Ethanol‐Lock Therapy for the Prevention of Central Venous Access Device Infections in Pediatric Patients With Intestinal Failure

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141158/1/jpen0067.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141158/2/jpen0067-sup-0001.pd

SdrF, a Staphylococcus epidermidis Surface Protein, Contributes to the Initiation of Ventricular Assist Device Driveline–Related Infections

Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneous driveline entry site acts as a potential portal of entry for bacteria, allowing development of either localized or systemic infections. A novel in vitro binding assay using explanted drivelines obtained from patients undergoing transplantation and a heterologous lactococcal system of surface protein expression were used to identify S. epidermidis surface components involved in the pathogenesis of driveline infections. Of the four components tested, SdrF, SdrG, PIA, and GehD, SdrF was identified as the primary ligand. SdrF adherence was mediated via its B domain attaching to host collagen deposited on the surface of the driveline. Antibodies directed against SdrF reduced adherence of S. epidermidis to the drivelines. SdrF was also found to adhere with high affinity to Dacron, the hydrophobic polymeric outer surface of drivelines. Solid phase binding assays showed that SdrF was also able to adhere to other hydrophobic artificial materials such as polystyrene. A murine model of infection was developed and used to test the role of SdrF during in vivo driveline infection. SdrF alone was able to mediate bacterial adherence to implanted drivelines. Anti-SdrF antibodies reduced S. epidermidis colonization of implanted drivelines. SdrF appears to play a key role in the initiation of ventricular assist device driveline infections caused by S. epidermidis. This pluripotential adherence capacity provides a potential pathway to infection with SdrF-positive commensal staphylococci first adhering to the external Dacron-coated driveline at the transcutaneous entry site, then spreading along the collagen-coated internal portion of the driveline to establish a localized infection. This capacity may also have relevance for other prosthetic device–related infections

First Human Model of In Vitro Candida albicans Persistence within Granuloma for the Reliable Study of Host-Fungi Interactions

BACKGROUND: The balance between human innate immune system and Candida albicans virulence signaling mechanisms ultimately dictates the outcome of fungal invasiveness and its pathology. To better understand the pathophysiology and to identify fungal virulence-associated factors in the context of persistence in humans, complex models are indispensable. Although fungal virulence factors have been extensively studied in vitro and in vivo using different immune cell subsets and cell lines, it is unclear how C. albicans survives inside complex tissue granulomas. METHODOLOGY/PRINCIPAL FINDING: We developed an original model of in vitro human granuloma, reproducing the natural granulomatous response to C. albicans. Persistent granulomas were obtained when the ratio of phagocytes to fungi was high. This in vitro fungal granuloma mimics natural granulomas, with infected macrophages surrounded by helper and cytotoxic T lymphocytes. A small proportion of granulomas exhibited C. albicans hyphae. Histological and time-lapse analysis showed that C. albicans blastoconidia were located within the granulomas before hyphae formation. Using staining techniques, fungal load calculations, as well as confocal and scanning electron microscopy, we describe the kinetics of fungal granuloma formation. We provide the first direct evidence that C. albicans are not eliminated by immunocompetent cells inside in vitro human granulomas. In fact, after an initial candicidal period, the remaining yeast proliferate and persist under very complex immune responses. CONCLUSIONS/SIGNIFICANCE: Using an original in vitro model of human fungal granuloma, we herein present the evidence that C. albicans persist and grow into immunocompetent granulomatous structures. These results will guide us towards a better understanding of fungal invasiveness and, henceforth, will also help in the development of better strategies for its control in human physiological conditions

Idiopathic toe walking and sensory processing dysfunction

<p>Abstract</p> <p>Background</p> <p>It is generally understood that toe walking involves the absence or limitation of heel strike in the contact phase of the gait cycle. Toe walking has been identified as a symptom of disease processes, trauma and/or neurogenic influences. When there is no obvious cause of the gait pattern, a diagnosis of idiopathic toe walking (ITW) is made. Although there has been limited research into the pathophysiology of ITW, there has been an increasing number of contemporary texts and practitioner debates proposing that this gait pattern is linked to a sensory processing dysfunction (SPD). The purpose of this paper is to examine the literature and provide a summary of what is known about the relationship between toe walking and SPD.</p> <p>Method</p> <p>Forty-nine articles were reviewed, predominantly sourced from peer reviewed journals. Five contemporary texts were also reviewed. The literature styles consisted of author opinion pieces, letters to the editor, clinical trials, case studies, classification studies, poster/conference abstracts and narrative literature reviews. Literature was assessed and graded according to level of evidence.</p> <p>Results</p> <p>Only one small prospective, descriptive study without control has been conducted in relation to idiopathic toe walking and sensory processing. A cross-sectional study into the prevalence of idiopathic toe walking proposed sensory processing as being a reason for the difference. A proposed link between ITW and sensory processing was found within four contemporary texts and one conference abstract.</p> <p>Conclusion</p> <p>Based on the limited conclusive evidence available, the relationship between ITW and sensory processing has not been confirmed. Given the limited number and types of studies together with the growing body of anecdotal evidence it is proposed that further investigation of this relationship would be advantageous.</p

Preferences of orthopedic surgeons for treating midshaft clavicle fracture in adults

Objective: To determine the current clinical practice in Latin America for treating midshaft clavicle fractures, including surgical and non-surgical approaches. Methods: A cross-sectional study using a descriptive questionnaire. Shoulder and elbow surgeons from the Brazilian Society of Shoulder and Elbow Surgery and from the Latin American Society of Shoulder and Elbow were contacted and asked to complete a short questionnaire (SurveyMonkey (R)) on the management of midshaft fractures of the clavicle. Incomplete or inconsistent answers were excluded. Results: The type of radiographic classification preferably used was related to description of fracture morphology, according to 41% of participants. Allman classification ranked second and was used by 24.1% of participants. As to indications for surgical treatment, only the indications with shortening and imminence of skin exposure were statistically significant. Conservative treatment was chosen in cortical contact. Regarding immobilization method, the simple sling was preferred, and treatment lasted from 4 to 6 weeks. Although the result was not statistically significant, the blocked plate was the preferred option in surgical cases. Conclusion: The treatment of midshaft clavicle fractures in Latin America is in accordance with the current literature.Objetivo: Determinar a prática clínica atual na América Latina para o tratamento das fraturas do terço médio da clavícula, incluindo abordagens cirúrgicas e não cirúrgicas. Métodos: Estudo transversal com aplicação de questionário descritivo. Cirurgiões de ombro e cotovelo da Sociedade Brasileira de Cirurgia do Ombro e Cotovelo e da Sociedade Latino-Americana de Ombro e Cotovelo foram contatados e convidados a completar um breve questionário (SurveyMonkey®) sobre o manejo das fraturas do terço médio da clavícula. Foram excluídas as respostas incompletas ou inconsistentes. Resultados: O tipo de classificação radiográfica utilizada de preferência esteve de acordo com a descrição da morfologia da fratura, representando 41% do total dos participantes. Em segundo lugar, apareceu a classificação de Allman, que foi utilizada por 24,1% dos participantes. Nas indicações de tratamento cirúrgico, as indicações com encurtamento e iminência de exposição da pele foram estatisticamente significativas. Tratamento conservador foi prescrito em caso de contato entre as corticais. Como método de imobilização, a tipoia simples foi a preferência, e o tempo de tratamento foi de 4 a 6 semanas. Apesar do resultado sem significância estatística, a placa bloqueada foi a opção preferencial nos casos cirúrgicos. Conclusão: A metodologia de tratamento das fraturas do terço médio da clavícula nos países da América Latina é semelhante, assim como com a literatura atual.Hosp Israelita Albert Einstein, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilFac Med ABC, Santo Andre, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilWeb of Scienc

A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains