Tuberculosis disease is associated with elevated plasma ribonuclease activity in antiretroviral treatment-naïve people with HIV.

BACKGROUND: The role of ribonucleases in tuberculosis (TB) among people with HIV (PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without TB. METHODS: Participants were identified from a cohort of treatment-naïve PWH in Ethiopia who had been classified for TB disease (HIV+/TB + or HIV+/TB-). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and qPCR, and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7 and T2 proteins was performed by ELISA. Ribonuclease activity and protein concentrations were correlated with markers of TB and HIV disease severity and with concentrations of inflammatory mediators. RESULTS: Ribonuclease activity was significantly higher in plasma of HIV+/TB + (n = 51) compared to HIV+/TB- (n = 78), causing reduced stability of synthetic spike-in RNAs. concentrations of ribonucleases 2, 3 and T2 were also significantly increased in HIV+/TB + compared to HIV+/TB-. Ribonuclease activity was correlated with HIV viral load, and inversely correlated with CD4 count, mid-upper arm circumference and body mass index. Moreover, ribonuclease activity correlated with concentrations of interleukin-27, kynurenine/tryptophan ratio and procalcitonin. CONCLUSION: PWH with TB disease have elevated plasma ribonuclease activity, which is also associated with HIV severity and systemic inflammation.

Kynurenine/tryptophan ratio for detection of active tuberculosis in adults with HIV prior to antiretroviral therapy.

OBJECTIVE: : The aim of this study was to assess the performance of kynurenine/tryptophan ratio for tuberculosis (TB) case-finding among antiretroviral therapy (ART)-naive people with HIV (PWH), and to investigate other factors associated with kynurenine/tryptophan ratio in this population. DESIGN: : A nested case--control study based on a cohort of 812 ambulatory PWH in the Oromia region, Ethiopia. METHODS: : At enrolment, all participants submitted sputum samples for bacteriological TB investigations. Concentrations of kynurenine and tryptophan in plasma were quantified using liquid chromatography-mass spectrometry. Receiver operator characteristic curves were constructed to assess diagnostic performance (area under the curve; AUC) for kynurenine, tryptophan, and kynurenine/tryptophan ratio. Sensitivity, specificity, and predictive values were calculated. Kynurenine/tryptophan ratios were correlated to plasma levels of nine inflammation mediators, plasma HIV RNA levels, CD4 + cell count, BMI, and mid-upper arm circumference (MUAC). RESULTS: : We included 124 individuals with HIV-TB coinfection (HIV+/TB+) and 125 with HIV mono-infection (HIV+/TB-). Tryptophan levels were lower in HIV+/TB+ than in HIV+/TB- (median 19.5 vs. 29.8 µmol/l, P  < 0.01), while kynurenine levels were similar between these groups (median 2.95 vs. 2.94 µmol/l, P  = 0.62). Median kynurenine/tryptophan ratio was 0.15 in HIV+/TB+, significantly higher compared with HIV+/TB- (0.11; P  < 0.01), with AUC 0.70 for TB detection. Kynurenine/tryptophan ratio was positively correlated to plasma HIV RNA levels, IP-10, IL-18, and IL-27, and negatively correlated to CD4 + cell count, BMI, and MUAC (all P  < 0.01). CONCLUSION: : Among ART-naive PWH, kynurenine/tryptophan ratio has modest potential for TB discrimination, limiting its utility for TB case-finding in this population.

Expression of MicroRNAs Is Dysregulated by HIV While Mycobacterium tuberculosis Drives Alterations of Small Nucleolar RNAs in HIV Positive Adults With Active Tuberculosis.

HIV infection affects the course of tuberculosis (TB), and HIV and Mycobacterium tuberculosis (Mtb) synergize in disease progression through complex immunological interplay. To gain further understanding of these mechanisms, we compared the microRNA (miRNA) and small nucleolar RNA (snoRNA) expression patterns in whole blood of individuals with active TB, with and without HIV coinfection (HIV+/TB+ and HIV-/TB+), and HIV and TB-negative individuals (HIV-/TB-). We found that 218 miRNAs were differentially expressed between HIV+/TB+ and HIV-/TB+, while no statistically significant difference in snoRNA expression was observed between these groups. In contrast, both miRNA (n = 179) and snoRNA (n = 103) expression patterns were significantly altered in HIV+/TB+ individuals compared to those of the HIV-/TB- controls. Of note, 26 of these snoRNAs were also significantly altered between the HIV-/TB+ and HIV-/TB- groups. Normalization toward the miRNA and snoRNA expression patterns of the HIV-/TB- control group was noted during anti-TB and antiretroviral treatment in HIV+/TB+ participants. In summary, these results show that HIV coinfection influences miRNA expression in active TB. In contrast, snoRNA expression patterns differ between individuals with and without active TB, independently of HIV coinfection status. Moreover, in coinfected individuals, therapy-induced control of HIV replication and clearance of Mtb appears to normalize the expression of some small non-coding RNA (sncRNA). These findings suggest that dysregulation of miRNA is a mechanism by which HIV may modify immunity against TB, while active TB alters snoRNA expression. Improved understanding of how regulation of sncRNA expression influences the disease course in coinfected individuals may have implications for diagnostics, risk stratification, and host-directed therapy. Here, we propose a novel mechanism by which HIV alters the immune response to TB.

Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals.

BACKGROUND: Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals. METHODS: Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV+/TB+) and 130 subjects without TB (HIV+/TB-) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels. RESULTS: The HIV+/TB+ subjects had higher levels of all markers, except IL12p70, compared with HIV+/TB- subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV+/TB+ and HIV+/TB-, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count <200 cells/mm3]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts. CONCLUSIONS: Although CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.

Pneumothorax following shoulder arthroscopy under combined regional and general anaesthesia-A case report.

INTRODUCTION: Pneumothorax is a most rare intraoperative event but jeopardise safety. Risk factors for its occurrence should be acknowledged and it should be considered in cases of unexpected deterioration of oxygenation that not respond to standard management to improve oxygenation. PRESENTATION OF CASE: We describe a patient with mild obesity and recent shoulder trauma scheduled for elective arthroscopy under combined interscalene block and general anaesthesia in the beach chair position. The block was performed with ultrasound guidance in accordance with the departmental routines and before the induction of general anaesthesia. The patient experienced low saturation shortly after administration of general anaesthesia. A thoracic ultrasound was performed in order to rule out pneumothorax and recruitment manoeuvres was done based on the suspicion of atelectasis. Surgery was commenced under pressure controlled ventilation and saturation was kept around 90 at FiO2 1.0 after recruitment manoeuvres. An initial postoperative lung X-ray on the operating table showed subcutaneous emphysema but no pneumothorax. A postoperative CT-thorax, patient still intubated, showed an extensive pneumothorax that was treated with pulmonary drainage. Patient had subsequently an uncomplicated postoperative course. DISCUSSION: We can not state "whom to blame", the interscalene block, intubation and pressures assisted ventilation, recruitment manoeuvres, or surgery? In this paper we discuss possible causes that should raise the suspicion around pneumothorax in patients exhibiting unexpected low saturation perioperatively. CONCLUSION: Compromised oxygenation during surgery that not respond to recruitment should raise suspicion about pneumothorax.