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Introduction: Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies., Methods: We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed., Results: Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD ( n = 7) or FSGS ( n = 7) were treated with 2 doses of 1,000 mg 2 weeks apart ( n = 13) or four doses of 375 mg/m 2 ( n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months), 10 patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline (14 [100%] vs. 5 [35.7%]; 8/14 [57.1%] vs. 4/12 [33.3%]; 13/14 [92.9%] vs. 7/12 [58.3%]; 20 mg/day vs. 5.25 mg/day, respectively). Maintenance RTX therapy was used in 6 patients, with sustained complete remission. Infusion reactions were observed in 4 patients (one required treatment withdrawal)., Conclusions: Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies., Competing Interests: There is no conflict of interest. The results presented in this paper have not been published previously in whole or part., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objectives: Microflow measurement devices are used in several science and health applications, mainly drug delivery. In the last decade, several new methods based on optical technology were developed, namely the front tracking and interferometric method, in which the knowledge of the inner diameter of the syringe or the capillary used is critical. Only a few National Metrology Institutes (NMIs) can perform inner diameter measurements below 1 mm, which requires expensive technology. Therefore, IPQ, in cooperation with CETIAT, CMI and UNIDEMI, under the EMPIR project 18HLT08 MeDDII - Metrology for Drug Delivery, developed new measurement methods for small inner diameter tubes based on the gravimetric principle and optical methods in order to simplify the apparatus used for this type of measurements without increasing uncertainty., Methods: The gravimetric experimental setup consists of measuring the liquid volume on a specific length of the glass tube. The optical method used is based on the front track principle that uses a high-resolution camera and ImageJ software, to determine the diameter at both ends of each capillary., Results: To validate the developed methods, a comparison was performed between CETIAT, CMI and IPQ and the results obtained were all consistent., Conclusions: This work allowed the determination of inner diameter of syringes or capillaries using two different methods with relative expanded uncertainties from 0.1 to 0.5% ( k =2), that can be applied for flow measurements using optical technology., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Background: In glomerular disease, the degree of proteinuria is closely related to the progression of chronic kidney disease, and its reduction is associated with a slower decline in the glomerular filtration rate (eGFR) and consequent improvement in the renal prognosis. The aim of this study was to evaluate the impact of proteinuria reduction on the decline of the eGFR in patients with glomerular disease, during the first year after the diagnosis. Methods: This was a retrospective analysis of patients with primary glomerular disease, followed at the Nephrology Department of Centro Hospitalar Universitário Lisboa Norte, during 2019. We analyzed demographic, clinical and laboratorial characteristics (creatinine, GFR, urine analysis and quantification of proteinuria determined by the proteinuria/creatinuria ratio, in the first morning urine or a 24 h urine sample). The outcome assessed was the decline in renal function, defined as a reduction in the GFR ≥ 25%, during the follow-up period. Results: We analyzed 197 patients with glomerular disease, with a mean age of 41.7 ± 19.7 years and follow-up time of 6.5 ± 5.3 years. At the time of the diagnosis, the eGFR was 81.5 ± 49.8 mL/min/1.73 m2 and proteinuria was 3.5 g/24 h (IQR 5.8). At one-year follow-up, median proteinuria was 0.9 g/24 h (IQR 2.4). At the end of the follow-up, mean eGFR was 72.1 ± 43.3 mL/min/1.73 m2. Proteinuria (p = 0.435) and the eGFR (p = 0.880) at the time of diagnosis did not correlate with long-term decline in the eGFR. Proteinuria < 1 g/24 h (HR 0.45 (95% CI 0.25−0.83) p = 0.011) after the first year was protective against long-term decline in the eGFR. It maintained this association with the long-term eGFR decline, independently of the duration of the follow-up (HR 0.30 (95% CI 0.17−0.52) p < 0.001). Conclusions: Proteinuria reduction to lower than 1 g/24 h, during the first year after diagnosis, was a protective factor for the long-term decline of kidney function, having a more important role than proteinuria or the GFR at the time of the diagnosis.

Introduction: The use of Rituximab (RTX) in glomerular diseases (GD) has increased in the past years, although it is still only used in a small fraction of patients., Methods: A single center retrospective study of adult patients with membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), and vasculitis treated with RTX as first or second-line therapy was conducted at our center from 2010 to 2020., Results: We identified 19 patients; 36.8% had MN and 25.0% each had FSGS, LN, and vasculitis. RTX was first-line therapy in 26.3% of patients and in 73.7% it was second-line therapy. Mean follow-up time was 7.7 ± 7.2 years. In MN, 2 patients (28.6%) had complete remission (CR), 2 patients (28.6%) had partial remission (PR), and 3 patients (42.9%) had no response (NR). In FSGS, 2 patients (50.0%) presented CR, 1 patient (25.0%) had no response, and 1 patient had renal deterioration. Two patients (50.0%) had a LN class IV with a CR after RTX, 1 patient with LN class IIIC/V had no response, and 1 patient with LN class II had renal deterioration. In vasculitis, 3 patients (75.0%) presented CR and 1 patient had PR. Infusion reactions were present in 2 patients (10.5%) and one patient had multiple infectious complications., Conclusions: The efficacy of RTX in treating different types of immune-mediated GD has been demonstrated with different response rates, but an overall safe profile. In our case series, the results are also encouraging. Longitudinal studies are needed to better understand the effect of RTX in GD.

Colorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15-25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agents is needed, to improve the patients' prognosis. Amino acids transporters, LAT1 and ASCT2, are described as upregulated in CRC, being associated with a poor prognosis. Extracellular vesicles have emerged as key players in cell-to-cell communication due to their ability to transfer biomolecules between cells, with a phenotypic impact on the recipient cells. Thus, this study analyzes the presence of LAT1 and ASCT2 mRNAs in CRC-EVs and evaluates their role in phenotype modulation in a panel of four recipient cell lines (HCA-7, HEPG-2, SK-HEP-1, HKC-8). We found that HCT 116-EVs carry LAT1 , ASCT2 and other oncogenic mRNAs being taken up by recipient cells. Moreover, the HCT 116-EVs' internalization was associated with the increase of LAT1 mRNA in SK-HEP-1 cells. We also observed that HCT 116-EVs induce a higher cell migration capacity and proliferation of SK-HEP-1 and HKC-8 cells. The present study supports the LAT1 -EVs' mRNA involvement in cell phenotype modulation, conferring advantages in cell migration and proliferation.

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign. Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes. Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3-4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2. Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years ( p = 2.01 × 10 -05 ), associated with immunosuppressive therapies ( p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10 -16 ). Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Weigert, Bergman, Gonçalves, Godinho, Duarte, Abrantes, Borges, Brennand, Malheiro, Matoso, Akpogheneta, Kosack, Cruz, Nogueira, Pereira, Ferreira, Marques, Nunes, Faro-Viana, Demengeot and Penha-Gonçalves.)

The human chr15q11-q13 imprinted cluster is linked to several disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes. Recently, disease modeling approaches based on induced pluripotent stem cells (iPSCs) have been used to study these syndromes. A concern regarding the use of these cells for imprinted disease modeling is the numerous imprinting defects found in many iPSCs. Here, by reprogramming skin fibroblasts from a control and AS individuals, we generated several iPSC lines and addressed the stability of imprinting status across the PWS/AS domain. We focused on three important regulatory DNA elements which are all differentially methylated regions (DMRs), methylated on the maternal allele: the PWS imprinting center (PWS-IC), which is a germline DMR and the somatic NDN and MKRN3 DMRs, hierarchically controlled by PWS-IC. Normal PWS-IC methylation pattern was maintained in most iPSC lines; however, loss of maternal methylation in one out of five control iPSC lines resulted in a monoallelic to biallelic switch for many imprinted genes in this domain. Surprisingly, MKRN3 DMR was found aberrantly hypermethylated in all control and AS iPSCs, regardless of the methylation status of the PWS-IC master regulator. This suggests a loss of hierarchical control of imprinting at PWS/AS region. We confirmed these results in established iPSC lines derived using different reprogramming procedures. Overall, we show that hierarchy of imprinting control in donor cells might not apply to iPSCs, accounting for their spectrum of imprinting alterations. Such differences in imprinting regulation should be taken into consideration for the use of iPSCs in disease modeling.

Although the prognostic effect of obesity has been studied in critically ill patients its impact on outcomes of septic patients and its role as a risk factor for acute kidney injury (AKI) is not consensual. We aimed to analyze the impact of obesity on the occurrence of AKI and on in-hospital mortality in a cohort of critically ill septic patients. This study is retrospective including 456 adult patients with sepsis admitted to the Division of Intensive Medicine of the Centro Hospitalar Lisboa Norte (Lisbon, Portugal) between January 2008 and December 2014. Obesity was defined as a body mass index of 30 kg/m 2 or higher. The Kidney Disease Improving Global Outcomes classification was used to diagnose and classify patients developing AKI. AKI occurred in 87.5% of patients (19.5% with stage 1, 22.6% with stage 2 and 45.4% with stage 3). Obese patients developed AKI more frequently than non-obese patients (92.8% versus 85.5%, p = .035; unadjusted OR 2.2 (95% CI: 1.04-4.6), p = .039; adjusted OR 2.31 (95% CI: 1.07-5.02), p = .034). The percentage of obese patients, however, did not differ between AKI stages (stage 1, 25.1%; stage 2, 28.6%; stage 3, 15.4%; p = .145). There was no association between obesity and mortality (p = .739). Of note, when comparing AKI patients with or without obesity in terms of in-hospital mortality there were also no significant differences between those groups (38.4% versus 38.4%, p = .998). Obesity was associated with the occurrence of AKI in critically ill patients with sepsis; however, it was not associated with in-hospital mortality.

Background: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. Renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. Less frequently, glomerulopathy can also be found., Case: We report a case of a 24-year-old Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and normal renal function who presented to us with fever. Laboratory findings revealed pancytopenia, elevated lactate dehydrogenase, and ferritin as well as liver and kidney failure. Renal biopsy showed a tubulointerstitial nephritis superimposed in a membranoproliferative glomerulonephritis with crescents. Extensive etiologic investigation was negative except for Epstein-Barr virus (EBV) viral load. EBV-DNA was then identified by in situ hybridization in the renal biopsy. HPS could be diagnosed with the presence of six criteria: fever, splenomegaly, bicytopenia, high ferritin, hypertriglyceridemia, and high levels of soluble CD25. Steroid therapy was initiated with resolution of HPS as well as complete recovery of renal and liver function., Conclusion: In this case, we believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid therapy successfully treated the inflammatory syndrome, allowing renal function recovery without compromising EBV infection resolution.
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Background: With the rising prevalence of living-donor kidney transplantation, evaluation of factors correlated with renal function in the donor-recipient pair constitutes a main goal for kidney transplantation clinicians. Our objective was to analyze the more relevant donor characteristics that contribute to donor and recipient estimated glomerular filtration rates (eGFR) after 1 year., Methods: We evaluated 48 consecutive donor-recipient pairs from our unit., Results: Mean donor age was 46 ± 11 years, with 71% being women. Mean recipient age was 35 ± 12 years, with 54% being men. Mean duration of donor hospitalization was 7 ± 2 days. Donor eGFR was 104 ± 11 mL/min/1.73 m 2 before donation and 70 ± 14 mL/min/1.73 m 2 at discharge. After 1 year, donor eGFR was 71 ± 12 mL/min/1.73 m 2 and recipient eGFR was 69 ± 10 mL/min/1.73 m 2 . Donor eGFR <100 mL/min/1.73 m 2 before donation and age >50 years correlated with 17.7- and 8.9-fold increased risks, respectively, of recipient eGFR <60 mL/min/1.73 m 2 after 1 year. Donor being female, although statistically associated with worse graft function, compared with a male donor (P = .020), did not represent a significantly increased risk of recipient eGFR <60 mL/min/1.73 m 2 . Higher donor body mass index (BMI) also associated with a lower kidney function for donors (P = .048). In multivariate linear regression to predict pairs' eGFRs after 1 year, only donor eGFR before donation and at discharge retained statistical significance (P ≤ .001 and P = .045, respectively)., Conclusions: Excluding unpredictable complications in the post-transplantation period, donor eGFR before donation, eGFR at discharge, and age were the best parameters to predict recipient and donor eGFRs after 1 year and can be used as a tool for managing expectations regarding the post-transplantation period., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Peritoneopleural shunt is an uncommon complication of peritoneal dialysis (PD) usually presenting early as a right pleural transudate. Peritoneopericardial shunt is an even rarer entity in PD, almost never occurring spontaneously. We present the case of a 37-year-old woman on PD for 24 months exhibiting a left pleural and pericardial effusion following pneumonia. Pleural fluid was initially compatible with an exudate with a high glucose concentration and later with a transudate. In order to clarify the suspicion of an ongoing shunt an abdominal scintigraphy was performed confirming the diagnosis of a peritoneopleuropericardial communication. This case underlines the importance of considering this unusual diagnosis in a patient on long-term PD. Its timely diagnosis is important to stop PD and start hemodialysis.
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Chronic kidney disease (CKD) commonly evolves with disturbances in mineral and bone metabolism, currently defined as CKD-MBD. Management strategies have progressed over the years, but our knowledge regarding evaluation and treatment is still sparse. Herein, we describe a rare case of a hemodialysis patient with apparently fairly controlled hyperparathyroidism (HPTH), who developed multiple symptomatic brown tumors involving the scull, mandible, vertebrae, pelvis, and metacarpus. Parathyroidectomy allowed complete resolution of the bone lesions preventing disastrous consequences.
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Deafness, kidney disease and diabetes are not a usual association, neither is a family history of these diseases. We present the case of a 47-year-old woman with non-nephrotic proteinuria, no haematuria, normal renal function, sensorineural hearing loss, recently diagnosed diabetes and maculopathy. There was a maternal family history of deafness, diabetes and renal disease. Renal biopsy revealed focal and segmental glomerulosclerosis (FSGS), leading to the pursuit of an m.3243A > G mitochondrial mutation and diagnosis of maternally inherited diabetes and deafness. The association of FSGS with mitochondrial diseases is not well known among nephrologists. Its timely diagnosis is important to avoid exposure to ineffective and unnecessary immunosuppression.

Competing Interests: The authors declare no funding or conflicts of interest.

Purpose: Using the Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) systems, the incidence of acute kidney injury (AKI) and their ability to predict in-hospital mortality in severe sepsis or septic shock was compared., Materials and Methods: We performed a retrospective analysis of 457 critically ill patients with severe sepsis or septic shock hospitalized between January 2008 and December 2014. Multivariate logistic regression was employed to evaluate the association between the RIFLE, AKIN and KDIGO systems with in-hospital mortality. Model fit was assessed by the goodness-of-fit test and discrimination by the area under the receiver operating characteristic (AUROC) curve. Statistical significance was defined as P < 0.05., Results: RIFLE (84.2%) and KDIGO (87.5%) identified more patients with AKI than AKIN (72.8%) (P < 0.001). AKI defined by AKIN and KDIGO was associated with in-hospital mortality {AKIN: adjusted odds ratio [OR] 2.3[95% confidence interval (CI) 1.3-4], P = 0.006; KDIGO: adjusted OR 2.7[95% CI 1.2-6.2], P = 0.021} while AKI defined by RIFLE was not [adjusted OR 2.0 (95% CI 1-4), P = 0.063]. The AUROC curve for in-hospital mortality was similar between the three classifications (RIFLE 0.652, P < 0.001; AKIN 0.686, P < 0.001; KDIGO 0.658, P < 0.001)., Conclusions: RIFLE and KDIGO diagnosed more patients with AKI than AKIN, but the prediction ability for in-hospital mortality was similar between the three systems.

Introduction: Intra-atrial catheter (IAC) placement through an open surgical approach has emerged as a life-saving technique in hemodialysis (HD) patients with vascular access exhaustion., Objective: To assess the complications of IAC placement, as well as patient and vascular access survival after this procedure., Methods: The authors retrospectively analyzed all seven patients with vascular capital exhaustion, without immediate alternative renal replacement therapy (RRT), who underwent IAC placement between January 2004 and December 2015 at a single center., Results: Seven patients were submitted to twelve IAC placements. Bleeding (6/7) and infections (3/7) were the main complications in the early postoperative period. Two (2/7, 29%) patients died from early complications and 5/7 were discharged with a properly functioning IAC. The most frequent late complication was catheter accidental dislodgement in all remaining five patients, followed by catheter thrombosis and catheter-related infections in the same proportion (2/5). During follow-up, two of five patients died from vascular accesses complications. After IAC failure, one patient was transferred to peritoneal dialysis and a kidney transplant was performed in the other. Only one patient remains on HD after the third IAC, with a survival of 50 months. The mean patient survival after IAC placement was 19 ± 25 (0-60) months and the mean IAC patency was 8 ± 11 (0-34) months., Conclusion: Placing an IAC to perform HD is associated to significant risks and high mortality. However, when alternative RRT are exhausted, or as a bridge to others modalities, this option should be considered.

Fermentative protein hydrolysates (FPH) were prepared with a proteolytic bacterium, Bacillus strain exhibiting high proteolytic activity. Three FPH with 1, 2, and 4 % of cod protein hydrolysate (CPH) and 0.5 % of yeast extract in the culture were prepared. The yields achieved varied between 30 and 58 % based on protein content. A general decrease of leucine, isoleucine, valine, alanine, arginine, threonine, proline, and glutamic acid was observed. All FPHs showed higher reducing power and DPPH radical scavenging activity than CPH, but similar ABTS radical scavenging activity. However, FPHs exhibited lower Cu(+2)-chelating activity than CPH. The ACE inhibitory activity of FPHs was not improved relatively to that recorded in CPH. The fermentative process seems to have potential to obtaining hydrolysates with improved biological activities or even to produce protein hydrolysates from native fish proteins.

When the frontal lobe of the brain is affected important behavioral changes may occur mainly at the level of executive functioning, i.e., planning, decision-making, judgment and self-perception. However, the behavioral changes may be of different nature with marked indifference and apathy. We report a clinical case of an 81-year-old patient with sudden onset of behavioral changes that were initially interpreted as an acute confusional episode of infectious etiology, but actually they were due to an ischemic lesion in the frontal lobe.

Q fever is a zoonosis caused by Coxiella burnetii that presents with a wide spectrum of acute and chronic manifestations. Progression to chronic Q fever is frequently associated with valve and vascular prosthesis, aneurisms, pregnancy, immunosuppression, and advanced chronic kidney disease. We present a case of a kidney transplant recipient with persistent fever of unknown origin, negative blood cultures, anemia, and increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Q fever serological tests were suggestive of chronic Q fever and the patient was diagnosed with probable chronic Q fever according to the Dutch Fever Consensus Group Guidelines. Initiation of doxycycline 200 mg/d and hydroxychloroquine 600 mg/d resulted in clinical remission. Chronic Q fever is a high-morbidity and -mortality disease if untreated and special attention has to be given to high-risk patients, such as kidney transplant recipients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The loss of CD45, the leukocyte-common antigen, has been described in rare cases of large B-cell lymphoma (LBCL) subtypes with extranodal involvement by immunohistochemical methods. Here we report a case of a patient with LBCL, with no extranodal lesions, which is CD45 negative by flow cytometry (FC) immunophenotyping., Methods: Immunophenotyping and DNA content analysis was performed by multiparametric FC on lymph node and bone marrow aspirate obtained from a 65 year old male patient., Results: Malignant B-lymphocytes were CD5-, CD10+/++, CD11c-, CD19+, CD20+/++, CD23-, CD34-, CD38-/+, CD45-, CD79b++/+++, BCL2 overexpressed, FMC7++, IgM++/+++, TdT- with Lambda light chain restriction. This pathological cellular population showed near-diploid DNA content, with a high proliferate rate., Conclusions: To our knowledge, we describe the first case of a CD19+ B-cell non-Hodgkin lymphoma without expression of CD45 detected by FC, and the first case without extranodal involvement presentation. This case is reported not only because it is a rare one but also to raise awareness of FC users of its correct diagnosis., (Copyright © 2012 International Clinical Cytometry Society.)

Genetic variability in purebred dogs is known to be highly structured, with differences among breeds accounting for approximately 30% of the genetic variation. However, analysis of the genetic structure in non-cosmopolitan breeds and local populations is still limited. Nine Portuguese native dog breeds, and other peripheral dog populations (five) with regional affinities, were characterized using 16 microsatellites and 225 amplified fragment length polymorphism (AFLP) markers, and the pattern of genetic differentiation was investigated. Although the level of breed differentiation detected is below that of other dog breeds, there is in most cases a correlation between breed affiliation and molecular structure. AFLP markers and Bayesian clustering methods allowed an average of 73.1% of individuals to be correctly assigned to source populations, providing robust genotypic assessment of breed affiliation. A geographical genetic structure was also detected, which suggests a limited influence of African dogs on the Iberian breeds. The sampling effect on the estimation of population structure was evaluated and there was a 2.2% decrease in genetic differentiation among breeds when working animals were included. Genetic diversity of stray dogs was also assessed and there is no evidence that they pose a threat to the preservation of the gene pool of native dog breeds.

Purpose: The aim of the present work was to evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse., Patients and Methods: Data from a hundred and eleven patients were submitted to two different approaches based on CA-125 AUC increase values to predict patient relapse. In Criterion A total CA-125 AUC normalized in time value (AUC(i)) was compared with the immediately previous one (AUC(i-1)) using the formulae AUC(i) > or = F * AUC(i-1) (several F values were tested) to find the appropriate close related increment associated to patient relapse. In Criterion B total CA-125 AUC normalised in time was calculated and several cut-off values were correlated with patient relapse prediction capacity., Results: In Criterion A the best accuracy was achieved with a factor (F) of 1.25 (increment of 25% from the previous status), while in Criterion B the best accuracies were achieved with cut-offs of 25, 50, 75 and 100 IU/mL. The mean lead time to relapse achieved with Criterion A was 181 days, while with Criterion B they were, respectively, 131, 111, 63 and 11 days., Conclusion: Based on our results we believe that conjugation and sequential application of both criteria in patient relapse detection should be highly advisable. CA-125 AUC rapid burst in asymptomatic patients should be firstly evaluated using Criterion A with a high accuracy (0.85) and with a substantial mean lead time to relapse (181 days). If a negative answer was obtained then Criterion B should performed to confirm the absence of relapse.

Objective: The aim of the present study was to investigate the usefulness of the CA-125 area under the curve (AUC) as a new kinetic parameter for predicting overall survival in patients with ovarian cancer. In addition, the relationship of CA-125 AUC with other prognostic factors of ovarian cancer was evaluated., Methods: Ninety-two patients that underwent primary line chemotherapy within 4 months after submission to cytoreductive surgery were included. For each patient, CA-125 AUC was calculated and a statistical analysis was conducted to compare CA-125 AUC behavior among patients according to several covariates., Results: The mean age at diagnostic time was found to be 55.5 (16.1-82.4) years with a mean survival of 39.2 (3.5-100.1; SE = 2.6) months. Across FIGO stage I, II, III, and IV patients had a mean CA-125 AUC of 18.2, 24.6, 147.8, and 574.6 IU/ml*days, respectively (P < 0.05). At the evaluation date, living patients had a mean CA-125 AUC of 40.1 in contrast to 234.1 IU/ml*days (P < 0.05) for deceased ones. Patients with a complete response to primary chemotherapy had a mean CA-125 AUC of 48.8, while patients with a partial response had a mean of 251.7 IU/ml*days, and patients with no response or disease progression had a mean of 316.5 IU/ml*days (P < 0.05). The best CA-125 AUC performance is in predicting patient complete response to chemotherapy with a cut-off of 100 IU/ml*days and an accuracy of 82%., Conclusions: Despite CA-125 AUC high correlation with the FIGO stage, residual disease, and patient final outcome, the main interest of CA-125 AUC calculation is to evaluate the treatment efficacy and to foresee a full chemotherapy response. Further studies should be carried out before extrapolating these results to other data sets.