First experience with multiple mini interview for medical school admission in Brazil: Does it work in a different cultural scenario?

PURPOSE: Evaluation of non-cognitive skills never has been used in Brazil. This study aims to evaluate Multiple Mini Interviews (MMI) in the admission process of a School of Medicine in São Paulo, Brazil. METHODS: The population of the study comprised 240 applicants summoned for the interviews, and 96 raters. MMI contributed to 25% of the applicants' final grade. Eight scenarios were created with the aim of evaluating different non-cognitive skills, each one had two raters. At the end of the interviews, the applicants and raters described their impressions about MMI. The reliability of the MMI was analyzed using the Theory of Generalization and Many-Facet Rasch Model (MFRM). RESULTS: The G-study showed that the general reliability of the process was satisfactory (coefficient G = 0.743). The MMI grades were not affected by the raters' profile, time of interview (p = 0.715), and randomization group (p = 0.353). The Rasch analysis showed that there was no misfitting effects or inconsistent stations or raters. A significant majority of the applicants (98%) and all the raters believed MMIs were important in selecting students with a more adequate profile to study medicine. CONCLUSIONS: The general reliability of the selection process was excellent, and it was fully accepted by the applicants and raters.

TNF-α depuration is a predictor of mortality in critically ill patients under continuous veno-venous hemodiafiltration treatment.

INTRODUCTION: Critically ill patients with acute kidney injury (AKI) present high mortality rates. The magnitude of inflammatory response could determine the prognosis of such patients. Continuous renal replacement therapy (CRRT) may play an important role in removing inflammatory mediators in patients with AKI. AIM: To investigate whether the magnitude of inflammatory mediator's removal is associated with mortality among critically ill patients on CVVHDF, a CRRT modality. METHODS: This study consisted of 64 critically ill patients requiring CVVHDF. Plasma levels of C3a, TNF-α, IL-10, IL-6, IL-1ß, sTNFRI and sTNFRII were determined by enzyme-linked immunosorbent assay (ELISA) at the beginning of CVVHDF and after 24h (outlet). Clearance of cytokines during the first 24h of CVVHDF was calculated. Clinical and laboratory data were acquired from patient's records data. RESULTS: Mean age of patients requiring CVVHDF was 63years, 67.2% were men and 87.3% were Caucasian. Thirty-five (35) patients (54.7%) died. Comparing non-survivors with the group of survivors we observed higher incidence of sepsis (68.6 versus 37.9%, p<0.05), higher APACHE II score (34.8±7.6 versus 29.2±7.1, p<0.05) and higher lactate levels (23.2±17.6 versus 16.4±6.6, p<0.05). According to the inter-tertile range of TNF-α clearance (ITR1 (<0.54); ITR2 (0.54-2.93); ITR3 (>2.93)) we found that those patients with higher TNF-α removal by RRT (ITR3) had a better survival. Multivariable analysis showed that lower clearance of TNF-α remained independently associated with high mortality after adjustment for sex, age, use of vasoactive drugs, APACHE II score sepsis, creatinine and lactate before CVVHDF (HR: 0.179, 95% IC: 0.049-0.661, p<0.01). CONCLUSION: The attenuation of inflammatory response may be related to the lower mortality observed on those patients with higher TNF-α removal by CVVHDF.

Low estimated glomerular filtration rate and chronic kidney failure following liver transplant: a retrospective cohort study.

BACKGROUND: Patients undergoing orthotropic liver transplant (LTx) often present with chronic kidney disease (CKD). Identification of patients who will progress to end-stage renal disease (ESRD) might allow not only the implementation of kidney protective measures but also simultaneous kidney transplant. STUDY DESIGN: Retrospective cohort study in adults who underwent LTx at a single center. ESRD, death, and composite of ESRD or death were studied outcomes. RESULTS: 331 patients, who underwent LTx, were followed up for 2.6 ± 1.4 years; 31 (10%) developed ESRD, 6 (2%) underwent kidney transplant after LTx and 25 (8%) remained on chronic hemodialysis. Patients with preoperative eGFR lesser than 60 ml/min per 1.73 m2 had a 4-fold increased risk of developing ESRD after adjustment for sex, diabetes mellitus, APACHE II score, use of nephrotoxic drugs, and severe liver graft failure (HR = 3.95, 95% CI 1.73, 9.01; p = 0.001). Other independent risk factors for ESRD were preoperative diabetes mellitus and post-operative severe liver graft dysfunction. CONCLUSION: These findings emphasize low eGFR prior to LTx as a predictor for ESRD or death. The consideration for kidney after liver transplant as a treatment modality should be taken into account for those who develop chronic kidney failure after LTx.

The use of regional citrate anticoagulation for continuous venovenous hemodiafiltration in acute kidney injury.

OBJECTIVE: Continuous renal replacement therapy is commonly used in the treatment of acute kidney injury. Although the optimal anticoagulation system is not well defined, citrate has emerged as the most promising method. We evaluated the data of 143 patients with acute kidney injury subjected to citrate-based continuous venovenous hemodiafiltration. DESIGN: Retrospective cohort study. SETTING: Intensive care unit of tertiary care private hospital. PATIENTS: Patients with acute kidney injury treated from February 2004 to July 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cause of acute kidney injury was sepsis (58%). The mean dialysis dose was 36.6 mL/kg/hr allowing for excellent metabolic control (last tests: creatinine, 1.1 mg/dL; urea, 46 mg/dL). No significant bleeding, severe electrolyte, or calcium disorders were observed. Of the 418 filters used, almost 28,000 hrs of treatment, hemofilter patency was 68% at 72 hrs. Hospital mortality was 59%, and 22% of survivors were dialysis-dependent at the time of discharge. Within our sample, we identified 21 patients with liver failure (mean prothrombin time index, 21% vs. 67%, p < 0.001). This group presented with a lesser median systemic ionized calcium level (1.06 vs. 1.12 mmol/L, p < 0.001) and similar mean total calcium level (8.5 vs. 8.6 mg/dL, not significant), compared with patients without liver failure. These subjects also showed acidemia (median pH, 7.31 vs. 7.40, p < 0.001); however, they exhibited higher levels of lactate (median 29 vs. 16 mg/dL, p < 0.001), chloride (mean 109 vs. 107 mEq/L, p = 0.045) and had a trend to higher mortality rate (76% vs. 56%). CONCLUSIONS: Besides a trend toward higher mortality rate observed in the group with liver failure, we found that citrate-based continuous venovenous hemodiafiltration allowed an effective dialysis dose and reasonable filter patency.

The developmental nephrome: systems biology in the developing kidney.

PURPOSE OF REVIEW: A set of important genes and signaling pathways involved in kidney development is emerging from analyses of mutant mice, in-vitro models, and global gene expression patterns. Conversion of data into dynamic models or networks through the synthesis of information at multiple levels is crucial for a better understanding of kidney development. RECENT FINDINGS: Genetic and in-vitro evidence is beginning to provide a limited sense of the network topology in stages of kidney development. Intriguing data from other fields suggest how, with the aid of large-scale gene expression studies, these stages might be represented as dynamic attractor states. It is also suggested how branching morphogenesis of the epithelial ureteric bud may be sustained by an autocatalytic set of proteins whose interactions lead to repeated rounds of tip and stalk generation. Accumulating data in lower organisms suggest network topologies may be quite flexible, and the implications of these results for varieties of tubulogenesis and renal regeneration after acute injury are discussed. SUMMARY: Currently it may be feasible to build tentative dynamic multistage models of nephrogenesis that facilitate experimental thinking. As data accumulate, it may become possible to test their predictive value.

Decreased renal organic anion secretion and plasma accumulation of endogenous organic anions in OAT1 knock-out mice.

The "classical" organic anion secretory pathway of the renal proximal tubule is critical for the renal excretion of the prototypic organic anion, para-aminohippurate, as well as of a large number of commonly prescribed drugs among other significant substrates. Organic anion transporter 1 (OAT1), originally identified as NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J. G., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478), has physiological properties consistent with a role in this pathway. However, several other transporters (e.g. OAT2, OAT3, and MRP1) have also been proposed as important PAH transporters on the basis of in vitro studies; therefore, the relative contribution of OAT1 has remained unclear. We have now generated a colony of OAT1 knock-out mice, permitting elucidation of the role of OAT1 in the context of these other potentially functionally redundant transporters. We find that the knock-out mice manifest a profound loss of organic anion transport (e.g. para-aminohippurate) both ex vivo (in isolated renal slices) as well as in vivo (as indicated by loss of renal secretion). In the case of the organic anion, furosemide, loss of renal secretion in the knock-out results in impaired diuretic responsiveness to this drug. These results indicate a critical role for OAT1 in the functioning of the classical pathway. In addition, we have determined the levels of approximately 60 endogenous organic anions in the plasma and urine of wild-type and knock-out mice. This has led to identification of several compounds with significantly higher plasma concentrations and/or lower urinary concentrations in knock-out mice, suggesting the involvement of OAT1 in their renal secretion. We have also demonstrated in xenopus oocytes that some of these compounds interact with OAT1 in vitro. Thus, these latter compounds might represent physiological substrates of OAT1.

Identification of a novel murine organic anion transporter family member, OAT6, expressed in olfactory mucosa.

The organic anion and cation transporters (OATs and OCTs) are a large family (SLC22) of transmembrane proteins that are able to transport a variety of compounds including drugs, environmental toxins, and endogenous metabolites. OATs are expressed in various tissues, primarily kidney and liver, but also in placenta, small intestine, and choroid plexus, which are all epithelial tissues that transport xenobiotics. The upper airway, particularly the nose, is also a site of frequent exposure to environmental toxins. Many drugs are administered intranasally. This raises the possibility that the olfactory epithelium contains OATs and OCTs. Here, we report the identification of a novel putative transporter, mouse OAT6, expressed predominantly in olfactory mucosa but not in kidney or brain. Sequence comparisons and intron phasing analysis indicated that OAT6 is closely related to OAT1 and OAT3. Unlike many other slc22 genes, OAT6 is unpaired in the genome, although it is in proximity to the OAT1/OAT3 gene pair. Expression of OAT6 was also observed in testis. Embryonic expression was observed at day 7, but not later in embryogenesis. This might be due to the need for a key metabolite transported by OAT6. The data raise the possibility that the olfactory mucosa may have a significant transport apparatus which could be important in the design of new therapeutic approaches for direct nose-to-brain transfer of drugs and olfaction. Supporting this possibility, we have demonstrated that OAT1, OCT1-2, and OCTN1-3 are also expressed in olfactory mucosa. Furthermore, e-blot data suggest very different expression of individual OATs, OCTs and OCTNs in kidney, brain, liver, and eye.

Novel slc22 transporter homologs in fly, worm, and human clarify the phylogeny of organic anion and cation transporters.

Slc22 family organic anion and cation transporters (OATs, OCTs, and OCTNs) are transmembrane proteins expressed predominantly in kidney and liver. These proteins mediate the uptake or excretion of numerous physiologically (and pharmacologically) important compounds, and accordingly have been the focus of intensive study. Here we investigate the molecular phylogeny of the slc22 transporters, identifying homologs in Drosophila and C. elegans, several of which are developmentally regulated, as well as reporting the cloning of a novel human family member, UST6, expressed exclusively in liver in both embryo and adult. The latter helps define a subfamily within the OATs, which appears to have human- and rodent-specific members, raising potential issues with respect to the use of rodents as models for the transport of organic anions (which include many pharmaceuticals) in humans. Although this phylogenetic inference could not be made on the basis of sequence alignment, analysis of intron phasing suggests that the OAT, OCT, and OCTN lineages of the slc22 family formed after the divergence of vertebrates and invertebrates. Subsequently, these lineages expanded through independent tandem duplications to produce multiple gene pairs. After analyzing over 200 other transporter genes, we find such pairing to be relatively specific to vertebrate organic anion and cation transporters, suggesting selection for gene pairing operating within this family in particular. This might reflect a requirement for redundancy or broader substrate specificity in vertebrates (compared to invertebrates), due to their greater physiological complexity and thus potentially broader exposure to organic ions.