Functionalized nanostructures with application in regenerative medicine

In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

INTRODUCTION Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. METHODS Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. RESULTS The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. CONCLUSIONS Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

Isolated office hypertension: a prehypertensive state?

OBJECTIVE AND METHOD: Isolated office hypertension, defined as hypertensive blood pressure values in a medical setting but normal self-measured or ambulatory-recorded blood pressures, is frequently encountered in clinical practice. Yet, whether this condition represents a transient state in the development of a sustained ambulatory hypertension is still unknown as no long-term analysis of the evolution of ambulatory blood pressure has been carried out in patients with isolated office hypertension. To evaluate whether such patients should be considered as truly normotensive or hypertensive, we have studied the long-term changes in office and ambulatory blood pressures in 81 patients in whom isolated office hypertension was observed between 1982 and 1988. RESULTS: After a 5-6 year follow-up, 60 of the 81 patients had a mean 12 h daytime ambulatory blood pressure greater than 140/90 mmHg, suggesting an evolution towards ambulatory hypertension. The development of hypertension could not be predicted on the basis of the follow-up office blood pressures as these tended to decrease during the follow-up period. CONCLUSIONS: The results of this study suggest that patients with isolated office hypertension should not be considered as truly normotensive individuals. Hence, these patients require a careful medical follow-up. Office blood pressure readings alone, however, do not appear to provide a good indicator of the long-term outcome of isolated office hypertension.

Use of Sensors in the Treatment and Follow-up of Patients with Diabetes Mellitus

Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although self-regulation using capillary glycemia (SRCG) still remains the best procedure in clinical practice, continuous glucose monitoring systems (CGM) offer the possibility of continuous and dynamic assessment of interstitial glucose concentration. CGM systems have the potential to improve glycemic control while decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG, is still debated. CGM systems have the greatest potential value in patients with hypoglycemic unawareness and in controlling daily fluctuations in blood glucose. The implementation of continuous monitoring in the standard clinical setting has not yet been established but a new generation of open and close loop subcutaneous insulin infusion devices are emerging making insulin treatment and glycemic control more reliable.

Breast cancer prognostic classification in the molecular era: the role of histological grade.

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers.

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.

Probióticos y prebióticos en la práctica clínica.

This article revises the concepts of prebiotics, probiotics and symbiotics, and their use in different situations of daily clinical practice. With a high level of evidence, it is concluded that the use of certain strains of probiotics significantly reduces the risk for antibiotic-induced diarrhea. Although further studies are needed, the use of probiotics, prebiotics, and symbiotics in people suffering from inflammatory bowel disease (particularly ulcerative colitis, and pouchitis) might improve the rates of remission induction/maintenance. The administration of probiotics and symbiotics to patients with liver transplant, severe acute pancreatitis, and intensive and surgical care patients, emerges as a promising therapeutic option that seems to reduce the number of infections; however, it is currently no possible to establish evidence-based recommendations, with a need for a higher number of better designed works. About safety of probiotics and symbiotics, the benefits/risks ratio clearly favors the former since the risk for infection is low, even in immunosuppressed patients. There are, however, selected groups of patients in which caution is advised.

Proceso INFORNUT: validación de la fase de filtro-FILNUT--y comparación con otros métodos de detección precoz de desnutrición hospitalaria.

INTRODUCTION According to several series, hospital hyponutrition involves 30-50% of hospitalized patients. The high prevalence justifies the need for early detection from admission. There several classical screening tools that show important limitations in their systematic application in daily clinical practice. OBJECTIVES To analyze the relationship between hyponutrition, detected by our screening method, and mortality, hospital stay, or re-admissions. To analyze, as well, the relationship between hyponutrition and prescription of nutritional support. To compare different nutritional screening methods at admission on a random sample of hospitalized patients. Validation of the INFORNUT method for nutritional screening. MATERIAL AND METHODS In a previous phase from the study design, a retrospective analysis with data from the year 2003 was carried out in order to know the situation of hyponutrition in Virgen de la Victoria Hospital, at Malaga, gathering data from the MBDS (Minimal Basic Data Set), laboratory analysis of nutritional risk (FILNUT filter), and prescription of nutritional support. In the experimental phase, a cross-sectional cohort study was done with a random sample of 255 patients, on May of 2004. Anthropometrical study, Subjective Global Assessment (SGA), Mini-Nutritional Assessment (MNA), Nutritional Risk Screening (NRS), Gassull's method, CONUT and INFORNUT were done. The settings of the INFORNUT filter were: albumin < 3.5 g/dL, and/or total proteins <5 g/dL, and/or prealbumin <18 mg/dL, with or without total lymphocyte count < 1.600 cells/mm3 and/or total cholesterol <180 mg/dL. In order to compare the different methods, a gold standard is created based on the recommendations of the SENPE on anthropometrical and laboratory data. The statistical association analysis was done by the chi-squared test (a: 0.05) and agreement by the k index. RESULTS In the study performed in the previous phase, it is observed that the prevalence of hospital hyponutrition is 53.9%. One thousand six hundred and forty four patients received nutritional support, of which 66.9% suffered from hyponutrition. We also observed that hyponutrition is one of the factors favoring the increase in mortality (hyponourished patients 15.19% vs. non-hyponourished 2.58%), hospital stay (hyponourished patients 20.95 days vs. non-hyponourished 8.75 days), and re-admissions (hyponourished patients 14.30% vs. non-hyponourished 6%). The results from the experimental study are as follows: the prevalence of hyponutrition obtained by the gold standard was 61%, INFORNUT 60%. Agreement levels between INFORNUT, CONUT, and GASSULL are good or very good between them (k: 0.67 INFORNUT with CONUT, and k: 0.94 INFORNUT and GASSULL) and wit the gold standard (k: 0.83; k: 0.64 CONUT; k: 0.89 GASSULL). However, structured tests (SGA, MNA, NRS) show low agreement indexes with the gold standard and laboratory or mixed tests (Gassull), although they show a low to intermediate level of agreement when compared one to each other (k: 0.489 NRS with SGA). INFORNUT shows sensitivity of 92.3%, a positive predictive value of 94.1%, and specificity of 91.2%. After the filer phase, a preliminary report is sent, on which anthropometrical and intake data are added and a Nutritional Risk Report is done. CONCLUSIONS Hyponutrition prevalence in our study (60%) is similar to that found by other authors. Hyponutrition is associated to increased mortality, hospital stay, and re-admission rate. There are no tools that have proven to be effective to show early hyponutrition at the hospital setting without important applicability limitations. FILNUT, as the first phase of the filter process of INFORNUT represents a valid tool: it has sensitivity and specificity for nutritional screening at admission. The main advantages of the process would be early detection of patients with risk for hyponutrition, having a teaching and sensitization function to health care staff implicating them in nutritional assessment of their patients, and doing a hyponutrition diagnosis and nutritional support need in the discharge report that would be registered by the Clinical Documentation Department. Therefore, INFORNUT would be a universal screening method with a good cost-effectiveness ratio.

Intravenous iron in inflammatory bowel disease

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

Use of palliative radiotherapy in brain and bone metastases (VARA II study).

INTRODUCTION Metastases are detected in 20% of patients with solid tumours at diagnosis and a further 30% after diagnosis. Radiation therapy (RT) has proven effective in bone (BM) and brain (BrM) metastases. The objective of this study was to analyze the variability of RT utilization rates in clinical practice and the accessibility to medical technology in our region. PATIENTS AND METHODS We reviewed the clinical records and RT treatment sheets of all patients undergoing RT for BM and/or BrM during 2007 in the 12 public hospitals in an autonomous region of Spain. Data were gathered on hospital type, patient type and RT treatment characteristics. Calculation of the rate of RT use was based on the cancer incidence and the number of RT treatments for BM, BrM and all cancer sites. RESULTS Out of the 9319 patients undergoing RT during 2007 for cancer at any site, 1242 (13.3%; inter-hospital range, 26.3%) received RT for BM (n = 744) or BrM (n = 498). These 1242 patients represented 79% of all RT treatments with palliative intent, and the most frequent primary tumours were in lung, breast, prostate or digestive system. No significant difference between BM and BrM groups were observed in: mean age (62 vs. 59 yrs, respectively); gender (approximately 64% male and 36% female in both); performance status (ECOG 0-1 in 70 vs. 71%); or mean distance from hospital (36 vs. 28.6 km) or time from consultation to RT treatment (13 vs. 14.3 days). RT regimens differed among hospitals and between patient groups: 10 × 300 cGy, 5 × 400 cGy and 1x800cGy were applied in 32, 27 and 25%, respectively, of BM patients, whereas 10 × 300cGy was used in 49% of BrM patients. CONCLUSIONS Palliative RT use in BM and BrM is high and close to the expected rate, unlike the global rate of RT application for all cancers in our setting. Differences in RT schedules among hospitals may reflect variability in clinical practice among the medical teams.

Aider les étudiants en médecine à approcher la mort [Helping medical students to approach death].

A project recently launched by the Faculty of biology and medicine of Lausanne introduces the approach of facing death during both the dissection and the course of clinical activities. Existential questions relating to mortality are bound to arise sooner or later during the course of the study. For the sake of humanized clinical practice, these questions must be confronted. In response to a request by a student association, an accompanying curriculum with active student's contribution through encounters with death in anatomy and clinical situations was created in Lausanne. Students will benefit from this new program throughout their curriculum. This program is the first of its kind in Switzerland.

Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain

BACKGROUND Adherence to interferon β-1b (INFβ-1b) therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS). For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%). Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients. CONCLUSION/SIGNIFICANCE Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

Iodine intakes of 100-300 μg/d do not modify thyroid function and have modest anti-inflammatory effects.

Little information is available as to whether doses of iodide similar to those recommended in clinical practice for the prevention of iodine deficiency in pregnant women affect thyroid function. The aim of the present study was to analyse whether doses of iodide can affect thyroid function in adults, and evaluate its effect on plasma markers of oxidative stress, inflammation and acute-phase proteins. A total of thirty healthy volunteers (ten men and twenty women) with normal thyroid function were randomly assigned to three groups (n 10). Each group received a daily dose of 100, 200 or 300 μg of iodide in the form of KI for 6 months. Free tetraiodothyronine (FT4) levels at day 60 of the study were higher in the groups treated with 200 and 300 μg (P = 0·01), and correlated with the increase in urinary iodine (r 0·50, P = 0·007). This correlation lost its significance after adjustment for the baseline FT4. The baseline urinary iodine and FT4 correlated positively with the baseline glutathione peroxidase. On day 60, urinary iodine correlated with C-reactive protein (r 0·461, P = 0·018), and free triiodothyronine correlated with IL-6 (r - 0·429, P = 0·025). On day 60, the changes produced in urinary iodine correlated significantly with the changes produced in α1-antitrypsin (r 0·475, P = 0·014) and ceruloplasmin (r 0·599, P = 0·001). The changes in thyroid-stimulating hormone correlated significantly with the changes in α1-antitrypsin (r - 0·521, P = 0·005) and ceruloplasmin (r - 0·459, P = 0·016). In conclusion, the administration of an iodide supplement between 100 and 300 μg/d did not modify thyroid function in a population with adequate iodine intake. The results also showed a slight anti-inflammatory and antioxidative action of iodide.

Prescripción enfermera en el entorno de las urgencias y emergencias. Marco conceptual vs entorno legislado en España

The prescription, widely discussed and defined conceptually in recent years in an environment of widening the spectrum of responsibilities nurse, has capacity for integration and definition in the area of accident and emergency care and carried out over the patient urgently, about emergencies and life-long commitment. Be necessary to frame throughout the legal framework, following the amendment of the Twelfth Additional Provision of Law 29/2006 of guarantees and rational use of drugs and medical devices, can be waived and implementation required, provided under model and through the nursing process and method and as an exponent and endorsementn of science and advanced clinical practice, to join the idea of interdisciplinary professional consensus that the law posed by the preparation and implementation of standardized protocols, algorithms and / or clinical practice guidelines in the context of what has come to be called "collaborative standard prescription": Prescription to the nurse in certain clinical situations in terms of a performance protocol, agreed with multidisciplinary team care health of the population (Group Protocols), which can be considered an intermediate step in the evolution towards independent nurse prescribing, providing nurses experience of a prescription under these protocols and demonstrating their capabilities.