Identification of immune biomarkers in recent active pulmonary tuberculosis.

Tuberculosis (TB) has remained an unsolved problem and a major public health issue, particularly in developing countries. Pakistan is one of the countries with the highest tuberculosis infection rates globally. However, methods or biomarkers to detect early signs of TB infection are limited. Here, we characterized the mRNA profiles of immune responses in unstimulated Peripheral blood mononuclear cells obtained from treatment naïve patients with early signs of active pulmonary tuberculosis without previous history of clinical TB. We identified a unique mRNA profile in active TB compared to uninfected controls, including cytokines such as IL-27, IL-15, IL-2RA, IL-24, and TGFß, transcription factors such as STAT1 and NFATC1 and immune markers/receptors such as TLR4, IRF1, CD80, CD28, and PTGDR2 from an overall 84 different transcripts analyzed. Among 12 significant differentially expressed transcripts, we identified five gene signatures which included three upregulated IL-27, STAT1, TLR4 and two downregulated IL-24 and CD80 that best discriminate between active pulmonary TB and uninfected controls with AUC ranging from 0.9 to 1. Our data identified a molecular immune signature associated with the early stages of active pulmonary tuberculosis and it could be further investigated as a potential biomarker of pulmonary TB.

Expression profile of KIR3DS1/KIR3DL1 receptors in association with immunological responses in TB, HIV and HIV/TB infected patients.

Several studies investigated KIR3DS1 and KIR3DL1 in the context of various infections. However, none of the studies were performed on KIR3DS1/L1 in association with IFN-É£/IL-10 in TB, HIV-1, and their confections. We aimed to evaluate KIR3DS1/KIR3DL1 expression in association with IFNÉ£/IL-10 in HIV-1 and TB mono-infections and HIV-1/TB confection and compared with uninfected controls using RTq PCR. We also performed correlation analysis between KIR3DS1, KIR3DL1, IFN-É£ and IL-10 in the respective cohorts. The overall expression of KIR3DS1 was found to be downregulated in all groups, whereas in HIV-1 and HIV-1/TB, the frequency of KIR3DS1(+) expression was significantly (p < 0.05) associated with undetected HIV-1 viral load. However, expression of KIR3DL1 was found to be significantly (p < 0.05) upregulated in HIV-1 only. In addition, IFNÉ£ expression was significantly (p < 0.05) decreased in TB, whereas in HIV-1/TB, IFNÉ£ expression was significantly (p < 0.05) increased. In contrast, IL-10 expression was significantly (p < 0.05) increased in HIV-1 and HIV-1/TB but not in TB. Also, we found significant positive correlation (p < 0.05, r = 0.61) between KIR3DL1 and IFNÉ£ expression in TB and negative correlation (p < 0.05, r = - 0.62) between KIR3DS1 and IL-10 in HIV-1/TB. In conclusion, we suggest that expression of KIR3DS1/L1 is associated with IFNÉ£/IL-10 responses and it is involved in modulating disease severity in HIV-1 and TB infections.

Macrophage morphology and distribution are strong predictors of prognosis in resected colorectal liver metastases: results from an external retrospective observational study.

INTRODUCTION: Tumor-associated macrophages (TAMs) are key components of a tumoral microenvironment and have been shown to impact prognosis in different cancers. Previously reported data showed that TAM morphology correlates with prognosis in colorectal liver metastases (CLMs) after hepatectomy, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger ones (L-TAMs). This study aims to externally validate this finding. MATERIAL AND METHODS: The external cohort consisted of 84 formalin-fixed and paraffin-embedded surgical samples of CLMs and peritumoral tissue. Two-micrometer-section slides were obtained; the area and perimeter of 21 macrophages in each slide were recorded. The endpoints were TAMs morphometrics and their prognostic significance in relation to disease-free survival (DFS). RESULTS: The average macrophage perimeter was 71.5±14.1 µm whilst the average area was 217.7±67.8 µm 2 . At univariate analysis, the TAM area demonstrated a statistically significant association with DFS ( P =0.0006). Optimal area cutoff value was obtained, showing a sensitivity and specificity of 92 and 56%, respectively. S-TAMs and L-TAMs were associated with 3-year DFS rates of 60 and 8.5%, respectively ( P <0.001). Multivariate analysis confirmed the predictive role of TAM area for DFS [hazard ratio (HR)=5.03; 95% CI=1.70-14.94; P =0.003]. Moreover, in a subset of patients ( n =12) characterized by unfavorable ( n =6, recurrence within 3 months) or favorable ( n =6, no recurrence after 48 months) prognosis, TAMs showed a different distribution: L-TAMs were more abundant and closer to the tumor invasive margin in patients that encountered early recurrence and tended to cluster in foci significantly larger ( P =0.02). CONCLUSIONS: This external validation confirms that morphometric characterization of TAMs can serve as a simple readout of their diversity and allows to reliably stratify patient outcomes and predict disease recurrence after hepatectomy for CLMs.

A Review and Comparison of the Efficacy of Prophylactic Interventional Radiological Arterial Occlusions in Placenta Accreta Spectrum Patients: A Meta-analysis.

RATIONALE AND OBJECTIVES: Placenta accreta spectrum (PAS) disorders are increasingly common and associated with significant maternal and neonatal morbidity and mortality due to the associated risk of massive haemorrhage. Currently prophylactic interventional radiology (IR) arterial occlusion is being performed occluding either the internal iliac artery (IIA), abdominal aorta (AA) or uterine artery (UA) in order to prevent this blood loss. The aim of this meta-analysis is to identify whether these IR procedures are effective in reducing estimated blood loss (EBL) and hysterectomy rates and if so which method achieves the optimal results METHODS: A literature search was conducted to acquire case-control studies assessing EBL and hysterectomies performed following IR arterial occlusion in PAS patients, yielding 16 results. Studies were analyzed together and later split into groups dependent on the artery occluded. The results of these were then inputted into forest plots to identify their overall estimated effect with confidence intervals. RESULTS: Prophylactic IR arterial occlusion was proven to reduce both EBL and hysterectomies. When separated by artery, IIA achieved the worst outcomes with no proven effect on EBL and a minimal reduction in hysterectomies. UA scored in the middle with a modest reduction in both outcomes, whilst AA occlusion had the most significant reduction in both EBL and hysterectomies. CONCLUSION: Prophylactic IR arterial occlusion should be routinely considered in PAS patients to reduce both EBL and rates of hysterectomies. Current literature promotes the use of IIA occlusion; however the findings of this analysis propose that AA and UA occlusion should be favoured.