Pohl Boskamp (Germany)

We report a case of severe outflow graft infection following left ventricular assist device (LVAD) implantation. A 51-year old male LVAD patient was readmitted to our hospital presenting signs of systemic infection. One year previously, LVAD implantation (HeartMate3, Abbott, Chicago, IL, USA) with concomitant patent foramen ovale closure had been performed in the context of end-stage heart failure due to dilative cardiomyopathy (INTERMACS III). The indication for LVAD-therapy was bridge-to-candidacy, since the patient did not instantly fulfill all criteria for cardiac transplantation. At admission, a PET-CT scan unveiled fluid accumulation, encircling the outflow-graft prosthesis (SUVmax 10.5) with contrast-enhancement involving the intrathoracic driveline (SUVmax 11.2). Since cardiac transplantation was not feasible, the patient underwent surgical revision. In the first step, redo sternotomy was performed with local debridement, including jet lavage. Intraoperative swabs confirmed bacterial infection with staphylococcus aureus. Following this, the patient underwent negative pressure wound therapy (NPWT) with instillation using the V.A.C. VERAFLO system (KCI-3M, San Antonio, TX, USA) for a total of 19 days. Due to the severity of infection, local bacteriophage application was performed within the wound closure. In order to concentrate phage therapy at the infection site, phages were applied using a novel semi-fluid galenic. After wound closure, the patient was discharged with an uneventful course. A control PET-CT scan 3 months after discharge showed a significant decrease in infection (outflow graft: SUVmax 7.2, intrathoracic driveline: SUVmax 3.0) correlated with contrast enhancement. Bacterial infection of intrathoracic VAD components represents a severe and potentially life-threatening complication. If cardiac transplantation is not feasible, complex wound management strategies are required. Local bacteriophage therapy might be a promising addition to already established therapeutical options. In order to improve bacteriophage retention at the wound site, application of a viscous galenic might be beneficial.

Bacterial infections of vascular grafts represent a major burden in cardiovascular medicine, which is related to an increase in morbidity and mortality. Different factors that are associated with this medical field such as patient frailty, biofilm formation, or immunosuppression negatively influence antibiotic treatment, inhibiting therapy success. Thus, further treatment strategies are required. Bacteriophage antibacterial properties were discovered 100 years ago, but the focus on antibiotics in Western medicine since the mid-20th century slowed the further development of bacteriophage therapy. Therefore, the experience and knowledge gained until then in bacteriophage mechanisms of action, handling, clinical uses, and limitations were largely lost. However, the parallel emergence of antimicrobial resistance and individualized medicine has provoked a radical reassessment of this approach and cardiovascular surgery is one area in which phages may play an important role to cope with this new scenario. In this context, bacteriophages might be applicable for both prophylactic and therapeutic use, serving as a stand-alone therapy or in combination with antibiotics. From another perspective, standardization of phage application is also required. The ideal surgical bacteriophage application method should be less invasive, enabling highly localized concentrations, and limiting bacteriophage distribution to the infection site during a prolonged time lapse. This review describes the latest reports of phage therapy in cardiovascular surgery and discusses options for their use in implant and vascular graft infections.

BackgroundIncreasing resistance of head lice against neurotoxic agents and safety concerns have led to the search for treatment alternatives. Dimeticones with a physical mode of action are safe, and bear a reduced risk for the development of resistance.MethodsWe performed in vitro bioassays to assess pediculicidal and ovicidal activities of a new dimeticone-based product, and a randomized controlled clinical trial to assess efficacy, following 10 min application. Of 153 individuals screened, 100 participants with active head louse infestations were randomly assigned to treatment with either a dimeticone-based test product, or a 0.5% permethrin-based reference product (50 participants per group). Participants received two topical applications of either the test (10 min) or reference products (45 min) at days 0 and 7 or 8. Outcome measures included the efficacies of treatment and their safety, as well as global and local tolerability at baseline, and days 1, 7, and 10.ResultsAfter 10 min exposure, all lice treated with the dimeticone test product were classified as non-viable in the in vitro assay. Ovicidal activity after treatment of eggs with the dimeticone test product was 96.8%. In the clinical trial, 96 patients completed all study visits. In the full analysis set (FAS) population, on day 1 after one application, 98% of patients were cured in the test group, as compared to 84% cured in the reference group. All participants in both groups were free of head lice on day 10, following two applications (100% cure rate). In total, 42 adverse events (AEs) in 23 patients of both treatment groups were recorded, with the majority of AEs classified as mild.ConclusionsWe have shown a high level of pediculicidal and ovicidal activity, and clinical efficacy and safety, of a brief application of a new dimeticone-based product. The short application time and reduced risk for the development of resistance are key drivers for improved patients’ compliance.Trial registrationEU Clinical Trials Register EudraCT 2016–004635-20. Registered 14 November 2016.

Background and Purpose- This pilot study aims to demonstrate the feasibility of targeting molecular characteristics of high-risk atherosclerotic plaque in symptomatic and asymptomatic carotid stenosis (CS), that is, upregulation of the translocator protein (TSPO) and the chemokine receptor type 4 (CXCR4), by means of molecular imaging. Methods- In a translational setting, specimens of carotid plaques of patients with symptomatic and asymptomatic CS obtained by carotid endarterectomy were analyzed for the presence of TSPO and CXCR4 by autoradiography, using the positron emission tomography tracers 18F-GE180 and 68Ga-Pentixafor and evaluated by histopathology. In addition, 68Ga-Pentixafor positron emission tomography/computed tomography was performed in a patient with high-grade CS. Results- Distinct patterns of upregulation of TSPO (18F-GE180 uptake) and CXCR4 (68Ga-Pentixafor uptake) were identified in carotid plaque by autoradiography. The spatial distribution was associated with specific histological hallmarks that are established features of high-risk plaque: TSPO upregulation correlated with activated macrophages infiltration, whereas CXCR4 upregulation also corresponded to areas of intraplaque hemorrhage. 68Ga-Pentixafor uptake was significantly higher in plaques of symptomatic compared with asymptomatic CS. Clinical positron emission tomography revealed marked 68Ga-Pentixafor uptake in carotid plaque of a patient with high-grade CS. Conclusions- Clinical imaging of molecular signatures of high-risk atherosclerotic plaque is feasible and may become a promising diagnostic tool for comprehensive characterization of carotid disease. This methodology provides a platform for future studies targeting carotid plaque.

Myrtol standardized (Gelomyrtol forte) is a phytotherapeutic extract (distillate) consisting mainly of three monoterpenes: (+)alpha-pinene, d-limonene and 1,8-cineole. This study describes and compares the efficacy, safety and tolerability of a 2-week treatment with myrtol stand. (4 x 300 mg, day 1-14), cefuroxime (CAS 55268-75-2) (2 x 250 mg daily for day 1-6), ambroxol (CAS 18683-91-5) (3 x 30 mg for day 1-3, 2 x 30 mg for days 4-14) and matched placebo in acute bronchitis. 676 male and female outpatients, aged > or = 18 years, with acute bronchitis of recent onset (within last 5 days), with an FEV1 > 75% of the normal EGKS-value and without evidence or suspicion of chronic pulmonary disease or any further confounding illness were included in the study. Patients were randomly assigned to a 2-week treatment course with either myrtol stand. (N = 170), cefuroxime (N = 171), ambroxol (N = 163) or placebo (N = 172) in a double-blind, placebo-matched, parallel-group fashion. Evaluations were at baseline (visit 1), after 1 and 2 weeks of treatment (visits 2 and 3) and at 2 weeks after conclusion of the treatments (visit 4). Responder- and non-responder rates (primary), signs (abnormal auscultation), symptoms (daily diary data on nightly cough, coughing fits during the day, sputum consistence and general well-being; visit data on bronchial hyperreactivity and absence/presence of associated symptoms), FEV1, overall efficacy, absence of relapse, safety and tolerability (adverse events, laboratory screens, vital signs and physical examination). Criteria were evaluated for the intention-to-treat data-set (ITT) and the 'efficacy evaluable' sample (EAP), i.e. excluding patients with missing values (incl. discontinued non-responders and drop-outs for other reasons) at the time of assessment. The signs and symptoms of acute bronchitis regressed readily in all treatment groups, but regression was slower and less complete in the patients treated with placebo. In patients treated with placebo, the acute bronchitis was considered to have deteriorated to such an extent that discontinuation was indicated ('non-responder') in 36 patients (ITT: 20.9%, 95% CI: 15.1 to 27.8% and EAP: 21.3%, CI: 15.4 to 28.3%) after 1 week (visit 2) and in 19 further patients (ITT: 11.0%, CI: 6.8 to 16.7%; EAP: 14.8%, CI: 9.2 to 22.2%) after 1 further week (visit 3). In contrast, in the group of patients treated with myrtol stand. the non-responder rates at visits 2 and 3 were only 5.3% (ITT, CI: 2.4 to 9.8%; EAP: 5.4%, CI: 2.5 to 10.0%) and 1.2% (ITT, CI: 0.1 to 4.2%; EAP: 1.3%, CI: 0.2 to 4.7%); the responder rates at visit 2 were statistically significantly higher (p < 0.001) for myrtol stand. (ITT: 92.9%, CI: 88.0 to 96.3) compared to placebo (ITT: 77.3%, CI: 70.3 to 83.4), and similar to those for cefuroxime (ITT: 92.4%, CI: 87.4 to 95.9) and ambroxol (ITT: 89.6%, CI: 83.8 to 93.8%). The superiority of the active treatments vs. placebo with little difference among the treatments was confirmed for all further criteria of evaluation. There was no evidence of bronchoconstriction or relapse in any treatment group for the patients continuing treatment (i.e. for those who were not discontinued because of non-response). The treatments were safe and comparably well tolerated. Compared to placebo, treatment with myrtol stand. was well tolerated but evidently superior in terms of efficacy, resulting in a more rapid and more complete recovery; although well comparable with the other active treatments, myrtol stand. tended to be superior to cefuroxime and ambroxol for several ancillary criteria. Myrtol stand. is a well-evidenced alternative to antibiotics for acute bronchitis without specified infective agent, without the risk to promote the development of bacterial resistance.

Abstract Poly(methyl methacrylate-acrylic acid-ethylene glycol dimethacrylate) copolymer particles abbreviated as P(MMA-AA-EGDM) copolymer particles were prepared by soap-free emulsion copolymerization. The concentration of carboxyl group on/near the surface of particles increased with the increase in acrylic acid (AA) content in the recipe. The carboxyl groups were reacted with amine nucleophiles such ethylene diamine and 1,6-diaminohexane through preactivation with dicyclohexyl carbodiimide as a coupling agent. The modified particles were characterized by electron micrographs and FTIR spectral analysis. Adsorption behaviours of some biomolecules were measured to have idea about=-0 the polarity of the particles surface