Pseudothrombocytopenia, beyond a laboratory phenomenon: study of 192 cases.

The platelet antibodies that cause pseudothrombocytopenia (PTCP) act only in vitro and do not produce clinical bleeding. Most studies on PTCP have focused on improving differential diagnosis with true thrombocytopenia but studies on the characteristics of patients with PTCP are limited. In this study, we aimed to evaluate the clinical and biological characteristics of 192 patients with PTCP. In addition to general variables, we evaluated automated and microscopic platelet counts, platelet clumps, platelet diameters, immature platelet fraction (IPF), and platelet antibodies. Adult women accounted for the largest subgroup of patients (n=82; 42.7%) and 67 patients (34.9%) were grouped into families. Forty-four patients (22.9%) had one or more associated autoimmune disorders (ADs); 39 relatives of these patients (19.8%) had ADs and 45 relatives (23.4%) had immune thrombocytopenia (ITP) or unspecified thrombocytopenia. Platelet cryptantibodies and/or autoantibodies were positive in 56 patients (30.1%). Most patients (n=169; 80%) had automated platelet counts >80×109/L. In all patients, microscopic platelet counts were ≥150×109/L. The platelet clump index (% increase in microscopic platelet count compared to automatic count) ranged from 30 to >7000%. Platelet diameters and IPF parameters were significantly greater in the PTCP versus healthy controls (p<0.001). A total of 17 patients (8.8%) had had previous ITP or the PTCP evolved into ITP. Our data suggest that PTCP should be considered a situation of autoimmunity; the assessment of platelet clumps has a high diagnostic value; the close association between ITP and PTCP suggests that these conditions could be different phases of the same process.

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The ß-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.

Clinical outcomes in patients with atrial fibrillation treated with DOACs in a specialized anticoagulation center: Critical appraisal of real-world data.

AIMS: Direct oral anticoagulants (DOAC) are progressively replacing vitamin K antagonists in the prevention of thromboembolism in patients with atrial fibrillation. However, their real-world clinical outcomes appear to be contradictory, with some studies reporting fewer and others reporting higher complications than the pivotal randomized controlled trials. We present the results of a clinical model for the management of DOACs in real clinical practice and provide a review of the literature. METHODS: The MACACOD project is an ongoing, observational, prospective, single-center study with unselected patients that focuses on rigorous DOAC selection, an educational visit, laboratory measurements, and strict follow-up. RESULTS: A total of 1,259 patients were included. The composite incidence of major complications was 4.93% py in the whole cohort vs 4.49% py in the edoxaban cohort. The rate of all-cause mortality was 6.11% py for all DOACs vs 5.12% py for edoxaban. There weren't differences across sex or between Edoxaban reduced or standard doses. However, there were differences across ages, with a higher incidence of major bleeding complications in patients >85 years (5.13% py vs 1.69% py in <75 years). CONCLUSIONS: We observed an incidence of serious complications of 4.93% py, in which severe bleeding predominated (3.65% py). Considering our results, more specialized attention seems necessary to reduce the incidence of severe complications and also a more critical view of the literature. Considering our results, and our indirect comparison with many real-world studies, more specialized attention seems necessary to reduce the incidence of severe complications in AF patients receiving DOACs.

Impact of increased kidney function on clinical and biological outcomes in real-world patients treated with Direct Oral Anticoagulants.

BACKGROUND AND PURPOSE: Renal excretion of direct oral anticoagulants (DOACs) varies depending on the drug. Hypothetically, an increased glomerular filtration rate (GFR) may lead to suboptimal dosing and a higher thromboembolic events incidence. However, real-world patient data do not support the theoretical risk. The aim is to analyse DOAC outcomes in patients with normal and high (≥90 mL/min) GFR, focusing on biological parameters and thrombotic/haemorrhagic events. METHODS: Observational prospective single-centre study and registry of patients on DOACs. Follow-up was 1,343 patient-years. A bivariate analysis was performed of baseline variables according to GFR (<90 mL/min vs ≥90 mL/min). Anti-Xa activity before and after drug intake (HemosIL, Liquid Anti-Xa, Werfen) was measured for edoxaban, apixaban, and rivaroxaban; diluted thrombin time for dabigatran (HEMOCLOT); and additionally, plasma concentrations in edoxaban (HemosIl, Liquid Anti-Xa suitably calibrated). RESULTS: 1,135 patients anticoagulated with DOACs were included and 152 patients with GFR ≥90 mL/min. Of 18 serious thrombotic complications during follow-up, 17 occurred in patients with GFR <90 mL/min, and 1 in a patient with GFR ≥90 mL/min. A higher incidence of complications was observed in patients with normal GFR, but the difference was not statistically significant (p>0.05). No statistically significant differences with clinical relevance were observed between the normal or supranormal groups in anti-Xa activity or in edoxaban plasma concentrations. CONCLUSIONS: There was no increased incidence of thrombotic/haemorrhagic complications in our patients treated with DOACs, including 66% treated with edoxaban, and patients with GFR ≥90 mL/min. Likewise, drug anti-Xa activity and edoxaban plasma concentration did not seem to be influenced by GFR.

TMAO and Gut Microbial-Derived Metabolites TML and γBB Are Not Associated with Thrombotic Risk in Patients with Venous Thromboembolism.

BACKGROUND: The present work evaluates the association between circulating concentrations of Trimethylamine-N-oxide (TMAO), gamma butyrobetaine (γBB), and trimetyllisine (TML) in controls and patients with venous thromboembolism (VTE) with coagulation parameters. METHODS: The study involved 54 VTE patients and 57 controls. Platelet function, platelet hyperreactivity, platelet adhesiveness, thrombosis-associated parameters, and thrombin generation parameters were studied. Plasma TMAO, γBB, and TML determination was performed using an ultra-high-performance liquid chromatography system coupled with mass spectrometry. RESULTS: No differences were found for TMAO, γBB, or TML concentrations between controls and VTE patients. In thrombin generation tests, TMAO, γBB, and TML showed a positive correlation with lag time and time to peak. TMAO, γBB, and TML negatively correlated with peak height. No significant differences were observed regarding TMAO, γBB, and TML concentrations between the two blood withdrawals, nor when the control and VTE patients were analyzed separately. No correlation was observed between these gut metabolites and platelet function parameters. CONCLUSIONS: No differences were found regarding TMAO, γBB, and TML concentrations between the control and VTE groups. Some correlations were found; however, they were mild or went in the opposite direction of what would be expected if TMAO and its derivatives were related to VTE risk.

Impact of pre-admission antithrombotic therapy on disease severity and mortality in patients hospitalized for COVID-19.

Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for ≥ 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18-0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.

Complementary value of electron microscopy and immunohistochemistry in the diagnosis of non-small cell lung cancer: A potential role for electron microscopy in the era of targeted therapy.

With the identification of therapeutic targets for lung adenocarcinoma, it has become mandatory to distinguish it from other entities. Some cases remain classified as non-small cell lung carcinoma, not otherwise specified (NSCLC-NOS) with immunohistochemistry. Electron microscopy (EM) can be useful, allowing the identification of glandular differentiation. The aim of this study was to determine the complementary value of immunohistochemistry and EM.Forty-eight NSCLC-NOS cases were selected (PSMAR-Biobank, Barcelona, Spain). Immunohistochemistry (TTF-1, p40) was performed. Tissue was retrieved from paraffin blocks. Results were compared to the final diagnosis, derived from combination of light microscopy, immunohistochemistry, EM, molecular studies and resection specimen.Immunohistochemistry concurred with final diagnosis in 36 cases (75%, Kappa = 0.517). EM agreed with final diagnosis in 35 (72.9%, Kappa = 0.471). Immunohistochemistry had a sensitivity = 73%, specificity = 100%, positive predictive value (PPV) = 100% and negative predictive value (NPV) = 52.4% for adenocarcinoma. All adenocarcinoma cases not solved by immunohistochemistry (n = 10) were classified by EM, and vice versa. Data from EM were identical to those of immunohistochemistry: sensitivity = 73%, specificity = 100%, PPV = 100% and NPV = 52.4%. Combining both techniques, 47 cases were coincident with final diagnosis (97.9%, Kappa = 0.943).EM can provide valuable information in subtyping NSCLC-NOS, being particularly useful when immunohistochemistry is inconclusive. EM could be considered as a complementary tool for decision-making in NSCLC-NOS.

Bloqueo del sistema renina-angiotensina-aldosterona en pacientes con enfermedad renal diabética avanzada / The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease

Antecedentes y objetivos: La enfermedad renal diabética es la primera causa de enfermedad renal crónica terminal en nuestro medio. El bloqueo del sistema renina-angiotensina aldosterona (BSRAA) enlentece la progresión de la enfermedad renal diabética. Nuestros objetivos son: estudiar pacientes tratados con BSRAA, comparando su evolución según el filtrado glomerular, su perfil de seguridad y si se asocia a una progresión mayor de la enfermedad renal crónica. Materiales y métodos: Estudio retrospectivo de 197 pacientes con enfermedad renal diabética. Se dividieron en tres grupos según tratamiento: pacientes que no recibieron BSRAA (no BSRAA), pacientes que en algún momento lo recibieron (BSRAA discontinuado) y pacientes que recibieron BSRAA (BSRAA mantenido). Se estudiaron características clínicas y analíticas: función renal, ionograma, hemoglobina glicosilada, filtrado glomerular según CKD-EPI y MDRD. Analizamos su evolución (basal, año y 3 años) en relación con el grupo de tratamiento, supervivencia, factores de riesgo y pronóstico renal. Resultados: Los pacientes no BSRAA presentaron en el momento basal peor función renal y edad más avanzada (p<0,05) en comparación con los que recibieron BSRAA. Los pacientes que recibieron BSRAA no mostraron mayor toxicidad, ni más progresión de la enfermedad renal crónica, y no evidenciamos diferencias en el pronóstico renal. La mortalidad fue mayor en pacientes no BSRAA, de mayor edad y peor función renal (p<0,05). En el análisis multivariado los factores de riesgo de mortalidad fueron edad avanzada y peor función renal. Conclusiones: El tratamiento con BSRAA es más frecuente en pacientes con FGe≥30mL/min/1,73m2. No observamos diferencias en la evolución de la función renal entre los tres grupos. La mayor mortalidad observada en pacientes que no recibieron BSRAA se relacionó con la edad avanzada y peor función renal (AU)

Background and objectives: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Materials and methods: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. Results: Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. Conclusions: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m2. In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade (AU)

The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease. / Bloqueo del sistema renina-angiotensina-aldosterona en pacientes con enfermedad renal diabética avanzada.

BACKGROUND AND OBJECTIVES: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. MATERIALS AND METHODS: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. RESULTS: Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. CONCLUSIONS: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m2. In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade.

Potential drug-drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir ± DASABUVIR ± ribavirin in clinical practice.

BACKGROUND & AIMS: Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice. METHODS: 177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy. RESULTS: At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients. CONCLUSIONS: Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.

Serum osteoprotegerin in prevalent hemodialysis patients: associations with mortality, atherosclerosis and cardiac function.

BACKGROUND: To assess whether serum osteoprotegerin (OPG) and/or fetuin-A predict mortality and cardiovascular (CV) morbidity and mortality in hemodialysis patients. METHODS: Multicenter, observational, prospective study that included 220 hemodialysis patients followed up for up to 6 years. Serum OPG and fetuin-A levels were measured at baseline and their possible association with clinical characteristics, CV risk biomarkers, carotid ultrasonographic findings, as well as their association with overall and CV mortality and CV events were assessed. RESULTS: During a mean follow-up of 3.22 ± 1.91 years, there were 74 deaths (33.6%) and 86 new cardiovascular events. In the Kaplan-Meier survival analysis, the highest tertile of OPG levels was associated with higher overall mortality (p = 0.005), as well as a higher, although non-significant, incidence of CV events and CV mortality. In contrast, fetuin-A levels did not predict any of these events. OPG levels were directly associated with age, the Charlson comorbidity index (CCI), prevalent cardiovascular disease, carotid intima-media thickness, adiponectin, troponin-I and brain natriuretic peptide (BNP). OPG showed a negative correlation with left ventricular ejection fraction (LVEF) and phosphate levels. In the multivariate Cox proportional hazard analysis, all-cause mortality was associated with the highest tertile of OPG (HR:1.957, p = 0.018), age (HR:1.031, p = 0.036), smoking history (HR:2.122, p = 0.005), the CCI (HR:1.254, p = 0.004), troponin-I (HR:3.894, p = 0.042), IL-18 (HR:1.061, p < 0.001) and albumin levels (HR:0.886, p < 0.001). In the bootstrapping Cox regression analysis, the best cut-off value of OPG associated with mortality was 17.69 pmol/L (95%CI: 5.1-18.02). CONCLUSIONS: OPG, but not fetuin-A levels, are independently associated with overall mortality, as well as clinical and subclinical atherosclerosis and cardiac function, in prevalent hemodialysis patients.

Cost and detection rate of glaucoma screening with imaging devices in a primary care center.

PURPOSE: To analyze the cost and detection rate of a screening program for detecting glaucoma with imaging devices. MATERIALS AND METHODS: In this cross-sectional study, a glaucoma screening program was applied in a population-based sample randomly selected from a population of 23,527. Screening targeted the population at risk of glaucoma. Examinations included optic disk tomography (Heidelberg retina tomograph [HRT]), nerve fiber analysis, and tonometry. Subjects who met at least 2 of 3 endpoints (HRT outside normal limits, nerve fiber index ≥30, or tonometry ≥21 mmHg) were referred for glaucoma consultation. The currently established ("conventional") detection method was evaluated by recording data from primary care and ophthalmic consultations in the same population. The direct costs of screening and conventional detection were calculated by adding the unit costs generated during the diagnostic process. The detection rate of new glaucoma cases was assessed. RESULTS: The screening program evaluated 414 subjects; 32 cases were referred for glaucoma consultation, 7 had glaucoma, and 10 had probable glaucoma. The current detection method assessed 677 glaucoma suspects in the population, of whom 29 were diagnosed with glaucoma or probable glaucoma. Glaucoma screening and the conventional detection method had detection rates of 4.1% and 3.1%, respectively, and the cost per case detected was 1,410 and 1,435€, respectively. The cost of screening 1 million inhabitants would be 5.1 million euros and would allow the detection of 4,715 new cases. CONCLUSION: The proposed screening method directed at population at risk allows a detection rate of 4.1% and a cost of 1,410 per case detected.

Cystatin C estimated glomerular filtration rate to assess renal function in early stages of autosomal dominant polycystic kidney disease.

BACKGROUND/AIMS: Height-adjusted total kidney volume (htTKV) is the best marker of disease progression in early autosomal dominant polycystic kidney disease (ADPKD) when renal function still remains normal. The usefulness of cystatin-C as a biomarker to assess renal function according to renal volume has not been studied in ADPKD patients. METHODS: Observational and cross-sectional study of 62 ADPKD patients. htTKV, creatinine and cystatin-C estimated glomerular filtration rate (eGFR) were determined. Correlations between htTKV and eGFR were studied. A control group was used to determine the association between renal function differences and htTKV. RESULTS: htTKV significantly correlated with cystatin-C-eGFR (r = -0.384, p = 0.002) but not with creatinine-eGFR (r = -0.225, p = 0.078). With htTKV stratified into tertiles, a significant difference of cystatin-C-eGFR but not in creatinine-eGFR was detected in the third tertile when compared with the first tertile group (110.0±22.2 vs 121.3±7.2; p = 0.023 and 101.8±17.2 vs 106.9±15.1; p = 0.327 respectively). When cystatin-C-eGFR of the controls was used as the reference, htTKV above 605 ml/m identified with a 75% sensitivity and 84.9% specificity those patients with a significant worse kidney function. However, this cut-off value could not be identified using creatinine-eGFR. CONCLUSIONS: Cystatin-C-eGFR but not creatinine-eGFR correlated with htTKV in ADPKD patients in early stages of the disease. Differences in cystatin-C-eGFR but not in creatinine-eGFR have been identified through htTKV tertiles. A htTKV above 605 ml/m is associated with a worse renal function only if cystatin-C-eGFR is used. Cystatin-C-eGFR should be studied in prospective studies of early stages of ADPKD to determine its usefulness as an early marker of disease progression.

Mammographic extent of microcalcifications and oestrogen receptor expression affect preoperative breast carcinoma in situ size estimation.

BACKGROUND: The aim of our study was to establish which clinical, radiologic and pathologic factors could predict the risk of under- and overestimation of the breast ductal carcinoma in situ (DCIS) size when preoperatively measuring the maximum mammographic extent of microcalcifications (MEM). METHODS: We made a retrospective review of patients with a DCIS treated in our Breast Unit between May 2005 and May 2012. Clinical, pathologic and radiologic data were evaluated as possible predictive factors for over- or underestimation of DCIS size when measuring MEM. RESULTS: We obtained precise measurements of MEM in 82 patients (84 DCIS lesions). Maximum MEM measurement correctly estimated maximum pathology size in 57 lesions (68.7 %). Patients with a correctly estimated DCIS, with an underestimated DCIS and with an overestimated DCIS significantly differed in DCIS ER expression (p = 0.022) and in maximum MEM measurement (p = 0.000). Constructing two ROC curves, we found that a maximum MEM measurement ≥25 mm and ER expression ≥90 % were both discrimination points for overestimation and ER ≤ 45 % was a discrimination point for underestimation. Using these cutoff points, we defined four groups of patients with different risks of over- and underestimation. CONCLUSIONS: Risk of over- or underestimation of DCIS size through MEM measurement depends on DCIS ER expression and MEM itself. Identifying which patients are at a significant risk of over- or underestimation could help the breast surgeon when discussing the surgical options with the patient.

Stability determinants of bone-borne force-transmitting components in three RME hybrid expanders-an in vitro study.

BACKGROUND: The aim was to test which component [wire arm, connecting abutment attachment, and orthodontic mini-implant (OMI)] of the force-transmitting system (FTS) in the anterior palate of three commonly used hybrid expanders (HEs; WILMES-HE, LUDWIG-HE, and WINSAUER-HE) deforms under increasing load. MATERIALS AND METHODS: Crude single and double wire arms were tested individually. Non-opening of the maxillae halves was simulated in artificial bone blocks with single wire and double wire FTS specimens. OMIs were inserted 8mm and underwent 6mm of continuous static lateral loading. Deformation angles were measured (X-ray, n = 6) at 0, 3 and 6mm feed. OMIs and abutments were scan electron microscope (SEM) evaluated. RESULTS: After 1.0mm of loading, the single wire arm of all FTS deformed between 63.4 (16.5) N and 76.2 (18.4) N, and the double wire arm of reinforced FTS (wires positioned 'side by side') deformed after 1.0mm between 110.0 (18.4) N and 134.8 (22.3) N. The crude single wire resisted 89 (5.1) N until plastic deformation, whereas the crude double wire positioned 'on top of each other' resisted 438 (21.3) N. At 6mm loading, the reinforced WINSAUER-HE FTS withstood a maximum load of 320.9 (31.1) N and the reinforced LUDWIG-HE FTS 19% less, both under great deformation of double wires and OMIs. The screw-fixated WILMES-HE FTS abutment attachment (overlapping OMI head 34%) detached around 250N. The bonded WINSAUER-HE and LUDWIG-HE abutment attachments did not detach. Nor did the modified bonded plus the modified screw-fixated WILMES-HE abutment attachment when overlapping 100%. CONCLUSION: Early OMI and single wire arm deformation in HEs are crucial for unsuccessful RME in more mature maxillae. Double wire arms should be obligatory. OMIs with inner diameter greater 1.36mm are recommended. One hundred per cent overlapping abutment attachments do not detach.

Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease.

INTRODUCTION: The basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease. METHODS: We screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity. RESULTS: Positive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks). CONCLUSIONS: The CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life.

Renal volume and cardiovascular risk assessment in normotensive autosomal dominant polycystic kidney disease patients.

Cardiovascular disease, closely related to an early appearance of hypertension, is the most common mortality cause among autosomal dominant polycystic kidney disease patients (ADPKD). The development of hypertension is related to an increase in renal volume. Whether the increasing in the renal volume before the onset of hypertension leads to a major cardiovascular risk in ADPKD patients remains unknown.Observational and cross-sectional study of 62 normotensive ADPKD patients with normal renal function and a group of 28 healthy controls. Renal volume, blood pressure, and renal (urinary albumin excretion), blood vessels (carotid intima media thickness and carotid-femoral pulse wave velocity), and cardiac (left ventricular mass index and diastolic dysfunction parameters) asymptomatic organ damage were determined and were considered as continuous variables. Correlations between renal volume and the other parameters were studied in the ADPKD population, and results were compared with the control group. Blood pressure values and asymptomatic organ damage were used to assess the cardiovascular risk according to renal volume tertiles.Even though in the normotensive range, ADPKD patients show higher blood pressure and major asymptomatic organ damage than healthy controls. Asymptomatic organ damage is not only related to blood pressure level but also to renal volume. Multivariate regression analysis shows that microalbuminuria is only associated with height adjusted renal volume (htTKV). An htTKV above 480 mL/m represents a 10 times higher prevalence of microalbuminuria (4.8% vs 50%, P < 0.001). Normotensive ADPKD patients from the 2nd tertile renal volume group (htTKV > 336 mL/m) show higher urinary albumin excretion, but the 3rd tertile htTKV (htTKV > 469 mL/m) group shows the worst cardiovascular risk profile.Normotensive ADPKD patients show in the early stages of the disease with slight increase in renal volume, higher cardiovascular risk than healthy controls. An htTKV above 468 mL/m is associated with the greatest increase in cardiovascular risk of normotensive ADPKD patients with normal renal function. Early strategies to slow the progression of the cardiovascular risk of these patients might be beneficial in their long-term cardiovascular survival.

Factores predictivos de nefropatía no diabética en pacientes diabéticos. Utilidad de la biopsia renal / Predictive factors for non-diabetic nephropathy in diabetic patients. The utility of renal biopsy

Antecedentes y objetivos: La afectación renal del diabético solo puede determinarse mediante biopsia renal, que presenta una elevada prevalencia de lesiones no diabéticas. Los objetivos del estudio fueron determinar la predictibilidad de nefropatía no diabética (NND) en diabéticos, estudiar diferencias de supervivencia y pronóstico renal, evaluar las lesiones histológicas en nefropatía diabética (ND) y el efecto de la proteinuria en la supervivencia y pronóstico renal en esta población. Material y métodos: Estudio descriptivo y retrospectivo de las biopsias renales de diabéticos entre 1990 y 2013 en nuestro centro. Resultados: Incluimos a 110 pacientes: 87 hombres (79%), con una edad media de 62 años (50-74), creatinina sérica media de 2,6mg/dl (0,9-4,3) y proteinuria de 3,5g/24h (0,5-6,5). El 34,5% presentaban ND, el 61,8% NND y el 3,6% ND+NND. La NND más frecuente fue nefropatía IgA (13,2%). En el análisis multivariado, se asociaron de forma independiente a NND: edad (OR 1,068; IC 95%: 1,010-1,129; p=0,022), años de diabetes (OR: 0,992; 0,987-0,998; p=0,004), creatinina (OR: 1,48; 1,011-2,172; p=0,044), proteinuria de 24 h (OR: 0.813; 0,679-0,974; p=0,025) y retinopatía diabética (OR: 0,23; 0,066-0,808; p=0,022). No hallamos diferencias de supervivencia ni de pronóstico renal. Entre los pacientes con ND, presentaban mayor expansión nodular mesangial los que tenían proteinuria nefrótica (p=0,02), así como peor pronóstico renal (p=0,004) comparado con proteinuria no nefrótica. No evidenciamos diferencias en la supervivencia del paciente. Conclusiones: La causa más frecuente de NND fue nefropatía IgA. Los pacientes con mayor edad, creatinina, menor duración de diabetes, ausencia de retinopatía diabética y menor proteinuria presentan mayor riesgo de NND. Los pacientes con ND y proteinuria en rango nefrótico tuvieron peor pronóstico renal (AU)

Background and objectives: Diabetic renal lesions can only be diagnosed by kidney biopsy. These biopsies have a high prevalence of non-diabetic lesions. The aims of the study were to determine the predictability of non-diabetic nephropathy (NDN) in diabetics and study differences in survival and renal prognosis. In addition, we evaluated histological lesions and the effect of proteinuria on survival and renal prognosis in patients with diabetic nephropathy (DN). Material and methods: A descriptive, retrospective study of kidney biopsies of diabetics between 1990 and 2013 in our centre. Results: 110 patients were included in the study: 87 men (79%), mean age 62 years (50-74), mean serum creatinine 2.6mg/dl (0.9-4.3) and proteinuria 3.5g/24hours (0.5-6.5). 61.8% showed NDN, 34.5% showed DN and 3,6% showed DN+NDN. The most common NDN was IgA nephropathy (13,2%). In the multivariate analysis, creatinine (OR: 1.48, 1.011-2.172, p=0.044), proteinuria/24hours (OR: 0.813, 0.679-0.974, p=0.025), duration of diabetes (OR: 0.992, 0.987-0.998, p=0.004), age (OR: 1.068, 95% CI: 1.010-1.129, p=0.022), and diabetic retinopathy (OR: 0.23, 0.066-0.808, p=0.022) were independently associated with NDN. We did not find any differences in survival or renal prognosis. Concerning patients with DN, increased nodular mesangial expansion (p=0.02) and worse renal prognosis (p=0.004) were observed in nephrotic proteinuria as compared to non-nephrotic proteinuria. We did not find differences in patient survival. Conclusions: The most common cause of NDN was IgA nephropathy. Higher creatinine levels, shorter duration of diabetes, absence of diabetic retinopathy, lower proteinuria, and older age were risk factors for NDN. Patients with DN and nephrotic-range proteinuria had worse renal prognosis (AU)