The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures. Mice received ATX-304 (1 mg/g) or control chow for 7 days before cisplatin-induced AKI (CI-AKI). Primary cultures of tubular epithelial cells (TECs) were pre-treated with ATX-304 (20 µM, 4 h) prior to exposure to cisplatin (20 µM, 23 h). ATX-304 increased acetyl-CoA carboxylase phosphorylation, indicating AMPK activation. It protected against CI-AKI measured by serum creatinine (control 0.05 + 0.03 mM vs ATX-304 0.02 + 0.01 mM, P = 0.03), western blot for neutrophil gelatinase-associated lipocalin (NGAL) (control 3.3 + 1.8-fold vs ATX-304 1.2 + 0.55-fold, P = 0.002), and histological injury (control 3.5 + 0.59 vs ATX-304 2.7 + 0.74, P = 0.03). In TECs, pre-treatment with ATX-304 protected against cisplatin-mediated injury, as measured by lactate dehydrogenase release, MTS cell viability, and cleaved caspase 3 expression. ATX-304 protection against cisplatin was lost in AMPK-null murine embryonic fibroblasts. Metabolomic analysis in TECs revealed that ATX-304 (20 µM, 4 h) altered 66/126 metabolites, including fatty acids, tricarboxylic acid cycle metabolites, and amino acids. Metabolic studies of live cells using the XFe96 Seahorse analyzer revealed that ATX-304 increased the basal TEC oxygen consumption rate by 38%, whereas maximal respiration was unchanged. Thus, ATX-304 protects against cisplatin-mediated kidney injury via AMPK-dependent metabolic reprogramming, revealing a promising therapeutic strategy for AKI.

Current Procedural Practices of Family Medicine Teaching Physicians.

BACKGROUND AND OBJECTIVES: Proficiency in procedural care achieved during residency is a major driver of family physician scope of practice. To date, no inventory exists of the advanced procedures and clinical skills performed by teaching family physicians. This study comprises the first such survey and assesses the attitude of respondents toward the importance of family physicians performing procedures. METHODS: We sent a clinical skills inventory to a convenience sample of teaching family physicians employed at 18 medical school-affiliated, community, and military residency programs across the United States. RESULTS: The overall response rate was 46% (N=337). Respondents performed a median of 12 advanced procedures and clinical skills (IQR: 8-18). Endorsed procedures ranged from skin biopsy (n=316, 93.8%) and joint injection (n=279, 82.8%) to colonoscopy (n=21, 6.2%) and cesarean delivery (n=23, 6.8%), and reported skills ranged from medication-assisted treatment (n=181, 53.7%) to highly active antiretrovial therapy (n=35, 10.4%). Gender and career stage were associated with statistically significant differences in endorsement of specific procedures. For example, fracture management was more likely to be performed by late- versus early-career faculty (54.1% vs 24.2%, P<.001) and by male versus female respondents (54.9% vs 24.2%, P<.001). Most respondents (84.3%) agreed that future family physicians should learn procedures and advanced clinical skills. CONCLUSIONS: Family medicine teaching faculty perform a wide array of procedures and advanced skills. Apparent differences by career stage and gender identity in the performance of some of the procedural and skill areas may portend a shift in the procedural training of future family physicians.

PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages.

Resolving-type macrophages prevent chronic inflammation by clearing apoptotic cells through efferocytosis. These macrophages are thought to rely mainly on oxidative phosphorylation, but emerging evidence suggests a possible link between efferocytosis and glycolysis. To gain further insight into this issue, we investigated molecular-cellular mechanisms involved in efferocytosis-induced macrophage glycolysis and its consequences. We found that efferocytosis promotes a transient increase in macrophage glycolysis that is dependent on rapid activation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), which distinguishes this process from glycolysis in pro-inflammatory macrophages. Mice transplanted with activation-defective PFKFB2 bone marrow and then subjected to dexamethasone-induced thymocyte apoptosis exhibit impaired thymic efferocytosis, increased thymic necrosis, and lower expression of the efferocytosis receptors MerTK and LRP1 on thymic macrophages compared with wild-type control mice. In vitro mechanistic studies revealed that glycolysis stimulated by the uptake of a first apoptotic cell promotes continual efferocytosis through lactate-mediated upregulation of MerTK and LRP1. Thus, efferocytosis-induced macrophage glycolysis represents a unique metabolic process that sustains continual efferocytosis in a lactate-dependent manner. The differentiation of this process from inflammatory macrophage glycolysis raises the possibility that it could be therapeutically enhanced to promote efferocytosis and resolution in chronic inflammatory diseases.

Elevated serum urea-to-creatinine ratio is associated with adverse inpatient clinical outcomes in non-end stage chronic kidney disease.

To better understand the role of the urea-to-creatinine ratio in chronic kidney disease patients, we assessed the epidemiology of the urea-to-creatinine ratio among hospitalised chronic kidney disease patients, and the association between the urea-to-creatinine ratio and inpatient clinical outcomes. This retrospective cohort study (n = 11,156) included patients with at least two eGFR values < 60 mL/min/1.73m2 measured greater than 90-days apart and admitted to a tertiary hospital between 2014 and 2019. Dialysis and renal transplant patients were excluded. Adjusted odds ratios for factors associated with an elevated urea-to-creatinine ratio were calculated. Multivariate regression was conducted to identify the relationship between elevated UCR and inpatient mortality, intensive care admission, hospital readmission and hospital length-of-stay. Urea-to-creatinine ratio > 100 was present in 27.67% of hospital admissions. Age ≥ 65 years, female gender, gastrointestinal tract bleeding, heart failure, acute kidney injury and lower serum albumin were associated with elevated urea-to-creatinine ratio. Higher urea-to-creatinine ratio level was associated with greater rates of inpatient mortality, hospital readmission within 30-days and longer hospital length-of-stay. Despite this, there was no statistically significant association between higher urea-to-creatinine ratio and intensive care unit admission. Elevated urea-to-creatinine ratio is associated with poor clinical outcomes in chronic kidney disease inpatients. This warrants further investigation to understand the pathophysiological basis for this relationship and to identify effective interventions.

Blocking AMPK signalling to acetyl-CoA carboxylase increases cisplatin-induced acute kidney injury and suppresses the benefit of metformin.

BACKGROUND: Acute kidney injury (AKI) is accompanied by dysregulation of cellular energy metabolism and accumulation of intracellular lipid. Phosphorylation of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) inhibits fatty acid synthesis and promotes fatty acid oxidation (FAO), vital for kidney tubular epithelial cells (TECs). The diabetes drug metformin is protective in models of AKI; however, it is not known whether ACC phosphorylation plays a role. METHODS: Cisplatin-induced AKI (CI-AKI) was established in ACC1/2 double knock-in (ACC1/2DKI) mice, harbouring mutations that disrupt fatty acid metabolism, and the role of metformin was studied in this model. Outcomes measured included serum biochemistry, expression of kidney injury markers such as neutrophil gelatinase-associated lipocalin (NGAL), and metabolomic analysis. FINDINGS: ACC1/2DKI mice demonstrated more severe CI-AKI than wild type (WT), as assessed by serum urea and creatinine, histological injury, and expression of NGAL and interleukin-6. Metformin protected against AKI in WT mice, shown by reduced NGAL, but this effect was absent in ACC1/2DKI mice. In cultured TECs exposed to cisplatin, metformin reduced expression of cleaved caspase-3, however, this effect was diminished in ACC1/2DKI TECs. Analysis of kidney polar metabolites found numerous differences between metformin-treated CI-AKI in ACC1/2DKI and WT mice, involving multiple pathways of amino acid, nucleoside, and energy metabolism. INTERPRETATION: Severity of CI-AKI is exacerbated by the inability to regulate metabolism via phosphorylation of ACC. ACC phosphorylation contributes to the protective effect of metformin against AKI, influencing multiple mechanisms involved in the pathogenesis of kidney injury.

Impact of target vessel choice on outcomes following percutaneous coronary intervention in patients with a prior coronary artery bypass graft.

OBJECTIVES: To evaluate and compare characteristics and clinical outcomes of percutaneous coronary intervention (PCI) among target vessel types in patients with a prior coronary artery bypass graft (CABG) surgery. BACKGROUND: Patients with a prior CABG often require repeat revascularization with PCI. Graft PCI has been associated with worse outcomes compared to native vessel PCI, yet the optimal PCI strategy in prior CABG patients remains unknown. METHODS: We stratified prior CABG patients who underwent PCI at a tertiary-care center between 2009 and 2017 by target vessel type: native vessel, venous graft, and arterial graft. The primary outcome of major adverse cardiac events (MACE) was a composite of all-cause death, myocardial infarction, stent thrombosis, or target vessel revascularization up to 1 year post-PCI. RESULTS: Prior CABG patients (n = 3983) represented 19.5% of all PCI interventions during the study period. PCI was most frequently performed on native vessels (n = 2928, 73.5%) followed by venous (n = 883, 22.2%) and arterial grafts (n = 172, 4.3%). Procedural success and complications were similar among the groups; however, slow- and no-reflow phenomenon was more common in venous graft PCI compared to native vessel PCI (OR 4.78; 95% CI 2.56-8.95; p < 0.001). At 1 year, there were no significant differences in MACE or in its individual components. CONCLUSIONS: Target vessel choice did not appear to affect MACE at 1 year in a large cohort of patients with prior CABG undergoing PCI. Whether PCI of surgical grafts versus native arteries truly results in similar outcomes warrants further investigation in randomized controlled trials.

Open repair of a type II endoleak facilitated by temporary disconnection of graft components.

Endoleaks are a frequent indication for reintervention after endovascular repair of an abdominal aortic aneurysm. Here we present a method of open repair of a persistent type II endoleak involving graft component separation and reconstruction, in a patient with symptomatic interval aneurysmal sac enlargement despite endovascular coiling and embolization. This case report demonstrates an alternative open technique of endograft component separation and reconstruction that may be required in cases where open repair with sac exploration and vessel oversewing is hindered by the graft position.

Diagnostic application of kidney allograft-derived absolute cell-free DNA levels during transplant dysfunction.

Graft-derived cell-free DNA (donor-derived cell-free DNA) is an emerging marker of kidney allograft injury. Studies examining the clinical validity of this biomarker have previously used the graft fraction, or proportion of total cell-free DNA that is graft-derived. The present study evaluated the diagnostic validity of absolute measurements of graft-derived cell-free DNA, as well as calculated graft fraction, for the diagnosis of graft dysfunction. Plasma graft-derived cell-free DNA, total cell-free DNA, and graft fraction were correlated with biopsy diagnosis as well as individual Banff scores. Sixty-one samples were included in the analysis. For the diagnosis of antibody mediated rejection, the receiver-operator characteristic area under the curves of graft-derived cell-free DNA and graft fraction were 0.91 (95% CI 0.82-0.98) and 0.89 (95% CI 0.79-0.98), respectively. Both measures did not diagnose borderline or type 1A cellular mediated rejection. Graft fraction was associated with a broader range of Banff lesions, including lesions associated with cellular mediated rejection, while graft-derived cell-free DNA appeared more specific for antibody mediated rejection. Limitations of this study include a small sample size and lack of a validation cohort. The capacity for absolute quantification, and lower barriers to implementation of this methodology recommend it for further study.

Optimal duration of dual antiplatelet therapy after PCI: integrating procedural complexity, bleeding risk and the acuteness of clinical presentation.

INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor constitutes the standard of care to prevent major adverse cardiac events in patients who undergo percutaneous coronary intervention (PCI) with drug-eluting stents (DES). However, the anti-ischemic benefits of DAPT are counterbalanced by an increased risk of hemorrhagic complications, which are known to be associated with increased morbidity and mortality. While the efficacy of DAPT in patients presenting with acute coronary syndrome (ACS) has been well established, the risk-benefit balance of DAPT in other subsets of patients remain controversial. As a result, multiple risk scores to inform optimal duration of DAPT have been developed recently for individuals with various degrees of coronary artery disease. Areas covered: Authors summarize the current evidence and guideline recommendations on the optimal duration and intensity of DAPT across the spectrum of coronary artery disease including those who undergo complex PCI and recapitulated the recently developed risk scores to inform clinical decision on the optimal duration of DAPT. Expert commentary: Clinical decision-making for upfront duration of DAPT after PCI with DES should consider the individual bleeding risk profile, the initial clinical presentation and the complexity of coronary stenting.

Phosphorylation of Acetyl-CoA Carboxylase by AMPK Reduces Renal Fibrosis and Is Essential for the Anti-Fibrotic Effect of Metformin.

BACKGROUND: Expression of genes regulating fatty acid metabolism is reduced in tubular epithelial cells from kidneys with tubulointerstitial fibrosis (TIF), thus decreasing the energy produced by fatty acid oxidation (FAO). Acetyl-CoA carboxylase (ACC), a target for the energy-sensing AMP-activating protein kinase (AMPK), is the major controller of the rate of FAO within cells. Metformin has a well described antifibrotic effect, and increases phosphorylation of ACC by AMPK, thereby increasing FAO. METHODS: We evaluated phosphorylation of ACC in cell and mouse nephropathy models, as well as the effects of metformin administration in mice with and without mutations that reduce ACC phosphorylation. RESULTS: Reduced phosphorylation of ACC on the AMPK site Ser79 occurred in both tubular epithelial cells treated with folate to mimic cellular injury and in wild-type (WT) mice after induction of the folic acid nephropathy model. When this effect was exaggerated in mice with knock-in (KI) Ser to Ala mutations of the phosphorylation sites in ACC, lipid accumulation and fibrosis increased significantly compared with WT. The effect of ACC phosphorylation on fibrosis was confirmed in the unilateral ureteric obstruction model, which showed significantly increased lipid accumulation and fibrosis in the KI mice. Metformin use was associated with significantly reduced fibrosis and lipid accumulation in WT mice. In contrast, in the KI mice, the drug was associated with worsened fibrosis. CONCLUSIONS: These data indicate that reduced phosphorylation of ACC after renal injury contributes to the development of TIF, and that phosphorylation of ACC is required for metformin's antifibrotic action in the kidney.

A Systematic Review and Meta-analysis of Thrombotic Events Following Endovenous Thermal Ablation of the Great Saphenous Vein.

OBJECTIVES: A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). METHODS: MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. RESULTS: Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. CONCLUSION: Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management.

What do medical students know about e-cigarettes? A cross-sectional survey from one U.S. medical school.

BACKGROUND: Although electronic cigarette (e-cigarette) use has rapidly increased, there is little data about what United States medical students know or are taught about them. This study examined medical students' experiences, knowledge, and attitudes regarding e-cigarettes, as well as their evaluation of their education on e-cigarettes. METHODS: A cross-sectional online survey of medical students currently enrolled at the University of Minnesota Medical School (n = 984) was conducted over a three-week period in August and September 2015. Primary outcomes included students' personal experiences with e-cigarettes, knowledge and attitudes about e-cigarettes, and students' assessment of their education on e-cigarettes. RESULTS: 66.9% medical students completed the survey. 58% (n = 382) of participants identified as female. 35.8% (n = 235) were "not sure" whether e-cigarettes were approved by the FDA for smoking cessation, while 4.1% (n = 27) falsely believed they were. While 82.9% (n = 543) agreed or strongly agreed that they felt confident in their ability to discuss traditional cigarette use with patients, only 12.4% (n = 81) agreed or strongly agreed that they felt confident in their ability to discuss e-cigarettes with patients. 94.8% (n = 619) of participants believed that they had not received adequate education about e-cigarettes in medical school. A higher proportion of males reported ever using an e-cigarette. CONCLUSIONS: The gaps in medical student knowledge and wide variances in attitudes about e-cigarettes at one medical school together with their report of inadequate education in an environment of increasing use of e-cigarette use in the U.S. speaks to a need for the development of medical school curriculum on e-cigarettes.

Malignant Hypertension Causing a Pulmonary-Renal Syndrome.

BACKGROUND: Pulmonary-renal syndrome is characterised by acute kidney injury, haematuria, and haemoptysis and is a well-recognised presentation of diseases such as ANCA vasculitis that require urgent immunosuppression. CASE PRESENTATION: A patient presented with a brief history of haemoptysis, acute renal failure, microscopic haematuria, and severe hypertension. The diagnosis was initially not clear so he was treated with antihypertensives, renal replacement therapy, and immunosuppression. Renal biopsy subsequently showed evidence of malignant hypertension. Autoantibodies were uniformly negative. CONCLUSIONS: This case demonstrates that malignant hypertension can present as pulmonary-renal syndrome.

Balancing the energy equation for healthy kidneys.

The high-energy requirement of the kidney and the importance of energy metabolism in renal physiology has been appreciated for decades, but only recently has there emerged a strong link between impaired renal energy metabolism and chronic kidney disease (CKD). The mechanisms underlying the association between changes in energy metabolism and progression of CKD, however, remain poorly understood. A new study from Qiu and colleagues reported in the Journal of Pathology has advanced this understanding by showing that, after renal injury, the energy sensor AMPK inhibits epithelial-mesenchymal transition and inflammation, processes important in the pathogenesis of CKD. Furthermore, this study identifies an interaction between AMPK and CK2ß as an important mechanism in the anti-fibrotic effect. CK2ß has previously been shown to interact with STK11 (also known as LKB1) to regulate cellular polarity. These findings are consistent with the known roles of the LKB1-AMPK pathway in sustaining cellular energy homeostasis and epithelial cell polarity, and add to growing evidence linking the suppression of energy metabolism to CKD. They emphasize the importance of energy metabolism in general and the LKB1-AMPK axis in particular as key investigational and therapeutic targets in the battle against CKD.

Absence of the lysosomal protein Limp-2 attenuates renal injury in crescentic glomerulonephritis.

In humans, mutations of the intrinsic lysosomal protein SCARB2 are associated with myoclonic epilepsy, collapsing focal and segmental glomerulosclerosis, and tubular proteinuria. Mice with deficiency of Limp-2 (the murine homologue) develop tubular proteinuria but not focal and segmental glomerulosclerosis and they have a defect in macrophage function. To further elucidate the role of Limp-2 in immune function, we induced anti-glomerular basement membrane (GBM) model of crescentic glomerulonephritis in wild-type (WT) and Limp-2(-/-) littermates by intraperitoneal injections of nephrotoxic sheep serum. Renal injury and immune responses were assessed on day 14. Compared with WT, Limp-2(-/-) mice had significantly reduced crescent formation, interstitial inflammation and a trend to reduced tubulointerstitial injury. On day 1 during the heterologous phase of the disease, albuminuria was significantly increased in WT but not in Limp-2(-/-) mice. On day 14, albuminuria and renal function were similar in the two groups. There was, however, a significant reduction in the influx of glomerular macrophages and CD4(+) T cells in Limp-2(-/-) mice. Interleukin (IL)-4 and macrophage chemoattractant protein-1 (MCP-1) mRNA expression levels were significantly reduced. Despite the reduction in numbers of infiltrating cells, flow cytometry showed no difference in macrophage or T-cell numbers in the peripheral blood from untreated mice. The systemic humoral immune response, determined by glomerular mouse immunoglobulin G (IgG) deposition and mouse anti-sheep IgG subclass production, was similar in both groups. These data suggest that absence of Limp-2 reduces inflammation in experimental crescentic glomerulonephritis with decreased macrophage and T-cell infiltration in the kidney. It suggests an important role for Limp-2 in mediating the inflammatory response.

AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a single-dose study in hemodialysis patients.

AMG 416 (velcalcetide), a novel peptide agonist of the calcium-sensing receptor, lowers plasma parathyroid hormone in preclinical uremic animal models and in normal healthy individuals. Here, we studied its efficacy in hemodialysis patients suffering from secondary hyperparathyroidism. Major inclusion criteria were hemodialysis for at least 3 months, serum parathyroid hormone over 300 pg/ml, a corrected serum calcium of 9.0 mg/dl or more, and stable doses of vitamin D analogs for at least 3 weeks prior to screening. Twenty-eight patients were enrolled in one of five cohorts (5, 10, 20, 40, 60 mg). Cohorts 1-3 (four patients each) were treated in a two-period crossover design, while cohorts 4 and 5 (eight patients each) were randomized 1:1 to AMG 416 or placebo. Patients were admitted to a clinical research unit following hemodialysis and studied for 3 days prior to discharge for hemodialysis. Single intravenous doses of AMG 416 from 5 to 60 mg were well tolerated, and plasma levels increased in a dose-related manner. AMG 416 treatment was associated with significant, dose-dependent reductions in serum parathyroid hormone and fibroblast growth factor 23. Compared with placebo, all dose groups of 10 mg or more were associated with attenuation in the rise in serum phosphate during the interdialytic period. Dose-dependent reductions in serum calcium were observed and were well tolerated. Thus, AMG 416 represents a novel therapeutic approach for the treatment of secondary hyperparathyroidism in hemodialysis patients.

Renal structure in normoalbuminuric and albuminuric patients with type 2 diabetes and impaired renal function.

OBJECTIVE: The structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria. RESEARCH DESIGN AND METHODS: In patients with normo- (n = 8) or microalbuminuria (n = 6), renal biopsies were performed according to a research protocol. In patients with macroalbuminuria (n = 17), biopsies were performed according to clinical indication. Findings were categorized according to the Fioretto classification: category 1 (C1), normal/near normal; category 2 (C2), typical diabetic nephropathy (DN) with predominantly glomerular changes; and category 3 (C3), atypical with disproportionately severe interstitial/tubular/vascular damage and with no/mild diabetic glomerular changes. RESULTS: In our study population (mean eGFR 35 mL/min/1.73 m2), typical glomerular changes (C2) of DN were observed in 22 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 subjects with normoalbuminuria (P = 0.002). By contrast, predominantly interstitial or vascular changes (C3) were seen in only 1 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 normoalbuminuric subjects (P = 0.08). Mesangial area increased progressively from normal controls to patients with type 2 diabetes and normo-, micro-, and macroalbuminuria. Varying degrees of arteriosclerosis, although not necessarily the predominant pattern, were seen in seven of eight subjects with normoalbuminuria. CONCLUSIONS: Typical renal structural changes of DN were observed in patients with type 2 diabetes and elevated albuminuria. By contrast, in normoalbuminuric renal insufficiency, these changes were seen less frequently, likely reflecting greater contributions from aging, hypertension, and arteriosclerosis.

Qualitative differences between traditional and rural-longitudinal medical student OSCE performance.

BACKGROUND AND OBJECTIVES: To ensure adequate observation, supervision, and mentoring of trainees, long-term preceptorships or apprenticeships are being reestablished in medical education. Equivalence in academic performance has been demonstrated between longitudinal students in the Rural Physician Associate Program (RPAP), who spend 9 months in a rural community during their third year of medical school, and their peers who complete their clerkships at different hospitals and clinics (traditional). We qualitatively reviewed the end of session Objective Structured Clinical Examination (OSCE) for both groups and compared their performances. METHODS: The high and low performers on four OSCE scenarios (cough, dysuria in a teen, preventive care in an older male, medication reconciliation) for two cohorts of students: longitudinal (n=47) and traditional primary care clerkship students (n=60) were selected for review. These 16 videotapes were reviewed independently by three researchers. The themes and subthemes were discussed over four meetings. RESULTS: Both high and low scoring longitudinal students demonstrated more consistent use of rapport building skills. Longitudinal students appeared to have an effective pattern in their patient interactions and were more rehearsed at explaining preventive care recommendations such as the pros and cons of the prostate-specific antigen (PSA) test. Traditional students displayed a more complete mastery of the adolescent interview and followed a mnemonic taught during lecture. CONCLUSIONS: Qualitative assessment of OSCE data reveals information not captured in the quantitative scores. In this study, longitudinal students demonstrated better mastery of rapport building and content knowledge and had an effective routine to their patient encounters not evident in the traditional students' scenarios.

GIMI: the past, the present and the future.

In keeping with the theme of this year's e-Science All Hands Meeting--past, present and future--we consider the motivation for, the current status of, and the future directions for, the technologies developed within the GIMI (Generic Infrastructure for Medical Informatics) project. This analysis provides insights into how some key problems in data federation may be addressed. GIMI was funded by the UK's Technology Strategy Board with the intention of developing a service-oriented framework to facilitate the secure sharing and aggregation of heterogeneous data from disparate sources to support a range of healthcare applications. The project, which was led by the University of Oxford, involved collaboration from the National Cancer Research Institute Informatics Initiative, Loughborough University, University College London, t+ Medical, Siemens Molecular Imaging and IBM UK.

Caring for the Karen. A newly arrived refugee group.

Since 2004, Minnesota has seen an influx of refugees from Burma. Many of these newcomers came from the Karen state and spent time in refugee camps in Thailand before resettling in the United States. To better understand the health needs of this population, the authors of this article conducted chart reviews at a St. Paul family medicine clinic that serves a number of Karen refugees and reviewed formal data from the Minnesota Department of Health's Refugee Health Program. Here, they briefly describe this community, the cultural issues that could affect health care providers' ability to care for Karen patients, and the health concerns of these refugees.