Resultados oncológicos en pacientes potencialmente candidatos a vigilancia activa sometidos a prostatectomía radical

ObjectiveTo determine whether there are differences in the oncological outcomes after radical prostatectomy (adverse patology and biochemical recurrence) based on clinical selection criteria used in two active surveillance (AS) protocols.Material and methods442 patients diagnosed with localized prostate cancer (CP) underwent radical prostatectomy at our institution between August 2003 and December 2009. We selected patients with low-risk CP, which could have been included in an AS program. Patients were divided into two groups: group i, those who met the most strict surveillance criteria described by Epstein (PSAD < .15; T1/T2a; < 2 positive core, Gleason ≤ 6,<  50% involvement of the core) and group ii, those meeting the more open criteria described by Klotz (PSA ≤ 10 or < 15 at age 70, Gleason ≤ 6 or < 7 [3 + 4] in over 70 years). We compared both groups to determine differences in pathological stage, positive surgical margins and biochemical recurrence after radical prostatectomy.ResultsOf the 442 patients 48% (213 patients) had low-risk PC, and become potential candidates for an AS program. Of the patients operated on 17% (76 patients) met the criteria for AS as of Epstein's and 48% (213 patients) according to Klotz. Comparing patients in both groups there were no statistically significant differences in the presence of pT3 (7.9% vs 10.8%) P = .55, positive margins (22.4% vs. 28.3%) P = .41, nor in biochemical recurrence at 3 years (5.3% vs 5.6%) P = .86.ConclusionsIn our series of patients theoretically candidates for inclusion in a program of active surveillance, we found no differences in the percentage of patients with pathological stage pT3, positive margins and biochemical recurrence according to clinical inclusion criteria currently used.     

Nitric oxide boosts TLR‐4 mediated lipocalin 2 expression in chondrocytes

Lipocalin 2 (LCN2) has recently emerged as a novel adipokine involved in different processes including arthritis and chondrocyte inflammatory response. However, little is known about its activity on chondrocyte homeostasis and its regulation by nitric oxide (NO) Hence, we performed a set of experiments aimed to achieve a better understanding of this relationship. Cell vitality was tested in the ATDC5 cell line by the MTT colorimetric assay. Protein expression and gene expression was evaluated by Western blot and real time RT‐PCR, respectively. NO production (determined as nitrite accumulation) was assayed by the Griess reaction. First, we demonstrated that LCN2 decreased murine chondrocytes vitality. Next, LCN2 co‐stimulation with LPS enhanced NOS2 protein expression by murine chondrocytes. In addition, inhibition of LPS‐induced nitric oxide production by aminoguanidine, a selective NOS2 inhibitor, significantly reduced LPS‐mediated LCN2 expression. In contrast, treatment of murine chondrocytes with sodium nitroprussiate (SNP), a classic NO donor, scarcely induced LCN2 expression. Intriguingly, SNP addition to LPS‐challenged chondrocytes, treated with aminoguanidine, provoked a strong induction of LCN2 expression. Finally, murine ATDC5 cells, co‐cultured with LPS pre‐challenged macrophages, had higher LCN2 expression in comparison with murine chondrocytes co‐cultured with non pre‐challenged macrophages. In this work we have described for the first time that NO is able to exert a control on LCN2 expression, suggesting the existence of a feedback loop regulating its expression. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1046–1052, 2013     

The heart and lithium. Apropos of a case of lithium poisoning with intracavitary electrocardiographic exploration]

Among the secondary effects of the salts of Li+, which are widely used in psychiatric treatment, cardiac toxicity appears to be rare. The authors report the case history of a female of 24 years of age, with no previous cardiac history, who presented with Li+ intoxication and a supra-His atrio-ventricular block, followed by episodes of sinus arrest (or of sino-atrial block), accompanied by either a junctional rhythm or by periods of prolonged asystole. The results of the endocavitary electrocardiographic investigation are described. These cardiac effects are compared with the general findings reported in the literature; ECG modifications of the T wave are more common, but Li+ may cause other changes: sinus, atrial or ventricular arrhythmiás, disorders of AV conduction, and cardiomyopathies. The main modes of action which have been suggested are of interference with the other cations (K+, Na+, Ca++) in exchanges across membranes, and an effect on membrane adenyl-cyclase stimulated by catechol-amines.     

Vascular access, an underestimated source of inflammation in dialysis patients

The surveillance of inflammation in dialysis patient, by means of sensitive markers such as CRP, is strongly recommended in a continuous quality improvement treatment approach. Chronic inflammation being deleterious via several pathways including malnutrition, accelerated arteriosclerosis and beta 2M-amyloidosis, microinflammation must diagnosed and corrected as soon as possible in dialysis patients. Vascular access represents an underestimated source of inflammation in hemodialysis patients. In the absence of organic cause of inflammation, the vascular access should be always incriminated and meticulously investigated. Withdrawing the suspected prosthetic or unused material (PTFE or catheter) should be considered as the best way of correcting the inflammation and restoring the recombinant erythropoietin (EPO) activity in the dialysis patient.     

Prognosis of Patients With Severe Aortic Stenosis After the Decision to Perform an Intervention

Introduction and objectives

Current therapeutic options for severe aortic stenosis (AS) include transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Our aim was to describe the prognosis of patients with severe AS after the decision to perform an intervention, to study the variables influencing their prognosis, and to describe the determinants of waiting time > 2 months.

ICON: The Early Diagnosis of Congenital Immunodeficiencies

Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies.     

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Background. Org 25969 is a cyclodextrin compound designed toreverse a rocuronium-induced neuromuscular block. The aim ofthis study was to explore the efficacy, dose–responserelation and safety of Org 25969 for reversal of a prolongedrocuronium-induced neuromuscular block. Methods. Thirty anaesthetized adult patients received rocuronium0.6 mg kg^–1 as an initial dose followed by incrementsto maintain a deep block at a level of <10 PTCs (post-tetaniccounts) recorded every 6 min. Neuromuscular monitoring was carriedout using accelerometry, in a train-of-four (TOF) mode usingTOF-Watch®SX. At recovery of T₂, following at least 2 hof neuromuscular block, patients received their randomly assigneddose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg^–1 of Org 25969.Anaesthesia and neuromuscular monitoring were continued fora minimum period of 30 min after Org 25969 administration. Themain end-point of the study was the time to achieve a sustainedrecovery of TOF ratio to 0.9. Patients were followed up for7 days after anaesthesia. Results. The results showed a dose-related decrease in the averagetime taken to attain a TOF ratio of 0.9 from 6:49 (min:s) withthe 0.5 mg kg^–1 dose to 1:22 with the 4.0 mg kg^–1dose. Weighted non-linear regression analysis showed the fastestachievable time to TOF ratio of 0.9 to be 1:35. Org 25969 producedno major adverse effects. Conclusion. Org 25969 effectively reversed a deep and prolongedneuromuscular block induced by rocuronium. The effective reversaldose appears to be 2–4 mg kg^–1.     

Guidelines of the Spanish Society of Cardiology for clinical practice in exercise testing

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain.This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.     

Cytoplasmic RNA quality control failure engages mTORC1-mediated autoinflammatory disease

Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. The SKIV2L RNA exosome is cytoplasmic RNA degradation machinery that was thought to be essential for preventing the self-RNA–mediated interferon (IFN) response. Here, we demonstrate the physiological function of SKIV2L in mammals. We found that Skiv2l deficiency in mice disrupted epidermal and T cell homeostasis in a cell-intrinsic manner independently of IFN. Skiv2l-deficient mice developed skin inflammation and hair abnormality, which were also observed in a SKIV2L-deficient patient. Epidermis-specific deletion of Skiv2l caused hyperproliferation of keratinocytes and disrupted epidermal stratification, leading to impaired skin barrier with no appreciable IFN activation. Moreover, Skiv2l-deficient T cells were chronically hyperactivated and these T cells attacked lesional skin as well as hair follicles. Mechanistically, SKIV2L loss activated the mTORC1 pathway in both keratinocytes and T cells. Both systemic and topical rapamycin treatment of Skiv2l-deficient mice ameliorated epidermal hyperplasia and skin inflammation. Together, we demonstrate that mTORC1, a classical nutrient sensor, also senses cytoplasmic RNA quality control failure and drives autoinflammatory disease. We also propose SKIV2L-associated trichohepatoenteric syndrome (THES) as a new mTORopathy for which sirolimus may be a promising therapy.     

Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study

Background

Burkholderia pseudomalleiis the causative agent for melioidosis. For many bacterial infections, cytokine dysregulation is one of the contributing factors to the severe clinical outcomes in the susceptible hosts. The C57BL/6 and BALB/c mice have been established as a differential model of susceptibility in murine melioidosis. In this study, we compared the innate IFN-γ response toB. pseudomalleibetween the C57BL/6 and BALB/c splenocytes and characterized the hyperproduction of IFN-γ in the relatively susceptible BALB/c micein vitro.

Results

Naïve BALB/c splenocytes were found to produce more IFN-γ in response to live bacterial infection compared to C57BL/6 splenocytes. Natural killer cells were found to be the major producers of IFN-γ, while T cells and Gr-1^intermediatecells also contributed to the IFN-γ response. Although anti-Gr-1 depletion substantially reduced the IFN-γ response, this was not due to the contribution of Gr-1^high, Ly-6G expressing neutrophils. We found no differences in the cell types making IFN-γ between BALB/c and C57BL/6 splenocytes. Although IL-12 is essential for the IFN-γ response, BALB/c and C57BL/6 splenocytes made similar amounts of IL-12 after infection. However, BALB/c splenocytes produced higher proinflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-18 than C57BL/6 splenocytes after infection withB. pseudomallei.

Conclusion

Higher percentages of Gr-1 expressing NK and T cells, poorer ability in controlling bacteria growth, and higher IL-18 could be the factors contributing to IFN-γ hyperproduction in BALB/c mice.