Consensus guidelines for the safe prescription and administration of oral bowel-cleansing agents.

Oral bowel-cleansing preparations are used before colonic surgery and endoscopic and radiological assessment of the intestine to minimise faecal contamination. In February 2009, the UK National Patient Safety Agency issued a Rapid Response Report highlighting the potential risk of harm associated with the use of these preparations and instructing local NHS Trusts to implement safeguards to reduce this risk. This guidance has been prepared to help NHS Trusts to respond to these concerns, as the risk of complications is influenced by both individual patient risk factors and the choice of bowel preparation, for which definitive guidance was not previously available. This document provides an outline of the different available oral bowel-cleansing agents and the complications that may arise. This is followed by recommendations for their use in different patient groups and circumstances. The recommendations are based on consensus between the authors, each of whom circulated drafts to members of their specialist society. The evidence for these recommendations has been assessed using the modified GRADE system. The recommendations cover the choice, administration and complications (relative and absolute) of the different oral bowel-cleansing agents, with specific guidance provided for different patient groups.

Antibiotic Prophylaxis in Plastic Surgery Correlation Between Practice and Evidence.

BACKGROUND: The use of appropriate preoperative antibiotic prophylaxis decreases the risk of surgical site infections (SSI); however, the breadth of plastic surgery procedures makes it challenging to ensure appropriate use for each unique procedure type. Currently, plastic surgeons lack a cohesive and comprehensive set of evidence-based guidelines (EBG) for surgical prophylaxis. We sought to profile the perioperative antibiotic prescribing patterns for plastic surgeons in British Columbia to investigate if they are congruent with published recommendations. In doing so, we aim to determine risk factors for antibiotic overprescribing in the context of surgical prophylaxis. METHODS: A literature review identifying EBG for antibiotic prophylaxis use during common plastic surgery procedures was performed. Concurrently, a provincial survey of plastic surgery residents, fellows, academic and community plastic surgeons was used to identify their antibiotic prophylaxis prescribing practices. These findings were then compared to recommendations identified from our review. The compliance of the provincial plastic surgery community with current EBG was determined for 38 surgical scenarios to identify which clinical factors and procedure types were associated with unsupported antibiotic use. RESULTS: Within the literature, 31 of the 38 categories of surveyed plastic surgery operations have EBG for use of prophylactic antibiotics. When surgical procedures have EBG, 19.5% of plastic surgery trainees and 21.9% of practicing plastic surgeons followed recommended prophylaxis use. Average adherence to EBG was 59.1% for hand procedures, 24.1% for breast procedures, and 23.9% for craniofacial procedures. Breast reconstruction procedures and contaminated craniofacial procedures were associated with a significant reduction in adherence to EBG resulting in excessive antibiotic use. CONCLUSION: Even when evidence-based recommendations for antibiotic prophylaxis exist, plastic surgeons demonstrate variable compliance based on their reported prescribing practices. Surgical procedures with low EBG compliance may reflect risk avoidant behaviors in practicing surgeons and highlight the importance of improving education on the benefits of antibiotic prophylaxis in these clinical situations.

HISTORIQUE: Une prophylaxie antibiotique préopératoire appropriée réduit le risque d'infections au foyer de l'opération (IFO), mais en raison de l'éventail des interventions de plasturgie, il est difficile d'en garantir la bonne utilisation pour chaque type d'intervention. À l'heure actuelle, les plasticiens ne possèdent pas d'ensemble de directives fondées sur des données probantes (DDP) cohésives et complètes à l'égard de la prophylaxie chirurgicale. Les chercheurs ont cherché à saisir les habitudes de prescription d'antibiotiques périopératoires des plasticiens de la Colombie-Britannique pour vérifier si elles concordent avec les recommandations publiées. Ce faisant, ils ont voulu déterminer les facteurs de risque de surprescription d'antibiotiques dans le cadre de la prophylaxie chirurgicale. MÉTHODOLOGIE: Les chercheurs ont effectué une analyse bibliographique faisant état des DDP relatives au recours à une prophylaxie antibiotique pendant des interventions de plasturgie courantes. Parallèlement, un sondage auprès des résidents, des associés, des scientifiques et des généralistes de la plasturgie a permis de déterminer les pratiques de prescription de prophylaxie antibiotique. Les chercheurs ont comparé ces observations aux recommandations relevées dans leur analyse. Ils ont établi l'adhésion du milieu provincial de la plasturgie aux DDP à jour dans 38 scénarios chirurgicaux pour déterminer les facteurs cliniques et les types d'intervention associés à l'utilisation d'antibiotiques non préconisés. RÉSULTATS: Dans les publications scientifiques, 31 des 38 catégories d'opérations de plasturgie sondées étaient assorties de DDP sur la prophylaxie antibiotique. Lorsque les interventions chirurgicales étaient ainsi associées à des DDP, 19,5% des stagiaires en plasturgie et 21,9% des plasticiens en exercice respectaient les recommandations relatives à l'utilisation de la prophylaxie. L'adhésion moyenne aux DDP s'élevait à 59,1 % dans le cas des interventions de la main, à 24,1 % dans celui des interventions mammaires et à 23,9 % dans celui des interventions craniofaciales. Les interventions de reconstruction mammaire et la contamination des interventions craniofaciales étaient liées à une diminution importante de l'adhésion aux DDP entraînant une utilisation excessive d'antibiotiques. CONCLUSION: Même en présence de recommandations fondées sur des données probantes relatives à la prophylaxie antibiotique, les pratiques de prescription déclarées par les plasticiens démontrent une adhésion variable aux DDP. Les interventions chirurgicales assorties d'une faible adhésion aux DDP pourraient refléter des comportements d'évitement risqués de la part des chirurgiens en exercice et font ressortir l'importance d'améliorer l'enseignement sur les avantages de la prophylaxie antibiotique dans ces situations cliniques.

Microbial community compositions in breast implant biofilms associated with contracted capsules.

Subclinical bacterial infections (biofilms) are strongly implicated in breast augmentation failure due to capsular contracture, and while these infections are generally ascribed to common skin commensals, this remains largely unsubstantiated through robust cultivation independent analyses. To determine capsule biofilm microbial community compositions, we employed amplicon sequencing of the 16S rRNA gene using DNA extracted from breast implant capsule samples. These cultivation independent analyses revealed that capsule associated biofilms are more diverse than canonical single-species infections, but have relatively low diversity (~ <100 species) compared to many host-associated microbial communities. In addition to taxa commonly associated with capsular contracture, the biofilms analyzed comprised a number of taxa that escaped detection in cultivation-dependent work. We have also isolated several key taxa identified through the culture-independent analyses. Together our analyses reveal that capsule biofilms are more diverse than cultivation studies suggest and can be heterogeneous within an individual capsule, between breasts of the same patient, across similar implant types, and over a range in severity of contracture. The complex nature of these communities requires further study across a broader suite of patients in addition to higher resolution analyses including metagenomics to better assess the fundamental role of microorganisms in capsular contracture.

Granzyme B inhibition reduces disease severity in autoimmune blistering diseases.

Pemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls. In vivo and in vitro studies show that granzyme B contributes to blistering by degrading key anchoring proteins in the dermal-epidermal junction that are necessary for dermal-epidermal adhesion. Further, granzyme B mediates IL-8/macrophage inflammatory protein-2 secretion, lesional neutrophil infiltration, and lesional neutrophil elastase activity. Clinically, granzyme B is elevated and abundant in human pemphigoid disease blister fluids and lesional skin. Collectively, granzyme B is a potential therapeutic target in pemphigoid diseases.

Granzyme B is elevated in autoimmune blistering diseases and cleaves key anchoring proteins of the dermal-epidermal junction.

In healthy skin, epidermis and dermis are anchored together at the dermal-epidermal junction (DEJ), a specialized basement membrane pivotal for skin integrity and function. However, increased inflammation in the DEJ is associated with the disruption and separation of this junction and sub-epidermal blistering. Granzyme B (GzmB) is a serine protease secreted by immune cells. Dysregulated inflammation may lead to increased GzmB accumulation and proteolysis in the extracellular milieu. Although elevated GzmB is observed at the level of the DEJ in inflammatory and blistering skin conditions, the present study is the first to explore GzmB in the context of DEJ degradation in autoimmune sub-epidermal blistering. In the present study, GzmB induced separation of the DEJ in healthy human skin. Subsequently, α6/ß4 integrin, collagen VII, and collagen XVII were identified as extracellular substrates for GzmB through western blot, and specific cleavage sites were identified by mass spectrometry. In human bullous pemphigoid, dermatitis herpetiformis, and epidermolysis bullosa acquisita, GzmB was elevated at the DEJ when compared to healthy samples, while α6/ß4 integrin, collagen VII, and collagen XVII were reduced or absent in the area of blistering. In summary, our results suggest that regardless of the initial causation of sub-epidermal blistering, GzmB activity is a common final pathway that could be amenable to a single targeted treatment approach.