Rosa Ortega

BACKGROUND AND OBJECTIVES: Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-to-perform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival. RESULTS: There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P<0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m(2) increase, 0.96; 95% CI, 0.94 to 0.97; P<0.001), T2 Oxford classification (tubular atrophy/interstitial fibrosis, >50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01). CONCLUSIONS: C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.

BACKGROUND: It has been shown that patients with IgA nephropathy can be divided into two groups on the basis of the pattern of complement activation. Activation of the lectin pathway of complement is associated with more severe renal disease. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. The aim of our study was to determine whether C4d staining at the time of the renal biopsy could identify patients with a different long-term prognosis in IgA nephropathy. METHODS: This retrospective cohort study included all patients with IgA nephropathy who underwent renal biopsy at our centre from January 1992 to December 2006. We evaluated baseline age, sex, presence of macroscopic haematuria, hypertension, serum creatinine and glomerular filtration rate (GFR), urine protein, mesangial C4d staining, glomerulosclerosis, interstitial fibrosis and extracapillary proliferation. Kaplan-Meier survival and Cox proportional hazards analyses were performed, with end-stage renal disease (ESRD) being defined as onset of dialysis or transplantation. RESULTS: Nineteen patients (32.2%) were C4d positive and 40 patients (67.8%) C4d negative. Age, hypertension, absence of macroscopic haematuria, serum creatinine levels, GFR, glomerular sclerosis, interstitial fibrosis and C4d-positive staining were all univariately associated with evolution to ESRD. Renal survival at 10 years was 43.9% in C4d-positive patients versus 90.9% in C4d-negative patients (log-rank, P = 0.0005). CONCLUSION: Negative mesangial C4d staining in glomeruli in patients with IgA nephropathy helps to identify patients with a good long-term prognostic for whom aggressive treatments are not justified.

BACKGROUND AND OBJECTIVES: Advanced ovarian cancer typically spreads in a diffuse intra-abdominal fashion. This characteristic suggests that combined radical surgery and intraperitoneal chemotherapy may be a useful treatment procedure. The purpose of this study was to review patients submitted to surgical debulking and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) and to evaluate the potential prognostic survival factors for advanced epithelial ovarian cancer in our center. METHODS: A series of patients (N = 33) diagnosed of peritoneal carcinomatosis for epithelial ovarian cancer (stage III) from January 1997 to December 2004 submitted to radical surgery-peritonectomy and HIIC with paclitaxel was included in this study; 19 primary ovarian cancer and 14 recurrent ovarian cancer. RESULTS: Cytoreduction R0 (P = 0.018) and negative lymph nodes (P = 0.005) were covariables for major prognostic survival. Patients with optimal cytoreduction R0 obtained survival rates of 63% at 5 years in recurrent ovarian cancer and 60% in primary ovarian cancer, 71% and 63%, respectively with associated subtotal infra-abdominal peritonectomy, and even better results if negative lymph nodes. CONCLUSIONS: Radical surgery-peritonectomy with HIIQ has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival, and prolonged disease-free interval in patients with peritoneal carcinomatosis so much for recurrent or primary ovarian cancer.

The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.

OBJECTIVES: The aim of this study was to calculate organ and effective doses for a range of available protocols in a particular cone beam CT (CBCT) scanner dedicated to dentistry and to derive effective dose conversion factors. METHODS: Monte Carlo simulations were used to calculate organ and effective doses using the International Commission on Radiological Protection voxel adult male and female reference phantoms (AM and AF) in an i-CAT CBCT. Nine different fields of view (FOVs) were simulated considering full- and half-rotation modes, and also a high-resolution acquisition for a particular protocol. Dose-area product (DAP) was measured. RESULTS: Dose to organs varied for the different FOVs, usually being higher in the AF phantom. For 360°, effective doses were in the range of 25-66 μSv, and 46 μSv for full head. Higher contributions to the effective dose corresponded to the remainder (31%; 27-36 range), salivary glands (23%; 20-29%), thyroid (13%; 8-17%), red bone marrow (10%; 9-11%) and oesophagus (7%; 4-10%). The high-resolution protocol doubled the standard resolution doses. DAP values were between 181 mGy cm(2) and 556 mGy cm(2) for 360°. For 180° protocols, dose to organs, effective dose and DAP were approximately 40% lower. A conversion factor (DAP to effective dose) of 0.130 ± 0.006 μSv mGy(-1) cm(-2) was derived for all the protocols, excluding full head. A wide variation in dose to eye lens and thyroid was found when shifting the FOV in the AF phantom. CONCLUSIONS: Organ and effective doses varied according to field size, acquisition angle and positioning of the beam relative to radiosensitive organs. Good positive correlation between calculated effective dose and measured DAP was found.