Novedades en el tratamiento quirúrgico del cáncer de mama

Adecuate surgical treatment is mandatory in order to achieve cure in patients with breast cancer. Breast surgeons have to choice the best surgical technique over the breast and over the axillary nodes. Two new surgical aproaches have been implemented in the last decade: oncoplastic conservative surgery and sentinel lymph node biopsy. Oncoplastic surgery provides oncologic safety results and good cosmetic outcome. In this paper the technical steps and indications of different oncoplastic techniques in conservative breast surgery are review. Concerning to axillary surgery sentinel lymph node biopsy is the gold standard. However there are several controversial points in sentinel node biopsy referring to indications, identification and histological findings

Laser-deposited beta type Ti-42Nb alloy with anisotropic mechanical properties for pioneering biomedical implants with a very low elastic modulus

Present commercial titanium alloy implants have an elastic modulus higher than 100 GPa, whereas that of the cortical bone is much smaller (17–28 GPa). This elastic modulus mismatch produces a stress shielding effect and the resorption of the bone surrounding the implant. In the present work, a fiber texture is developed in ß type Ti-42Nb (wt%) alloy ingots generated by laser-directed energy deposition (LDED) in order to achieve anisotropic mechanical properties. In addition, we demonstrate that laser-deposited ß type Ti-42Nb alloy ingots with an intense fiber texture exhibit a very low elastic modulus in the building direction (Ez 700 MPa) and tensile (UTSz > 700 MPa) strengths. Laser-deposited Ti-42Nb alloy enhances the osteoinductive effect, promoting the adhesion, proliferation, and spreading of human osteoblast-like cells. Hence, we propose that laser-deposited ß type Ti-42Nb alloy is a potentially promising candidate for the manufacturing of pioneering biomedical implants with a very low elastic modulus that can suppress stress shielding.Peer ReviewedPostprint (published version

Effect of Chronic Kidney Diseases on Mortality among Digoxin Users Treated for Non-Valvular Atrial Fibrillation: A Nationwide Register-Based Retrospective Cohort Study.

PURPOSE: This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin. METHODS: All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription. RESULTS: We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription. CONCLUSIONS: This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation

Nuevos horizontes en cirugía mamaria. Cirugía radioguiada y biopsia selectiva de ganglio centinela

Although needle-wire localization is the most commonly used localization technique for nonpalpable breast lesion biopsy, the technique of radioguided occult lesion localization (ROLL), is becoming increasingly used for open-surgery diagnosis in such cases. Sentinel lymph node biopsy(SLNB) is based on the hypothesis that lymphatic drainage from a tumor reaches the sentinel node(SLN) first and that it can be identified accurately and removed. If SLN exactly reflects the lymph-node status, a negative SLN for metastasis might allow complete axillary lymph node dissection (ALDN) to be avoided

Single-step pulsed electrodeposition of calcium phosphate coatings on titanium for drug delivery

Metallic implants have some limitations related to bioactivity and bacteria colonization leading to infections. In this regard, calcium phosphate coatings can be used as carrier for drug delivery in order to improve the mentioned drawbacks. The present work proposes the introduction of an antibacterial agent in the course of a pulsed and reverse pulsed electrodeposition. Calcium phosphate coatings were prepared in 30min using different pulse waveforms (unipolar-bipolar), current densities (2–5mA/cm2) and temperatures (40–60°C). Mechanical stability of the as-coated surfaces was studied in order to select the optimal electrodeposition conditions. Subsequently, selected coatings were loaded with an antiseptic agent, chlorhexidine digluconate (CHX), via a single-step co-deposition procedure. CHX concentration added to the electrolyte was adjusted to 3mM based on the antibacterial efficacy of the loaded coatings evaluated in vitro with Staphylococcus aureus and Escherichia coli bacteria strains. Whereasthe same chlorhexidineconcentration was addedto the electrolyte, results showedthat the amount of CHX loaded was different for each condition while release kinetics was maintained. The results of this work demonstrate that a pulsed co-deposition strategy has great potential to modulate local delivery of antibacterial agents such as chlorhexidine digluconate, which may prevent early phase infections of metallic implants after insertion

Therapy-Related Chronic Myelomonocytic Leukemia Does Not Have the High-Risk Features of a Therapy-Related Neoplasm

Therapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome-7 abnormalities (4% vs 13%; P = .005) but not complex karyotype (3% vs 7%; P = .15), were more frequent in tCMML. tCMML was characterized by higher TP53 mutation frequency (4% vs 12%; P = .04) and lower NRAS (6% vs 22%, P = .007) and CBL (4% vs 12%, P = .04) mutation frequency. Prior therapy with antimetabolites (odd ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.42; P = .01) and mitotic inhibitors (OR, 1.24; 95% CI, 1.06-1.44; P = .009) was associated with NF1 and SETBP1 mutations whereas prior mitotic inhibitor therapy was associated with lower TET2 mutation frequency (OR, 0.71; 95% CI, 0.55-0.92; P = .01). Although no differences in median overall survival (OS) were observed among tCMML and dnCMML (34.7 months vs 35.9 months, P = .26), multivariate analysis for OS revealed that prior chemotherapy was associated with increased risk of death (hazard ratio, 1.76; 95% CI, 1.07-2.89; P = .026). Compared with a cohort of therapy-related myelodysplastic syndrome, tCMML had lower TP53 mutation frequency (12% vs 44.4%, P \u3c .001) and less unfavorable outcomes. In summary, tCMML does not exhibit the high-risk features and poor outcomes of t-MNs

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies

Propuesta de un nuevo modelo microquirúrgico para el estudio de la endometriosis inducida en rata Wistar. Resultados preliminares

The current knowledge status on the patogenesis of endometriosis as well as devastating consequences of disease evolution in women's reproductive health, have promoted researchers advances in a great manner during last years. The immunologic and neangiogenesis systems implication have opened new ways of knowledge over classic theories from the beginning of the xx century. The experimental resesearch, using animal induction models. Below we explain the first steps a new induction model ("PGR1-HotDog"), based on Wistar rats using a new disease autogeneration system, created for te study of the early stages of the endometriosis

Third-party umbilical cord blood-derived regulatory T cells prevent xenogenic graft-versus-host disease

Background aims: Naturally occurring regulatory T cells (Treg) are emerging as a promising approach for prevention of graft-versus-host disease (GvHD), which remains an obstacle to the successful outcome of allogeneic hematopoietic stem cell transplantation. However, Treg only constitute 1-5% of total nucleated cells in cord blood (CB) (&lt;3× 106 cells), and therefore novel methods of Treg expansion to generate clinically relevant numbers are needed. Methods: Several methodologies are currently being used for ex vivo Treg expansion. We report a new approach to expand Treg from CB and demonstrate their efficacy in vitro by blunting allogeneic mixed lymphocyte reactions and in vivo by preventing GvHD through the use of a xenogenic GvHD mouse model. Results: With the use of magnetic cell sorting, naturally occurring Treg were isolated from CB by the positive selection of CD25+ cells. These were expanded to clinically relevant numbers by use ofCD3/28 co-expressing Dynabeads and interleukin (IL)-2. Ex vivo-expanded Treg were CD4+25+FOXP3+127lo and expressed a polyclonal T-cell receptor, Vβ repertoire. When compared with conventional T-lymphocytes (CD4+25- cells), Treg consistently showed demethylation of the FOXP3 TSDR promoter region and suppression of allogeneic proliferation responses in vitro. Conclusions: In our NOD-SCID IL-2Rγnull xenogeneic model of GvHD, prophylactic injection of third-party, CB-derived, ex vivo-expanded Treg led to the prevention of GvHD that translated into improved GvHD score, decreased circulating inflammatory cytokines and significantly superior overall survival. This model of xenogenic GvHD can be used to study the mechanism of action of CB Treg as well as other therapeutic interventions

Distinct Molecular and Immune Hallmarks of Inflammatory Arthritis Induced by Immune Checkpoint Inhibitors for Cancer Therapy

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD