Propeller states in locally super-critical ULXs

An expected signature of the presence of neutron stars in the population of ultraluminous X-ray sources (ULXs) are large scale changes in X-ray luminosity, as systems reach spin equilibrium and a propeller state ensues. We explore the predicted luminosity changes when the disc is locally super-critical, finding that a significant parameter space in dipole field strength and accretion rate (at large radius) can be accompanied by changes of less than an order of magnitude in luminosity. We discuss the spectral signature and locate three ULXs (IC 342 X-1, Cir ULX-5 and NGC 1313 X-1) which appear to show changes consistent with super-Eddington systems entering a propeller state, and place rough constraints on the dipole field strength of NGC 1313 X-1 of $<$ 10$^{10}$ G. This work implies that the most reliable means by which to search for putative propeller states will be to search for changes in hardness ratio and at high energies.Comment: 11 pages, 7 figures, accepted for publication in MNRA

Scoliosis induced by medullary damage: an experimental study in rabbits

To date, there have been no reports of experiments designed to induce scoliosis by direct damage of different areas of the spinal cord. In a series of rabbits with medullary damage, the authors attempted selectively to interrupt the pathways that mediate proprioceptive input. Unilateral lesion of the dorsal column and posterior horn of the spinal cord was performed using three different techniques: coagulation with laser, stereotaxic microcoagulation, and longitudinal electrocoagulation. Of 32 operated rabbits, 17 developed scoliosis, exhibiting clear pathologic damage of the spinal cord. Electrophysiologic study, including EMG and analysis of the tonic -- vibratory reflex, was performed on 10 rabbits with medullary damage (scoliotic and non-scoliotic) and 12 matched controls. The data suggest disturbance of the sensory afferences that control the postural tone and consequent muscular imbalance, expressed as reduced activity in the muscles of the convex side. This work supports the view that loss of proprioceptive neural impulses caused by medullary damage can induce scoliosi

Resultados a medio y largo plazo de la utilización de videotoracoscopia en la cirugía de resección de las metástasis pulmonares

The surgical resection of pulmonary metastases is a method of treatment accepted as habitual in thoracic surgery. However, it continues to be a source of controversy if this resection must be realised by thoracotomy or by modern video-assisted techniques. With the aim of finding a response to this controversy in our work milieu, a review was made of the surgical interventions carried out in order to resect pulmonary metastases. Between January 1997 and December 2001, 56 patients were found whose pulmonary metastases had been resected by videothorascopy out of a total of 252 metastasectomies (22.2%). The primary tumours were classified in 4 groups: sarcoma (n=11); colorectal (n=25); renal (n=5); and others (n=15). Videothoroscopy was carried out on the right hemithorax (n=28), left hemithorax (n=22) or on both at once (n=6). Operational mortality was nil and the only morbidity attributable to the technique was a defect of re-expansion following the removal of the thoracic drainage in one patient. Using the Kaplan-Meier method, the probability of survival in this series of patients was 60.4% after 5 years, with an average survival time of 48 months. All of this data supports the use of videothorascopy in our milieu on patients with pulmonary metastases. However, in the light of the results, it is important in using this technique to place special emphasis on obtaining good margins of resection, due to the real risk of local recurrence on these margins in the medium term

Selection of extreme phenotypes: the role of clinical observation in translational research

Systematic collection of phenotypes and their correlation with molecular data has been proposed as a useful method to advance in the study of disease. Although some databases for animal species are being developed, progress in humans is slow, probably due to the multifactorial origin of many human diseases and to the intricacy of accurately classifying phenotypes, among other factors. An alternative approach has been to identify and to study individuals or families with very characteristic, clinically relevant phenotypes. This strategy has shown increased efficiency to identify the molecular features underlying such phenotypes. While on most occasions the subjects selected for these studies presented harmful phenotypes, a few studies have been performed in individuals with very favourable phenotypes. The consistent results achieved suggest that it seems logical to further develop this strategy as a methodology to study human disease, including cancer. The identification and the study with high-throughput techniques of individuals showing a markedly decreased risk of developing cancer or of cancer patients presenting either an unusually favourable prognosis or striking responses following a specific treatment, might be promising ways to maximize the yield of this approach and to reveal the molecular causes that explain those phenotypes and thus highlight useful therapeutic targets. This manuscript reviews the current status of selection of extreme phenotypes in cancer research and provides directions for future development of this methodology

Infecciones no tuberculosas del raquis

La espondilodiscitis infecciosa no tuberculosa es una entidad rara que afecta con mayor frecuencia a niños y adultos de sexo masculino. La zona con mayor incidencia es la región lumbar. Habitualmente el germen causal se propaga por vía hemática desde un foco infeccioso extrarraquídeo. El cuadro clínico comienza con una fase aguda de raquialgia segmentaria y contractura muscular paravertebral en un contexto febril. En casos especiales de niños muy pequeños o ante la presencia de dolor irradiado la forma de presentación puede ser más confusa. Hay invariablemente una rigidez vertebral en la exploración física y un aumento de la velocidad de sedimentación globular. Una fórmula leucocitaria séptica en la analítica es más inconstante. Entre el comienzo de los síntomas y la aparición de alteraciones radiológicas (disminución de altura del disco, erosión y destrucción vertebral, neoformación ósea reactiva) hay un período de latencia variable entre 2 y 8 semanas. La escintigrafía con Tc 99 y Ga 67 y la TAC tienen un gran interés de cara al diagnóstico definitivo. Para llegar al diagnóstico bacteriológico empleamos la punción-aspiración del disco. El germen aislado con mayor frecuencia es el estafilococo aureus. El diagnóstico diferencial más complejo resulta en ocasiones con espondilodiscitis tuberculosas. La evolución es favorable si el tratamiento es precoz y adecuado (antibioterapia e inmovilización). Si no es así, pueden presentarse recurrencias y cronificación de la infección, así como complicaciones de tipo ortopédico (cifosis) y/o neurológico

Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology

Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often causes dose reductions and/or delays in administering the prescribed therapy, which can affect patient survival and quality of life. It is, therefore, important to prevent the occurrence of these adverse effects, or to treat unavoidable ones as soon as possible. This requires cooperation between medical oncologists and dermatologists. This article reviews the various dermatological toxicities associated with targeted therapies and immunotherapies, along with their diagnosis and therapeutic management

Tratamiento del cáncer de próstata en función de la esperanza de vida, la comorbilidad y las guías de práctica clínica

En un número anterior de la revista de Anales del Sistema Sanitario de Navarra, Barceló y col realizaron una interesante y útil revisión de los pacientes con cáncer de próstata tratados en un gran centro hospitalario español durante un año, centrándose en sus características basales, el tratamiento realizado y el grado de seguimiento de las Guías de Práctica Clínica (GPC) y las complicaciones asociadas a los tratamientos realizados

Frozen cancellous bone allografts: positive cultures of implanted grafts in posterior fusions of the spine

We have carried out a study on the behaviour pattern of implanted allografts initially stored in perfect conditions (aseptically processed, culture-negative and stored at -80 degrees C) but which presented positive cultures at the implantation stage. There is no information available on how to deal with this type of situation, so our aim was to set guidelines on the course of action which would be required in such a case. This was a retrospective study of 112 patients who underwent a spinal arthrodesis and in whom a total of 189 allograft pieces were used. All previous bone and blood cultures and tests for hepatitis B and C, syphilis and HIV (via PCR techniques) were negative. The allografts were stored by freezing them at -80 degrees C. A sample of the allograft was taken for culture in the operating theatre just before its implantation in all cases. The results of the cultures were obtained 3-5 days after the operation. There were 22 allografts with positive culture results (12%) after implantation. These allografts were implanted in 16 patients (14%). Cultures were positive for staphylococci coagulase negative (ECN) in 10 grafts (46%), Pseudomonas stutzeri in two grafts (9%), Corynebacterium jeikeium in two grafts (9%), staphylococci coagulase positive in two grafts (9%) and for each of the following organisms in one case each (4%): Corynebacterium spp., Actinomyces odontolyticus, Streptococcus mitis, Peptostreptococcus spp., Rhodococcus equi and Bacillus spp. No clinical infection was seen in any of these patients. Positive cultures could be caused by non-detected contamination at harvesting, storing or during manipulation before implantation. The lack of clinical signs of infection during the follow-up of our patients may indicate that no specific treatment different from our antibiotic protocol is required in the case of positive culture results of a graft piece after implantation

The dynamic use of EGFR mutation analysis in cell-free DNA as a follow-up biomarker during different treatment lines in non-small-cell lung cancer patients

Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median = 11, IQR = 9 5-13) to the best response (median = 0, IQR = 0-0, p < 0 01), followed by a significant increase at progression (median = 11, IQR = 11-15, p < 0 01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received

Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation

BACKGROUND: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogenesis promotion. PRINCIPAL FINDINGS: IL-8 effects on human monocyte-derived DC biology were explored upon DC exposure to recombinant IL-8 and with the help of an IL-8 neutralizing mAb. In vivo experiments were performed in immunodeficient mice xenografted with IL-8-producing human colon carcinomas and comparatively with cell lines that do not produce IL-8. Allogenic T lymphocyte stimulation by DC was explored under the influence of IL-8. DC and neutrophil chemotaxis were measured by transwell-migration assays. Sera from tumor-xenografted mice contained increasing concentrations of IL-8 as the tumors progress. IL-8 production by carcinoma cells can be modulated by low doses of cyclophosphamide at the transcription level. If human DC are injected into HT29 or CaCo2 xenografted tumors, DC are retained intratumorally in an IL-8-dependent fashion. However, IL-8 did not modify the ability of DC to stimulate T cells. Interestingly, pre-exposure of DC to IL-8 desensitizes such cells for IL-8-mediated in vitro or in vivo chemoattraction. Thereby DC become disoriented to subsequently follow IL-8 chemotactic gradients towards malignant or inflamed tissue. CONCLUSIONS: IL-8 as produced by carcinoma cells changes DC migration cues, without directly interfering with DC-mediated T-cell stimulation