Predictive Models for Assessing Patients' Response to Treatment in Metastatic Prostate Cancer: A Systematic Review.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients' response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Psychometric Properties of the Spanish Version of the Satisfaction With Daily Occupations and Occupational Balance in Spanish Stroke Survivors.

IMPORTANCE: Stroke survivors experience changes in participation level, satisfaction with participation, and participation balance, making it necessary to have a validated tool for their assessment. OBJECTIVE: To evaluate the psychometric properties of the Spanish version of the Satisfaction With Daily Occupations and Occupational Balance (SDO-OB) in stroke survivors. DESIGN: Psychometric study. SETTING: National multicenter study (rehabilitation centers, and hospitals). PARTICIPANTS: One hundred forty stroke survivors with and without a primary caregiver. OUTCOMES AND MEASURES: Participants completed the SDO-OB, the five-level version of the EQ-5D (EQ-5D-5L), and the Activity Card Sort (ACS). Internal consistency, convergent validity, known-groups validity, and floor and ceiling effects were assessed. Intraobserver reliability was assessed 1 wk apart. RESULTS: The internal consistency was acceptable; Cronbach's α = .80, 95% confidence interval (CI) [0.75, 0.85]. A moderate correlation was found between the SDO-OB summed participation level and summed participation satisfaction (ρ = .53). Both SDO-OB summed scores correlated with ACS scores (0.25 < ρ < .61). However, only summed participation satisfaction scores correlated with the emotional component of the EQ-5D-5L (ρ = .32). The SDO-OB discriminated between groups with and without a caregiver (p = .001) and had no floor or ceiling effects (<7%). Good intraclass correlation coefficients (ICCs) were obtained for summed participation level (ICC = .91; 95% CI [.85, .94]) and summed participation satisfaction (ICC = .86; 95% CI [.78, .92]). Standard error of measurement and minimum detectable change were 0.7 and 1.9 points, respectively, for summed participation level and 4.5 and 12.4, respectively, for summed participation satisfaction. CONCLUSIONS: The Spanish version of the SDO-OB presented good psychometric properties, making it a suitable instrument to address participation level, participation satisfaction, and participation balance in stroke survivors. Plain-Language Summary: After a stroke, survivors experience changes in their participation in daily activities and how satisfied they are with them. This study examined whether a tool called Satisfaction With Daily Occupations and Occupational Balance (SDO-OB) could provide reliable information about this. We looked at 140 stroke survivors from different places in Spain to see whether they had someone caring for them, how healthy they were, and how their participation in daily activities changed after stroke. We found that the SDO-OB is helpful for understanding a stroke survivor's situation and can identify areas needing intervention and track changes caused by intervention plans.

Recovery of spatio-temporal gait and functional parameters following unilateral eccentric exercise-induced muscle damage in the hamstrings.

OBJECTIVES: This study aimed to analyze how spatiotemporal gait parameters, active knee extension range of motion, muscle activity, and self-perceived function change over a seven-day period in healthy individuals after exercise-induced muscle damage (EIMD) in the hamstrings. DESIGN: Longitudinal cohort study. METHODS: Twenty-four healthy males participated in four sessions before and after EIMD (pre-EIMD, 48 h, 96 h, and 168 h post-EIMD). A single-leg deadlift exercise was performed to provoke EIMD in the hamstrings of the dominant leg. Lower limb function perception, spatiotemporal gait parameters, active knee extension range of motion, and electromyographic (EMG) activity of the semitendinosus and biceps femoris muscles during gait and maximal isometric contraction were assessed bilaterally. RESULTS: At 48 h, the EIMD-side showed reduced step length, active knee extension range of motion, maximal strength and EMG activity compared to baseline (P < 0.042), while increased relative EMG activity in the biceps femoris during gait (P = 0.001). At 96 h, step length and EMG activity on the EIMD-side reached similar values to those at baseline, whereas lower limb function perception and active knee extension range of motion returned to baseline state at 168 h post-EIMD. No changes over time were observed on the control-side. CONCLUSIONS: Recovery from EIMD requires a multimodal assessment since the different parameters affected by EIMD recover at different paces. Active range of motion appears to be the last variable to fully recover. Self-perceived function should not be considered in isolation as it does not represent complete functional recovery.

Occurrence of area postrema syndrome during follow-up: phenotype and influence over NMOSD activity in LATAM in real-world settings.

INTRODUCTION: We aimed to assess the frequency, duration, and severity of area postrema syndrome (APS) during follow-up in neuromyelitis optica spectrum disorder (NMOSD) patients, as well as its association with inflammatory activity and prognostic factors of APS severity in a real-world setting. METHODS: We conducted a retrospective study on a cohort of Latin American (LATAM) NMOSD patients who had experienced APS during their follow-up. Patients from Mexico, Peru, Brazil, Colombia, Panama, Chile and Argentina patients who met 2015 NMOSD criteria were included. We evaluated data on symptom type (nausea, vomiting and/or hiccups), frequency, duration, severity (measured by APS severity scale), association with other NMOSD core relapses, and acute treatments (symptomatic and immunotherapy or plasmapheresis). Logistic regression was conducted to evaluate factors associated with APS severity (vs. mild-moderate). RESULTS: Out of 631 NMOSD patients, 116 (18.3%) developed APS during their follow-up. The most common APS phenotype was severe. Inflammatory activity (i.e., relapses) significantly decreased after the onset of APS. Half of the patients experienced isolated APS with a median duration of 10 days, and the most frequently used acute treatment was IV steroids. All three symptoms were present in 44.6% of the patients. APS symptoms resolved following immunotherapy. Logistic regression did not identify independent factors associated with the severity of APS. CONCLUSIONS: Our findings indicate that 18.3% of NMOSD patients developed APS during the follow-up period, with most patients fulfilling criteria for severe APS. The inflammatory activity decreased after the onset of APS compared to the previous year.

Dual role of signaling pathways in myeloma requires cell-type specific targeting of ligand-receptor interactions.

Although most patients with multiple myeloma respond to treatment initially, therapy resistance develops almost invariably and only a subset of patients show durable responses to immunomodulatory (IMiD) therapies. While the immune microenvironment has been extensively studied in myeloma patients, its composition is currently not used as prognostic markers in clinical routine. We hypothesized that the outcome of immune signaling pathway engagement can be highly variable, depending on which two cellular populations participate in this interaction. This would have important prognostic and therapeutic implications, suggesting that it is crucial for immune pathways to be targeted in a specific cellular context. To test this hypothesis, we investigated a cohort of 27 patients with newly diagnosed multiple myeloma. We examined the complex regulatory networks within the immune compartment and their impact on disease progression. Analysis of immune cell composition and expression profiles revealed significant differences in the B cell compartment associated with treatment response. Transcriptional states in patients with short time to progression demonstrated an enrichment of pathways promoting B cell differentiation and inflammatory responses, which may indicate immune dysfunction. Importantly, the analysis of molecular interactions within the immune microenvironment highlights the dual role of signaling pathways, which can either be associated with good or poor prognosis depending on the cell types involved. Our findings therefore argue that therapeutic strategies targeting ligand-receptor interactions should take into consideration the composition of the microenvironment and the specific cell types involved in molecular interactions.

Metabolomic and Lipidomic Tools for Tracing Fish Escapes from Aquaculture Facilities.

During adverse atmospheric events, enormous damage can occur at marine aquaculture facilities, as was the case during Storm Gloria in the southeastern Spanish Mediterranean in January 2020, with massive fish escapes. Fishes that escape were caught by professional fishermen. The objective of this study was to identify biomarkers in fish that enable differentiation among wild fish, escaped farm-raised fish, and farm-raised fish kept in aquaculture facilities until their slaughter. We focused on gilthead sea bream (Sparus aurata). We used nuclear magnetic resonance to search for possible biomarkers. We found that wild gilthead sea bream showed higher levels of taurine and trimethylamine-N-oxide (TMAO) in their muscle and higher levels of ω-3 fatty acids, whereas farm-escaped and farmed gilthead sea bream raised until slaughter exhibit higher levels of ω-6 fatty acids. From choline, carnitine, creatinine, betaine, or lecithin, trimethylamine (TMA) is synthesized in the intestine by the action of bacterial microflora. In the liver, TMA is oxidized to TMAO and transported to muscle cells. The identified biomarkers will improve the traceability of gilthead sea bream by distinguishing wild specimens from those raised in aquaculture.

Neural Computation-Based Methods for the Early Diagnosis and Prognosis of Alzheimer's Disease Not Using Neuroimaging Biomarkers: A Systematic Review.

Background: The growing number of older adults in recent decades has led to more prevalent geriatric diseases, such as strokes and dementia. Therefore, Alzheimer's disease (AD), as the most common type of dementia, has become more frequent too. Background: Objective: The goals of this work are to present state-of-the-art studies focused on the automatic diagnosis and prognosis of AD and its early stages, mainly mild cognitive impairment, and predicting how the research on this topic may change in the future. Methods: Articles found in the existing literature needed to fulfill several selection criteria. Among others, their classification methods were based on artificial neural networks (ANNs), including deep learning, and data not from brain signals or neuroimaging techniques were used. Considering our selection criteria, 42 articles published in the last decade were finally selected. Results: The most medically significant results are shown. Similar quantities of articles based on shallow and deep ANNs were found. Recurrent neural networks and transformers were common with speech or in longitudinal studies. Convolutional neural networks (CNNs) were popular with gait or combined with others in modular approaches. Above one third of the cross-sectional studies utilized multimodal data. Non-public datasets were frequently used in cross-sectional studies, whereas the opposite in longitudinal ones. The most popular databases were indicated, which will be helpful for future researchers in this field. Conclusions: The introduction of CNNs in the last decade and their superb results with neuroimaging data did not negatively affect the usage of other modalities. In fact, new ones emerged.

Burnout in Neurosurgery.

BACKGROUND: Burnout is a pervasive psychosocial syndrome that manifests as a chronic response to interpersonal stressors encountered in the occupational setting. Neurosurgeons exhibit a high prevalence rate of burnout, ranging from 33% to 67%. The primary objective of this study is to examine the prevalence of Burnout syndrome within the neurosurgical community and identify the contributing factors. METHODS: A prospective observational study was conducted utilizing an anonymous survey format, incorporating the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) questionnaire. Additional inquiries were made regarding demographic characteristics, occupational factors, lifestyle choices, and the Hospital Anxiety and Depression Scale (HADS) questionnaire. The survey was disseminated between March 23rd, 2023, and April 4th, 2023, utilizing the email registries of the Spanish Society of Neurosurgery (SENEC) and the Latin American Federation of Neurosurgical Societies (FLANC). Descriptive analysis was performed, comparing responses between participants with and without burnout syndrome using cross-tabulation and the Chi-square test to assess the presence of dependency. RESULTS: A total of 282 neurosurgeons completed the survey. The sample comprised 30.1% females and 69.9% males, with a median age within the 30-40 range. Among the surveyed neurosurgeons, 66.7% exhibited a prevalence of burnout, while 23.4% met the criteria for defined burnout. Significantly higher rates of burnout syndrome were observed among residents, specifically those in their fifth year of residency, as well as those whose departments perform a moderate range of surgeries (500-1000), participating in on-call duties, lacking regular physical exercise (at least twice a week), engaging infrequently in social activities with friends, lacking extracurricular hobbies, and obtaining scores exceeding 10 points in any of the HADS subscales. CONCLUSIONS: Burnout syndrome affects nearly a quarter of the neurosurgical specialists included in this study. Moreover, a distinct profile associated with defined burnout among neurosurgeons emerges, encompassing characteristics such as being a fifth-year resident, belongs to departments with a moderate number of surgeries, with few extra-occupational distractions and exhibiting symptoms of depression or anxiety.

Entrenamiento microneuroquirúrgico en el espécimen anatómico. Propuesta de un plan estructurado de disección endoscópica y microquirúrgica basicraneal durante la residencia / Microneurosurgical training in the anatomical specimen: A structured plan for endoscopic and microsurgical skull base training during the residency

Antecedentes y objetivo: El desarrollo de una elevada capacidad crítica y competencia técnica constituye uno de los objetivos principales de todo programa de formación en Neurocirugía. Por múltiples factores, esta adquisición progresiva de habilidades técnicas puede resultar compleja durante la residencia. A pesar de su elevado coste y necesidad de infraestructura, existe un interés renovado respecto al papel de los laboratorios de anatomía. El estudio y disección del espécimen anatómico ha sido el contexto donde muchos neurocirujanos han desarrollado y perfeccionado la técnica microneuroquirúrgica. Proponemos un plan estructurado de disección y entrenamiento endoscópico y microquirúrgico que permita al residente obtener el máximo provecho durante su estancia en un laboratorio.Material y métodosDurante los meses de septiembre, octubre y noviembre de 2021 se realizó una estancia en el Laboratorio de Microneurocirugía y Base Craneal de la Universidad Miguel Hernández de Alicante. Se emplearon un total de 2 especímenes formolados e inyectados con silicona roja y azul. En el primer espécimen se realizó una primera fase de disección endoscópica endonasal. Tras completar la fase endonasal se plantearon un conjunto de incisiones para realizar los abordajes transcraneales. En el segundo espécimen se realizó primero la parte transcraneal dejando el trabajo endoscópico endonasal para la segunda fase.ResultadosSe muestran los resultados de la disección de los 2 especímenes. Durante la fase endoscópica endonasal se simuló el abordaje transesfenoidal a la silla incidiendo sobre los abordajes extendidos en el plano sagital. Durante la fase transcraneal se realizaron abordajes anterolaterales derecho e izquierdo, un abordaje interhemisférico transcalloso anterior izquierdo, un abordaje posterolateral transcondilar izquierdo y un abordaje lateral derecho combinado. (AU)

Background and objective: The development of a high level of competence and technical proficiency is one of the main objectives of any neurosurgical training program. Due to many factors, this progressive skill development can be complex during the residency. Despite its high cost and infrastructure requirements, there is renewed interest regarding the role of anatomy labs. The study and dissection of the human cadaver has been the environment where many surgeons have developed the necessary skills for microneurosurgery. We propose a structured endoscopic and microsurgical training dissection program to enable residents to maximize the benefits of their training in the lab.Material and methodsDuring the months of September, October and November 2021, a stay was done at the Microneurosurgery and Skull Base Laboratory of the Miguel Hernández University of Alicante. A total of 2 specimens were used. The first specimen underwent a first endoscopic endonasal dissection phase. After completing the endonasal part, a set of incisions were made to perform the transcranial part. In the second specimen, the transcranial part was performed first, leaving the endonasal endoscopic work for the last phase.ResultsThe results of the dissection program are presented. During the endonasal endoscopic phase, the transsphenoidal approach to the sella was simulated while focusing on the extended approaches in the sagittal plane. During the transcranial phase, right and left anterolateral approaches, a left anterior transcallosal interhemispheric approach, a left transcondylar posterolateral approach and a combined right lateral approach were performed. (AU)

The Integration of 3D Virtual Reality and 3D Printing Technology as Innovative Approaches to Preoperative Planning in Neuro-Oncology.

Our study explores the integration of three-dimensional (3D) virtual reality (VR) and 3D printing in neurosurgical preoperative planning. Traditionally, surgeons relied on two-dimensional (2D) imaging for complex neuroanatomy analyses, requiring significant mental visualization. Fortunately, nowadays advanced technology enables the creation of detailed 3D models from patient scans, utilizing different software. Afterwards, these models can be experienced through VR systems, offering comprehensive preoperative rehearsal opportunities. Additionally, 3D models can be 3D printed for hands-on training, therefore enhancing surgical preparedness. This technological integration transforms the paradigm of neurosurgical planning, ensuring safer procedures.

Physical Therapist Interventions Versus or Combined with Surgical Treatment in Nontraumatic Degenerative Meniscal Pathology: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: This study aimed to synthesize the evidence from randomized clinical trials (RCTs) in people with nontraumatic degenerative meniscal pathology, comparing physical therapist interventions versus or combined with arthroscopic partial meniscectomy (APM). METHODS: Seven electronic databases were searched. Methodological quality was evaluated using the Physiotherapy Evidence Database scale. Data synthesis was performed with random-effects network meta-analysis, and results were summarized using the standardized mean differences. RESULTS: From 2103 studies, 10 RCTs comprising 1411 individuals were included. Ninety percent of the selected RCTs were classified as good quality according to the Physiotherapy Evidence Database scale. All interventions (physical therapist interventions, APM, and APM plus physical therapist interventions) showed reduced pain and physical impairments at 3 months follow-up. However, when a physical therapist intervention was included, greater reductions in pain at rest (APM versus physical therapist interventions: 0.73 [95% CI = 0.20 to 1.26]; APM versus APM plus physical therapist interventions: 0.59 [95% CI = 0.15 to 1.03]) and greater increases in the strength of knee extensor muscles (APM versus physical therapist interventions: 0.44 [95% CI = 0.07 to 0.80]; APM versus APM plus physical therapist interventions: 0.73 [95% CI = 0.29 to 1.16]) were observed at 3 months. In contrast, no differences were found between treatments beyond 3 months. CONCLUSIONS: Physical therapist interventions based on exercise programs demonstrate superior short-term outcomes in pain reduction and knee extensor strength compared to surgical treatment. IMPACT: For nontraumatic degenerative meniscal pathology, conservative treatment utilizing a physical therapist intervention approach should be prioritized as the first choice over surgical treatment. It offers comparable or superior short-term pain reduction and strength improvements, with a lower risk of side effects. In cases where surgery is deemed necessary, including postsurgical physical therapist interventions are highly recommended to enhance muscle strength and alleviate pain.

Does the distribution of musculoskeletal pain shape the fate of long-term sick leave? A prospective cohort study with register follow-up.

ABSTRACT: Although multisite pain can markedly reduce work ability, the relevance of the bodily pain distribution as a predictor of long-term sick leave is still unknown. This study aimed to investigate the association between musculoskeletal pain distributions and long-term sick leave in the general working population of Denmark and included 66,177 currently employed wage earners without long-term sick leave during the prior 52 weeks. Participants reported whether they had pain in the lower extremity (hips/knees), upper extremity (neck/shoulders), or the low back. The analysis controlled for age, sex, year of survey reply, educational level, occupational group, psychosocial work factors, body max index, smoking, leisure-time physical activity, and mental health confounders. The results demonstrated that the risk of long-term sick leave increased with the number of pain sites. Compared with no pain, localized pain in any body region increased the risk/hazard by 25% to 29% (HR [95% CI]: 1.29 [1.07-1.54] for pain only in the low back), whereas pain in 2 regions increased the risk by 39% to 44% (HR [95% CI]: 1.41 [1.18-1.69] for pain in the low back + hips/knees). Workers reporting pain in all 3 regions experienced a 72% increased risk (HR [95% CI]: 1.72 [1.55-1.91]). Thus, the number of pain regions seems to matter more than the exact pain location. The spatial extension of musculoskeletal pain in workers functions as a gradient system, where pain spread throughout the body is an independent indicator of the high risk of long-term sick leave.

Microneurosurgical training in the anatomical specimen: A structured plan for endoscopic and microsurgical skull base training during the residency.

BACKGROUND AND OBJECTIVE: The development of a high level of competence and technical proficiency is one of the main objectives of any neurosurgical training program. Due to many factors, this progressive skill development can be complex during the residency. Despite its high cost and infrastructure requirements, there is renewed interest regarding the role of anatomy labs. The study and dissection of the human cadaver has been the environment where many surgeons have developed the necessary skills for microneurosurgery. We propose a structured endoscopic and microsurgical training dissection program to enable residents to maximize the benefits of their training in the lab. MATERIAL AND METHODS: During the months of September, October and November 2021, a stay was done at the Microneurosurgery and Skull Base Laboratory of the Miguel Hernández University of Alicante. A total of 2 specimens were used. The first specimen underwent a first endoscopic endonasal dissection phase. After completing the endonasal part, a set of incisions were made to perform the transcranial part. In the second specimen, the transcranial part was performed first, leaving the endonasal endoscopic work for the last phase. RESULTS: The results of the dissection program are presented. During the endonasal endoscopic phase, the transsphenoidal approach to the sella was simulated while focusing on the extended approaches in the sagittal plane. During the transcranial phase, right and left anterolateral approaches, a left anterior transcallosal interhemispheric approach, a left transcondylar posterolateral approach and a combined right lateral approach were performed. CONCLUSIONS: The structured dissection of the specimen allowed both endonasal endoscopic and transcranial microsurgical training in the same specimen. This design facilitated the realization of the core skull base approaches in the same specimen. According to our initial experience, we believe that developing common dissection programs is a powerful tool to maximize the results of our residents' laboratory training.

Incidence of SARS-CoV-2 infection in patients with multiple sclerosis who received SARS-CoV-2 vaccines and are under treatment with high-efficacy therapies in Argentina.

We aimed to evaluate the incidence of SARS-CoV-2 breakthrough infection of SARS-CoV-2 vaccines in people with MS (PwMS) on high-efficacy disease-modifying therapies (HET) included in the national MS registry in Argentina (RelevarEM). METHODS: Non-interventional, retrospective cohort study that collected information directly from RelevarEM. Adult PwMS who had been treated for at least 6 months with a HET (ocrelizumab, natalizumab, alemtuzumab, cladribine) who had received at least two doses of SARS-CoV-2 vaccines available in Argentina were included. Full course of vaccination was considered after the second dose of the corresponding vaccines. Cumulative incidence of SARS-CoV-2 infection was reported for the whole cohort by Kaplan-Meier survival curves (which is expressed in percentage) as well as incidence density (which is expressed per 10.000 patients/day with 95% CI). RESULTS: Two hundred twenty-eight PwMS were included. Most frequent first and second dose received was AstraZeneca vaccine, followed by Sputnik vaccine. Most frequent HETs used in included patients were cladribine in 79 (34.8%). We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina. We described the incidence rate after vaccination for every HET used, it being significantly higher for ocrelizumab compared with other HETs (p = 0.005). Only five patients presented a relapse during the follow-up period with no differences regarding the pre-vaccination period. CONCLUSIONS: We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina.

Longitudinal Changes and Associations Between Quantitative Sensory Testing and Psychological Factors in Whiplash-Associated Disorders: A Systematic Review and Meta-Analyses-Based Data Synthesis.

Whiplash-associated disorders (WAD) represent a multifactorial condition often accompanied by altered nociceptive processing and psychological factors. This systematic review on acute and chronic WAD aimed to investigate the relationship between quantitative sensory testing (QST) and psychological factors and quantify whether their trajectories over time follow a similar pattern to disability levels. Eight databases were searched until October 2022. When 2 prospective studies examined the same QST or psychological variable, data synthesis was performed with random-effects meta-analysis by pooling within-group standardized mean differences from baseline to 3-, 6-, and 12-month follow-ups. From 5,754 studies, 49 comprising 3,825 WAD participants were eligible for the review and 14 for the data synthesis. Altered nociceptive processing in acute and chronic WAD, alongside worse scores on psychological factors, were identified. However, correlations between QST and psychological factors were heterogeneous and inconsistent. Furthermore, disability levels, some QST measures, and psychological factors followed general positive improvement over time, although there were differences in magnitude and temporal changes. These results may indicate that altered psychological factors and increased local pain sensitivity could play an important role in both acute and chronic WAD, although this does not exclude the potential influence of factors not explored in this review. PERSPECTIVE: Acute WAD show improvements in levels of disability and psychological factors before significant improvements in nociceptive processing are evident. Facilitated nociceptive processing might not be as important as psychological factors in chronic WAD-related disability, which indicates that chronic and acute WAD should not be considered the same entity although there are similarities. Nonetheless, pressure pain thresholds in the neck might be the most appropriate measure to monitor WAD progression.

Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies.

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon regeneration of peripheral nerves, where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers. Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632. Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity. In contrast, the same dose showed toxic effects on the regeneration of myelinated fibers. Interestingly, scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632. Overall, these findings confirm the in vivo participation of RhoA/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody. Our findings open the possibility of therapeutic pharmacological intervention targeting RhoA/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

The role of clinically relevant intra-abdominal collections after pancreaticoduodenectomy : Clinical impact and predictors. A retrospective analysis from a European tertiary centre.

BACKGROUND: There is controversial evidence regarding the impact of clinically relevant postoperative intra-abdominal collections (CR-IC) on the clinical course after pancreaticoduodenectomy. C-reactive Protein (CRP) has been validated as a predictor of postoperative pancreatic fistula (POPF). Still, its role in predicting CR-IC has not been studied. METHODS: A retrospective analysis was conducted on patients who underwent PD at a tertiary hospital between October 2012 and October 2017. The incidence of CR-IC, clinically relevant POPF and other complications, as well as mortality and length of hospitalisation, was retrieved. The impact of CR-IR on mortality and major complications was analysed. The serum CRP levels were retrieved on the third and fifth postoperative days (POD3 and POD5), followed by an analysis of sensitivity, specificity, and area under the curve to predict CR-IC using CRP. RESULTS: One hundred forty patients were enrolled following inclusion and exclusion criteria. The mean age was 66.5 years (15-83). The incidence of CR-IC was 33.7% (47), and CR-POPF was 24.3%. Pancreatic duct diameter ≤ 4 mm was identified as a risk factor related to CR-IC occurrence. The group of patients who developed CR-IC after PD exhibited a higher rate of complications Clavien-Dindo ≥ III compared to patients without CR-IC (40.4% vs 7.5%, p < 0.001), as well as other events such as admission to the intensive care unit (25.5% vs 4.3%, p < 0.001), the incidence of CR-POPF (66% vs 3.2%, p < 0.001), prolonged hospital stay (32 vs 13 days, p < 0.001), postoperative haemorrhage (23.4 vs 5.4%, p = 0.002), and delayed gastric empty (38.8% vs 11.8%, p < 0.001) respectively. Logistic regression analysis identified CR-IC related to POPF as a risk factor for Clavien-Dindo > III: OR = 10.6 (95% CI: 3.90-28.7). No differences in mortality were reported between the CR-IC group and non-CR-IC group. CRP at postoperative day 3 (POD3) > 17.55 mg/dl and CRP at postoperative day 5 (POD5) > 13.46 mg/dl were predictors of CR-IC (AUC: 0.731 and AUC:0.821, respectively). CONCLUSIONS: CR-IC has a significant impact after pancreaticoduodenectomy and is associated with a higher incidence of Clavien-Dindo ≥ III complications. Additionally, CRP levels at POD3 and POD5 play a role in predicting CR-IC. Prospective studies are essential to explore strategies for mitigating the occurrence of CR-IC after PD.

Robot-assisted implantation of a microelectrode array in the occipital lobe as a visual prosthesis: technical note.

The prospect of direct interaction between the brain and computers has been investigated in recent decades, revealing several potential applications. One of these is sight restoration in profoundly blind people, which is based on the ability to elicit visual perceptions while directly stimulating the occipital cortex. Technological innovation has led to the development of microelectrodes implantable on the brain surface. The feasibility of implanting a microelectrode on the visual cortex has already been shown in animals, with promising results. Current research has focused on the implantation of microelectrodes into the occipital brain of blind volunteers. The technique raises several technical challenges. In this technical note, the authors suggest a safe and effective approach for robot-assisted implantation of microelectrodes in the occipital lobe for sight restoration.

Mortality of neuromyelitis optica spectrum disorder patients in an Argentinean population: A study from the RelevarEM registry.

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75-2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients.