Eligibility for antiamyloid treatment: preparing for disease-modifying therapies for Alzheimer's disease.

BACKGROUND: Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) have early evidence of efficacy. Widespread delivery of DMTs will require major service reconfiguration. Treatment pathways will need to include triaging for eligibility, regular infusions and baseline and follow-up MRI scanning. A critical step in planning is provision of real-world estimates of patients likely to be eligible for triaging, but these are challenging to obtain. METHODS: We performed a retrospective service evaluation of patients attending five memory services across North and East London and a national specialist cognitive disorders service. We examined the likely proportion of patients who would (1) be referred for triaging for DMTs and (2) potentially be suitable for treatments. RESULTS: Data from a total of 1017 patients were included, 517 of whom were seen in community memory services and 500 in a specialist clinic. In the memory services, 367/517 (71%) were diagnosed with possible AD. After exclusions of those in whom cognitive and frailty scores, MRI contraindications or anticoagulant use indicated they would be unlikely to be suitable, an estimated 32% would be eligible for triaging. In the specialist cognitive clinic, where additional investigations are available, 14% of those seen (70/500) would be potentially eligible for treatment. CONCLUSIONS: While a sizeable proportion of patients attending memory clinics may be referred for triaging for DMTs for AD, only a minority are likely to be suitable for these, as demonstrated in patients seen in specialist cognitive services. This will need to be considered when designing pathways for DMT delivery.

Contemporary management of heart failure patients with reduced ejection fraction: the role of implantable devices and catheter ablation.

Heart failure (HF) is a complex clinical syndrome characterised by significant morbidity and mortality worldwide. Evidence-based therapies for the management of HF include several well-established neurohormonal antagonists and antiarrhythmic drug therapy to mitigate the onset of cardiac arrhythmia. However, the degree of rate and rhythm control achieved is often suboptimal and mortality rates continue to remain high. Implantable cardioverter-defibrillators (ICDs), cardiac resynchronization (CRT), and combined (CRT-D) therapies have emerged as integral and rapidly expanding technologies in the management of select patients with heart failure with reduced ejection fraction (HFrEF). ICDs treat ventricular arrhythmia and are used as primary prophylaxis for sudden cardiac death, while CRT resynchronizes ventricular contraction to improve left ventricular systolic function. Left ventricular assist device therapy has also been shown to provide clinically meaningful survival benefits in patients with advanced HF, and His-bundle pacing has more recently emerged as a safe, viable, and promising pacing modality for patients with CRT indication. Catheter ablation is another important and well-established strategy for managing cardiac arrhythmia in HF, demonstrating superior efficacy when compared with antiarrhythmic drug therapy alone. In this article, we provide a comprehensive and in-depth evaluation of the role of implantable devices and catheter ablation in patients with HFrEF, outlining current applications, recent advances, and future directions in practice.

Objective Scoring of Information Websites for Vascular Anomalies.

ABSTRACT: One of the challenging aspects of caring for patients with vascular anomalies has been the use of inconsistent terminologies which has resulted in inconsistencies with treatment, miscommunication between clinicians, and subsequently patient misinformation and confusion. In this study, we objectively assessed the quality of online information on vascular anomalies. Our results emphasize the crucial role of vascular anomaly services in the communication and provision of patient information.

Use of Augmented Reality in Reconstructive Microsurgery: A Systematic Review and Development of the Augmented Reality Microsurgery Score.

BACKGROUND: Augmented reality (AR) uses a set of technologies that overlays digital information into the real world, giving the user access to both digital and real-world environments in congruity. AR may be specifically fruitful in reconstructive microsurgery due to the dynamic nature of surgeries performed and the small structures encountered in these operations. The aim of this study was to conduct a high-quality preferred reporting items for systematic reviews and meta-analyses (PRISMA) and assessment of multiple systematic reviews 2 (AMSTAR 2) compliant systematic review evaluating the use of AR in reconstructive microsurgery. METHODS: A systematic literature search of Medline, EMBASE, and Web of Science databases was performed using appropriate search terms to identify all applications of AR in reconstructive microsurgery from inception to December 2018. Articles that did not meet the objectives of the study were excluded. A qualitative synthesis was performed of those articles that met the inclusion criteria. RESULTS: A total of 686 articles were identified from title and abstract review. Five studies met the inclusion criteria. Three of the studies used head-mounted displays, one study used a display monitor, and one study demonstrated AR using spatial navigation technology. The augmented reality microsurgery score was developed and applied to each of the AR technologies and scores ranged from 8 to 12. CONCLUSION: Although higher quality studies reviewing the use of AR in reconstructive microsurgery is needed, the feasibility of AR in reconstructive microsurgery has been demonstrated across different subspecialties of plastic surgery. AR applications, that are reproducible, user-friendly, and have clear benefit to the surgeon and patient, have the greatest potential utility. Further research is required to validate its use and overcome the barriers to its implementation.

The STROCSS 2024 guideline: strengthening the reporting of cohort, cross-sectional, and case-control studies in surgery.

INTRODUCTION: First released in 2017, the STROCSS guidelines have become integral for promoting high-quality reporting of observational research in surgery. However, regular updates are essential to ensure they remain relevant and of value to surgeons. Building on the 2021 updates, the authors have developed the STROCSS 2024 guidelines. This timely revision aims to address residual reporting gaps, assimilate recent advances, and further strengthen observational study quality across all surgical disciplines. METHODS: A core steering committee compiled proposed changes to update the STROCSS 2021 guidelines based on identified gaps in prior iterations. An expert panel of surgical research leaders then evaluated the proposed changes for inclusion. A Delphi consensus exercise was used. Proposals that scored between 7-9 on a nine-point Likert agreement scale, by ≥70% of Delphi participants, were integrated into the STROCSS 2024 checklist. RESULTS: In total, 46 of 56 invited participants (82%) completed the Delphi survey and hence participated in the development of STROCSS 2024. All suggested amendments met the criteria for inclusion, indicating a high level of agreement among the Delphi group. All proposed items were therefore integrated into the final revised checklist. CONCLUSION: The authors present the updated STROCSS 2024 guidelines, which have been developed through expert consensus to further enhance the transparency and reporting quality of observational research in surgery.

Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3-7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47-0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76-1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.

Catheter Ablation for the Management of Atrial Fibrillation: An Update of the Literature.

Catheter ablation has been shown to be more effective at maintaining sinus rhythm and improving quality of life when compared to antiarrhythmic drugs. Radiofrequency and cryoablation are two effective methods. However, catheter-only ablation strategies have not consistently produced high success rates in treating longstanding and persistent AF patients. The emerging treatment of choice for such cases is hybrid ablation, which involves a multidisciplinary and minimally invasive approach to achieve surgical ablation of the direct posterior left atrial wall in combination with endocardial catheter ablation. Studies have shown promising results for the hybrid approach when compared with catheter ablation alone, but it is not without risks. Large and randomised studies are necessary to further evaluate these strategies for managing AF.

Preferred Reporting Of Case Series in Surgery (PROCESS) 2023 guidelines.

INTRODUCTION: The Preferred Reporting Of CasE Series in Surgery (PROCESS) guidelines were developed in 2016 in order to improve the reporting quality of surgical case series. Since its inception, it has been updated twice, in 2018 and 2020, and has been cited over 1000 times. PROCESS guidelines have enjoyed great acceptance within the surgical research community. Our aim is to update the PROCESS guidelines in order to maintain its applicability in the field of surgical research. METHODS: A PROCESS 2023 steering group was created. By working in collaboration, members of this group came up with proposals to update the PROCESS 2020 guidelines. These proposals were presented to an expert panel of researchers, who in turn scrutinised these proposals and decided whether they should become part of PROCESS 2023 guidelines or not, through a Delphi consensus exercise. RESULTS: A total of 38 people participated in the development of PROCESS 2023 guidelines. The majority of items received a score between 7 and 9 from greater than 70% of the participants, indicating consensus with the proposed changes to those items. However, two items (3c and 6a) received a score between 7 and 9 from less than 70% of the participants, indicating a lack of consensus with the proposed changes to those items. Those items will remain unchanged. DISCUSSION: The updated PROCESS 2023 guidelines are presented with an aim to continue improving the reporting quality of case series in surgery.

The SCARE 2023 guideline: updating consensus Surgical CAse REport (SCARE) guidelines.

BACKGROUND: The Surgical CAse REport (SCARE) guidelines were first published in 2016 as a tool for surgeons to document and report their surgical cases in a standardised and comprehensive manner. However, with advances in technology and changes in the healthcare landscape, it is important to revise and update these guidelines to ensure they remain relevant and valuable for surgeons. MATERIALS AND METHODS: The updated guidelines were produced through a Delphi consensus exercise. Members of the SCARE 2020 guidelines Delphi group, editorial board members, and peer reviewers were invited to participate. Potential contributors were contacted by e-mail. An online survey was completed to indicate their agreement with the proposed changes to the guideline items. RESULTS: A total of 54 participants were invited to participate and 44 (81.5%) completed the survey. There was a high degree of agreement among reviewers, with 36 items (83.7%) meeting the threshold for inclusion. CONCLUSION: Through a completed Delphi consensus exercise we present the SCARE 2023 guidelines. This will provide surgeons with a comprehensive and up-to-date tool for documenting and reporting their surgical cases while highlighting the importance of patient-centred care.

Outcome measures reported following feminizing genital gender affirmation surgery for transgender women and gender diverse individuals: A systematic review.

Background: Feminizing genital gender affirmation surgery (fgGAS) may be an essential adjunct in the care of some transgender women and gender diverse individuals with gender incongruence. However, the comparison of different techniques of fgGAS may be confounded by variable outcome reporting and the use of inconsistent outcomes in the literature. This systematic review provides the most in-depth examination of fgGAS studies to date, and summarizes all reported outcomes, definitions, and the times when outcomes were assessed following these surgical interventions. Aims/Methods: This work intends to quantify the levels of outcome variability and definition heterogeneity in this expanding field and provides guidance on outcome reporting for future study authors. Candidate studies for this systematic review were sourced via an electronic, multi-database literature search. All primary, clinical research studies of fgGAS were included with no date limits. Paired collaborators screened each study for inclusion and performed data extraction to document the outcomes, definitions, and times of outcome assessment following fgGAS. Results: After screening 1225 studies, 93 studies proceeded to data extraction, representing 7681 patients. 2621 separate individual outcomes were reported, 857 (32.7%) were defined, and the time of outcome assessment was given for 1856 outcomes (70.8%) but relied on nonspecific ranges of follow-up dates. "Attainment of orgasm", "Neovaginal stenosis", and "Neovaginal depth/length" were among the most commonly reported outcomes. Profound heterogeneity existed in the definitions used for these and for all outcomes reported in general. Discussion: The results demonstrate a need for clear outcomes, agreed definitions, and times of outcome assessment following fgGAS in transgender women and gender diverse individuals. The adoption of a consistent set of outcomes and definitions reported by all future studies of fgGAS (a Core Outcome Set) will aid in improving treatment comparisons in this patient group. This review is the first step in that process.

Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) has been proposed as a means of improving outcomes among patients with heart failure and reduced ejection fraction (HFrEF) who are otherwise receiving appropriate treatment. Unlike HFrEF, treatment options are more limited in patients with preserved ejection fraction (HFpEF) and the data pertaining to the management of AF in these patients are controversial. The aim of this systematic review and meta-analysis was to investigate the effects of CA on outcomes of patients with AF and HFpEF, such as functional status, post-procedural complications, hospitalization, morbidity and mortality, based on data from observational studies. METHODS: We systematically searched the electronic databases MEDLINE, PUBMED, EMBASE and the Cochrane Library for Central Register of Clinical Trials until May 2020. RESULTS: Overall, the pooling of our data showed that sinus rhythm was achieved long-term in 58.0% (95% CI 0.44-0.71). Long-term AF recurrence was noticed in 22.3% of patients. Admission for HF occurred in 6.2% (95% CI 0.04-0.09) whilst all-cause mortality was identified in 6.3% (95% CI 0.02-0.13). CONCLUSION: This meta-analysis is the first to focus on determining the benefits of a rhythm control strategy for patients with AF and HFpEF using CA, suggesting it may be worthwhile to investigate the effects of a CA rhythm control strategy as the default treatment of AF in HFpEF patients in randomized trials.

Long-term Outcomes of Catheter Ablation for Ventricular Arrhythmias in Post-Myocarditis Patients: Insights from a Meta-Analysis of Current Data.

BACKGROUND: In the past decade, catheter ablation (CA) has become a rapidly expanding treatment option for ventricular tachycardia (VT); however it is not commonly utilised for patients with post-myocarditis VT. We aimed to systematically review up-to-date evidence regarding feasibility, effectiveness, and safety of CA, with a specific focus on long-term relapse rate and procedural complications. METHODS: A structured electronic database search (PubMed, Embase, Cochrane) of the scientific literature was performed according to PRISMA guidelines for studies describing outcomes at up to 7.3 years after CA. The primary outcome measured was VT recurrence post-ablation. Procedural success was defined as freedom of ventricular arrhythmias (at the end of follow-up after an ablation procedure). The secondary outcome was significant procedural complications which included procedural death, stroke, cardiac tamponade, acute myocardial infarction, major vascular complications, and major bleeding, assessed on a study-by-study basis. RESULTS: A total of 186 patients were included in analysis with most patients (88%) being male. Over the follow-up period, there was a 18% relapse rate (n = 34) (confidence interval (CI); 0.12-0.24, I 2≈0, p = 0.77) with the majority of patients remaining VT free for the duration of follow-up. The overall procedural complication rate was 3.0% (n = 7) (CI; 0.01-0.07, I 2≈0, p = 0.44), and of note, there were no peri-procedural deaths or heart transplant surgeries reported. However, a single study reported a mortality of 10% (n = 2) during the follow-up period. CONCLUSIONS: CA is an effective and durable long-term therapeutic strategy for post-myocarditis VT patients with limited relapse rate and very low complication rates based on these non-randomised data. Larger randomised-controlled trials with standardised treatment and long follow-up are required to compare CA versus conventional treatment in the post-acute myocardial phase. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42399-022-01137-w.

High sensitivity troponin and COVID-19 outcomes.

BACKGROUND: Recent reports have demonstrated high troponin levels in patients affected with COVID-19. In the present study, we aimed to determine the association between admission and peak troponin levels and COVID-19 outcomes. METHODS: This was an observational multi-ethnic multi-centre study in a UK cohort of 434 patients admitted and diagnosed COVID-19 positive, across six hospitals in London, UK during the second half of March 2020. RESULTS: Myocardial injury, defined as positive troponin during admission was observed in 288 (66.4%) patients. Age (OR: 1.68 [1.49-1.88], p < .001), hypertension (OR: 1.81 [1.10-2.99], p = .020) and moderate chronic kidney disease (OR: 9.12 [95% CI: 4.24-19.64], p < .001) independently predicted myocardial injury. After adjustment, patients with positive peak troponin were more likely to need non-invasive and mechanical ventilation (OR: 2.40 [95% CI: 1.27-4.56], p = .007, and OR: 6.81 [95% CI: 3.40-13.62], p < .001, respectively) and urgent renal replacement therapy (OR: 4.14 [95% CI: 1.34-12.78], p = .013). With regards to events, and after adjustment, positive peak troponin levels were independently associated with acute kidney injury (OR: 6.76 [95% CI: 3.40-13.47], p < .001), venous thromboembolism (OR: 11.99 [95% CI: 3.20-44.88], p < .001), development of atrial fibrillation (OR: 10.66 [95% CI: 1.33-85.32], p = .026) and death during admission (OR: 2.40 [95% CI: 1.34-4.29], p = .003). Similar associations were observed for admission troponin. In addition, median length of stay in days was shorter for patients with negative troponin levels: 8 (5-13) negative, 14 (7-23) low-positive levels and 16 (10-23) high-positive (p < .001). CONCLUSIONS: Admission and peak troponin appear to be predictors for cardiovascular and non-cardiovascular events and outcomes in COVID-19 patients, and their utilisation may have an impact on patient management.

Preparing for COVID-19 exit strategies.

The COVID-19 pandemic has affected 20 million people worldwide with over 732,000 deaths and trillions of dollars of lost economic productivity. It has put many countries into lockdown to contain the virus and save lives. As COVID-19 cases in some countries start to plateau and societies work hard to 'flatten the curve', leaders are being asked to formulate plans for safe and staged 'exit strategies' to reopen society. Each country will decide on their own exit strategy but many plans are considering similar vital healthcare principles including the maintenance of social distancing to prevent ongoing community transmission, testing capacity, protection of the healthcare systems and the health of their care workers. This review aims to provide an overview of essential factors that plans for exit strategy should consider and their effect on the societies' social and healthcare life.

PRISMA 2020 statement: What's new and the importance of reporting guidelines.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, first published in 2009 [1], was developed in an attempt to increase the clarity, transparency, quality and value of these reports [2]. The 27-item checklist and four-phase flow diagram have become the hallmark of academic rigour in the publication of systematic reviews and meta-analyses, having been cited by over 60,000 papers [3]. These are frequently endorsed by journals in their 'Instructions to Authors' [4]. Developments in the methodology and terminology used when conducting systematic reviews [5], alongside the identification of limitations responsible for poor adherence, such as the use of ambiguous wording [6], have warranted an update to the PRISMA statement. The PRISMA 2020 statement, therefore, is intended to reflect this recent evolution in the identification, selection, appraisal and synthesis of research [7]. Here, we present an interpretive analysis of the updated statement, with a view towards encouraging its adoption by both journals and authors in the pursuit of advancing evidence-based medicine.

Impact of the coronavirus (COVID-19) pandemic on scientific research and implications for clinical academic training - A review.

A pneumonia outbreak of unknown aetiology emerged in Wuhan, China in December 2019. The causative organism was identified on 7th January 2020 as a novel coronavirus (nCoV or 2019-nCoV), later renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The resulting coronavirus disease (COVID-19) has infected over 88 million individuals, resulted in over 1.9 million deaths, and has led to an unprecedented impact on research activities worldwide. Extraordinary challenges have also been imposed on medical and surgical trainees following redeployment to full-time clinical duties. Moreover, the introduction of travel restrictions and strict lockdown measures have forced the closure of many institutions and laboratories working on research unrelated to the pandemic. The lockdown has similarly stifled supply chains and slowed research and development endeavours, whilst research charities have endured significant financial strains that have since reshaped the allocation and availability of funds. However, worldwide scientific adaptation to the COVID-19 pandemic has been observed through unprecedented levels of international collaboration alongside the uprise of remote telecommunication platforms. Although the long-term consequence of the COVID-19 pandemic on research and academic training is difficult to ascertain, the current crises will inevitably shape working and teaching patterns for years to come. To this end, we provide a comprehensive and critical evaluation of the impact of COVID-19 on scientific research and funding, as well as academic medical and surgical training.

Outcomes of posterior malleolar fixation in ankle fractures in a major trauma centre.

AIMS: Ongoing controversy exists over the indications and benefits of posterior malleolar fixation in ankle fractures. The aim of this pragmatic study was to evaluate the outcomes of posterior malleolar fracture fixation in ankle fractures in the setting of a major trauma centre. Our hypothesis is that posterior malleolus fixation leads to improved clinical outcomes. METHODS: A total of 320 patients were identified with operatively treated ankle fractures involving a posterior malleolus component, at our institution between January 2012 and January 2018, ensuring a minimum 2 year follow-up. Of these patients, 160 had the posterior malleolus fixed as part of their surgery and 160 did not. Patient demographics, surgical details and complications were assessed. The Manchester-Oxford Foot Questionnaire (MOXFQ) was the primary patient outcome measure. RESULTS: Fixation of the posterior malleolus was associated with a statistically significant improvement in patient outcomes. Mean MOXFQ score in the unfixed posterior malleolus group was 24.03 (0 - 62), compared to 20.10 (0 - 67) in the fixed posterior malleolus group (p = 0.04). Outcomes were worse with increasing size of posterior malleolar fragment. Metalwork-related issues were higher in the posterior malleolus fixed group (24/160 (15%) versus 10/160 (6.2%)) and re-operation rate was double. CONCLUSION: This study demonstrates that in the practical setting of a major trauma unit, fixation of the posterior malleolar fracture leads to improved patient outcomes but with increased metalwork risks and reoperation rates.

Long-Term Impact of Body Mass Index on Survival of Patients Undergoing Cardiac Resynchronization Therapy: A Multi-Centre Study.

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 ± 12.7 years, 44.1% women, and mean BMI: 28.3 ± 5.6 Kg/m2) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for ≥10 years. Patients were classified according to BMI as normal: <25.0 Kg/m2, overweight: 25.0 to 29.9 Kg/m2 and obese: ≥30.0 Kg/m2. 364 patients had normal weight, 494 were overweight and 419 were obese. CRT-Ds were implanted in >75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m2 (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m2 at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class.

The use of botulinum toxin in keloid scar management: a literature review.

INTRODUCTION: Administration of botulinum toxin is an increasingly popular procedure in the medical and aesthetic field. There is emerging evidence that it can influence fibroblast activity and minimise tension around the scar by virtue of muscular chemoimmobilisation. This review aims to explore the current evidence base behind the treatment of keloid scars with botulinum toxin. METHODS: A detailed literature review was conducted using PubMed Medline, Embase and Web of Science databases. Manuscripts were appraised and classified in accordance with the Joanna Briggs Institute Levels of Evidence by an independent consultant in evidence synthesis. The results of this search are presented in descending order of evidence for botulinum toxin as a primary management agent as well as a secondary adjunct following extralesional keloid excision. DISCUSSION: On the basis of level 1 evidence, botulinum toxin appears to be equivalent to triamcinolone in producing a short-term reduction in keloidal volume, height and vascularity. A number of level 1 and 2 studies also suggest that botulinum toxin may be particularly helpful in alleviating symptoms of keloid associated pain and itch. There are currently limited studies appraising the value of botulinum toxin in the postoperative management of keloid scars. CONCLUSION: Botulinum toxin may represent a promising agent in the management of keloid scars. However, further research involving large-scale studies with comparative designs and long-term follow-up is warranted to delineate the value of this therapeutic modality in scar management protocols.

Methods for generating and screening libraries of genetically encoded cyclic peptides in drug discovery.

Drug discovery has traditionally focused on using libraries of small molecules to identify therapeutic drugs, but new modalities, especially libraries of genetically encoded cyclic peptides, are increasingly used for this purpose. Several technologies now exist for the production of libraries of cyclic peptides, including phage display, mRNA display and split-intein circular ligation of peptides and proteins. These different approaches are each compatible with particular methods of screening libraries, such as functional or affinity-based screening, and screening in vitro or in cells. These techniques allow the rapid preparation of libraries of hundreds of millions of molecules without the need for chemical synthesis, and have therefore lowered the entry barrier to generating and screening for inhibitors of a given target. This ease of use combined with the inherent advantages of the cyclic-peptide scaffold has yielded inhibitors of targets that have proved difficult to drug with small molecules. Multiple reports demonstrate that cyclic peptides act as privileged scaffolds in drug discovery, particularly against 'undruggable' targets such as protein-protein interactions. Although substantial challenges remain in the clinical translation of hits from screens of cyclic-peptide libraries, progress continues to be made in this area, with an increasing number of cyclic peptides entering clinical trials. Here, we detail the various platforms for producing and screening libraries of genetically encoded cyclic peptides and discuss and evaluate the advantages and disadvantages of each approach when deployed for drug discovery.