ObjectiveA hallmark of chronic HBV (cHBV) infection is the presence of impaired HBV-specific CD8+ T cell responses. Functional T cell exhaustion induced by persistent antigen stimulation is considered a major mechanism underlying this impairment. However, due to their low frequencies in chronic infection, it is currently unknown whether HBV-specific CD8+ T cells targeting different epitopes are similarly impaired and share molecular profiles indicative of T cell exhaustion.DesignBy applying peptide-loaded MHC I tetramer-based enrichment, we could detect HBV-specific CD8+ T cells targeting epitopes in the HBV core and the polymerase proteins in the majority of 85 tested cHBV patients with low viral loads. Lower detection rates were obtained for envelope-specific CD8+ T cells. Subsequently, we performed phenotypic and functional in-depth analyses.ResultsHBV-specific CD8+ T cells are not terminally exhausted but rather exhibit a memory-like phenotype in patients with low viral load possibly reflecting weak ongoing cognate antigen recognition. Moreover, HBV-specific CD8+ T cells targeting core versus polymerase epitopes significantly differed in frequency, phenotype and function. In particular, in comparison with core-specific CD8+ T cells, a higher frequency of polymerase-specific CD8+ T cells expressed CD38, KLRG1 and Eomes accompanied by low T-bet expression and downregulated CD127 indicative of a more severe T cell exhaustion. In addition, polymerase-specific CD8+ T cells exhibited a reduced expansion capacity that was linked to a dysbalanced TCF1/BCL2 expression.ConclusionsOverall, the molecular mechanisms underlying impaired T cell responses differ with respect to the targeted HBV antigens. These results have potential implications for immunotherapeutic approaches in HBV cure.
BackgroundCOPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality. Only 10%–25% of COPD exacerbations are eosinophilic.AimTo assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU.MethodsThis retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014. Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included. Data were collected electronically from the hospital database. Subjects’ characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded. COPD subjects were grouped according to eosinophil levels (>2% or ≤2%) (group 1, eosinophilic; group 2, non-eosinophilic). These groups were compared with the recorded data.ResultsOver the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2). Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU. Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (2–7 days) vs 6 days (3–9 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively.ConclusionCOPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%. NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management.
AIMS:Extrapulmonary tuberculosis (EPTB) still constitutes an important clinical problem. We aimed to evaluate the incidence and features of extrapulmonary tuberculosis.MATERIALS AND METHODS:We retrospectively evaluated 14,266 tuberculosis patients diagnosed between January 1999 and December 2003 in a tertiary care hospital in Istanbul. As many as 2,435 patients (17.1%) with EPTB were evaluated for the incidence and features.RESULTS:Of the 14,266 patients, 4,154 were female (29%) and 10,112 were male (71%) and were aged between 14 and 86 years with a mean age of 35 ± 14 years. As many as 660 (17.9%) patients were diagnosed as EPTB in 1999, 568 (17.8%) in 2000, 357 (13.7%) in 2001, 462 (22%) in 2002 and 388 (14.5%) in 2003. EPTB presented most commonly as pleurisy (66%), followed by lymphadenitis (23%). Lymphadenitis and pleurisy were more commonly observed among female TB patients (60%) and among male TB patients (59%) respectively. EPTB showed a significant female predilection (26.8%) compared to male patients (13.1%). Multi-organ involvement was observed in 37 (1.5%) patients (two organs in 33 and three organs in 4). As many as 197 (8%) EPTB cases had pulmonary tuberculosis simultaneously.CONCLUSIONS:EPTB still constitutes an important clinical problem. The rates of EPTB have remained constant despite the decline in pulmonary tuberculosis cases. In the current study, we present our experience of the incidence and features of EPTB patients without HIV infection. In this study, EPTB cases constituted one-fifth of all tuberculosis cases presented to our center in the study period.
Background: Elevated red blood cell distribution width (RDW) levels were associated with mortality in patients with stable chronic obstructive lung pulmonary diseases (COPD). There are limited data about RDW levels in acute exacerbation of COPD (AECOPD).Aim/Objective: The association of the RDW levels with the severity of AECOPD was evaluated according to admission location, (outpatient-clinic, ward and intensive care unit (ICU)).Methods: Cross sectional retrospective study was designed in tertiary care hospital for chest diseases in 2015. Previously COPD diagnosed patients admitted to hospital outpatient-clinic, ward and ICU due to AECOPD were included in the study. Patients demographics, RDW, biomarkers (CRP, RDW, Neutrophil to lymphocyte ratio (NLR), platelet to mean platelet volume (PLT-MPV)) C-CRP, biochemistry values were recorded from hospital electronic system. RDW values were subdivided below 0.11% (low), above and equal 0.15% (high) and between 0.11%-0.15% (normal). Neutrophil to lymphocyte ratio (NLR) and platelet to mean platelet volume (PLT-MPV) were also calculated. Biomarker values were compared according to where AECOPD was treated.Results: 2771 COPD patients (33% female) and 1429 outpatients-clinic, 1156 ward and 186 ICU were enrolled in the study. The median RDW values in outpatientsclinic, ward and ICU were 0.
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