[Emergency detection of HIV infection in patients consulting for conditions potentially related to occult infection: Initial results of the "Urgències VIHgila" program]. / Detección en urgencias de infección por VIH en pacientes que consultan por condiciones potencialmente relacionadas con infección oculta: Resultados iniciales del programa "Urgències VIHgila".

OBJECTIVE: To estimate the prevalence of unknown HIV infection in patients who consulted in hospital emergency services (ED) for conditions defined in the SEMES-GESIDA Consensus Document (DC), evaluate the efficiency of its im-plementation and investigate the efficiency of HIV serology determination in other conditions. METHODS: Results were reviewed in 10 Catalan EDs for 12 months (July-21-June-22) after implementing CD recommendations: request HIV serology in case of suspected sexually transmitted infection, chemsex, post-exposure prophylaxis (PEP), mononucleosis syndrome, community pneumonia (18-65 y-o) or herpes zoster (18-65 y-o). Other reasons for request were included. Prevalence (%) of global seropositivity and for each circumstance was calculated, with a 95% confidence interval (95%CI). The efficient strategy was considered if the lower limit of the CI95%>0.1%. RESULTS: A total of5,107 HIV serologies were performed: 2,847(56%) in situations specified in CD, and 2,266 (44%) in other 138 circumstances. Forty-eight unknown HIV infections were detected (prevalence=0.94%;95%CI=0.69-1.24). The prevalence was somewhat higher in DC requests (30 cas-es 1.12%) than the rest (18 cases 0.71%; p=0.16). The individualized prevalence of CD reasons ranged between 7.41% (95%CI=0.91-24.3) in chemsex and 0.42% 95%CI=0.14-0.98) in PPE, always efficient except herpes zoster (0.76%; CI95%=0.02-4.18). In other reasons, cases were detected in 12 circumstances, and in four the determination could be efficient: lymphopenia (10%;CI95%=0.25-44.5), fever with polyarthralgia-polyarthritis (7.41%;CI95% =0.91-24.3), behavioral alteration-confusion-encephalopathy (3.45%;95%CI=0.42-11.9) and fever of unknown origin (2.50%;95%CI=0.82-5.74). CONCLUSIONS: The determination of HIV serology in HES in the processes defined by DC SEMES-GESIDA is efficient. Some circumstances are identified that could be added to those previously contemplated to increase efficiency.

Miocarditis y miocardiopatía inflamatoria confirmadas por biopsia endomiocárdica: perfil clínico y pronóstico / Endomyocardial biopsy-confirmed myocarditis and inflammatory cardiomyopathy: clinical profile and prognosis

Introducción y objetivos La biopsia endomiocárdica (BEM) es la única técnica capaz de establecer el diagnóstico etiológico de pacientes con miocarditis o miocardiopatía inflamatoria (MI). El objetivo de este estudio es conocer el perfil clínico, la evolución y los factores pronósticos de los pacientes con sospecha de miocarditis o MI sometidos a BEM. Métodos Se analizaron retrospectivamente las características clínicas, los hallazgos histológicos y la evolución de todos los pacientes con sospecha de miocarditis o MI sometidos a BEM entre 1997 y 2019 en un hospital terciario español. Se evaluó el rendimiento del diagnóstico histológico mediante los criterios de Dallas frente a los criterios inmunohistoquímicos (IHQ). Resultados Se realizó BEM a 99 pacientes (el 67% varones; edad, 42± 15 años; fracción de eyección media, 34±14%). El 28% presentaba miocarditis o MI confirmada por criterios de Dallas y el 54% aplicando los criterios IHQ (p <0,1). Se diagnosticaron 47 miocarditis linfocitarias, 6 miocarditis eosinofílicas, 3 sarcoidosis y 1 miocarditis de células gigantes. Tras una mediana de seguimiento de 18 meses, 23 pacientes (23%) precisaron trasplante cardiaco o asistencia ventricular o fallecieron. El 21% de los pacientes con miocarditis confirmada mediante IHQ precisó trasplante cardiaco o asistencia o falleció, frente al 7% de aquellos sin inflamación (p=0,056). La fracción de eyección ≤ 30%, un diámetro telediastólico del ventrículo izquierdo ≥60mm y una clase NYHA III-IV iniciales se asociaron con peor pronóstico, especialmente en presencia de inflamación. Conclusiones La BEM permite establecer un diagnóstico etiológico en más de la mitad de los casos de sospecha de miocarditis o MI cuando se emplean técnicas IHQ. La inflamación confirmada por IHQ añade valor pronóstico y permite identificar a los pacientes con mayor probabilidad de sufrir complicaciones (AU)

Introduction and objectives Endomyocardial biopsy (EMB) is the only technique able to establish an etiological diagnosis of myocarditis or inflammatory cardiomyopathy (ICM). The aim of this study was to analyze the clinical profile, outcomes, and prognostic factors of patients with suspected myocarditis/ICM undergoing EMB. Methods We retrospectively analyzed the clinical characteristics, histological findings, and follow-up data of all patients with suspected myocarditis or ICM who underwent EMB between 1997 and 2019 in a Spanish tertiary hospital. The diagnostic yield was compared using the Dallas criteria vs immunohistochemical criteria (IHC). Results A total of 99 patients underwent EMB (67% male; mean age, 42±15 years; mean left ventricular ejection fraction [LVEF], 34%±14%). Myocarditis or ICM was confirmed in 28% with application of the Dallas criteria and in 54% with the IHC criteria (P <.01). Lymphocytic myocarditis was diagnosed in 47 patients, eosinophilic myocarditis in 6, sarcoidosis in 3, and giant cell myocarditis in 1 patient. After a median follow-up of 18 months, 23 patients (23%) required heart transplant (HTx), a left ventricular assist device (LVAD), and/or died. Among the patients with IHC-confirmed myocarditis, 21% required HTx/LVAD or died vs 7% of those without inflammation (P=.056). The factors associated with a worse prognosis were baseline LVEF ≤ 30%, left ventricular end-diastolic diameter ≥ 60mm, and NYHA III-IV, especially in the presence of inflammation. Conclusions EMB allows an etiological diagnosis in more than half of patients with suspected myocarditis/ICM when IHC techniques are used. IHC-confirmed inflammation adds prognostic value and helps to identify patients with a higher probability of developing complications (AU)

Impact of music on the dynamic perception of coffee and evoked emotions evaluated by temporal dominance of sensations (TDS) and emotions (TDE).

The aim of the present work was to study the temporal effect of music on sensory perception and on the emotional changes while drinking coffee. Two different commercial filter coffees were evaluated by a group of 48 consumers using the Temporal Dominance of Sensations (TDS) method. The description was performed in silence and also while listening to two different musical fragments: one with a "sweet" connotation and the other with a "bitter" one. Under the same conditions (drinking coffee with and without musical stimuli), a different group of 72 consumers evaluated their perceived emotions (joy, fear, neutral, rejection, disgust, surprise, sadness and anger) by Temporal Dominance of Emotions (TDE). Data was analyzed by dominance curves and by ANOVA and MANOVA of the durations of dominance (for emotions and sensations). Coffee perception, in both cases, was modified by the musical stimuli. The duration of dominance of bitter was increased in the presence of "bitter" music, while it decreased with the "sweet" music. Moreover, the sweet attribute was practically not chosen for describing the coffee on its own, but its choice and duration as dominant increased while listening to the "sweet" musical fragment. Music had a larger impact on the perceived emotions. The "sweet" music was related to the emotion of joy, which was accompanied by surprise and also some sadness when drinking coffee (regardless of the type of coffee being drunk). The "bitter" music was linked to the emotions anger and fear. The effect of "sonic seasoning" and translation of emotions with a familiar product was observed.

Modulation of dopamine tone induces frequency shifts in cortico-basal ganglia beta oscillations.

Βeta oscillatory activity (human: 13-35 Hz; primate: 8-24 Hz) is pervasive within the cortex and basal ganglia. Studies in Parkinson's disease patients and animal models suggest that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine tone remains unclear. We recorded neural activity in the cortex and basal ganglia of healthy non-human primates while acutely and chronically up- and down-modulating dopamine levels. We assessed changes in beta oscillations in patients with Parkinson's following acute and chronic changes in dopamine tone. Here we show beta oscillation frequency is strongly coupled with dopamine tone in both monkeys and humans. Power, coherence between single-units and local field potentials (LFP), spike-LFP phase-locking, and phase-amplitude coupling are not systematically regulated by dopamine levels. These results demonstrate that beta frequency is a key property of pathological oscillations in cortical and basal ganglia networks.

Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE).

BACKGROUND: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. METHODS: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA- memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 × 105 cells/kg), the next three received the intermediate dose (5 × 105 cells/kg) and the last three received the highest dose (1 × 106 cells/kg) of CD45RA- memory T cells. Clinicaltrials.gov registration: NCT04578210. FINDINGS: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. INTERPRETATION: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA- memory T cells is feasible and safe. FUNDING: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovación Grant AVI-GVA COVID-19-68 to BS.

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy.

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus' complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA- memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA- subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available "off-the-shelf" to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.

Injuria miocárdica luego de cirugía no cardíaca / Myocardial injury after non-cardiac surgery

Resumen Las complicaciones cardiovasculares mayores en el postoperatorio son frecuentes y el principal factor contribuyente es la injuria miocárdica o infarto (MINS, Myocardial Injury after Noncardiac Surgery) asociado a cirugía no cardíaca. El riesgo de mortalidad a 30 días de los pacientes con injuria miocárdica es 4-5 veces mayor que los pacientes que no lo presentan. Se estima que 85% de los pacientes con MINS no presentan síntomas, por lo que la única manera de detectarlos es mediante screening sistemático de troponinas. Si bien no existen intervenciones de aplicación sistemática que permitan prevenir esta complicación, existen alternativas de tratamiento y manejo, por lo que la pesquisa activa es costo-efectiva y relevante desde el punto de visto clínico.

Major cardiovascular complications in the postoperative period are frequent and the main contributing factor is myocardial injury or infarction (MINS, Myocardial Injury after Noncardiac Surgery) associated with non-cardiac surgery. The 30-day mortality risk in patients with myocardial injury is 4-5 times higher than in patients without this complication. It is estimated that 85% of patients with MINS/infarction are asymptomatic, hence the only way to detect them is through systematic screening of troponins. Although there are no systematic interventions to prevent this complication, there are treatment and management alternatives, so the active early diagnosis is cost effective and relevant from a clinical point of view.

Chemical and physical properties of nanocrystalline chitosan by the method: Modified nanochitosan complex and process of obtaining modified nanochitosan.

Nanocrystalline chitosan (NCC) is a modified form of chitosan, prepared from the method for obtaining chitosan acetate (CA). Due to the greater crystallinity of chitosan nanoparticles in relation to CA, NCC is more thermally stable and thus has great potential in the development of a new generation of biomaterials potentially useful in regenerative medicine and tissue engineering. NCC is also characterized by having similar properties to its precursor chitosan, such as its biocompatibility, bioactivity, ability to be bioabsorbed and lack of toxicity. One of the major problems associated with obtaining NCC is the low productivity of the methods. While known methods of obtaining nanostructures produce small amounts (milligrams), the method of synthesis for creating NCC from its salt is often more productive and less costly, and is patented by the authors of this work (registration number: BR10201702272). Thus, the objective of this study was to characterize NCC obtained through this innovative method, and analyze its chemical and physical properties using Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and mechanical property analysis with the mean values for the elasticity module, the resistance to tensile strength and the tensile strength. The results indicate that this new process of obtaining the NCC did not modify the chemical structure of the chitosan. The structure of the film surface created was homogeneous and the mechanical properties emphasized the plastifying effect of glycerol under NCC. The thermogravimetric analysis of NCC indicated greater stability in the polysaccharide structure of the nanocrystalline, due to an increased crystalline region compared to the CA which was confirmed by DSC.

Coleta de sêmen em Leopardus guttulus pelo método do cateterismo uretral / Leopardus guttulus semen collection using urethral catheter method

Considerando a realidade conservacionista dos animais mantidos em cativeiro, em especial os pequenos felídeos silvestres, objetivou-se, com este estudo, descrever o método de coleta de sêmen por cateterismo uretral em Leopardus guttulus cativos, anestesiados com cetamina-dexmedetomidina. Inicialmente foram utilizados 13 animais para coleta de sêmen por cateterismo mediante o uso de diferentes doses de cetamina-dexmedetomidina. Após determinação da dose anestésica ideal para coleta de sêmen nessa espécie, cinco L. guttulus machos foram submetidos a coletas seriadas de sêmen pelo método do cateterismo. A dose ideal para coleta de sêmen foi de 0,008mg/kg de dexmedetomidina e 10mg/kg de cetamina. Os valores médios para volume e concentração foram de 35,9µL e 552,8x106sptz/mL. Com média de 71% de motilidade e 3,1 de vigor, 68% dos espermatozoides apresentaram vitalidade (integridade de membrana) e 77% integridade acrossomal. Sobre as patologias espermáticas, obteve-se uma média de 28% de espermatozoides com defeitos maiores, 6% com defeitos menores e 67% normais. As vantagens do método, como a facilidade e o baixo custo, fazem recomendar sua utilização em L. guttulus, pois foram apresentados bons resultados quanto à concentração espermática, à motilidade, ao vigor, à viabilidade espermática e à integridade acrossomal, sendo uma técnica promissora para utilização em felinos selvagens.(AU)

Considering the conservationist reality of animals kept in captivity, especially the small wild felids, this study aimed to describe the semen collection method using urethral catheterization in captive Leopardus guttulus, anesthetized with ketamine-dexmedetomidine. Initially, 13 animals were used for semen collection using catheterization with different ketamine-dexmedetomidine doses. After determination of the best anesthetic dose for semen collection in this species, five male L. guttulus were submitted to serial semen collections using the catheter method. The dose for semen collection was 0.008mg/kg dexmedetomidine and 10mg/kg ketamine. The mean values for volume and concentration were 35.9µL and 552.8x106sptz/mL, with a mean of 71% motility, 3.1 vigor, and 68% of spermatozoa presented vitality and 77% presented acrosomal integrity. Sperm pathologies obtained an average of 28% of spermatozoa with major defects, 6% of spermatozoa with minor defects and 67% of normal spermatozoa. The method advantages such as ease and low cost lead us to recommend the use in L. guttulus, since it presented good results regarding sperm concentration, motility, vigor, sperm viability and acrosomal integrity, being a promising technique for use in wild cats.(AU)

Aspectos da biologia reprodutiva de Boa constrictor constrictor: um estudo histológico dos testículos nos períodos reprodutivos de quiescência e máxima atividade / Boa constrictor constrictor reproductive biology aspects: the testes histological study in the reproductive periods of quiescence and maximal activity

As serpentes pertencem ao segundo maior grupo dentro dos répteis, podendo apresentar sazonalidade quanto à espermatogênese, com produção descontínua ou contínua. O presente trabalho tem como objetivo caracterizar aspectos da biologia reprodutiva de Boa constrictor constrictor com base nos achados histológicos dos testículos nos períodos de máxima atividade (período de gametogênese) e quiescência. Os testículos de dois espécimes de Boa c. constrictor (7767 e 11752) foram cortados a uma espessura de 3µm em micrótomo, corados com azul de toluidina 1%, fotodocumentados e descritos. A presença de espermatozoides na luz do túbulo seminífero no indivíduo 7767 indica um período de máxima gametogênese, enquanto o lúmen dos túbulos seminíferos pouco evidentes, sem a presença de espermatozoides e de células gaméticas em divisão, caracteriza o indivíduo 11752 em período quiescente. Mediante os achados histológicos descritos no presente estudo, concluiu-se que Boa c. constrictor apresenta sazonalidade em relação à gametogênese, sendo esse padrão de sazonalidade associado ao período de cópulas relatado em literatura característico de serpentes com padrão pré-nupcial.(AU)

These snakes belong to the second largest group within the reptiles, being able to present seasonality regarding spermatogenesis, with discontinuous or continuous production. The present study aims to characterize Boa constrictor constrictor reproductive biology aspects from histological findings in testicles during periods of maximum activity (period of gametogenesis) and quiescence. The testicles of two specimens of Boa c. constrictor (7767 and 11752) were cut to a thickness of 3µm in microtome, stained with 1% toluidine blue, photodocumented and described. The spermatozoa presence in the seminiferous tubule lumen in individual 7767 indicates a period of maximum gametogenesis, whereas the seminiferous tubules lumen is not very evident without spermatozoa and the absence of dividing gametic cells characterizes individual 11752 in the quiescent period. Through the histological findings we concluded that Boa c. constrictor presents seasonality in relation to gametogenesis, and the pattern of reproductive seasonality observed along with the period of copulas reported in the literature resembles the pre-nuptial pattern.(AU)

Sexagem em tamanduá-bandeira (Myrmecophaga tridactyla) por meio do teste da reação em cadeia da polimerase / Polymerase chain reaction for sexing in giant anteater's (Myrmecophaga tridactyla)

Em tamanduá-bandeira (Myrmecophaga tridactyla) não há dimorfismo sexual, tornando-se necessária a diferenciação entre machos e fêmeas, em especial naqueles indivíduos com finalidade reprodutiva. Entre as diversas técnicas empregadas para a caracterização sexual, a reação em cadeia da polimerase (PCR) é utilizada em mamíferos para identificar uma sequência genética especifica do cromossomo Y (SRY), sendo considerado um meio moderno e eficaz de determinação sexual. O objetivo deste trabalho é padronizar um protocolo para determinação sexual de tamanduá-bandeira por meio da técnica de PCR, utilizando material genético extraído do bulbo capilar desses animais. Mediante esse protocolo, foi possível determinar o sexo de sete animais testados, sendo compatível com o sexo de cada indivíduo. Conclui-se que o protocolo padronizado apresentou total eficácia, sendo possível determinar o sexo de tamanduás-bandeira utilizando material genético extraído do bulbo capilar.(AU)

There is no sexual dimorphism in the giant anteater (Myrmecophaga tridactyla), so the distinction between males and females become necessary, especially in animals with reproductive purpose. The Polymerase Chain Reaction (PCR), among the various techniques used for characterization, is considered a modern and effective means of sex determination and used in mammals to identify the Y chromosome (SRY) specifies genetic sequence. The objective of this work is to standardize a protocol for sex determination of giant anteater by PCR technique, using genetic material extracted from the capillary bulb of these animals. With this protocol was possible the sex determination of seven tested animals, being compatible with the sex of each individual. In conclusion, this protocol showed total effectiveness, being possible to determine the giant anteater sex using genetic material extracted from the capillary bulb.(AU)

A bacterial biosensor encoding a genetically modified LuxR receptor exhibits improved detection of Pseudomonas aeruginosa's biomarker molecule 2-aminoacetophenone.

2-Aminoacetophneone (2-AA) is a volatile molecule produced in high amounts by the opportunistic pathogen Pseudomonas aeruginosa. We have previously shown that 2-AA activates the quorum sensing (QS) LuxR receptor of Aliivibrio fischeri. In the present study we were able to improve LuxR's affinity and detection limit for 2-AA by genetic modification of three amino acids within the binding pocket of the receptor. Expression of the modified LuxR receptor in a luminescent bacterial biosensor provided an efficient detection assay of 2-AA in clinical P. aeruginosa strains isolated from blood and lung infections, as well as in phlegm samples obtained from subjects suffering from lung infections.

Implicit aversive memory under anaesthesia in animal models: a narrative review.

Explicit memory after anaesthesia has gained considerable attention because of its negative implications, while implicit memory, which is more elusive and lacks patients' explicit recall, has received less attention and dedicated research. This is despite the likely impact of implicit memory on postoperative long-term well-being and behaviour. Given the scarcity of human data, fear conditioning in animals offers a reliable model of implicit learning, and importantly, one where we already have a good understanding of the underlying neural circuitry in awake conditions. Animal studies provide evidence that fear conditioning occurs under anaesthesia. The effects of different anaesthetics on memory are complex, with different drugs interacting at different stages of learning. Modulatory suppressive effects can be because of context, specific drugs, and dose dependency. In some cases, low doses of general anaesthetics can actually lead to a paradoxical opposite effect. The underlying mechanisms involve several neurotransmitter systems, acting mainly in the amygdala, hippocampus, and neocortex. Here, we review animal studies of aversive conditioning under anaesthesia, discuss the complex picture that arises, identify the gaps in knowledge that require further investigation, and highlight the potential translational relevance of the models.

EpiTools, A software suite for presurgical brain mapping in epilepsy: Intracerebral EEG.

BACKGROUND: In pharmacoresistant epilepsy, exploration with depth electrodes can be needed to precisely define the epileptogenic zone. Accurate location of these electrodes is thus essential for the interpretation of Stereotaxic EEG (SEEG) signals. As SEEG analysis increasingly relies on signal processing, it is crucial to make a link between these results and patient's anatomy. Our aims were thus to develop a suite of software tools, called "EpiTools", able to i) precisely and automatically localize the position of each SEEG contact and ii) display the results of signal analysis in each patient's anatomy. NEW METHOD: The first tool, GARDEL (GUI for Automatic Registration and Depth Electrode Localization), is able to automatically localize SEEG contacts and to label each contact according to a pre-specified nomenclature (for instance that of FreeSurfer or MarsAtlas). The second tool, 3Dviewer, enables to visualize in the 3D anatomy of the patient the origin of signal processing results such as rate of biomarkers, connectivity graphs or Epileptogenicity Index. RESULTS: GARDEL was validated in 30 patients by clinicians and proved to be highly reliable to determine within the patient's individual anatomy the actual location of contacts. COMPARISON WITH EXISTING METHODS: GARDEL is a fully automatic electrode localization tool needing limited user interaction (only for electrode naming or contact correction). The 3Dviewer is able to read signal processing results and to display them in link with patient's anatomy. CONCLUSION: EpiTools can help speeding up the interpretation of SEEG data and improving its precision.

Osteoporosis y cirugía de raquis: estrategias de tratamiento médico / Osteoporosis and spinal surgery: strategies for medical and surgical treatment

La prevalencia de osteoporosis en pacientes sometidos a cirugía de raquis se ha estimado en el 50% de las mujeres de más de 50 años, cifra superior a la de la población en general ajustada por edad. Consecuentemente, muchos autores recomiendan la evaluación sistemática y el tratamiento oportuno de la osteoporosis en la mayoría de pacientes que se van a someter a una cirugía de artrodesis. La disminución de la densidad mineral ósea (DMO) es el principal factor de riesgo independiente relacionado con el fracaso de la instrumentación en las cirugías de fusión lumbar. Las complicaciones derivadas de la cirugía de fusión vertebral son más frecuentes en pacientes mayores de 65 años y osteoporóticos. Las complicaciones tempranas más frecuentes son el pullout o arrancamiento de los tornillos pediculares, la fractura pedicular y la fractura por mecanismo de compresión en el segmento vertebral adyacente. Después de los 3 meses, las complicaciones más frecuentes son la pseudoartrosis, la fractura o la movilización de las barras, la subsidencia de cajas intersomáticas vertebral y la cifosis de la unión proximal. Existen algunos ensayos clínicos de cirugía de artrodesis de columna con tratamiento perioperatorio con alendronato, ácido zoledrónico, o teriparatida que han demostrado ser efectivos en la mejoría clínica y el incremento de las tasas de fusión. Existen diversas modificaciones en el arsenal quirúrgico que pueden mejorar las tasas de fusión y disminuir las complicaciones quirúrgicas, a destacar la artrodesis con tornillos pediculares cementados y tornillos expansibles. Finalmente existen ensayos clínicos aleatorizados que han demostrado que los tratamientos de refuerzo vertebral en fracturas vertebrales osteoporóticas son claramente beneficiosos a corto y a largo plazo

The prevalence of osteoporosis in patients undergoing spinal surgery is estimated at 50% in women over 50 years, a higher figure than in the general population adjusted for age. Consequently, many authors recommend the systematic assessment and timely treatment of osteoporosis in most patients who are going to undergo arthrodesis. The decrease in bone mineral density (BMD) is the main factor in independent risk related to the failure of the instrumentation in spinal fusion surgeries. Complications arising from spinal fusion are more frequent in osteoporotic patients over 65. The most frequent early complications are pullout or tearing pedicular screws, pedicular fracture and fracture by compression in the adjacent vertebral segment. After 3 months, the most frequent complications are pseudoarthrosis, fracture or mobilization of the bars, subsidence of vertebral intersomatic boxes and the kyphosis of the proximal joint. There are some clinical trials of spinal arthrodesis surgery with perioperative treatment with alendronate, zoledronic acid, or teriparatide that have been shown to be effective in clinical improvement and increase in fusion rates. Several modifications in the surgical arsenal may improve fusion rates and decrease surgical complications. Arthrodesis has been highlighted with cemented and expandable pedicle screws. Finally, randomized clinical trials have shown that vertebral reinforcement treatments in osteoporotic vertebral fractures are beneficial in the short and long term

Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia.

Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates <40%. Here we present a post-hoc analysis assessing safety and efficacy of infusing activated and expanded Natural Killer cells (NKAE) from haploidentical donors in patients from 2 clinical trials. In total, 18 children, adolescents and young adults with relapse or refractory acute leukemia were treated with two cycles of rescue chemotherapy followed by fresh NKAE cells infusions and low doses of IL-2. The overall response rate, complete remission achievement at the end of the study, was 72% (13 of 18). We infused 52 NKAE cell products containing a median of 6.76 × 106 NK cells/kg (0.7-34.16) and 0.49 × 106 T cells/kg (0-11). All infusions were well tolerated with no graft versus host disease nor other serious adverse events. Among the 14 patients who completed treatment, 4 of them are alive and leukemia-free more than 750 days post-transplant. We conclude that infusion of fresh NKAE cell therapy is feasible and safe in heavily pretreated pediatric population, and should be further investigated in advanced-phase clinical trials as well as a consolidation therapy to decrease relapse in patients with high-risk leukemia. TRIALS REGISTRATION: Registered at www.clinicaltrials.gov as NCT01944982 and NCT02074657.

Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans.

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the lack of soft-tissue evidence in the fossil record turns difficult any comparative study of respiratory performance. Here, we reconstruct the internal nasal cavity of a Neanderthal plus two representatives of climatically divergent MH populations (southwestern Europeans and northeastern Asians). The reconstruction includes mucosa distribution enabling a realistic simulation of the breathing cycle in different climatic conditions via computational fluid dynamics. Striking across-specimens differences in fluid residence times affecting humidification and warming performance at the anterior tract were found under cold/dry climate simulations. Specifically, the Asian model achieves a rapid air conditioning, followed by the Neanderthals, whereas the European model attains a proper conditioning only around the medium-posterior tract. In addition, quantitative-genetic evolutionary analyses of nasal morphology provided signals of stabilizing selection for MH populations, with the removal of Arctic populations turning covariation patterns compatible with evolution by genetic drift. Both results indicate that, departing from important craniofacial differences existing among Neanderthals and MHs, an advantageous species-specific respiratory performance in cold climates may have occurred in both species. Fluid dynamics and evolutionary biology independently provided evidence of nasal evolution, suggesting that adaptive explanations regarding complex functional phenotypes require interdisciplinary approaches aimed to quantify both performance and evolutionary signals on covariation patterns.

Impact of anaemia on health-related quality of life and cardiac remodelling in patients with lower risk myelodysplastic syndromes. Results of GlobQoL study.

The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.