OB-FSG indicates a poor prognosis with almost one-half of patients developing advanced renal failure. Knowledge of the clinico-pathological features of this entity (obesity, FSG lesions with glomerulomegaly, absence of nephrotic syndrome despite nephrotic-range proteinuria) should be helpful in establishing an accurate and early diagnosis.

No abstract

Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2 þ tumours, Po0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P ¼ 0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P ¼ 0.022, 0.005 and o0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics. Modern Pathology (2007) 20, 474-481.

Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; =0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from -6.45±14.66 to -0.18±2.56 ml/min per 1.73 m per year (=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.

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Insulin resistance is present in almost all patients with nonalcoholic steatohepatitis (NAFLD), and mitochondrial dysfunction likely plays a critical role in the progression of fatty liver into nonalcoholic steatohepatitis. Rosiglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPAR␥), is an insulin sensitizer drug that has been used in a number of insulin-resistant conditions, including NAFLD. The aim of this study was to analyze the effects of rosiglitazone on the liver histology and mitochondrial function in a model of NAFLD. All studies were carried out in wild-type and leptin-deficient (ob/ob) C57BL/6J mice. Ob/ob mice were treated with 1 mg/kg/day, and activity of mitochondrial respiratory chain (MRC), beta-oxidation, lipid peroxidation, glutathione content in mitochondria, and 3-tyrosine-nitrated proteins in mitochondria were measured. In addition, histological and ultrastructural changes induced by rosiglitazone were also noted. Rosiglitazone treatment increased liver steatosis, particularly microvesicular steatosis. In these animals, mitochondria were markedly swollen with cristae peripherally placed. In ob/ob mice, this drug increased PPAR␥ protein expression and lipid peroxide content in liver tissue and decreased glutathione concentration in mitochondria. Rosiglitazone suppressed the activity of complex I of the MRC in ob/ob mice, but did not affect beta-oxidation. 3-Tyrosine nitrated mitochondrial proteins, significantly increased in ob/ob mice, were not modified by rosiglitazone treatment. Conclusion: Treatment of ob/ob mice with rosiglitazone did not reverse histological lesions of NAFLD or improve MRC activity. On the contrary, rosiglitazone reduced activity of complex I and increased oxidative stress and liver steatosis.

Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalinfixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens. (Blood. 2011; 118(4):1034-1040) IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in adults, accounting for Ͼ 80% of aggressive lymphomas. 1 DLBCL is a heterogeneous group of tumors with different genetic abnormalities, clinical features, responses to treatment, and prognosis. 2 This heterogeneity hinders outcome prediction based on clinical and/or molecular parameters.Combination therapy that associates CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with rituximab (R-CHOP) has become a standard treatment for DLBCL, leading to complete remission rates of 75%-80% and a 3-to 5-year PFS of 50%-60%. [3][4][5][6][7][8] Nevertheless, patients who fail to respond to first-line therapy or relapse continue to pose a challenge, and identification at diagnosis of poor-outcome cases is crucial for deciding between alternative treatment schemes.The International Prognostic Index (IPI) has been the primary clinical tool for predicting the outcome of patients with aggressive non-Hodgkin lymphoma. 9 Original IPI factors were redistributed in patients treated with R-CHOP to give a revised score (R-IPI) that distinguishes 3 prognostic categories, with 4-year survival rates ranging from 94%-55% for poor-risk patients. 7 Nevertheless, the R-IPI does not discriminate patients with Ͻ 50% probability of survival, which restricts its clinical value. 7 The biologic heterogeneity of DLBCL has been shown substantially to reflect the cell origin of these tumors from germinal center or activated B cells. These differences are significant ind...

Simultaneous double kidney transplantations make it possible to use kidneys from extremely elderly donors (>75 years) or those whose GE>15%. In addition, kidneys from donor 60-74 years old in which the GE<15% can be used for single kidney transplantations in two different recipients with excellent results.