Bioengineered human skeletal muscle capable of functional regeneration.

BACKGROUND: Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology. RESULTS: Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl2) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo. CONCLUSIONS: This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.

Impact of anxio-depressive symptoms and cognitive function on oral anticancer therapies adherence.

PURPOSE: Oral anticancer therapies have an important place in the therapeutic arsenal, but factors influencing adherence to oral treatment are poorly documented in oncology. The objective of this study was to assess the impact of anxio-depressive symptoms and cognitive functioning on oral medication adherence. METHODS: This prospective study included cancer patients initiating a first oral therapy. Before initiation of treatment, an assessment of depression, anxiety, and cognition was performed. Using self-report questionnaires, we collected information on socio-demographic conditions and the non-adherence at 1 (M1) and 3 months (M3) after the beginning of treatment. RESULTS: Among 129 patients enrolled, median age was 70 years and 81% of patients were treated for metastatic cancer. Before initiating treatment, 16% and 8% of patients presented respectively depression and anxiety symptoms. Global cognitive impairment was observed in 51% of patients. Ten percent of the patients were non-adherent at M1 and 13% at M3. Depression was strongly associated with non-adherence at M1 (P = 0.046) and M3 (P = 0.014), but not anxiety. Non-adherence was associated with lower working memory (P = 0.037) and digit memory (P = 0.018) at M1 and short-term memory (P = 0.04) at M3. Patients with more than eight co-medications were more often non-adherents (P = 0.055). CONCLUSIONS: Non-adherence to oral anticancer therapies was mainly associated to depression. Focusing on depressive symptoms before initiation of oral anticancer therapy could help to identify patient profiles more likely to fail self-management. Working memory, digit memory, and short-term memory also seem to play a role in non-adherence. Further studies should include a more specific population, especially according to age.

Impact of type-1 collagen hydrogel density on integrin-linked morphogenic response of SH-SY5Y neuronal cells.

Cellular metabolism and behaviour is closely linked to cytoskeletal tension and scaffold mechanics. In the developing nervous system functional connectivity is controlled by the interplay between chemical and mechanical cues that initiate programs of cell behaviour. Replication of functional connectivity in neuronal populations in vitro has proven a technical challenge due to the absence of many systems of biomechanical regulation that control directional outgrowth in vivo. Here, a 3D culture system is explored by dilution of a type I collagen hydrogel to produce variation in gel stiffness. Hydrogel scaffold remodelling was found to be linked to gel collagen concentration, with a greater degree of gel contraction occurring at lower concentrations. Gel mechanics were found to evolve over the culture period according to collagen concentration. Less concentrated gels reduced in stiffness, whilst a biphasic pattern of increasing and then decreasing stiffness was observed at higher concentrations. Analysis of these cultures by PCR revealed a program of shifting integrin expression and highly variable activity in key morphogenic signal pathways, such as mitogen-associated protein kinase, indicating genetic impact of biomaterial interactions via mechano-regulation. Gel contraction at lower concentrations was also found to be accompanied by an increase in average collagen fibre diameter. Minor changes in biomaterial mechanics result in significant changes in programmed cell behaviour, resulting in adoption of markedly different cell morphologies and ability to remodel the scaffold. Advanced understanding of cell-biomaterial interactions, over short and long-term culture, is of critical importance in the development of novel tissue engineering strategies for the fabrication of biomimetic 3D neuro-tissue constructs. Simple methods of tailoring the initial mechanical environment presented to SH-SY5Y populations in 3D can lead to significantly different programs of network development over time.

[Williams-Beuren syndrome: a multidisciplinary approach]. / Le syndrome de Williams-Beuren: une approche pluridisciplinaire.

Williams-Beuren syndrome (WBS) (OMIM# 194050) is a rare, most often sporadic, genetic disease caused by a chromosomal microdeletion at locus 7q11.23 involving 28 genes. Among these, the elastin gene codes for the essential component of the arterial extracellular matrix. Developmental disorders usually associate an atypical face, cardiovascular malformations (most often supravalvular aortic stenosis and/or pulmonary artery stenosis) and a unique neuropsychological profile. This profile is defined by moderate mental retardation, relatively well-preserved language skills, visuospatial deficits and hypersociability. Other less known or rarer features, such as neonatal hypercalcemia, nutrition problems in infancy, ophthalmological anomalies, hypothyroidism, growth retardation, joint disturbances, dental anomalies and hypertension arising in adolescence or adulthood, should be treated. The aim of this paper is to summarize the major points of WBS regarding: (i) the different genes involved in the deletion and their function, especially the elastin gene and recent reports of rare forms of partial WBS or of an opposite syndrome stemming from a microduplication of the 7q11.23 locus, (ii) the clinical features in children and adults with a focus on cardiovascular injury, and (iii) the specific neuropsychological profile of people with WBS through its characteristics, the brain structures involved, and learning.

Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan Criteria After Downstaging: Is It Worth It?

BACKGROUND: The outcome of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is excellent if it is performed within the Milan criteria (ie, single tumor less than 5 cm or 3 tumors less than 3 cm each one and no macrovascular invasion). However, after a few studies, it has become possible to have a similar survival expanding those criteria. The aim of this study is to evaluate the survival of patients with advanced HCC who, after downstaging, did not met the Milan criteria although they were within the "up to seven" benchmark, and were transplanted at our center in the last 5 years. PATIENTS AND METHODS: This is a retrospective study of patients who underwent OLT for HCC in the last 5 years in our center exceeding Milan criteria despite remaining within the "up to seven" benchmark. An observational study of associated factors with overall survival based on patient characteristics after OLT was performed. For the statistical study, the statistical program SPSS v. 17.0 (Chicago, Illinois, United States) was used. RESULTS: We studied 95 patients who had been transplanted for HCC in this period, 11 of whom met the study requirements. There were 10 (91%) males and 1 female. The mean age of the patients was 54.73 ± 8.75 years, with an average waiting list time of 279 days. Nine patients had a Child A status, with a mean Model for End-stage Liver Disease score of 9.64 (range, 6 to 16). The most frequent etiology of cirrhosis was hepatitis C virus infection in 6 patients (50%) followed by hepatitis B virus infection and ethanolic and cryptogenic cirrhosis. Ten patients (91%) had at least one pretransplantation transarterial chemoembolization. The survival of patients after 1 year was 75%, whereas after 4 years that rate decreases to 25%. At this time, we do not have any patients with a 5-year survival rate. The longest survival rate is 55 months. CONCLUSIONS: Although the expanded indication of transplantation in HCC raises controversies, especially after downstaging, it is possible to provide acceptable survival rates for patients within the expanded criteria of "up to seven" after locoregional therapies. The performance of a liver transplant in the patient profile shown in this article should also be evaluated from the perspective of the relative lack of organs for transplantation.

Successful stent-grafting for iatrogenic aortic rupture and life-threatening hemoptysis.

Bronchiectasis presenting as massive hemoptysis and iatrogenic lesions of the thoracic aorta are life-threatening processes with very difficult management. We report a case of massive hemoptysis from bronchiectasis complicated with contained rupture of the descending thoracic aorta during bronchial artery embolization. Both lesions were confirmed by angiography and successfully treated by implantation of an endovascular stent-graft in the thoracic aorta. As far as we know, there are no previous reports of successful management of massive hemoptysis from bronchiectasis with an endovascular covered stent-graft prosthesis.

Prognostic Value of 18-Fluorodeoxyglucose-Positron Emission Tomography After Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma Undergoing Orthotopic Liver Transplantation.

INTRODUCTION: The aim of this study was to analyze the correlation between 18-FDG positron emission tomography (PET)/computed tomography (CT), histological necrosis, and prognosis after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients undergoing orthotopic liver transplantation (OLT). PATIENTS: From January 2007 through December 2013, 81 patients with HCC and liver cirrhosis were included in our liver transplantation program. For this study we selected patients who underwent 18-FDG PET/CT pre-TACE and post-TACE. All patients underwent liver transplantation within 8 weeks after PET/CT. RESULTS: Twenty patients with a median age of 58 years (range, 46-69 years) underwent an 18-FDG PET/CT before and after TACE. The median Standardized Uptake Value (SUV) before TACE was 3.8 (range, 2.6-8.7), with a median post-TACE SUV of 0% (range, 0-4). Among patients whose post-TACE SUV decreased to <3, >70% necrosis was observed upon study of a hepatectomy sample, with a survival rate of 100% and 80% at 1 and 3 years, respectively. CONCLUSION: In conclusion, performance of an 18-FDG PET/CT before and after TACE with comparison of SUV values among patients with HCC awaiting OLT provided valuable information regarding the effectiveness of TACE.

Case report: Conservative management of an arteriovenous fistula of the inferior epigastric artery.

We present a case of pseudoaneurysm and arteriovenous fistula of the inferior epigastric artery secondary to the placement of a drain during a surgical intervention. We stress the utility of colour Doppler ultrasound and arteriography embolisation in diagnosis and treatment, respectively.

[Tetralogy of Fallot complicated by severe hemoptysis in the adult]. / Tetralogía de Fallot en el adulto complicada con hemoptisis grave. Tratamiento mediante embolización de la arteria tirocervical izquierda.

Fallot tetralogy with pulmonary artery atresia is a special situation in which the patient can survive up to middle-age. In these cases some complications such as hemoptysis can appear with difficult treatment that endangers the life of the patient. When the cause of bleeding is the arteriovenous shunts, which are frequent in the multiple vascular malformations originated in this congenital cardiopathy, the selective embolization of these malformations can be an effective option of treatment.

[Inguinal tumor as the first manifestation of a pancreatic pseudocyst]. / Tumoración inguinal como primera manifestación de un seudoquiste pancreático.

We report a case of pancreatic pseudocyst in alcoholic pancreatitis, that presented as a mass in the inguinal region. The mechanism of this peculiar clinical presentation was the dissemination of the content of the pseudocyst along the psoas muscle. We review the involvement of psoas muscle in pancreatic pathology, giving emphasis to reports of inguinal or thigh masses as initial manifestations.

[Pleural effusion due to Listeria monocytogenes. A case report and review of the literature]. / Derrame pleural por Listeria monocytogenes. Presentación de un caso y revisión de la literatura.

The infection caused by Listeria monocytogenes is a relatively common condition in immunosuppressed patients. The most frequent presentation in adults are sepsis and meningitis. Pleural fluid infection due to this pathogen is a rare finding in the literature. Most cases are found in immunosuppressed patients, particularly in those with haematologic malignancies. We report one case of pleural fluid infection due to Listeria monocytogenes in a patient with hepatic cirrhosis (the third case in the literature). We also review the seventeen cases previously reported and describe the clinical manifestations, its immunosuppression states relationship, the treatment of choice and the mortality.

Comparative study of right portal vein ligation versus embolisation for induction of hypertrophy in two-stage hepatectomy for multiple bilateral colorectal liver metastases.

AIM: In patients with two-stage hepatectomy (TSH) for multiple bilobar liver metastases from colorectal cancer, few clinical series compare functional remnant hypertrophy of the liver volume between right portal vein ligation (PVL) and embolisation (PVE). Our objective is to analyse the effectiveness of portal vein ligation to achieve hypertrophy of the functional remnant volume (FRV) of the liver and to compare the results with portal vein embolisation in a series of patients with multiple bilobar liver metastases from colorectal carcinoma. PATIENTS AND METHODS: Between September 2001 and September 2011 we performed a TSH in 41 patients with multiple bilobar colorectal liver metastases. A right PVL was performed in 23 patients with an insufficient FRV (three patients did not complete the second stage due to tumour progression and were excluded). We prospectively compare these results with the increased remnant volume obtained in 18 patients with right PVE. RESULTS: The median FRV was higher in the patients with PVE, rising from 501 ml (range 309-703) to 636 ml (range 387-649), than those with PVL, rising from 510 ml (range 203-824) to 595 ml (range 313-1213) (p < 0.05). The median %FRVI was higher in the patients with PVE (median 40%; range 21-65%) than those with PVL (median 30%; range 21-60%) (p < 0.05). CONCLUSIONS: PVL and PVE were effective in all cases for obtaining hypertrophy of the FRV before major liver resection. Right PVE obtains better results and should be used where necessary to achieve a further increase in volume.

The evolution of therapeutic strategies for biliary tract complications after liver transplantation over a period of 20 years.

Despite the improved overall outcomes of liver transplantation as a result of advances in surgical techniques and improved immunosuppressive control, biliary complications (BCs) continue to be the most common cause of morbidity in liver transplant recipients. The objectives of this study were to analyze the incidence, type, and management of BCs over a 20-year period. We performed a comparative study of two groups of liver transplant patients in our unit operated on by the same surgical team: group I consists of the first 300 liver transplant patients (1989-1992), and group II is composed of the last 300 liver transplants (2007-2011). We found no significant differences in the number of cases of biliary leakage whether or not a Kehr T-tube was used. However, there was a significant relationship between a greater number of anastomotic strictures and less use of a Kehr T-tube. In our series, there has been a decrease over the years in the number of surgical interventions required to resolve these complications and an increase in radiologic and endoscopic treatment.

Impact of a telemetry-transmitter implant on daily behavioral rhythms and physiological stress indicators in gilthead seabream (Sparus aurata).

The effect of intracoelomic tagging of an acoustic telemetry transmitter (1.65% ratio of tag mass in the air to fish mass in the air) on behavioral (food intake and locomotor activity) and physiological (blood glucose and plasma cortisol) parameters of gilthead seabream was investigated. To this end, fish (289 ± 53 g, mean ± SD) were divided into 3 experimental groups: control (C), transmitter (T, inserted surgically) and sham group (S, subjected to surgery but without transmitter insertion). Blood was extracted during surgery and 9 days later. Throughout the trial, fish were fed by means of self-feeders and locomotor activity was measured by means of an infrared photocell. Two days after the first manipulation, a significant decrease in food intake could be observed in all the experimental groups. The fact that food intake was not affected after the second manipulation seems to indicate that a learning process took place for handling. The rhythmicity of feeding and locomotor activity was not affected by handling in any experimental group. However, group T showed increased plasma cortisol levels 9 days after surgery. In conclusion, while most behavioral parameters were not affected by handling, the plasma cortisol levels of seabream 9 days after insertion of the transmitter indicated a physiological impact that should be taken into account in long-term radiotracking studies, since such an operation could have negative effects on wild individuals after the end of the tracking experiments.

The child with a mass on its head: diagnostic and surgical strategies.

A series of 65 pediatric patients with scalp or calvarial masses is reported on. The majority of children presented with a disfiguring or painful mass on the head. Clinical findings suggested the correct diagnosis in 39/65 cases, skull radiographs in 46/65, and CT in 49/65. Taking the combined results of clinical and radiological studies, 54/65 of the lesions were accurately diagnosed. Tumor excision was curative in 43 of 48 patients who were operated on. Most scalp and calvarial neoplasms were benign; only 5/65 children harboured a malignant lesion. There was no mortality related to surgery in the series. Surgical intervention seems to be indicated in most cases, both for diagnosis and for treatment.