https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Tumors are cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-β, whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, through cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance, as well as therapeutic strategies to overcome this clinically.

/pdf/emt-cancer-stem-cells-and-drug-resistance-an-emerging-axis-3ztp4dopjd.pdf

EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

No highly integrated sphincter prosthesis for therapy of major fecal incontinence exists. Therefore, we developed a novel neosphincter, made of polyurethane. The GASS consists of a support ring (SR) which includes a fluid reservoir, fixed on the outer diameter of the SR, and a multi-chamber occluding cuff (C(int)) on the inside diameter. The total inflation volume of C(int) is about 23 cc. The integrated micropump based on piezotechnology measures 30x13x1 mm3 (flowrate 1.4 cc/min, max. backpressure 40,000 Pa) . GASS was evaluated around the external sphincter of isolated porcine anal canals. The threshold of continence was defined as the inflating volume which water ceased to leak through the area occluded by C(int) under an induced rectal pressure of 150 cm H2O. Minimal filling volumes maintained continence for liquids against high luminal pressures. A low intraanal resting pressure (delta p(anal)) induced by activated GASS indicates a little risk of ischemic injury of the anal canal in vivo (median delta p(anal) 24.1 mm hg:15 cc vs 46.9 mm hg:21 cc). In summary, a highly integrated and efficient high-tech neosphincter for the therapy of major fecal incontinence could be realized.

[German Artificial Sphincter System--GASS. Development and in vitro evaluation of a novel, fully-implantable, highly integrated sphincter prosthesis for therapy of high-grade fecal incontinence].

Objectives Enzymatic digestion of donor pancreas is a vital step in islet isolation process. Recently, human and large mammalian islet isolation has been improved by Liberase. However, there are no data to show the improvement of rat islet isolation with Liberase. We hypothesized that commercially available Liberase has variable activities from batch to batch and that a short culture period might improve the function of isolated islets in vivo. We therefore isolated islets with Liberase and cultured them for a short period before transplantation to reverse diabetes in a syngenic rat model. Methods Islets of high inbred Lewis rats were isolated with Liberase, purified by discontinuous density gradients, hand-picked, and cultured at 37 degrees C for 24 hours. The same batch of Liberase was used for all experiments in this study. Freshly isolated and cultured islets were implanted intraportally into rats rendered diabetic by streptozotocin. Results In this study, we were not able to reverse diabetes by syngenic transplantation of freshly isolated islets from 2 donors with Liberase in the rat model. Surprisingly, for the first time, we successfully achieved normoglycemia for more than 100 days in the diabetic rats by syngenic transplantation of the cultured islets isolated with Liberase. These normoglycemic diabetic rats showed normal glucose tolerance curves. Histologic examination of the livers of the islet recipients revealed intact islets, with numerous well-granulated insulin-containing cells and only few glucagon-expressing cells. In islets of the recipients' pancreata, the remaining native islets consisted mainly of glucagon-expressing cells, with few insulin-expressing cells in the center. Conclusions We conclude that Liberase isolation followed by a short culture period may be a good substitute for collagenase in rats. Islet culture before transplantation can promote the success of single-donor-single-recipient islet transplantation to reverse diabetes in the rat model.

Persistent normoglycemia in the streptozotocin-diabetic rat by syngenic transplantation of islets isolated from a single donor with Liberase.

Incisional hernia is a late complication of laparotomy for which an evidence-based prohylactic approach is still lacking. Postoperatively, incisional hernias occur because of multiple factors. Preoperative comorbidities belong to these risk factors. A risk reduction related to concomitant diseases mostly does not succeed. There is a range of studies comparing the techniques of surgical wound closure. A consensus of these is that a running suture of the fascia with slowly absorbable or non-absorbable sutures results in the lowest incidence of incisional hernias. A one-cm distance between the stitches and a minimal distance of one cm to the fascial margin as well as a 4:1 suture length to wound length ratio are still valid principles. In any case, solely optimising the surgical technique of the abdominal wall closure is not able to reduce the incidence of incisional hernias. Prevention of postoperative complications by adequate pain management, respiratory training and early mobilisation are procedures to reduce the incidence of incisional hernias. However, systematic studies are lacking. To avoid an incisional hernia, only a practical approach remains which, however, does not meet the requirements of evidence-based medicine.

[Risk factors and prevention of incisional hernia--what is evidence-based?].

Aims Comprehensive Geriatric Assessment (CGA) provides information on aspects of older patients to predict risks and benefits of interventions. Methods To evaluate the application of CGA (including quality of life (QOL)) for the risk prediction of postoperative dependence and QOL in elderly patients with malignant tumours, a prospective observational study including 200 patients >70 years was performed. The primary outcome was postoperative activities of daily living (ADL  Results Median age of patients was 75 (70–88) years with 69% males. The majority of operations was for colon carcinoma; morbidity was 24.8%, mortality 1.5%. Impairment in ADL ( Conclusions Those considered for oncologic surgery can be assured that few lose independence. CGA/QOL highlight signs of vulnerability and options for pre-habilitation. Registries including a minimal CGA data set will make pre-selections reproducible and objectify risk/benefit estimations – relevant for those withheld from potentially curative surgery.

Independence and health related quality of life in 200 onco-geriatric surgical patients within 6 months of follow-up: Who is at risk to lose?

BACKGROUND Pancreatic resections in specialized centers are associated with low mortality, however, still with high morbidity. The complication rate can be reduced by long-term experience in high volume centers. In this study the influence of complications on costs in the German DRG system were analyzed. PATIENTS AND METHODS Data regarding operation time, hospital stay, complications and costs of 36 patients undergoing pancreatic head resection in the years 2005 and 2006 were collected and analyzed retrospectively. Statistical analysis was performed using the Mann-Whitney U-test. A p-value of p<0.05 was considered statistically significant. RESULTS Postoperative complications caused an increase in the duration of hospital stay from a median of 16 (range 11-38) to 33 (10-69) days. Costs, especially for ICU treatment and radiographic diagnostics, rose significantly. The average overall costs were 10,015 EUR (range 8,099-14,785 EUR) in patients without complications (n = 21) and 15,340 EUR (9,368-31,418 EUR) in patients with complications (n = 15). In contrast, according to the German DRG system 13,835 EUR (10,441-15,062 EUR) and 15,062 EUR (10,441-33,217 EUR) were refunded on average, respectively. CONCLUSIONS This case-cost calculation proves that pancreatic surgery in the context of the German DRG system can only be performed economically neutral in centers with low complications rates. The concentration of pancreatic surgery to centers with low complications rates, namely high volume centers, must be recommended from an economic point of view.

Ulrich T. Hopt

Papers

[German Artificial Sphincter System--GASS. Development and in vitro evaluation of a novel, fully-implantable, highly integrated sphincter prosthesis for therapy of high-grade fecal incontinence].

Persistent normoglycemia in the streptozotocin-diabetic rat by syngenic transplantation of islets isolated from a single donor with Liberase.

[Risk factors and prevention of incisional hernia--what is evidence-based?].

Independence and health related quality of life in 200 onco-geriatric surgical patients within 6 months of follow-up: Who is at risk to lose?

[Insurance costs in pancreatic surgery : does the pecuniary aspect indicate formation of centers?].