The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

BACKGROUND: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. METHODS: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. DISCUSSION: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Yeyunostomía laparoscópica / Laparoscopic jejunostomy / Jejunostomia laparoscópica

La yeyunostomía implica el abocamiento del yeyuno a la piel y se utiliza como vía de nutrición enteral en pacientes con imposibilidad de alimentarse por vía oral; en quienes la gastrostomía no es una opción adecuada. La misma puede realizarse por vía mínimamente invasiva, como percutánea y laparoscópica

Apendicetomía electiva: caso clínico y revisión de la bibliografía / Elective appendectomy: clinical case and literature review / Apendectomia eletiva: caso clínico e revisão da literatura

Las masas inflamatorias de origen apendicular son cuadros de presentación poco frecuente, el 3 % de las apendicitis agudas. Su manejo terapéutico puede ser sistematizado en cirugía de inicio o tratamiento conservador. Este último consiste en antibioticoterapia exclusiva, o asociada al drenaje percutáneo. Es una alternativa frente a emprender una apendicectomía demandante, con riesgo de no identificar el apéndice cecal, lesión visceral y necesidad de conversión o resecciones extendidas. Sin embargo, en estos pacientes, la ausencia de la confirmación diagnóstica anatomo-patológica obliga a un seguimiento protocolizado a fin de descartar diagnósticos diferenciales de mayor relevancia pronóstica. Objetivo: Presentar el caso de un paciente en el que se realizó manejo conservador y apendicetomía electiva. Se realizó una revisión bibliográfica de las pautas de seguimiento e indicación de la apendicectomía electiva. Discusión y conclusiones: Las masas inflamatorias de origen apendicular representan un desafío diagnóstico y terapéutico, requiriendo un manejo y seguimiento específico. La indicación de apendicectomía electiva es controversial, es planteable frente a la persistencia de imágenes patológicas y dudas diagnósticas, o en pacientes con apendicitis recurrentes.

Inflammatory masses of appendiceal origin are infrequent; represent 3 % of acute appendicitis. Its therapeutic management can be systematized in initial surgery or conservative treatment. The latter consists of exclusive antibiotic therapy, or associated with percutaneous drainage. it is an alternative to undertaking a demanding appendectomy, with the risk of not identifying the cecal appendix, visceral injury, and the need for conversion or extended resections. However, the absence of pathological diagnostic confirmation requires protocolized follow-up in order to rule out differential diagnoses of greater prognostic relevance. Objective: present the case of a patient who underwent conservative management and elective appendectomy. a bibliographic review was carried out in the databases: pubmed, cochrane library, scielo and lilacs. Discussion and conclusions: inflammatory masses of appendiceal origin represent a diagnostic and therapeutic challenge, requiring specific management and follow-up. The indication for elective appendectomy is controversial, it is considered in the presence of persistent pathological images and diagnostic doubts, or in patients with recurrent appendicitis.

Massas inflamatórias de origem apendicular são quadros de apresentação pouco frequentes, 3 % de as apendicites agudas. seu manejo terapêutico pode ser sistematizado em cirurgia inicial ou tratamento conservador. esta última consiste na antibioticoterapia exclusiva, ou associada à drenagem percutânea. é uma alternativa à realização de uma apendicectomia exigente, com risco de não identificação do apêndice cecal, lesão visceral e necessidade de conversão ou ressecções extensas. no entanto, nesses pacientes, a ausência de confirmação diagnóstica patológica requer acompanhamento protocolarizado para afastar diagnósticos diferenciais de maior relevância prognóstica. Objetivo: apresentar o caso de um paciente submetido a tratamento conservador e apendicectomia eletiva. foi realizada revisão bibliográfica nas bases de dados: pubmed, biblioteca cochrane, scielo e lilacs. Discussão e conclusões: as massas inflamatórias de origem apendicular representam um desafio diagnóstico e terapêutico, exigindo manejo e seguimento específicos. a indicação de apendicectomia eletiva é controversa, sendo considerada na presença de imagens patológicas persistentes e dúvidas diagnósticas, ou em pacientes com apendicite recorrente.

Recidiva paraesofágica de hernia hiatal: diagnóstico radiológico y resolución quirúrgica laparoscópica / Paraesophageal recurrence of hiatal hernia: radiological diagnosis and laparoscopic surgical resolution / Recorrência paraesofágica de hérnia hiatal: diagnóstico radiológico e resolução cirúrgica laparoscópica

La tasa de recidiva radiológica luego de la cirugía de las hernias hiatales grandes tipo IV es cercana al 50%. La mayoría de las veces la recidiva supone un ascenso parcial de la funduplicatura al tórax (telescopaje), y si no tiene expresión clínica puede optarse por un manejo conservador (solo 3-6% requieren cirugía de revisión). Sin embargo, en ocasiones hay otro tipo de recidivas (paraesofágicas) que deben valorarse mediante estudios funcionales, endoscópicos y radiológicos, que dan disfagia con mayor frecuencia. Un tránsito contrastado digestivo superior permite en este caso identificar el tipo de recidiva herniaria, con migración parcial del fundus gástrico hacia el tórax paraesofágico izquierdo, y una funduplicatura continente pero realizada técnicamente en por debajo de lo deseable (cuerpo alto) (figura). La resolución del cuadro implica la reducción de la hernia a la cavidad abdominal, con cierre del defecto diafragmático, desmontar la funduplicatura anterior anatomizando la zona y la reconfección de una nueva funduplicatura.

Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial.

BACKGROUND: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). METHODS/STUDY DESIGN: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. DISCUSSION: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Morbimortalidad de la colecistectomía laparoscópica electiva en un servicio universitario / Morbimortality of elective laparoscopic cholecystectomy in a university hospital / Morbimortalidade da colecistectomia laparoscópica eletiva em um serviço universitário

Resumen: Introducción: la colecistectomía laparoscópica (CL) es la cirugía más frecuente del tracto digestivo. A pesar de considerarse un procedimiento seguro, la morbilidad se reporta hasta en un 10%, no existiendo registro a nivel nacional. Objetivo: describir la incidencia de complicaciones y morbimortalidad de la CL electiva en una población no seleccionada de un servicio universitario. Método: se realizó un estudio retrospectivo observacional de los pacientes intervenidos en forma electiva de CL, entre el 1/1/2010 y el 31/12/2019 en la Clínica Quirúrgica B del Hospital de Clínicas y en la Unidad Docente Asistencial de Cirugía del Hospital Español. Las variables incluidas fueron demográficas, diagnóstico operatorio, conversión, morbimortalidad, reintervenciones y readmisiones. Resultados: se reclutó un total de 1.499 CL electivas, edad promedio 49 años (15-87), 79% sexo femenino, incidencia de litiasis de vía biliar principal (LVBP) en 210 (17%) casos; 25 conversiones (1,7%). Hubo un total de 64 complicaciones (4,3%) con una incidencia significativamente mayor en pacientes con LVBP (2,8% vs 7,6%, p 0,01). Hubo dos lesiones del hepato-colédoco (0,13%) (tipo Hannover D y C), ambas detectadas y reparadas en la misma cirugía y tres lesiones viscerales (0,20%). Hubo 16 readmisiones (1,07%) y 9 reintervenciones (0,6%). Dos pacientes fallecieron (0,13%) en el posoperatorio (insuficiencia hepatocítica crónica descompensada y pancreatitis grave pos-CPRE posoperatoria). Conclusiones: la CL en la población no seleccionada del servicio universitario analizado en este trabajo demuestra ser un procedimiento seguro, con tasas de complicaciones, reintervenciones y readmisiones que en este estudio se comparan favorablemente con las reportadas en la literatura. La presencia de litiasis en la vía biliar principal se asoció a una incidencia significativamente mayor de complicaciones posoperatorias y de mayor severidad.

Summary: Introduction: laparoscopic cholecystectomy (LC) is the most frequent surgery of the digestive tract. Despite it being considered a safe procedure, morbidity is reported to be up to 10%, there being no record at the national level. Objective: to describe the incidence of complications and morbimortality of elective LC in a non-selected population group in a university hospital. Method: retrospective observational study of patients who underwent elective LC between January 1, 2010 and December 31, 2019 in the Surgical Clinic B at the Clinicas Hospital and the surgery assistance Teaching Unit at Español Hospital. The following variables were included: demographics, surgical diagnosis, conversion, morbimortality, reoperations and readmissions. Results: 1.499 CL were found, average age was 49 years old (15-87), 79% were women, main bile duct lithiasis in 210 cases (17%), 25 conversions (1.7%). There were 64 complications (4.3%), the incidence being significantly higher in patients with main bile duct lithiasis (2.8% vs 7.6%, p 0,01). Two bile duct-hepatic lesions (Hannover type D and C), both detected and repaired in the same surgery, and three visceral lesions (0.20 %). There were 16 readmissions (1.07%) and 9 reoperations (0.6%). Two patients died (0.13%) in the postoperative: decompensated chronic liver failure and post Endoscopic retrograde cholangiopancreatography (ERCP) severe pancreatitis. Conclusions: CL in a non-selected population at the university service analysed in the study proved to be a safe procedure, and complications, reoperation and readmission rates found in the study are positively compared to those reported in literature. The presence of lithiasis in the bile duct was associated with postoperative complications and a greater severity.

Resumo: Introdução: a colecistectomia laparoscópica (CL) é a cirurgia mais comum do trato digestivo. Apesar de ser considerado um procedimento seguro, a morbidade descrita é de 10%, e não há um registro nacional. Objetivo: descrever a incidência de complicações e morbimortalidade das CL eletivas, em uma população não selecionada em serviço universitário. Método: estudo observacional retrospectivo de pacientes submetidos à CL eletiva, realizado no período 1 de janeiro de 2010 - 31 de dezembro de 2019 na Clínica Cirúrgica B do Hospital de Clínicas e Unidade Docente Assistencial de Cirurgia do Hospital Espanhol. Foram incluidas variáveis demográficas, diagnóstico operatório, conversão, morbimortalidade, reoperações e reinternações. Resultados: foram incluidas 1.499 LCs eletivas, a idade média dos pacientes foi 49 anos (15-87), sendo 79% mulheres com incidência de cálculos biliares principais (LVBP) em 210 (17%) casos; 25 conversões (1,7%). Houve um total de 64 complicações (4,3%) com uma incidência significativamente maior em pacientes com LVBP (2,8% vs 7,6%, p 0,01). Ocorreram duas lesões hepato-colédoco (0,13%) (Hannover tipos D e C), ambas detectadas e reparadas na mesma cirurgia, e três lesões viscerais (0,20%). Ocorreram 16 readmissões (1,07%) e 9 reoperações (0,6%). Dois pacientes morreram (0,13%) no pós-operatório (insuficiência hepatocítica crônica descompensada e pancreatite pós-operatória grave por CPRE). Conclusões: a LC na população não selecionada do serviço universitário analisado neste estudo, mostrou-se como um procedimento seguro, com índices de complicações, reoperações e reinternações que neste estudo se comparam favoravelmente com os relatados na literatura. A presença de litíase no ducto biliar principal foi associada a uma incidência significativamente maior de complicações pós-operatórias e de maior gravidade.

Towards a unification of treatments and interventions for tinnitus patients: The EU research and innovation action UNITI.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.

Facial palsy after embolization with Squid® 12.

Endovascular procedures with liquid embolic agents such as ethylene-vinyl alcohol (EVOH) copolymers are indicated before surgical treatment of cervical paraganglioma. Consequently, these agents are now available as low viscosity formulations, one of which is Squid 12, which are demonstrating superior vascular penetration. Cases of facial paralysis secondary to embolization of cervical vascular lesions with classic embolic agents have been reported in the English literature, however, this complication has not been described with new generation options such as Squid 12.We describe the case of a 43-year-old patient with a left neck carotid paraganglioma. Embolization was performed under general anaesthesia before surgical excision. In the immediate postoperative period, the patient developed total left facial palsy. Since the imaging tests (Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)) and neurological examination showed no involvement of additional cranial nerves (CN), we hypothesise that the main cause of this complication is ischemia of the vasa nervorum of CN VII secondary to embolization. Almost six months later, the patient continues to present total facial paralysis (Grade VI House-Brackmann facial paralysis scale), and palsy of the left CN X and XII as a complication secondary to surgical resection of the paraganglioma.This case is relevant since it is the first clinical case of permanent facial paralysis secondary to embolization with Squid 12.

Vowel recognition with four coupled spin-torque nano-oscillators.

In recent years, artificial neural networks have become the flagship algorithm of artificial intelligence1. In these systems, neuron activation functions are static, and computing is achieved through standard arithmetic operations. By contrast, a prominent branch of neuroinspired computing embraces the dynamical nature of the brain and proposes to endow each component of a neural network with dynamical functionality, such as oscillations, and to rely on emergent physical phenomena, such as synchronization2-6, for solving complex problems with small networks7-11. This approach is especially interesting for hardware implementations, because emerging nanoelectronic devices can provide compact and energy-efficient nonlinear auto-oscillators that mimic the periodic spiking activity of biological neurons12-16. The dynamical couplings between oscillators can then be used to mediate the synaptic communication between the artificial neurons. One challenge for using nanodevices in this way is to achieve learning, which requires fine control and tuning of their coupled oscillations17; the dynamical features of nanodevices can be difficult to control and prone to noise and variability18. Here we show that the outstanding tunability of spintronic nano-oscillators-that is, the possibility of accurately controlling their frequency across a wide range, through electrical current and magnetic field-can be used to address this challenge. We successfully train a hardware network of four spin-torque nano-oscillators to recognize spoken vowels by tuning their frequencies according to an automatic real-time learning rule. We show that the high experimental recognition rates stem from the ability of these oscillators to synchronize. Our results demonstrate that non-trivial pattern classification tasks can be achieved with small hardware neural networks by endowing them with nonlinear dynamical features such as oscillations and synchronization.

Learning through ferroelectric domain dynamics in solid-state synapses.

In the brain, learning is achieved through the ability of synapses to reconfigure the strength by which they connect neurons (synaptic plasticity). In promising solid-state synapses called memristors, conductance can be finely tuned by voltage pulses and set to evolve according to a biological learning rule called spike-timing-dependent plasticity (STDP). Future neuromorphic architectures will comprise billions of such nanosynapses, which require a clear understanding of the physical mechanisms responsible for plasticity. Here we report on synapses based on ferroelectric tunnel junctions and show that STDP can be harnessed from inhomogeneous polarization switching. Through combined scanning probe imaging, electrical transport and atomic-scale molecular dynamics, we demonstrate that conductance variations can be modelled by the nucleation-dominated reversal of domains. Based on this physical model, our simulations show that arrays of ferroelectric nanosynapses can autonomously learn to recognize patterns in a predictable way, opening the path towards unsupervised learning in spiking neural networks.

A Nanotechnology-Ready Computing Scheme based on a Weakly Coupled Oscillator Network.

With conventional transistor technologies reaching their limits, alternative computing schemes based on novel technologies are currently gaining considerable interest. Notably, promising computing approaches have proposed to leverage the complex dynamics emerging in networks of coupled oscillators based on nanotechnologies. The physical implementation of such architectures remains a true challenge, however, as most proposed ideas are not robust to nanotechnology devices' non-idealities. In this work, we propose and investigate the implementation of an oscillator-based architecture, which can be used to carry out pattern recognition tasks, and which is tailored to the specificities of nanotechnologies. This scheme relies on a weak coupling between oscillators, and does not require a fine tuning of the coupling values. After evaluating its reliability under the severe constraints associated to nanotechnologies, we explore the scalability of such an architecture, suggesting its potential to realize pattern recognition tasks using limited resources. We show that it is robust to issues like noise, variability and oscillator non-linearity. Defining network optimization design rules, we show that nano-oscillator networks could be used for efficient cognitive processing.

Controlling the phase locking of stochastic magnetic bits for ultra-low power computation.

When fabricating magnetic memories, one of the main challenges is to maintain the bit stability while downscaling. Indeed, for magnetic volumes of a few thousand nm(3), the energy barrier between magnetic configurations becomes comparable to the thermal energy at room temperature. Then, switches of the magnetization spontaneously occur. These volatile, superparamagnetic nanomagnets are generally considered useless. But what if we could use them as low power computational building blocks? Remarkably, they can oscillate without the need of any external dc drive, and despite their stochastic nature, they can beat in unison with an external periodic signal. Here we show that the phase locking of superparamagnetic tunnel junctions can be induced and suppressed by electrical noise injection. We develop a comprehensive model giving the conditions for synchronization, and predict that it can be achieved with a total energy cost lower than 10(-13) J. Our results open the path to ultra-low power computation based on the controlled synchronization of oscillators.

Efficient Synchronization of Dipolarly Coupled Vortex-Based Spin Transfer Nano-Oscillators.

Due to their nonlinear properties, spin transfer nano-oscillators can easily adapt their frequency to external stimuli. This makes them interesting model systems to study the effects of synchronization and brings some opportunities to improve their microwave characteristics in view of their applications in information and communication technologies and/or to design innovative computing architectures. So far, mutual synchronization of spin transfer nano-oscillators through propagating spinwaves and exchange coupling in a common magnetic layer has been demonstrated. Here we show that the dipolar interaction is also an efficient mechanism to synchronize neighbouring oscillators. We experimentally study a pair of vortex-based spin transfer nano-oscillators, in which mutual synchronization can be achieved despite a significant frequency mismatch between oscillators. Importantly, the coupling efficiency is controlled by the magnetic configuration of the vortices, as confirmed by an analytical model and micromagnetic simulations highlighting the physics at play in the synchronization process.

Spin-transfer torque magnetic memory as a stochastic memristive synapse for neuromorphic systems.

Spin-transfer torque magnetic memory (STT-MRAM) is currently under intense academic and industrial development, since it features non-volatility, high write and read speed and high endurance. In this work, we show that when used in a non-conventional regime, it can additionally act as a stochastic memristive device, appropriate to implement a "synaptic" function. We introduce basic concepts relating to spin-transfer torque magnetic tunnel junction (STT-MTJ, the STT-MRAM cell) behavior and its possible use to implement learning-capable synapses. Three programming regimes (low, intermediate and high current) are identified and compared. System-level simulations on a task of vehicle counting highlight the potential of the technology for learning systems. Monte Carlo simulations show its robustness to device variations. The simulations also allow comparing system operation when the different programming regimes of STT-MTJs are used. In comparison to the high and low current regimes, the intermediate current regime allows minimization of energy consumption, while retaining a high robustness to device variations. These results open the way for unexplored applications of STT-MTJs in robust, low power, cognitive-type systems.