Preventing E. coli Biofilm Formation with Antimicrobial Peptide-Functionalized Surface Coatings: Recognizing the Dependence on the Bacterial Binding Mode Using Live-Cell Microscopy.

Antimicrobial peptides (AMPs) can kill bacteria by destabilizing their membranes, yet translating these molecules' properties into a covalently attached antibacterial coating is challenging. Rational design efforts are obstructed by the fact that standard microbiology methods are ill-designed for the evaluation of coatings, disclosing few details about why grafted AMPs function or do not function. It is particularly difficult to distinguish the influence of the AMP's molecular structure from other factors controlling the total exposure, including which type of bonds are formed between bacteria and the coating and how persistent these contacts are. Here, we combine label-free live-cell microscopy, microfluidics, and automated image analysis to study the response of surface-bound Escherichia coli challenged by the same small AMP either in solution or grafted to the surface through click chemistry. Initially after binding, the grafted AMPs inhibited bacterial growth more efficiently than did AMPs in solution. Yet, after 1 h, E. coli on the coated surfaces increased their expression of type-1 fimbriae, leading to a change in their binding mode, which diminished the coating's impact. The wealth of information obtained from continuously monitoring the growth, shape, and movements of single bacterial cells allowed us to elucidate and quantify the different factors determining the antibacterial efficacy of the grafted AMPs. We expect this approach to aid the design of elaborate antibacterial material coatings working by specific and selective actions, not limited to contact-killing. This technology is needed to support health care and food production in the postantibiotic era.

Lateral membrane organization as target of an antimicrobial peptidomimetic compound.

Antimicrobial resistance is one of the leading concerns in medical care. Here we study the mechanism of action of an antimicrobial cationic tripeptide, AMC-109, by combining high speed-atomic force microscopy, molecular dynamics, fluorescence assays, and lipidomic analysis. We show that AMC-109 activity on negatively charged membranes derived from Staphylococcus aureus consists of two crucial steps. First, AMC-109 self-assembles into stable aggregates consisting of a hydrophobic core and a cationic surface, with specificity for negatively charged membranes. Second, upon incorporation into the membrane, individual peptides insert into the outer monolayer, affecting lateral membrane organization and dissolving membrane nanodomains, without forming pores. We propose that membrane domain dissolution triggered by AMC-109 may affect crucial functions such as protein sorting and cell wall synthesis. Our results indicate that the AMC-109 mode of action resembles that of the disinfectant benzalkonium chloride (BAK), but with enhanced selectivity for bacterial membranes.

Clinimetrics of performance-based functional outcome measures for vascular amputees: A systematic review.

BACKGROUND: Objective physical performance-based outcome measures (PerBOMs) are essential tools for the holistic management of people who have had an amputation due to vascular disease. These people are often non-ambulatory, however it is currently unclear which PerBOMs are high quality and appropriate for those who are either ambulatory or non-ambulatory. RESEARCH QUESTION: Which PerBOMs have appropriate clinimetric properties to be recommended for those who have had amputations due to vascular disease ('vascular amputee')? DATA SOURCES: MEDLINE, CINAHL, EMBASE, EMCARE, the Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus databases were searched for the terms: "physical performance" or "function", "clinimetric properties", "reliability", "validity", "amputee" and "peripheral vascular disease" or "diabetes". REVIEW METHODS: A systematic review of PerBOMs for vascular amputees was performed following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and PRISMA guidelines. The quality of studies and individual PerBOMs was assessed using COSMIN risk of bias and good measurement properties. Overall PerBOM quality was evaluated with a modified GRADE rating. Key clinimetric properties evaluated were reliability, validity, predictive validity and responsiveness. RESULTS: A total of 15,259 records were screened. Forty-eight studies (2650 participants) were included: 7 exclusively included vascular amputees only, 35 investigated validity, 20 studied predictive validity, 23 investigated reliability or internal consistency and 7 assessed responsiveness. Meta-analysis was neither possible nor appropriate for this systematic review in accordance with COSMIN guidelines, due to heterogeneity of the data. Thirty-four different PerBOMs were identified of which only 4 are suitable for non-ambulatory vascular amputees. The Amputee Mobility Predictor no Prosthesis (AMPnoPro) and Transfemoral Fitting Predictor (TFP) predict prosthesis use only. PerBOMs available for assessing physical performance are the One-Leg Balance Test (OLBT) and Basic Amputee Mobility Score (BAMS). CONCLUSION: At present, few PerBOMs can be recommended for vascular amputees. Only 4 are available for non-ambulatory individuals: AMPnoPro, TFP, OLBT and BAMS.

The Impact of the COVID-19 Pandemic on a Dedicated Vascular Emergency Clinic.

BACKGROUND: Vascular Emergency Clinics (VEC) improve patient outcomes in chronic limb-threatening ischemia (CLTI). They provide a "1 stop" open access policy, whereby "suspicion of CLTI" by a healthcare professional or patient leads to a direct review. We assessed the resilience of the outpatient VEC model to the first year of the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective review of a prospectively maintained database of all patients assessed in our VEC for lower limb pathologies between March 2020 and April 2021 was performed. This was cross-referenced to national and loco-regional Governmental COVID-19 data. Individuals with CLTI were further analysed to determine Peripheral Arterial Disease-Quality Improvement Framework compliance. RESULTS: Seven hundred and ninety one patients attended for 1,084 assessments (Male n = 484, 61%; Age 72.5 ± standard deviation 12.2 years; White British n = 645, 81.7%). In total, 322 patients were diagnosed with CLTI (40.7%). A total of 188 individuals (58.6%) underwent a first revascularization strategy (Endovascular n = 128, 39.8%; Hybrid n = 41, 12.7%; Open surgery n = 19, 5.9%; Conservative n = 134, 41.6%). Major lower limb amputation rate was 10.9% (n = 35) and mortality rate was 25.8% (n = 83) at 12 months of follow-up. Median referral to assessment time was 3 days (interquartile range: 1-5). For the nonadmitted patient with CLTI, the median assessment to intervention was 8 days (interquartile range: 6-15) and median referral to intervention time of 11 days (11-18). CONCLUSIONS: The VEC model has demonstrated strong resilience to the COVID-19 pandemic with rapid treatment timelines maintained for patients with CLTI.

Chronic hand eczema in Europe: Patient experiences and perspectives (CHEPEP) in qualitative interviews.

BACKGROUND: Chronic hand eczema (CHE) is a very common skin disease among the European population. It causes itch and pain and, in more severe cases, seriously impairs hand functioning at work and in private life. OBJECTIVES: To explore perspectives of people with lived experience on CHE-related problems, wishes and goals. METHODS: Following a qualitative approach, we conducted topic-guided interviews in five European countries and applied template analysis to identify recurrent themes among patients with CHE. RESULTS: We interviewed 60 patients in seven outpatient dermatological and occupational medicine clinics in Croatia, Denmark, Germany, the Netherlands and Spain. Five main themes were identified: (1) knowledge about the disease and its course, (2) preventive behaviour, (3) hand eczema therapy, (4) impact on everyday life and (5) attitudes towards CHE and healthcare. Participants did not feel well informed about CHE, especially about causes, triggers and treatment options. Preventive measures were experienced as more or less effective but also cumbersome. Experiences with therapy were diverse. Treatment satisfaction depended on the results and on the perceived support from the treatment teams. Participants found it important to be taken seriously, to receive practical advice, to try out additional treatments or examinations, find new hope and have occupational perspectives. They wished that others could better understand the physical and emotional burden of CHE. Patient support groups were not mentioned. Participants found it important to learn to take care of themselves and accept life with CHE. CONCLUSIONS: Due to its annoying symptoms, high visibility and impaired functioning at work and in private life, CHE has a high emotional and social impact. Some people may require support to learn coping with CHE and its prevention. Patients wish for information about causes and triggers. They value physicians who listen to them and keep looking for solutions.

Clinical outcome of a quadrifocal (trifocal) intraocular lens in Chinese patients: prospective, observational case series.

PURPOSE: To report the visual outcomes and quality of vision and life after bilateral implantation of a single-piece trifocal intraocular lens (IOL) in Chinese patients. SETTING: Hong Kong Sanatorium & Hospital, Hong Kong, China. DESIGN: Prospective, observational case series. METHODS: Patients with bilateral implantation of AcrySof IQ PanOptix multifocal IOL were included. Distance, intermediate (60 cm), and near (40 cm) visual acuities (VAs) and contrast sensitivity (CS), defocus curve, preoperative higher-order aberration (HOA), dysphotopsia (0 to 5), satisfaction (1 to 5), spectacle independence, and quality of life were evaluated. The association between preoperative HOA and postoperative halos was also assessed. RESULTS: 54 eyes of 27 patients were included. The mean binocular distance, intermediate, and near uncorrected VA was -0.05 ± 0.06 (20/18), 0.06 ± 0.10 (20/23), and 0.04 ± 0.05 (20/22), respectively. No eyes lost more than 1 line of vision. Binocular CS was comparable with the monocular population norm of older adults. The defocus curve demonstrated that the binocular VA of 20/25 or better was achieved at a power of -3.00 to +0.50 diopters. The mean scores for halos, glare, and starbursts were 2.4 ± 1.4, 0.2 ± 0.8, and 1.4 ± 1.4 (of 5), respectively. The mean satisfaction score was 4.3 ± 0.7 (of 5). All the patients (100%) reported total spectacle independence. The mean vision-targeted composite score of the vision-related quality-of-life questionnaire was 97.2 ± 9.7 (of 100). Preoperative HOA was not associated with postoperative halos. CONCLUSIONS: Implantation of the trifocal IOL provided satisfactory visual outcomes and quality of vision and life, which resulted in a high rate of spectacle independence.

Acceptance of skin products in healthcare workers: an empirical investigation.

BACKGROUND: Healthcare workers (HCWs) are at high risk of developing hand eczema (HE). This can be exacerbated by hygiene measures related to the coronavirus disease (COVID-19). Using mild skin cleansers and emollients or moisturizers is central in the prevention of HE-especially with increased COVID-19 hygiene regimes. AIMS: This study aimed to assess parameters important for the acceptance of a skincare concept in HCWs. METHODS: In this proof-of-concept user trial, HCWs were provided ad libitum with hand wash oil and hand cream during the 6-month period, when occupationally acquired COVID-19 infections among HCWs were peaking in Germany and then surveyed about acceptance of the products using questionnaires. RESULTS: Of 135 HCWs, 115 (85%) responded. Skin tolerance of the hand wash oil and the hand cream was rated very good by 63% and 52% of the 115 participants, respectively. Of the 115 participants, 58% and 57% were very satisfied with the hand wash oil and the hand cream, respectively. CONCLUSIONS: Acceptance of skin cleansing and skincare products in HCWs seems influenced by parameters such as self-assessed skin tolerance and self-reported overall satisfaction. It must be assumed that products are only used as recommended if they are well-accepted. Employers might survey employees about acceptance of products using the parameters identified to adjust concepts if necessary to sustainably contribute to the prevention of HE.

Interaction between gut microbiota and COVID-19 and its vaccines.

The whole world has been continuously afflicted by the coronavirus disease 2019 (COVID-19) pandemic for the past 3 years. Many countries have tried many methods to control this virus infection with varying successes and failures. The gut microbiota is a biosystem spanning the entire length of the digestive tract and playing important roles in health and disease. It is much affected by COVID-19. In return it also substantially impacts infection. In particular, the gut microbiota has established a bidirectional interaction with the COVID-19 vaccines, enhancing or reducing vaccine efficacy by virtue of its varying components. Conversely, COVID-19 vaccines also make a substantial impact on the gut microbiota, re-ducing its overall population and biodiversity. It is hoped that by exploring and harnessing this bidirectional interaction we may break new ground and develop new methods to prevent and treat this formidable virus infection.

Effect of high-pain versus low-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis.

BACKGROUND: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). METHODS: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. RESULTS: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. CONCLUSION: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).

Toric intraocular lenses for astigmatism correction after keratoplasty in phakic and pseudophakic eyes.

Residual astigmatism and anisometropia significantly affect patients' vision and quality of life even in clear grafts after corneal transplant. This study reviewed and summarized the role of toric intraocular lenses (IOLs) in phakic and pseudophakic eyes after penetrating keratoplasty (PKP) and deep anterior lamellar keratoplasty in correcting residual astigmatism. 342 eyes from 20 studies with iris-clipped toric IOL, ciliary sulcus toric implantable collamer lens, piggyback sulcus toric IOL, or posterior chamber toric IOL implantations for phakic, pseudophakic, or eyes undergoing cataract surgery after keratoplasty were included. Visual, refractive, and predictability outcomes were encouraging. Secondary realignment rate and complications were low. Endothelial cell loss secondary to phakic toric IOLs might be a concern over the long-term, particularly in iris-clipped IOLs in PKP eyes. Toric IOLs represent a viable option in the treatment of residual astigmatism in postkeratoplasty eyes, resulting in improved visual acuity and reduced anisometropia.

Effect of time since primary laser-assisted in situ keratomileusis on flap relift success and epithelial ingrowth risk.

PURPOSE: To assess the association of time since primary laser-assisted in situ keratomileusis (LASIK) with flap relift success and risk for epithelial ingrowth (EI) in eyes undergoing flap relift after primary LASIK. SETTING: Hong Kong Sanatorium & Hospital, Hong Kong Special Administrative Region. DESIGN: Retrospective observational case series. METHODS: 73 eyes with flaps relifted for refractive enhancement LASIK were included. Main outcome measures included rate of relift success and EI; associations of time since primary LASIK, sex, age at relift, year of relift, and flap creation method in primary LASIK with relift success and EI. RESULTS: Of the 73 eyes included, relifting was successful in 71 eyes (97.3%). Among the successfully relifted eyes, 12 (16.9%) developed EI, of which 3 (4.2%) were clinically significant. No eyes lost more than 1 line of corrected distance visual acuity. The time since primary LASIK (up to 22 years), sex, age at relift, year of relift, and flap creation method in primary LASIK were not associated with relift success or EI. CONCLUSIONS: With the described surgical technique, flaps could be successfully relifted without much difficulty up to 22 years after primary LASIK with a low incidence of EI.

Understanding variations in reported epidemiology of major lower extremity amputation in the UK: a systematic review.

OBJECTIVE: Estimate the prevalence/incidence/number of major lower extremity amputations (MLEAs) in the UK; identify sources of routinely collected electronic health data used; assess time trends and regional variation; and identify reasons for variation in reported incidence/prevalence of MLEA. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, EMcare, CINAHL, The Cochrane Library, AMED, Scopus and grey literature sources searched from 1 January 2009 to 1 August 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Reports that provided population-based statistics, used routinely collected electronic health data, gave a measure of MLEA in adults in the general population or those with diabetes in the UK or constituent countries were included. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Instruments were performed by two reviewers independently. Due to considerable differences in study populations and methodology, data pooling was not possible; data were tabulated and narratively synthesised, and study differences were discussed. RESULTS: Twenty-seven reports were included. Incidence proportion for the general population ranged from 8.2 to 51.1 per 100 000 and from 70 to 291 per 100 000 for the population with diabetes. Evidence for trends over time was mixed, but there was no evidence of increasing incidence. Reports consistently found regional variation in England with incidence higher in the north. No studies reported prevalence. Differences in database use, MLEA definition, calculation methods and multiple procedure inclusion which, together with identified inaccuracies, may account for the variation in incidence. CONCLUSIONS: UK incidence and trends in MLEA remain unclear; estimates vary widely due to differences in methodology and inaccuracies. Reasons for regional variation also remain unexplained and prevalence uninvestigated. International consensus on the definition of MLEA and medical code list is needed. Future research should recommend standards for the reporting of such outcomes and investigate further the potential to use primary care data in MLEA epidemiology. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020165592.

Patch test informed consent form: position statement by European Academy of Dermatology and Venereology Task Force on Contact Dermatitis.

BACKGROUND: To our knowledge, an international consensus is lacking regarding the development of an adequate informed consent form for a patch test (PT) and the information that should be included in such document. OBJECTIVES: The aim of the study was to reach a consensus on the specific points that need to be addressed in a PT consent form. METHODS: A Delphi survey, comprising 2 rounds and 1 final discussion, was used to gather and analyse data, which was conducted over the Internet. Each statement that reached a consensus with the respondents (9 expert dermatologists from Europe) was defined as a median consensus score (MED) of ≥7 and agreement among panelists as an interquartile range (IQR) of ≤3. All study participants were members of the EADV task force on contact dermatitis. RESULTS: The expert panel addressed several topics that should be included in an informed consent form for a PT: introduction, preparation for PT, testing procedure, allowed activities, adverse events and additional authorizations. CONCLUSIONS: Our results assess recommendations regarding points to be contained in an informed consent form for a PR. Future actions towards standardization and harmonization of this specific consent form are needed.

Does the Introduction of a Vascular Limb Salvage Service Improve One Year Amputation Outcomes for Patients with Chronic Limb-Threatening Ischaemia?

OBJECTIVE: Vascular limb salvage services are recommended by the Global Vascular Guidelines to help improve outcomes for patients with chronic limb-threatening ischaemia (CLTI), although their description within the literature is limited. This study reports the 12 month outcomes for an outpatient based vascular limb salvage (VaLS) clinic. METHODS: An analysis of a prospectively maintained database, involving all consecutive patients diagnosed with CLTI within the VaLS clinic from February 2018-February 2019, was undertaken. Data were compared with two comparator cohorts, identified from coding data: 1) patients managed prior to the clinic, between May 2017 and February 2018 (Pre-Clinic [PC]); and 2) patients managed outside of clinic, between February 2018 and February 2019 (Alternative Pathways [AP]). Freedom from major amputation at 12 months was the primary outcome. Kaplan-Meier plots and adjusted Cox's proportional hazard models (aHR) were used to compare outcomes. RESULTS: Five hundred and sixty-six patients (VaLS 158, AP 173, PC 235) were included (median age 74 years). Patients managed within the VaLS cohort were statistically significantly more likely to be free from major amputation (90.5%) compared with both the AP (82.1%, aHR 0.52, 95% confidence interval [CI] 0.28 - 0.98, p = .041) and the PC (80.0%; aHR 0.50, 95% CI 0.28 - 0.91, p = .022) cohorts at 12 months, after adjustment for age, disease severity, and presence of diabetes. CONCLUSION: This study supports the recommendations of the Global Vascular Guidelines that vascular limb salvage clinics may improve the rate of major amputation. Furthermore, the study provides a reproducible service model that delivers timely vascular assessment in an ambulatory setting. Further evaluation is required to assess longer term outcomes.

Prevalence of Cognitive Impairment in Individuals with Vascular Surgical Pathology: a Systematic Review and Meta-Analysis.

OBJECTIVE: A significant proportion of vascular surgery patients may have undiagnosed cognitive impairment; however, its true prevalence and impact on outcomes are unknown. The aim of this review was to estimate the prevalence of cognitive impairment among individuals with clinically significant vascular surgical pathology and investigate its associations with post-operative outcomes in those undergoing vascular surgery. METHODS: MEDLINE, EMBASE, EMCare, CINAHL, PsycINFO, and Scopus were searched for relevant studies. Included studies assessed cognitive function among individuals with either symptomatic vascular surgical pathology, or disease above threshold for intervention, using a validated cognitive assessment tool. The primary outcome measure was prevalence of cognitive impairment. Secondary outcomes included incidence of post-operative delirium (POD). Two reviewers independently extracted relevant study data and assessed risk of bias (ROBINS-E or RoB 2 tool). Prevalence (%) of cognitive impairment was calculated for individual studies and presented with 95% confidence intervals (CI). Prevalence data from comparable studies were pooled using the Mantel-Haenszel method (random effects model) for separate vascular disease types. Certainty of effect estimates was assessed using the GRADE criteria. RESULTS: Twenty-four studies (2 564 participants) were included in the systematic review, and nine studies (1 310 participants) were included in the meta-analyses. The prevalence of cognitive impairment was 61% (95% CI 48 - 74; 391 participants; low certainty) in studies including multiple vascular surgical pathologies, 38% (95% CI 32 - 44; 278 participants; very low certainty) in carotid artery disease, and 19% (95% CI 10 - 33; 641 participants; low certainty) in those with intermittent claudication. Lower cognitive assessment scores were associated with POD (five studies; 841 participants), but data were not suitable for pooling. CONCLUSION: Screening elective vascular surgery patients for cognitive impairment may be appropriate given its high prevalence, and the association of worse cognition with POD, among individuals with clinically significant vascular surgical pathology.