Anal dysplasia among solid organ transplant recipients; a cross sectional study / Displasia anal entre receptores de transplantes de órgãos sólidos - um estudo transversal

ABSTRACT Introduction: The incidence of anal cancer in United States has increased over of the last few decades impacting immunosuppressed populations like solid organ transplant recipients, in particular. The aim of this study was to evaluate the prevalence of anal dysplasia among solid organ transplant patients. We also attempted to identify factors that predispose solid organ transplant recipients to developing anal dysplasia. Methods and materials: Patients presenting to transplant office for routine care were recruited to participate in the study. All anal cytology specimens were collected using standard anal pap technique. The results were assessed using Bethesda classification. Information on perceived risk factors for development of anal dysplasia among our subjects was obtained. Results: Among 80 patients approached, 47 agreed to participate in the study. Of all the samples 19.1% had an inadequate amount of specimen to perform any analysis. Dysplastic cells were found in 10.5% of the specimens available for analysis. We were not able to identify any risk factors including age, gender distribution, smoking, and duration of immunosuppression that were statistically significant different between patients with anal dysplasia versus those without anal dysplasia. Conclusions: The rate of anal dysplasia detectable on cytology is high enough to warrant anal dysplasia screening in transplant recipients, which can then be followed up with high-resolution anoscopy with biopsy. Defining a cohort of patients among solid organ transplant recipients who are at an increased risk for the development of anal dysplasia mandating screening continues to be a challenge.

RESUMO Introdução: A incidência de câncer anal nos Estados Unidos aumentou nas últimas décadas, afetando populações imunossuprimidas, especialmente receptores de órgãos sólidos. O objetivo deste estudo foi avaliar a prevalência de displasia anal entre pacientes que receberam transplante de órgãos sólidos. Os autores buscaram identificar fatores que predispõem os receptores de transplante de órgãos sólidos a desenvolverem displasia anal. Métodos e materiais: Pacientes que se apresentaram ao consultório de transplante para acompanhamento de rotina foram recrutados para participar do estudo. Todos os espécimes de citologia foram coletados usando a técnica padrão de Papanicolau anal. Os resultados foram avaliados usando a classificação de Bethesda. Foram coletados dados sobre os fatores de risco percebidos para o desenvolvimento de displasia anal entre os participantes. Resultados: Dos 80 pacientes abordados, 47 concordaram em participar do estudo. Do total de amostras, 19,1% tinham uma quantidade inadequada para realizar qualquer análise. Células displásicas foram encontradas em 10,5% dos espécimes disponíveis para análise. Não foi possível identificar quaisquer fatores de risco, incluindo idade, distribuição de gênero, tabagismo e duração da imunossupressão, que foram estatisticamente diferentes entre pacientes com displasia anal e aqueles sem displasia anal. Conclusões: A taxa de displasia anal detectável na citologia é alta o suficiente para justificar a triagem em receptores de transplante, que pode então ser acompanhada com anuscopia de alta resolução com biópsia. A definição de triagem para uma coorte de pacientes entre os receptores de transplantes de órgãos sólidos que apresentam risco aumentado para o desenvolvimento displasia anal continua a ser um desafio.

Adipose-derived stem cells extract has a proliferative effect on myogenic progenitors.

Finding an effective method to regenerate muscle is a growing issue in the orthopedic field. Platelet-rich plasma (PRP) has recently been considered for therapeutic use due to its capacity to induce proliferation of myogenic progenitor cells (MPCs). Adipose-derived stem cells (ASCs) and its extract are regarded as a promising treatment for various disorders within the orthopedic field but their therapeutic relevance in the muscle regeneration is poorly investigated. In this study, rabbit MPCs were cultured from the supraspinatus of rabbit and characterized by myogenic markers. To investigate the paracrine effect of ASCs on MPCs, coculture experiments were performed. In order to see the anabolic effect of ASC-extracts (ASC-ex) in MPCs, cell proliferation assays were performed and compared with the PRP-added condition. Coculture experiment showed ASCs had an anabolic paracrine effect on proliferation of MPCs. PRP had a positive effect on proliferation of MPCs when compared to the control (100 ± 7.4% vs 195.2 ± 19.2%, p < 0.001); however, ASC-ex promoted greater proliferation than the PRP condition (467.3 ± 38.7%, p < 0.001 compared with PRP). Similarly, in C2C12 cells, PRP showed an increased rate when compared to the control (100 ± 5.9% vs 205.1 ± 45.4%, p < 0.001), and treatment of ASC-ex showed dramatic increase in proliferation (335.9 ± 37.8%, p < 0.001 compared with PRP). ASC-ex had positive effect on expanding MPCs of rabbit and myoblast cell line, and its capacity to induce proliferation was notably stronger than that of PRP. In conclusion, the study suggests that rabbit ASC-ex have stronger proliferative effect on MPCs than rabbit PRP. Thus, ASC-ex could be a therapeutic candidate for muscle regeneration by activation of endogenous MPCs.

Fifteen days of microgravity causes growth in calvaria of mice.

Bone growth may occur in spaceflight as a response to skeletal unloading and head-ward fluid shifts. While unloading causes significant loss of bone mass and density in legs of animals exposed to microgravity, increased blood and interstitial fluid flows accompanying microgravity-induced fluid redistribution may elicit an opposite effect in the head. Seven 23-week-old, adult female wild-type C57BL/6 mice were randomly chosen for exposure to 15 days of microgravity on the STS-131 mission, while eight female littermates served as ground controls. Upon mission completion, all 15 murine calvariae were imaged on a micro-computed tomography scanner. A standardized rectangular volume was placed on the parietal bones of each calvaria for analyses, and three parameters were determined to measure increased parietal bone volume: bone volume (BV), average cortical thickness (Ct.Th), and tissue mineral density (TMD). Microgravity exposure caused a statistically significant increase in BV of the spaceflight (SF) group compared to that of the ground control (GC) group, the mean BV±SD for the SF group was 1.904±0.842 mm3, compared to 1.758±0.122 mm3 for the GC group (p<0.05). Ct.Th demonstrated a trend of increase from 0.099±0.006 mm in the GC group to 0.104±0.005 mm in the SF group (p=0.12). TMD was similar between the two groups with 0.878±0.029 g/cm3 for the GC group and 0.893±0.028 g/cm3 for the SF group (p=0.31). Our results indicate that microgravity causes responsive changes in calvarial bones that do not normally bear weight. These findings suggest that fluid shifts alone accompanying microgravity may initiate bone adaptation independent of skeletal loading by tissue.

Space physiology VI: exercise, artificial gravity, and countermeasure development for prolonged space flight.

When applied individually, exercise countermeasures employed to date do not fully protect the cardiovascular and musculoskeletal systems during prolonged spaceflight. Recent ground-based research suggests that it is necessary to perform exercise countermeasures within some form of artificial gravity to prevent microgravity deconditioning. In this regard, it is important to provide normal foot-ward loading and intravascular hydrostatic-pressure gradients to maintain musculoskeletal and cardiovascular function. Aerobic exercise within a centrifuge restores cardiovascular function, while aerobic exercise within lower body negative pressure restores cardiovascular function and helps protect the musculoskeletal system. Resistive exercise with vibration stimulation may increase the effectiveness of resistive exercise by preserving muscle function, allowing lower intensity exercises, and possibly reducing risk of loss of vision during prolonged spaceflight. Inexpensive methods to induce artificial gravity alone (to counteract head-ward fluid shifts) and exercise during artificial gravity (for example, by short-arm centrifuge or exercise within lower body negative pressure) should be developed further and evaluated as multi-system countermeasures.