Circulating miR-145 as a marker of therapeutic response to anti-TNF therapy in patients with ankylosing spondylitis.

Circulating miRNAs appear promising therapeutic and prognostic biomarkers. We aimed to investigate the predictive value of circulating miRNAs on the disease outcome following anti-TNF therapy in patients with ankylosing spondylitis (AS). Our study included 19 AS patients assessed at baseline (M0), after three (M3) and twelve months (M12) of therapy. Total RNA was isolated from plasma. A comprehensive analysis of 380 miRNAs using TaqMan Low Density Array (TLDA) was followed by a single assay validation of selected miRNAs. All AS patients had high baseline disease activity and an excellent response to anti-TNF therapy at M3 and M12. TLDA analysis revealed the dysregulation of 17 circulating miRNAs, including miR-145. Single assay validation confirmed that miR-145 is significantly downregulated at M3 compared to baseline. The decrease in the levels of miR-145 from M0 to M3 negatively correlated with the change in BASDAI from M0 to M3; and positively correlated with disease activity improvement from M3 to M12 as per BASDAI and ASDAS. The predictive value of the early change in miR-145 and levels of miR-145 at M3 were further validated by Receiver operating curves analysis. We show thatthe early change in circulating miR-145 may be a predictor for the future outcome ofAS patients treated with TNF inhibitors. Patients with a more significant decrease in miR-145 levels may show further significant improvement of disease activity after 12 months. Monitoring the expression of miR-145 in plasma in AS patients may, therefore, influence our therapeutic decision-making.

The comparison of modified minimally invasive and open surgical approaches in the treatment of epithelial thymic tumours.

OBJECTIVES: Exploring the efficacy of a modified combined minimally invasive approach in patients with thymoma regardless of myasthenia gravis involvement in contrast to open surgery as the mainstay of treatment. BACKGROUND: Primary epithelial thymic tumours are rare malignancies of the anterior mediastinum, often present with myasthenia gravis, and with good prognosis when assuming complete surgical resection. We present a modified mini-invasive technique (MIT) that is unique in its extent. METHODS: Fifty-two patients were included in this retrospective study. Two groups of patients who had undergone different types of surgery were compared using the Mann-Whitney test (ordinal variables) and Fisher's exact test (binary variables). Changes after completing the surgical learning curve were observed. RESULTS: There was a statistical difference when comparing early Masaoka stages (I‒II) with later stages in favour of the mini-invasive method (p=0.013). The duration of surgery was longer in the mini­invasive group with a median value of 260 vs 133 min (p=0.001). The analysis of operation times revealed that after overcoming the learning curve period, the duration of surgery decreased (2008‒2012: 297 min; 2013‒2018: 199 min; p=0.005). The systemic complication rate was lower in the mini­invasive method (26.1 % vs 3.4 %; p=0.035). CONCLUSION: Our results showed the modified maximal minimally invasive thymectomy to be an effective and safe method, and after overcoming the learning curve, even superior to open surgery in cases with lower tumour stages in terms of its extent (Tab. 3, Fig. 1, Ref. 49).

Intra-abdominal candidiasis in surgical intensive care unit - epidemiology characteristics and trends.

OBJECTIVES: Intra-abdominal candidiasis (IAC) is an invasive fungal infection representing the most common type of invasive Candida infection in surgical intensive care units (ICUs). Recently, decreased antifungal susceptibility and progressive shift in the aetiology of invasive candidiasis has been observed worldwide. We explored IAC epidemiology in surgical ICU. MATERIAL AND METHODS: We retrospectively reviewed the records of 64 patients with IAC admitted at our surgical ICU over a 4-year period (2013-2016). IAC incidence, microbiological results, antifungal therapy, and mortality were analysed. RESULTS: The cumulative IAC incidence was 18.4 cases per 1000 admissions (2013: 12.6; 2014: 17.7; 2015: 16.8; 2016: 24.5), including hospital-acquired IAC incidence (2013: 9.8; 2014: 13.3; 2015 10.1; 2016: 13.3) and community-acquired IAC incidence (2013: 2.8; 2014: 4.4; 2015: 6.7; 2016: 11.2). Candida albicans represented the most common species (n = 35, 50.0%) followed by Candida glabrata (n = 15, 21.4%), Candida tropicalis (n = 6, 8.6%) and other yeasts (each < 5.0%). Incidence rate of C. albicans (2013: 7(78%); 2014: 10(59%); 2015: 6(35%); 2016: 12(44%)) and incidence rate of C. non-albicans (2013: 2(22%); 2014: 7(41%); 2015: 9(53%); 2016: 14(52%)) were different in trend. All fungal isolates were susceptible to echinocandins, amphotericin B and voriconazole. Regarding fluconazole susceptibility, C. krusei (n = 3) was resistant and C. glabrata (n = 9) was susceptible-dose dependent (SDD). The ratio of SDD C. glabrata isolates to all isolated C. glabrata strains was 9/15 (60%) (2013: 0/2; 2014: 0/2; 2015: 1/3; 2016: 8/8). Decreased fluconazole susceptibility for C. glabrata isolates was reported in both community-acquired IAC (n = 3) and hospital-acquired IAC (n = 6). Overall 30-day mortality rate was 25.0% (16/64). CONCLUSIONS: We have revealed slowly raising of overall IAC incidence, more increasing trend in incidence of community-acquired IAC compared to rather steady incidence of hospital-acquired IAC. During period 2013-2016 we have observed a significant shift in the aetiology of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates.

Markers of oxidative damage of nucleic acids and proteins among workers exposed to TiO2 (nano) particles.

OBJECTIVE: The use of nanotechnology is growing enormously and occupational physicians have an increasing interest in evaluating potential hazards and finding biomarkers of effect in workers exposed to nanoparticles. METHODS: A study was carried out with 36 workers exposed to (nano)TiO2 pigment and 45 controls. Condensate (EBC) titanium and markers of oxidation of nucleic acids (including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU)) and proteins (such as o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr) and 3-nitrotyrosine (3-NOTyr)) were analysed from samples of their exhaled breath. RESULTS: In the production workshops, the median total mass 2012 and 2013 TiO2 concentrations were 0.65 and 0.40 mg/m(3), respectively. The median numbers of concentrations measured by the scanning mobility particle sizer (SMPS) and aerodynamic particle sizer (APS) were 1.98 × 10(4) and 2.32 × 10(4) particles/cm(3), respectively; and about 80% of those particles were smaller than 100 nm in diameter. In the research workspace, lower aerosol concentrations (0.16 mg/m(3) and 1.32 × 10(4) particles/cm(3)) were found. Titanium in the EBC was significantly higher in production workers (p<0.001) than in research workers and unexposed controls. Accordingly, most EBC oxidative stress markers, including in the preshift samples, were higher in production workers than in the two other groups. Multiple regression analysis confirmed an association between the production of TiO2 and the levels of studied biomarkers. CONCLUSIONS: The concentration of titanium in EBC may serve as a direct exposure marker in workers producing TiO2 pigment; the markers of oxidative stress reflect the local biological effect of (nano)TiO2 in the respiratory tract of the exposed workers.