Cirugía de las metástasis en la glándula suprarrenal: resultados de una serie de 35 pacientes

IntroductionThe objectives of this study are to present the results of adrenalectomies due to metastasis, and to analyse the prognostic factors that may help to predict long-term survival in this patient group.Patients and methodsA retrospective study was conducted on 35 patients who underwent adrenalectomy for metastases in the Hospital de Cruces from 1996 to January 2010. The survival analysis was performed using the Kaplan and Meier method.ResultsNon-small cell lung cancer (NSCLC) was the most frequent primary tumour, with 18 cases. In 15 patients the diagnosis of adrenal metastasis was synchronous with the primary tumour, and in 20 cases it was metachronous. Only 7 patients survived without disease for 12, 22, 26, 58, 60, 65 and 120 months after the adrenalectomy. The disease free survival at 5 years was 16% in the whole series, and 27% in the NSCLC sub-group. None of the prognostic factors evaluated (size greater than 4.5 cm, cell type, differentiation grade, chemotherapy, surgical technique, disease free interval) was statistically significant in the overall survival, either in the general series or in the sub-group of patients with NSCLC. However, in the general series with tumour recurrence, the difference in survival between metachronous and synchronous metastasis was statistically significant (P=.05), in favour of the former.ConclusionsAdrenalectomy improves the expected survival particularly in patients with NSCLC. Patients with metachronous metastases do not have a higher rate of disease free survival at 5 years than those with synchronous metastases, although they do have a longer survival with the disease. When there is tumour recurrence, it is usually early.     

Effects of Spray and Stretch on Postneedling Soreness and Sensitivity After Dry Needling of a Latent Myofascial Trigger Point

Objectives

To investigate (1) the effect of spray and stretch versus control on reducing postneedling soreness of 1 latent myofascial trigger point (MTrP) and (2) whether higher levels of psychological distress are associated with increased postneedling pain intensity.

Design

A 72-hour follow-up, single-blind randomized controlled trial.

Setting

University community.

Participants

Healthy volunteers (N=70; 40 men, 30 women) aged 18 to 36 years (mean age, 21±4y) with latent MTrP in 1 upper trapezius muscle.

Intervention

All subjects received a dry needling application over the upper trapezius muscle. Then, participants were randomly divided into 2 groups: an intervention group, which received spray and stretch over the needled trapezius muscle, and a control group, which did not receive any intervention.

Main Outcome Measures

Visual analog scale (at postneedling, posttreatment, and 6, 12, 24, 48, and 72h after needling), pressure pain threshold (at preneedling, postneedling, and 24 and 48h after needling). Psychological distress was evaluated by using the Symptom Checklist-90-Revised.

Results

Repeated-measures analysis of variance demonstrated a significant interaction between group and time (F_3,204.8=3.19; P<.05; η_p²=.04) for changes in postneedling soreness. Between-group differences were significant only immediately after intervention (P=.002), and there were no differences found between groups after 6 hours of the intervention (P>.05). Repeated measures of covariance showed that none of the psychological covariates affected these results. Somatization, anxiety, interpersonal sensitivity, and hostility were significantly correlated (P<.05) with postneedling pain intensity. Repeated-measures analysis of variance did not show a significant effect of spray and stretch on mechanical hyperalgesia (F_2.6,175=1.9; P=.131; η_p²=.02).

Conclusions

The spray and stretch had a short-term (<6h) effect in reducing postneedling soreness of a latent MTrP. Pressure pain threshold did not significantly change after spray and stretch. Psychological factors are related to postneedling pain.     

MicroRNA9 regulates neural stem cell differentiation by controlling Hes1 expression dynamics in the developing brain

Earlier studies show that Hes1 expression is oscillatory in neural stem cells but sustained and high in the roof plate and the floor plate, and that such different dynamics of Hes1 expression (oscillatory versus sustained) regulate different proliferation and differentiation characteristics of these cells (active in neural stem cells but rather dormant in roof/floor plate cells). The mechanism of how different dynamics of Hes1 expression is controlled remains to be determined. Here, we found that the seed sequence of microRNA‐9 (miR‐9) is complementary to the 3′‐UTR sequence of Hes1 mRNA. MiR‐9 is highly expressed in the ventricular zone of the developing brain, which contains neural stem cells, but it is not expressed in the roof plate or the floor plate. Over‐expression of miR‐9 negatively regulates the Hes1 protein expression by interacting with the 3′‐UTR of Hes1 mRNA, thereby inducing cell cycle exit and neuronal differentiation. Conversely, knockdown of miR‐9 inhibits neuronal differentiation. Furthermore, knockdown of miR‐9 inhibits the oscillatory expression of Hes1 mRNA in neural stem cells. These results indicate that miR‐9 regulates the proliferation and differentiation of neural stem cells by controlling the dynamics of Hes1 expression in the developing brain.     

Echocardiographic assessment of pulmonary arterial pressure in the follow-up of patients with pulmonary embolism

Background

Echocardiography remains a clinically useful screening test for chronic thromboembolic pulmonary hypertension (CTEPH) in patients with a history of pulmonary embolism (PE). To devise an effective screening strategy, the definition of a high-risk group is necessary.

Methods

We examined a total of 744 patients with acute symptomatic pulmonary embolism (PE) who were enrolled in a Spanish multicenter study. Patients were monitored every 6 months during the first two years, and then once a year thereafter. Transthoracic echocardiography was used to screen patients with a clinical suspicion of CTEPH during follow-up. Pulmonary arterial hypertension was defined as an estimated pulmonary artery systolic pressure (PAP) > 50 mm Hg. The index thromboembolic episode was considered severe if: (a) the patient was immobilized for medical reasons; or (b) systolic blood pressure was less than 90 mm Hg; or (c) troponin T values were above the reference range.

Results

The incidence of PAP > 50 mm Hg at 36 months was 8.3% (95% confidence interval = 4.6%-14.5%). Statistical analysis showed a highly significant association between a severe index thromboembolic episode and the subsequent detection of PAP > 50 mm Hg on echocardiography, with high positive likelihood ratio (2.40) and negative predictive value (> 0.97).

Conclusions

Patients with a severe index thromboembolic episode would constitute a high-risk group for the development of CTEPH. This group of patients should be subjected to a strict follow-up protocol.     

A New Master Donor Virus for the Development of Live-Attenuated Influenza B Virus Vaccines

Influenza B viruses (IBV) circulate annually, with young children, the elderly and immunocompromised individuals being at high risk. Yearly vaccinations are recommended to protect against seasonally influenza viruses, including IBV. Live attenuated influenza vaccines (LAIV) provide the unique opportunity for direct exposure to the antigenically variable surface glycoproteins as well as the more conserved internal components. Ideally, LAIV Master Donor Viruses (MDV) should accurately reflect seasonal influenza strains. Unfortunately, the continuous evolution of IBV have led to significant changes in conserved epitopes compared to the IBV MDV based on B/Ann Arbor/1/1966 strain. Here, we propose a recent influenza B/Brisbane/60/2008 as an efficacious MDV alternative, as its internal viral proteins more accurately reflect those of circulating IBV strains. We introduced the mutations responsible for the temperature sensitive (ts), cold adapted (ca) and attenuated (att) phenotype of B/Ann Arbor/1/1966 MDV LAIV into B/Brisbane/60/2008 to generate a new MDV LAIV. In vitro and in vivo analysis demonstrated that the mutations responsible of the ts, ca, and att phenotype of B/Ann Arbor/1/1966 MDV LAIV were able to infer the same phenotype to B/Brisbane/60/2008, demonstrating its potential as a new MDV for the development of LAIV to protect against contemporary IBV strains.     

Multifocal lymphangioendotheliomatosis without thrombocytopenia or clinical signs of systemic bleeding

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is an extremely rare recently described disorder characterized by diffuse congenital skin and gastrointestinal vascular lesions that may be associated with gastrointestinal bleeding and thrombocytopenia. We herein present a case report of multifocal lymphangioendotheliomatosis without thrombocytopenia or extensive extracutaneous involvement (gastrointestinal bleeding). Given the high morbidity and mortality associated with this disease, it is important for clinicians to recognize this disorder in order to select the most appropriate therapeutic approach.     

The role of osmolarity adjusting agents in the regulation of encapsulated cell behavior to provide a safer and more predictable delivery of therapeutics

Transplantation of cells within alginate microspheres has been extensively studied for sustained drug delivery. However, the lack of control over cell behavior represents a major concern regarding the efficacy and the safety of the therapy. Here, we demonstrated that when formulating the biosystem, an adequate selection of osmolarity adjusting agents significantly contributes to the regulation of cell responses. Our data showed that these agents interact in the capsule formation process, influencing the alginate crosslinking degree. Therefore, when selecting inert or electrolyte-based osmolarity adjusting agents to encapsulate D1 multipotent mesenchymal stromal cells (MSCs), alginate microcapsules with differing mechanical properties were obtained. Since mechanical forces acting on cells influence their behavior, contrasting cell responses were observed both, in vitro and in vivo. When employing mannitol as an inert osmolarity adjusting agent, microcapsules presented a more permissive matrix, allowing a tumoral-like behavior. This resulted in the formation of enormous cell-aggregates that presented necrotic cores and protruding peripheral cells, rendering the therapy unpredictable, dysfunctional, and unsafe. Conversely, the use of electrolyte osmolarity adjusting agents, including calcium or sodium, provided the capsule with a suitable crosslinking degree that established a tight control over cell proliferation and enabled an adequate therapeutic regimen in vivo. The crucial impact of these agents was confirmed when gene expression studies reported pivotal divergences not only in proliferative pathways, but also in genes involved in survival, migration, and differentiation. Altogether, our results prove osmolarity adjusting agents as an effective tool to regulate cell behavior and obtain safer and more predictable therapies.     

Disconnecting bones within the jaw‐otic network modules underlies mammalian middle ear evolution

The origin of the mammalian middle ear ossicles from the craniomandibular articulation of their synapsid ancestors is a key event in the evolution of vertebrates. The richness of the fossil record and the multitude of developmental studies have provided a stepwise reconstruction of this evolutionary innovation, highlighting the homology between the quadrate, articular, pre‐articular and angular bones of early synapsids with the incus, malleus, gonial and ectotympanic bones of derived mammals, respectively. There are several aspects involved in this functional exaptation: (i) an increase of the masticatory musculature; (ii) the separation of the quadrate bone from the cranium; and (iii) the disconnection of the post‐dentary bones from the dentary. Here, we compared the jaw‐otic complex for 43 synapsid taxa using anatomical network analysis, showing that the disconnection of mandibular bones was a key step in the mammalian middle ear evolution, changing the skull anatomical modularity concomitant to the acquisition of new functions. Furthermore, our analysis allows the identification of three types of anatomical modules evolving through five evolutionary stages during the anatomical transformation of the jawbones into middle ear bones, with the ossification and degradation of Meckel's cartilage in mammals as the key ontogenetic event leading the change of anatomical modularity.