response to traditional therapeutic agents and newer targeted agents. CONCLUSION: A greater understanding of the pathogenesis has improved our ability to image and treat uterine sarcomas, both at initial staging and on follow-up. Targeted therapy is assuming an increasingly important role in the management of these lesions. It is imperative for radiologists to be aware of response characteristics and potential complications of these agents as well as conventional chemotherapeutic agents.     

Impact of oral potentially malignant disorders on quality of life

Background

Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients.

Methods

Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF‐12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF‐12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS).

Results

A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, “physical impairment and functional limitations” than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased.

Conclusions

OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.