[Laparoscopic cholecystectomy: what we can learn about]. / Colecistectomía laparoscópica en niños y adultos: lo que podemos aprender.

BACKGROUND: Laparoscopic cholecystectomy (LC) is a very usual procedure within adult population, but not as frequent in childhood. The aim of this study was to assess the outcome of LC in children compared with those performed in adulthood. MATERIALS AND METHODS: We reviewed 39 consecutive patients who underwent LC between 2003 and 2013 at our Department and a similar sample of patients from 18 to 40 years of age from the General Surgery Department. RESULTS: 39 children and 40 adults fulfilled criteria to be included in the study. The most frequent indication was cholelithiasis in both groups. The mean operating time was significantly higher among children (127 min, adults 71 min, p < 0.01) but we didn't find differences neither in conversion nor in complication rates (children 5% and 7.7%, adults 2.5% and 15% respectively). In regard to preoperative factors, only male gender was correlated to a higher complication rate (p 0.037). On the other hand we found out that, in absence of complications, both the average length of stay (children 2.1 days, adults 0.5 days) and mean time to first feeding (children 21 hours, adults 8 hours) were significantly higher among children (p < 0.01). CONCLUSIONS: 1) LC in childhood is a safe procedure that does not imply more morbidity than the same intervention in adults, even though a more prolonged operating time. 2) We believe that our longer hospital stay is due to certain lack of confidence with the technique and, in the future, the trend should be bent on encouraging a shorter time to first feeding and an earlier discharge.

Prevalence and Characterization of Urinary Tract Infection in Owned Dogs and Cats From Spain.

Bacterial urinary tract infection (UTI) is a common clinical concern in dogs. However, incidence of feline UTI is much lower than in dogs although an increasing prevalence has been registered. The main objective of the present study was to describe and characterize the prevalence of urinary tract pathogens in urine samples of dogs and cats with urinary clinical signs throughout different Spanish provinces. Secondary aims were to determine if there were differences in urine sample characterizations based on species (i.e., dog and cat) or season. Dogs were found to have a higher rate of positive urinary cultures than cats (39.3% and 24.7% of the cultures submitted, respectively). The bacterial genera most commonly isolated in dogs were Escherichia spp. (45.3%), Proteus spp. (13.2%), Staphylococcus spp. (11%), and Enterococcus spp. (8.6%). Whereas in the feline population, Escherichia spp. (42.7%), Enterococcus spp. (22.2%), and Staphyloccoccus spp. (15.2%) were the most frequently isolated bacteria. The highest rates of positive urine cultures were registered in Melilla (70%), Zamora (66.7%), Teruel (64.3%), and Guadalajara (60%). Moreover, the proportion of positive urine cultures was not homogeneously distributed across provinces. Finally, some seasonality was found among most isolated bacterias. Enterococcus spp. was significantly more prevalent in summer, whereas Escherichia spp. and Proteus spp. were more commonly isolated in spring and Pseudomonas spp. in autumn.

microRNAs and cancer: role in tumorigenesis, patient classification and therapy.

MicroRNAs (miRNAs) are small non-coding RNAs that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent work supports a role for miRNAs in the initiation and progression of human malignancies. Moreover, large high-throughput studies in patients revealed that miRNA profiling has the potential to classify tumours and predict patient outcome with high accuracy. Functional studies, some of which involve animal models, indicate that miRNAs act as tumour suppressors and oncogenes. This review examines the role of miRNAs in the pathogenesis of cancer as well as miRNA-profiling studies performed in human malignancies. Implications of these findings for the diagnosis and treatment of cancer patients are also discussed.

The M2DM Project--the experience of two Italian clinical sites with clinical evaluation of a multi-access service for the management of diabetes mellitus patients.

OBJECTIVES: This paper presents a multi-access service for the management of diabetes mellitus patients and the results of its assessment in two Italian clinical sites. METHODS: The service was evaluated for one year in order to prove the advantages of these kind of systems from different points of view. In this paper the clinical, usability and technical outcomes are presented. RESULTS: The evaluation results show that, thanks to the high flexibility of the implemented service, the telemedicine management of diabetes patients is feasible, well accepted by patients and clinically effective. However, in Italy the problem of quantifying the reimbursement rate of telematic services and the impact they have on the organization are factors that may hamper their introduction in routine clinical practice. CONCLUSIONS: The evaluation study showed that the telemedicine intervention has been satisfactory both for physicians because it allows to constantly monitor the patients' blood glucose level and for patients because it strengthens their motivation to self-monitor the metabolic situation.

[Therapeutic strategy in cloacal exstrophy]. / Estrategia terapéutica en la extrofia de cloaca femenina.

Cloacal exstrophy is a complex multisistemic anomaly that involves gastrointestinal and genitourinary issues. The aim of our paper is to report our experience in dealing with genital reconstruction and faecal and urinary continence in patients with female cloacal anomalies. We reviewed the clinical records from the three patients we have achieved a final reconstruction. We recorded the surgical management and both functional and anatomic results. The three of them required a bladder neck closure associated with a continent stoma, they are dry with intermittent catheterization and free of upper urinary complications. Genital reconstruction required a unique plan for each one, according to their anatomy and their cosmetic desires. One of the patients reported satisfactory sexual intercourse. Management of patients with cloacal exstrophy has major concerns about urinary and fecal continence and about genital reconstruction and function. Knowing the long-term results may help to develop management strategies and improve counselling for patients who have under-gone reconstruction.

SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150.

SPROUTY-2 (SPRY2) is a modulator of tyrosine kinase receptor signaling with receptor- and cell type-dependent inhibitory or enhancing effects. Studies on the action of SPRY2 in major cancers are conflicting and its role remains unclear. Here we have dissected SPRY2 action in human colon cancer. Global transcriptomic analyses show that SPRY2 downregulates genes encoding tight junction proteins such as claudin-7 and occludin and other cell-to-cell and cell-to-matrix adhesion molecules in human SW480-ADH colon carcinoma cells. Moreover, SPRY2 represses LLGL2/HUGL2, PATJ1/INADL and ST14, main regulators of the polarized epithelial phenotype, and ESRP1, an epithelial-to-mesenchymal transition (EMT) inhibitor. A key action of SPRY2 is the upregulation of the major EMT inducer ZEB1, as these effects are reversed by ZEB1 knock-down by means of RNA interference. Consistently, we found an inverse correlation between the expression level of claudin-7 and those of SPRY2 and ZEB1 in human colon tumors. Mechanistically, ZEB1 upregulation by SPRY2 results from the combined induction of ETS1 transcription factor and the repression of microRNAs (miR-200 family, miR-150) that target ZEB1 RNA. Moreover, SPRY2 increased AKT activation by epidermal growth factor, whereas AKT and also Src inhibition reduced the induction of ZEB1. Altogether, these data suggest that AKT and Src are implicated in SPRY2 action. Collectively, these results show a tumorigenic role of SPRY2 in colon cancer that is based on the dysregulation of tight junction and epithelial polarity master genes via upregulation of ZEB1. The dissection of the mechanism of action of SPRY2 in colon cancer cells is important to understand the upregulation of this gene in a subset of patients with this neoplasia that have poor prognosis.

First Spanish Trauma Registry: analysis of 1500 cases.

OBJECTIVES: To develop the first Spanish Pediatric Trauma Registry to collect and evaluate infomation concerning aspects of injuries in our pediatric population. METHODS: From January 1995 to August 1998, 35,946 children younger than 16 years were treated in our hospital for acute injury: 1500 were admitted and included in our database. Our file registry consists of 108 data points including: patient identification, type, place and mechanism of injury, pre-hospital care, transport, assessment on admission, severity scores, diagnostic studies, injuries, treatment morbidity and mortality. RESULTS: Accidents were more frequent in males (68%) than in females. The predominant age group was 12-15 years of age (34%). Accidents were more frequent in the street (35.1%) than at home (18.9%) or school (13%). Falls and traffic-related accidents were the leading cause of injury (39% and 21.2%, respectively). Two hundred and thirty-five (15.7%) had a Pediatric Trauma Score < or = 8. Fifty of these sustained multiple trauma (33%) (Injury Severity Score > or = 15). Musculoskeletal and head trauma were the most frequent injuries (48.5% and 42.0%, respectively). Surgical or orthopedic procedures were performed in 906 patients (56.5%). The average length of stay was 4.5 days (range 1-93 days). Functional impairment in children older than 4 years of age was found in 413 children (33.3%). We encountered 7 deaths in the 1500 patients, or an overall mortality of 0.5%. These 7 deaths were only seen in the I.S.S. > or = 15 group (50 patients) with 14% mortality. CONCLUSIONS: The goals of this Registry are to establish the epidemiology of our injured pediatric population, to review patient care, to develop prevention programs and to compare results with other centers so that potential deficiencies can be corrected.

[Myocardial contusion with and without coronary artery involvement]. / Contusión miocárdica con y sin lesión de las arterias coronarias.

We present the first case of myocardial contusion secondary to blunt chest trauma with injury in two different areas, with and without coronary lesions. The akinesis of the anterolateral wall was secondary to the obstruction of the left anterior descending coronary artery and the severe hypokinesis of the posterior wall, without lesion of the right coronary artery, was probably related with the compression between the sternum and vertebral column.

[Repeated cerebral embolism in a patient with papillary fibroelastoma of the mitral valve detected by two-dimensional echocardiography]. / Embolismo cerebral de repetición en una enferma portadora de fibroelastoma papilar de la válvula mitral, detectado mediante ecocardiografía bidimensional.

We report a 68 years-old woman with repeated cerebral embolism, secondary to a papillary fibroelastoma of mitral valve, located in its ventricular side. It was detected by two-dimensional echocardiography. Surgical treatment was satisfactory.

[QT interval dispersion in hospital patients admitted with cardiac insufficiency. Determinants and prognostic value]. / Dispersión del intervalo QT en pacientes ingresados por insuficiencia cardíaca. Determinantes y valor pronóstico.

INTRODUCTION AND OBJECTIVES: The determinants and the prognostic value of the QT interval dispersion are analysed in a group of consecutive patients admitted to hospital with heart failure. METHODS: One hundred twenty-two consecutive patients admitted because of heart failure in whom a reliable measurement of QT dispersion in the first electrocardiogram was obtained (maximum QT-minimum QT) were studied. The main clinical, analytic and echocardiographic data were recorded. A control group (n = 35) matched in age and sex with the study group was also analysed. RESULTS: The study group showed a greater QT dispersion than the control group (62 +/- 30 vs 40 +/- 21 ms; p = 0.01). Those cases with a QT dispersion > 80 ms (n = 50; 41%) exhibited a lower natremia (138 +/- 6 vs 141 +/- 4 mEq/l; p = 0.01), a higher probability of ischemic aetiology (52 vs 33%; RR = 2.2; IC95% 1.05-4.7; p = 0.04), an increased mortality during the first year (20 vs 6%; RR = 4.7; IC95% 1.3-16; p = 0.01) and during the whole follow-up (38 vs 19%; RR = 3.4; IC95% 1.3 a 8.6; p = 0.01) than those patients with a QT dispersion < 80 (n = 72; 59%). There were no significant differences between both groups with regard to the clinical, analytic or echocardiographic data. In the multivariate analysis only the ischemic etiology (p = 0.002) and the NYHA grade (p = 0.02) were related to a greater mortality. CONCLUSIONS: Patients with heart failure show an increased QT interval dispersion. This parameter is a simple tool that suggests an ischemic etiology and can help in prognosis stratification.

A telemedicine support for diabetes management: the T-IDDM project.

In the context of the EU funded Telematic Management of Insulin-Dependent Diabetes Mellitus (T-IDDM) project, we have designed, developed and evaluated a telemedicine system for insulin dependent diabetic patients management. The system relies on the integration of two modules, a Patient Unit (PU) and a Medical Unit (MU), able to communicate over the Internet and the Public Switched Telephone Network. Using the PU, patients are allowed to automatically download their monitoring data from the blood glucose monitoring device, and to send them to the hospital data-base; moreover, they are supported in their every day self monitoring activity. The MU provides physicians with a set of tools for data visualization, data analysis and decision support, and allows them to send messages and/or therapeutic advice to the patients. The T-IDDM service has been evaluated through the application of a formal methodology, and has been used by European patients and physicians for about 18 months. The results obtained during the project demonstration, even if obtained on a pilot study of 12 subjects, show the feasibility of the T-IDDM telemedicine service, and seem to substantiate the hypothesis that the use of the system could present an advantage in the management of insulin dependent diabetic patients, by improving communications and, potentially, clinical outcomes.

[Hepatic hydatidosis. Review of a series of 677 surgically treated patients]. / Hidatidosis hepática. Revisión de una serie de 677 pacientes intervenidos quirúrgicamente.

A retrospective study of 677 patients who underwent surgery for hepatic hidatidosis in the Department of Surgery A and B of the Hospital Miguel Servet in Zaragoza, Spain, over the last 21 years is presented. The frequency was analyzed in regards to sex, age, symptomatology, cyst data, surgical techniques performed and postoperative morbidity. The mean age of the patients was 39 years with the incidence being practically equal in both sexes. Dyspeptic symptoms (60%), hepatomegaly and/or palpable mass in the right hypochondria (58%) and pain (46%) were the most frequent clinical signs and symptoms observed. Radical surgery was performed in 21% of all the surgical treatments, while conservative surgery was undergone in 79%. Solitary cysts were most frequent (65.7%) with localization in the right hepatic lobe (65.4%). The most frequent postoperative complication was biliary fistula (72 cases). The rate of reintervention was 18% and operative mortality 1.6% with a mean hospitalization period of 25 days.

[Pediatric trauma registry: analysis of 1200 cases]. / Registro de trauma pediátrico: análisis de 1.200 casos.

OBJECTIVES: We developed the first Spanish Pediatric Trauma Registry in order to collect and evaluate information concerning aspects of injuries in our pediatric population. METHODS: From January'95 to September'97, 28,713 children younger than 16 years were treated in our Hospital for acute injury: 1,200 were admitted and included in our database. Our file-registry consists of 108 data points including: patient identification, type, place and mechanism of injury, pre-hospital care, transport, assessment on admission, severity scores, diagnostic studies, injuries, treatments and morbidity-mortality. RESULTS: Accidents were more frequent in males (69%) than in females. The age-group predominantly was 12-15 years old (34%). Accidents were more frequent in the street (35.3%) than at home (18.7%) or school (14%). Falls and traffic-related accidents were the leading cause of injury (38 and 21.1%, respectively). The 16.7% of cases had Pediatric Trauma Score < or = 8 (n = 201). The 3.6% of this sustained multiple trauma (43 cases with Injury Severity Score > or = 15). Musculoskeletal and head trauma was the most frequent (62 and 42.3%, respectively). Surgical or orthopedic procedures were performed in 678 patients (56.5%). Average length of stay were 4.8 days (range 1-93 days), and functional impairments at discharge were found in 33.9% of patients older than 3 years (n = 338). Mortality rate in our series was 0.5% (n = 6), and 13.9% in children with ISS > or = 15. CONCLUSIONS: The utility of this Registry is to know the epidemiology of our injured pediatric population, to review patient care, to develop prevention programs and to compare results with other centers so potential deficiencies can be identified and corrected.

Efficient in vivo microRNA targeting of liver metastasis.

Targeting oncogenic microRNAs (miRNAs) is emerging as a promising strategy for cancer therapy. In this study, we provide proof of principle for the safety and efficacy of miRNA targeting against metastatic tumors. We tested the impact of targeting miR-182, a pro-metastatic miRNA frequently overexpressed in melanoma, the in vitro silencing of which represses invasion and induces apoptosis. Specifically, we assessed the effect of anti-miR-182 oligonucleotides synthesized with 2' sugar modifications and a phosphorothioate backbone in a mouse model of melanoma liver metastasis. Luciferase imaging showed that mice treated with anti-miR-182 had a lower burden of liver metastases compared with control. We confirmed that miR-182 levels were effectively downregulated in the tumors of anti-miR-treated mice compared with tumors of control-treated mice, both in the liver and in the spleen. This effect was accompanied by an upregulation of multiple miR-182 direct targets. Transcriptional profiling of tumors treated with anti-miR-182 or with control oligonucleotides revealed an enrichment of genes controlling survival, adhesion and migration modulated in response to anti-miR-182 treatment. These data indicate that in vivo administration of anti-miRs allows for efficient miRNA targeting and concomitant upregulation of miRNA-controlled genes. Our results demonstrate that the use of anti-miR-182 is a promising therapeutic strategy for metastatic melanoma and provide a solid basis for testing similar strategies in human metastatic tumors.

A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas.

Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKalpha show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoKalpha plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoKalpha is constitutively altered in human bladder tumor cells. Furthermore, in vivo murine models, including an orthotopic model to mimic as much as possible the physiological conditions, revealed that increased levels of ChoKalpha potentiate both tumor formation (P< or =0.0001) and aggressiveness of the disease on different end points (P=0.011). Accordingly, increased levels of ChoKalpha significantly reduce survival of mice with bladder cancer (P=0.05). Finally, treatment with a ChoKalpha-specific inhibitor resulted in a significant inhibition of tumor growth (P=0.02) and in a relevant increase in survival (P=0.03).

Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology.

Cellular senescence is characterized by an irreversible cell cycle arrest that, when bypassed by mutation, contributes to cellular immortalization. Activated oncogenes induce a hyperproliferative response, which might be one of the senescence cues. We have found that expression of such an oncogene, Akt, causes senescence in primary mouse hepatoblasts in vitro. Additionally, AKT-driven tumors undergo senescence in vivo following p53 reactivation and show signs of differentiation. In another in vivo system, i.e., liver fibrosis, hyperproliferative signaling through AKT might be a driving force of the senescence in activated hepatic stellate cells. Senescent cells up-regulate and secrete molecules that, on the one hand, can reinforce the arrest and, on the other hand, can signal to an innate immune system to clear the senescent cells. The mechanisms governing senescence and immortalization are overlapping with those regulating self-renewal and differentiation. These respective control mechanisms, or their disregulation, are involved in multiple pathological conditions including fibrosis, wound healing, and cancer. Understanding extracellular cues that regulate these processes may enable new therapies for these conditions.