Background and purpose
Myasthenia gravis (MG) may become life‐threatening if patients have respiratory insufficiency or dysphagia. This study aimed to determine the incidence, demographic ...characteristics, risk factors, response to treatment and outcome of these life‐threatening events (LTEs) in a recent, population‐based sample of MG patients.
Methods
A retrospective analysis of MG patients who presented with an LTE between 2000 and 2013 was performed. Participants were identified from a neuromuscular diseases registry in Spain that includes 648 patients with MG (NMD‐ES).
Results
Sixty‐two (9.56%) patients had an LTE. Thirty‐two were classified as class V according to the MG Foundation of America, and 30 as class IVB. Fifty per cent were previously diagnosed with MG and median duration of the disease before the LTE was 24 months (3–406). The most common related factor was infection (n = 18). All patients received intravenous human immunoglobulin; 11 had a second infusion and six had plasma exchange. Median time to feeding tube removal was 13 days (1–434). Median time to weaning from ventilation was 12 days (3–176), and it was significantly shorter in late onset MG (≥50 years) (P = 0.019). LTEs improved <2 weeks in 55.8% but did not improve until after 1 month in 20% of patients. Four patients died. No other factors influenced mortality or duration of LTEs.
Conclusions
The percentage of LTEs in MG patients was low, particularly amongst those previously diagnosed and treated for the disease. The significant percentage of treatment‐resistant LTEs indicates that more effective treatment approaches are needed for this vulnerable sub‐population.
Glomerular hyperfiltration and albuminuria are two pathological conditions that could alter renal drug elimination, but they have been rarely studied in a critical care setting. The aims of this ...descriptive, prospective study performed on 89 critically ill patients are to determine rates of glomerular hyperfiltration (main objective) and albuminuria (secondary objective). On admission, 17.9% of patients presented with glomerular hyperfiltration, climbing to rates as high as 30% during the first week of admission. Seventy-five percent showed albuminuria on admission, with rates remaining high throughout the week of the study. Since glomerular hyperfiltration as well as albuminuria are frequent pathophysiological conditions in critical care patients, the implications that these phenomena may have regarding drug elimination need further evaluation.
Abstract Aims The gold standard for detection of Sentinel Lymph Nodes (SLN) is a combined radioisotope and blue dye breast injection, using a gamma probe (GP). A new, non-radioactive method was ...developed, using a tracer (Sienna+® ) of superparamagnetic iron oxide (SPIO) nanoparticles and a manual magnetometer (SentiMag® ) (SM). The IMAGINE study was designed to show the non-inferiority of SM compared to GP, for the detection of SLN in breast cancer patients with SLN biopsy indication. Methods From November 2013 to June 2014, 181 patients were recruited, and 321 nodes were excised and assessed ex-vivo. Readings from both SM and GP devices were recorded during transcutaneous, intraoperative, and ex-vivo detection attempts. Results At the patient level, ex-vivo detection rates (primary variable) with SM and GP were 97.8% and 98.3% (concordance rate 99.4%). Transcutaneous and intraoperative detection rates were 95.5% vs 97.2%, and 97.2% vs 97.8% for SM and GP respectively (concordance rates > 97%). At the node level, intraoperative and ex-vivo detection rates were 92.5% vs 89.3% and 91.0% vs 86.3% for SM and GP respectively. In all cases the non-inferiority of SM compared to SM was shown by ruling out a predefined non-inferiority margin of 5%. Conclusions Our study showed the non-inferiority of SM as compared to GP. Moreover, the ex-vivo and intraoperative detection rates at the node level were slightly higher with SM.
•Little is known about what role the TRPV1 receptor and Endocannabinoid system (ECS) interactions within the NAc shell play in regulating anxiety response.•Endocannabinoid system (ECS) within the NAc ...shell modulates anxiety-like behaviors via CB1 and TRPV1 receptors.•Simultaneous blockade of TRPV1 and FAAH enzyme elicited a significant down-regulation of the CB1 receptor within the NAC shell.
The functional role of the endocannabinoid system (ECS) and Transient Receptor Potential Vanilloid type-1 (TRPV1) within the Nucleus Accumbens shell (NAc shell) remains unknown. Preclinical studies in rodents have reported that the ECS modulates emotional responses such as anxiety. The NAc shell has a high density of synaptically co-localized cannabinoid receptor type-1 (CB1R) and TRPV1, suggesting a potential involvement in the modulation of anxiety.
The present study aims to establish the role of ECS-TRPV1 interactions within the NAc shell and its effects on anxiety. It is hypothesized that the neurochemical regulation elicited by ECS within the NAc shell mediates anxiety-like behaviors in rodents.
In this study, male Sprague Dawley rats were implanted with bilateral brain cannula targeting the NAc shell. Following recovery from surgery, animals received microinfusion pretreatments (0, 0.125, 0.5 nmol/0.4 μl) of N-arachidonoyl-serotonin (AA-5-HT), a dual blocker of the endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH) and a TRPV1 antagonist in the NAc shell. Following treatment, animals were tested in an elevated plus maze (EPM) paradigm for a period of 5 minutes. At the end of the experiment, animals were sacrificed and their brains collected for histological and biochemical analysis.
Results showed that animals treated with AA-5-HT in a dose dependent manner spent significantly more time in the open arms than vehicle-treated animals. In addition, AA-5-HT administration induced a significant downregulation of CB1R expression in the NAc shell.
The present findings suggest that the ECS within the NAc shell modulates anxiety-like behaviors via FAAH and CB1R activity.
The β-delayed neutron emission probabilities of neutron rich Hg and Tl nuclei have been measured together with β-decay half-lives for 20 isotopes of Au, Hg, Tl, Pb, and Bi in the mass region N≳126. ...These are the heaviest species where neutron emission has been observed so far. These measurements provide key information to evaluate the performance of nuclear microscopic and phenomenological models in reproducing the high-energy part of the β-decay strength distribution. This provides important constraints on global theoretical models currently used in r-process nucleosynthesis.
An oxamato‐bridged CoIICuII chain compound has been obtained via the self‐assembly of mononuclear bis‐bidentate copper(II) anionic building blocks and cobalt(II) cations. It is the first example of a ...heterobimetallic ferrimagnetic chain that incorporates slow magnetic relaxation behavior (see Figure).
Outputs from the nucleus accumbens (NAc) include projections to the ventral pallidum and the ventral tegmental area and subtantia nigra in the ventral mesencephalon. The medium spiny neurons (MSN) ...that give rise to these pathways are GABAergic and consist of two populations of equal number that are segregated by differentially expressed proteins, including D1- and D2-dopamine receptors. Afferents to the ventral pallidum arise from both D1- and D2-MSNs, whereas the ventral mesencephalon is selectively innervated by D1-MSN. To determine the extent of collateralization of D1-MSN to these axon terminal fields we used retrograde labeling in transgenic mice expressing tdTomato selectively in D1-MSN, and found that a large majority of D1-MSN in either the shell or core subcompartments of the accumbens collateralized to both output structures. Approximately 70% of D1-MSNs projecting to the ventral pallidum collateralized to the ventral mesencephalon, whereas >90% of mesencephalic D1-MSN afferents collateralized to the ventral pallidum. In contrast, <10% of dorsal striatal D1-MSNs collateralized to both the globus pallidus and ventral mesencephalon. D1-MSN activation is required for conditioned cues to induce cocaine seeking. To determine which D1-MSN projection mediates cued cocaine seeking, we selectively transfected D1-MSNs in transgenic rats with an inhibitory Gi-coupled DREADD. Activation of the transfected Gi-DREADD with clozapine-N-oxide administered into the ventral pallidum, but not into the ventral mesencephalon, blocked cue-induced cocaine seeking. These data show that, although accumbens D1-MSNs largely collateralize to both the ventral pallidum and ventral mesencephalon, only D1-MSN innervation of the ventral pallidum is necessary for cue-induced cocaine seeking.
Activity in D1 dopamine receptor-expressing neurons in the NAc is required for rodents to respond to cocaine-conditioned cues and relapse to drug seeking behaviors. The D1-expressing neurons project to both the ventral pallidum and ventral mesencephalon, and we found that a majority of the neurons that innervate the ventral pallidum also collateralize to the ventral mesencephalon. However, despite innervating both structures, only D1 innervation of the ventral pallidum mediates cue-induced cocaine seeking.
•Epidemiological report of mesothelioma treatment patterns and outcomes in Spain.•Despite multimodal intervention, outcomes remain poor (1-year OS of 53.2 %).•Performance status, histology and ...treatment response were independent factors for survival.•Trend toward survival benefit was observed among patients receiving maintenancechemotherapy.
Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain.
Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments.
A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1–14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7–57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8–16.0 months), reaching 20.2 months (95 % CI, 17.2–23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy.
Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.
The COVID-19 pandemic has resulted in complete saturation of healthcare capacities, making it necessary to reorganise healthcare systems. In this context, we must guarantee the provision of acute ...stroke care and optimise code stroke protocols to reduce the risk of SARS-CoV-2 infection and rationalise the use of hospital resources. The Madrid Stroke multidisciplinary group presents a series of recommendations to achieve these goals.
We conducted a non-systematic literature search using the keywords "stroke" and "COVID-19" or "coronavirus" or "SARS-CoV-2." Our literature review also included other relevant studies known to the authors. Based on this literature review, a series of consensus recommendations were established by the Madrid Stroke multidisciplinary group and its neurology committee.
These recommendations address 5 main objectives: 1) coordination of action protocols to ensure access to hospital care for stroke patients; 2) recognition of potentially COVID-19-positive stroke patients; 3) organisation of patient management to prevent SARS-CoV-2 infection among healthcare professionals; 4) avoidance of unnecessary neuroimaging studies and other procedures that may increase the risk of infection; and 5) safe, early discharge and follow-up to ensure bed availability. This management protocol has been called CORONA (Coordinate, Recognise, Organise, Neuroimaging, At home).
The recommendations presented here may assist in the organisation of acute stroke care and the optimisation of healthcare resources, while ensuring the safety of healthcare professionals.
Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these ...guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain.
These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons.
The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient’s functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice.
La enfermedad de Charcot-Marie-Tooth (CMT) se clasifica según las características neurofisiológicas e histológicas, el patrón de herencia y el defecto genético subyacente. El objetivo de esta guía es establecer recomendaciones prácticas para el diagnóstico, pronóstico, seguimiento y tratamiento de esta enfermedad en España.
Se trata de un proyecto colaborativo y multidisciplinar contando con un grupo amplio de profesionales expertos en la materia e incluyendo neurólogos, neuropediatras, neurofisiólogos, genetistas, rehabilitadores y cirujanos ortopédicos.
El diagnóstico de sospecha en CMT es clínico, habitualmente detectando un fenotipo común o clásico. La evaluación clínica se debe seguir de un estudio neurofisiológico adecuado y se establecen recomendaciones concretas sobre los parámetros que deben ser recogidos. El diagnóstico genético debe abordarse secuencialmente; una vez descartada la duplicación del gen PMP22 si corresponde, se recomienda realizar un estudio de secuenciación masiva teniendo en cuenta las limitaciones de las técnicas. No existe tratamiento farmacológico modificador del curso de la enfermedad, si bien es importante el manejo sintomático guiado por un equipo multidisciplinar, así como el adecuado abordaje rehabilitador y ortopédico. Éste debe iniciarse precozmente para identificar y mejorar los déficits funcionales del paciente e incluye pautas individualizadas de ejercicio, adaptación ortésica y valoración de cirugías conservadoras como la transposición de tendones. El seguimiento de los pacientes es clínico, no siendo necesario la realización de pruebas complementarias en la práctica clínica habitual.
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