Induction immunosuppression strategies and outcomes post-lung transplant: A single center experience.

PURPOSE: Currently 80% of lung transplant centers use induction immunosuppression. However, there is a lack of standardization of induction protocols within and across lung transplant centers. This study explores the association of two different induction immunosuppression strategies used at our center [single dose rabbit antithymocyte globulin (rATG) vs. alemtuzumab] compared to no induction with immunologic and clinical outcomes after lung transplantation. METHODS: A total of 174 consecutive lung transplant recipients (LTR) between 2016 and 2019 were included in the analysis. Twenty nine LTR (16.7%) received no induction, 22 LTR (12.6%) received alemtuzumab, 123 LTR (70.6%) received a single dose of rATG; 1.5 mg/kg within 24 h of transplant for induction. All LTR had a negative flow cytometry crossmatch on the day of the transplant. All LTR were assessed for de novo HLA donor-specific antibodies (DSA) development and clinical outcomes, including the risk of acute cellular rejection (ACR), antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and overall survival post-transplant. RESULTS: The median lung allocation score (LAS) was significantly higher in LTR that did not receive Induction immunosuppression (76; range = 35.3-94.3) compared to induction with rATG (41.6; range = 31.6-91) and alemtuzumab (51; range = 33.1-88.2) (p < 0.001). De novo HLA DSA were detected in 50/174 (28.7%) LTR within 12 months post-transplant. They were detected in 13/29 (44.8%) LTR without induction immunosuppression compared to 28/123 (22.8%) and 9/22 (40.9%) LTR with rATG and alemtuzumab induction, respectively (p = 0.02). The percent freedom from ACR rates between LTR who received alemtuzumab induction was significantly higher compared to LTR who received rATG or no induction at 1 (p = 0.02), 2 (p = 0.01) and 3 (p = 0.05) years post-transplant. In addition, the overall 1-year survival rates were significantly higher in LTR who received rATG or alemtuzumab induction compared to LTR without induction immunosuppression (p = 0.02). CONCLUSION: Induction immunosuppression strategies utilizing rATG or Alemtuzumab have unique and contrasting benefits in LTR. Combination of alemtuzumab induction and a lower dose of maintenance immunosuppression may reduce the incidence of ACR in LTR. Single-dose rATG or alemtuzumab induction immunosuppression may also improve the 1 year overall LTR survival compared to no induction.

Xanthogranulomatous Pyelonephritis in Peritoneal Dialysis.

Introduction: Xanthogranulomatous pyelonephritis (XGP) is a rare illness that consists of a destructive chronic inflammatory process of the renal parenchyma associated with recurrent infection and obstructions of the urinary tract. Peritoneal dialysis (PD) is a form of renal replacement therapy used in advanced kidney disease. PD patients demonstrate a systemic inflammatory state, secondary to the increase in uremic toxins, decreased filtration of proinflammatory cytokines, as well as constant exposure to bioincompatible dialysis solutions or a foreign body reaction from the catheter, among other factors, as peritoneal infections. Case Presentation: We present the clinical case of a 74-year-old woman, with a history of recurrent urinary tract infections associated with nephrolithiasis and stage 5D chronic kidney disease, on a PD program. The patient presented a non-specific 3-month state of progressive asthenia, with increased inflammatory parameters in the analytical controls. After presenting multiple negative urine cultures and peritoneal fluid cultures, she was hospitalized to study the constitutional syndrome. The imaging test revealed bilateral staghorn lithiasis with severe dilatation of the right renal pelvis and great cortical thinning. Given the suspicion of XGP, it was decided to perform right renal nephrectomy, which was confirmed after the anatomopathological study. Prior to the intervention, she was transferred to hemodialysis. Over the following months, significant clinical and analytical improvement was observed. Conclusion: The systemic inflammatory state and the risk of infections in PD can mask the diagnosis of XGP in PD patients. There are no reported cases of XGP in patients in PD.

Evaluation of Different Types of Stimuli in an Event-Related Potential-Based Brain-Computer Interface Speller under Rapid Serial Visual Presentation.

Rapid serial visual presentation (RSVP) is currently a suitable gaze-independent paradigm for controlling visual brain-computer interfaces (BCIs) based on event-related potentials (ERPs), especially for users with limited eye movement control. However, unlike gaze-dependent paradigms, gaze-independent ones have received less attention concerning the specific choice of visual stimuli that are used. In gaze-dependent BCIs, images of faces-particularly those tinted red-have been shown to be effective stimuli. This study aims to evaluate whether the colour of faces used as visual stimuli influences ERP-BCI performance under RSVP. Fifteen participants tested four conditions that varied only in the visual stimulus used: grey letters (GL), red famous faces with letters (RFF), green famous faces with letters (GFF), and blue famous faces with letters (BFF). The results indicated significant accuracy differences only between the GL and GFF conditions, unlike prior gaze-dependent studies. Additionally, GL achieved higher comfort ratings compared with other face-related conditions. This study highlights that the choice of stimulus type impacts both performance and user comfort, suggesting implications for future ERP-BCI designs for users requiring gaze-independent systems.

Temporal Dynamics of Adverse Effects across Five Sessions of Transcranial Direct Current Stimulation.

(1) Background: Transcranial direct current stimulation (tDCS) is a safe intervention, only producing mild and transient adverse effects (AEs). However, there is no detailed analysis of the pattern of adverse effects in an application transferable to the clinic. Therefore, our objective is to describe the AEs produced by tDCS and its temporal evolution. (2) Methods: A total of 33 young volunteers were randomized into a tDCS or sham group. Participants performed a hand dexterity task while receiving the tDCS or sham intervention (20 min and 1 mA), for five consecutive days. AEs were assessed daily after each intervention and classified as somatosensory, pain, or other effects. (3) Results: The number of AEs was generally increased by tDCS intervention. Specifically, tDCS led to more frequent somatosensory discomfort, characterized by sensations like itching and tingling, alongside painful sensations such as burning, compared to the sham intervention. Additionally, certain adverse events, including neck and arm pain, as well as dizziness and blurry vision, were exclusive to the tDCS group. Interestingly, tDCS produced similar AEs across the days; meanwhile, the somatosensory AEs in the sham group showed a trend to decrease. (4) Conclusions: tDCS produces mild and temporary somatosensory and pain AEs during and across sessions. The different evolution of the AEs between the tDCS and sham protocol could unmask the blinding protocol most used in tDCS studies. Potential solutions for improving blinding protocols for future studies are discussed.

Recent Advances on the Chemistry of Transition Metal Complexes with Monoanionic Bidentate Silyl Ligands.

The chemistry of transition-metal (TM) complexes with monoanionic bidentate (κ2-L,Si) silyl ligands has considerably grown in recent years. This work summarizes the advances in the chemistry of TM-(κ2-L,Si) complexes (L=N-heterocycle, phosphine, N-heterocyclic carbene, thioether, ester, silylether or tetrylene). The most common synthetic method has been the oxidative addition of the Si-H bond to the metal center assisted by the coordination of L. The metal silicon bond distances in TM-(κ2-L,Si) complexes are in the range of metal-silyl bond distances. TM-(κ2-L,Si) complexes have proven to be effective catalysts for hydrosilylation and/or hydrogenation of unsaturated molecules among other processes.

Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study / Morbilidad y mortalidad de pacientes de edad avanzada con enfermedad pancreaticobiliar con relación a su edad y la evaluación geriátrica integral: un estudio prospectivo observacional

Background This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. Methods A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75–79 years old; group 2: 80–84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. Results Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). Conclusions No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications. (AU)

Antecedentes Este estudio fue diseñado para analizar la influencia de la edad y la evaluación geriátrica integral en los resultados clínicos del manejo de la enfermedad pancreatobiliar en pacientes de edad avanzada. Métodos Se ha realizado un estudio observacional prospectivo en el que se incluyeron 140 pacientes de edad avanzada (mayores de 75 años) con enfermedad pancreatobiliar benigna. Los pacientes se dividieron según la edad en los siguientes grupos: Grupo 1: 75-79 años; Grupo 2: 80-84 años; Grupo 3: 85 años y más. Se les realizó una valoración geriátrica integral con diferentes escalas: Barthel Index, Pfeiffer Index, Charlson Index y Fragility scale, al ingreso y seguimiento 90 días después del alta hospitalaria para analizar su influencia en la morbimortalidad. Resultados En total, se incluyeron 140 pacientes (Grupo 1=51; Grupo 2=43 y Grupo 3=46). La mayoría de ellos, 52 casos (37,8%), presentaron colecistitis aguda, seguido de colangitis aguda con 29 casos (20,2%) y pancreatitis aguda con 25 casos (17,9%). Se han observado diferencias significativas en las complicaciones en diferentes grupos de edad (p=0,033). Especialmente en pacientes con un índice de Barthel ≤60, lo que sugiere que estos pacientes menos funcionales tuvieron complicaciones más severas después de su tratamiento (p=0,037). La tasa de mortalidad fue de 7,1% (10 pacientes). Conclusiones No se encontraron diferencias significativas entre la edad, la morbilidad y la mortalidad en pacientes ancianos con enfermedad pancreatobiliar. Las escalas geriátricas integrales mostraron cierta utilidad en su asociación con complicaciones específicas. (AU)

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation.

Anomalous expression of potassium channels in cancer tissues is associated with several cancer hallmarks that support deregulated proliferation and tumor progression. Ion channels seem to influence cell proliferation; however, the crucial molecular mechanisms involved remain elusive. Some results show how extracellular mitogenic signals modulate ion channel activity through intracellular secondary messengers. It is relevant because we are beginning to understand how potassium channels can affect the proliferative capacity of cells, either in normal mitogen-dependent proliferation or in mitogen-unresponsive proliferation. Calciumdependent potassium channels have been implicated in cell cycle signaling in many cancerous cell lines. In particular, the so-called intermediate conductance KCa3.1 (IKCa) is reported to play a significant role in uncontrolled cell cycle signaling, among other malignant processes driven by cancer hallmarks. In addition to these features, this channel can be subjected to specific pharmacological regulation, making it a promising cornerstone for understanding the signaling behavior of several types of cancer and as a target for chemotherapeutic approaches. This review is dedicated to the connection of KCa3.1 activity, in canonical and non-canonical ways, to the cell cycle signaling, including the cooperation with calcium channels to generate calcium signals and its role as a mediator of proliferative signals.

Microfracture-coagulation for the real robotic liver parenchymal transection.

The use of the robotic approach in liver surgery is exponentially increasing. Although technically the robot introduces several innovative features, the instruments linked with the traditional laparoscopic approach for the liver parenchymal transection are not available, which may result in multiple technical variants that may bias the comparative analysis between the different series worldwide. A real robotic approach, minimally efficient for the liver parenchymal transection, with no requirement of external tool, available for the already existing platforms, and applicable to any type of liver resection, counting on the selective use of the plugged bipolar forceps and the monopolar scissors, or "microfracture-coagulation" (MFC) transection method, is described in detail. The relevant aspects of the technique, its indications and methodological basis are discussed.

Transcranial magnetic stimulation therapy for central post-stroke pain: systematic review and meta-analysis.

Introduction: Although rare, central post-stroke pain remains one of the most refractory forms of neuropathic pain. It has been reported that repetitive transcranial magnetic stimulation (rTMS) may be effective in these cases of pain. Aim: The aim of this study was to investigate the efficacy of rTMS in patients with central post-stroke pain (CPSP). Methods: We included randomized controlled trials or Controlled Trials published until October 3rd, 2022, which studied the effect of rTMS compared to placebo in CPSP. We included studies of adult patients (>18 years) with a clinical diagnosis of stroke, in which the intervention consisted of the application of rTMS to treat CSP. Results: Nine studies were included in the qualitative analysis; 6 studies (4 RCT and 2 non-RCT), with 180 participants, were included in the quantitative analysis. A significant reduction in CPSP was found in favor of rTMS compared with sham, with a large effect size (SMD: -1.45; 95% CI: -1.87; -1.03; p < 0.001; I2: 58%). Conclusion: The findings of the present systematic review with meta-analysis suggest that there is low quality evidence for the effectiveness of rTMS in reducing CPSP. Systematic review registration: Identifier (CRD42022365655).

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia.

Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.

Air-stepping in the neonatal mouse: a powerful tool for analyzing early stages of rhythmic limb movement development.

There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study l-3,4-dihydroxyphenylalanine (l-DOPA)-induced air-stepping in mice at postnatal day (P)7 and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion but without constraints imposed by weight bearing, postural adjustments, or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of l-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation, we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10 but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages, indicating maturation of flexion-extension cycles as the animal starts to walk. EMG recordings of TA and LG show alternation but with more focused activation particularly in the LG from P7 to P10. We discuss similarities to neonatal rat l-DOPA-induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and pave the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry.NEW & NOTEWORTHY We present novel methods to study neonatal air-stepping in newborn mice. These methods allow analyses at the onset of limb coordination during the period in which altricial species like rats, mice, and humans "learn" to walk. The methods will be useful to test a large variety of mutations that serve as models of motor disease in newborns or that are used to probe for specific circuit mechanisms that generate coordinated limb motor output.

El sello de calidad FECYT, un reconocimiento y un estímulo para Archivos / The FECYT seal of quality, a recognition and a stimulus for Archivos

Un año más, mediante esta nota editorial, damos cuenta de los principales avan-ces de nuestra revista y las estadísticas editoriales.En cuanto a las estadísticas editoriales, que se detallan en los apartados poste-riores, podemos afirmar que son las de una revista consolidada: flujo nutrido y constante de trabajos recibidos/publicados, tasas de aceptación y rechazo pro-porcionadas, tiempos de gestión razonables y diversidad en las autorías.El logro más destacable del 2023 fue superar con éxito el proceso de evaluación de la Octava edición de Evaluación de la calidad editorial y científica de las revistas científicas españolas, comúnmente conocido como ‘Sello FECYT’.El Sello de Calidad FECYT (Figura 1) identifica a aquellas publicaciones científicas que cumplen unos requisitos de profesionalización internacionalmente reconoci-dos. Gracias a este distintivo, muchas revistas científicas se han posicionado de manera importante en el ámbito nacional e internacional Este reconocimiento lo otorga la FECYT por un periodo de un año desde la resolu-ción definitiva, y la evaluación para su renovación se realizará de oficio por parte de la Fundación una vez finalizado dicho periodo (AU)

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.