Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.
Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Anti-microbial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the “gold standard” in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 µg/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 µg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 µg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures.
Bacterial colonization of biliary stents is one of the driving forces behind sludge formation which may result in stent occlusion. Major focus of the study was to analyze the spectrum and number of microorganisms in relation to the indwelling time of stents and the risk factors for sludge formation. 343 stents were sonicated to optimize the bacterial release from the biofilm and identified by matrix-associated laser desorption/ionization-time of flight mass spectrometer (MALDI-TOF). 2283 bacteria were analyzed in total. The most prevalent microorganisms were Enterococcus species (spp.) (504;22%), followed by Klebsiella spp. (218;10%) and Candida spp. (188;8%). Colonization of the stents mainly began with aerobic gram-positive bacteria (43/49;88%) and Candida spp. (25/49;51%), whereas stents with an indwelling time>60 days(d) showed an almost equal colonization rate by aerobic gram-negative (176/184;96%) and aerobic gram-positive bacteria (183/184;99%) and a high proportion of anaerobes (127/184;69%). Compared to stents without sludge, more Clostridium spp. [(P = 0.02; Odds Ratio (OR): 2.4; 95% confidence interval (95%CI): (1.1–4.9)]) and Staphylococcus spp. [(P = 0.03; OR (95%CI): 4.3 (1.1–16.5)] were cultured from stents with sludge. Multivariate analysis revealed a significant relationship between the number of microorganisms [P<0.01; OR (95%CI): 1.3(1.1–1.5)], the indwelling time [P<0.01; 1–15 d vs. 20–59 d: OR (95%CI): 5.6(1.4–22), 1–15 d vs. 60–3087 d: OR (95% CI): 9.5(2.5–35.7)], the presence of sideholes [P<0.01; OR (95%CI): 3.5(1.6–7.9)] and the occurrence of sludge. Stent occlusion was found in 70/343(20%) stents. In 35% of cases, stent occlusion resulted in a cholangitis or cholestasis. In conclusion, microbial colonization of the stents changed with the indwelling time. Sludge was associated with an altered spectrum and an increasing number of microorganisms, a long indwelling time and the presence of sideholes. Interestingly, stent occlusion did not necessarily lead to a symptomatic biliary obstruction.
BackgroundSutures colonized by bacteria represent a challenge in surgery due to their potential to cause surgical site infections. In order to reduce these type of infections antimicrobially coated surgical sutures are currently under development. In this study, we investigated the antimicrobial drug octenidine as a coating agent for surgical sutures. To achieve high antimicrobial efficacy and required biocompatibility for medical devices, we focused on optimizing octenidine coatings based on fatty acids. For this purpose, antimicrobial sutures were prepared with either octenidine-laurate or octenidine-palmitate at 11, 22, and 33 μg/cm drug concentration normalized per length of sutures. Octenidine containing sutures were compared to the commercial triclosan-coated suture Vicryl® Plus. The release of octenidine into aqueous solution was analyzed and long-term antimicrobial efficacy was assessed via agar diffusion tests using Staphylococcus aureus. For determining biocompatibility, cytotoxicity assays (WST-1) were performed using L-929 mouse fibroblasts.ResultsIn a 7 days elution experiment, octenidine-palmitate coated sutures demonstrated much slower drug release (11 μg/cm: 7 %; 22 μg/cm: 5 %; 33 μg/cm: 33 %) than octenidine-laurate sutures (11 μg/cm: 82 %; 22 μg/cm: 88 %; 33 μg/cm: 87 %). Furthermore sutures at 11 μg/cm drug content were associated with acceptable cytotoxicity according to ISO 10993–5 standard and showed, similar to Vicryl® Plus, relevant efficacy to inhibit surrounding bacterial growth for up to 9 days.ConclusionsOctenidine coated sutures with a concentration of 11 μg/cm revealed high antimicrobial efficacy and biocompatibility. Due to their delayed release, palmitate carriers should be preferred. Such coatings are candidates for clinical testing in regard to their safety and efficacy.
Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.
Stent therapy was found to be a risk factor for increased antimicrobial resistance in patients with acute cholangitis, particularly those who had undergone numerous interventional procedures prior to the onset of the cholangitis.
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