Multicentric Pediatric Stroke Code: Insight to the first years after implementation.

BACKGROUND: The development of unicentric pediatric acute stroke protocols has improved stroke diagnosis and treatment. The impact of the implementation of a multicentric Pediatric Stroke Code (PSC) remains unknown. AIM: to describe the characteristics of the PSC activations and identify clinical features associated with stroke compared to stroke mimics in children in whom a multicentric PSC had been activated and compare them to reported monocentric PSC results. METHODS: Observational, retrospective, case and control multicentric study, performed in the Pediatric Emergency Department (PED) of the three Primary Pediatric Stroke Centers (PPSCs) in Madrid (Spain). Study population corresponded to children between 28 days and 16 years old in whom PSC was activated that consulted or were referred to any of the PPSC PED between March 2019 and June 2022. The main outcome was to compare the characteristics of patients with final diagnosis of stroke versus stroke mimics, among all patients for which PSC had been activated. Logistic regression modeling was used to investigate associations between independent variables and stroke diagnosis. Odds ratio (ORs) and 95 % confidence intervals (95%CIs) were estimated. RESULTS: PSC was activated in 196 patients. Stroke was confirmed in 39 patients (19.9 %): 20 (10.2 %) had an ischemic stroke and 19 (9.7 %) a hemorrhagic stroke. Stroke mimics represented 80.1 % of the PSC activations. Migraine was the most frequent stroke mimic (38.3 %). Time from symptom onset to brain imaging was 233.00 min (IQR 153.00-373.00) when patients self-presented at the PPSC compared to 231.00 min (IQR 129.00-400.00) when PSC was triggered at other settings (p0.580). Five patients (25.3 %) were eligible for hyperacute recanalization treatment. Low level of consciousness (OR4.373, 95%IC 0.247-0.652, p < 0.001), sensory disruption/motor disability of face/limbs (OR3.633, 95%IC 0.103-0.349, p < 0.001), aphasia (OR2.311, 95%IC 0.023-0.284, p0.022) and altered mental status (OR2.517, 95%IC 0.043-0.357, p0.013) were associated with an increased probability of stroke. CONCLUSION: multicentric PSC achieved similar results to previously reported unicentric PSCs, showing the feasibility of such an organization.

Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.

BACKGROUND: Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment. OBJECTIVES: This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction. METHODS: In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity). RESULTS: A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity. CONCLUSION: This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS.

Toxicological Evaluation of Kaempferol and Linearolactone as Treatments for Amoebic Liver Abscess Development in Mesocricetus auratus.

Several studies with kaempferol (KP) and linearolactone (LL) have demonstrated their antiparasitic activity. However, the toxicity of these treatments is unknown. Therefore, this study aimed to evaluate the possible toxicological effects of intraperitoneal (i.p.) administration of KP or LL on the amoebic liver abscess model (ALA) in Mesocricetus auratus. An ALA was induced in male hamsters with 1.5 × 105Entamoeba histolytica (E. histolytica) trophozoites inoculated in the left hepatic lobe. The lesion evolved for 4 days, and then KP (5 mg/kg body weight/day) or LL (10 mg/kg body weight/day) was administered for 4 consecutive days. Then, magnetic resonance imaging (MRI), paraclinical analyses, and necropsy for histopathological evaluation were performed. There was similar ALA inhibition by KP (19.42%), LL (28.16%), and metronidazole, the antiamoebic control (20.87%) (p ≤ 0.05, analysis of variance [ANOVA]). There were hepatic and renal biochemical alterations in all treatment groups, mainly for KP (aspartate aminotransferase: 347.5 ± 37.5 U/L; blood urea nitrogen: 19.4 ± 1.9 g/dL; p ≤ 0.05, ANOVA). Lesions found in the organs were directly linked to the pathology. In conclusion, KP and LL decreased ALA development and exerted fewer toxicological effects compared with metronidazole. Therefore, both compounds exhibit therapeutic potential as an alternative treatment of amoebiasis caused by E. histolytica. However, additional clinical studies in different contexts are required to reaffirm this assertion.

Eco-friendly technologies for obtaining antioxidant compounds and protein hydrolysates from edible insect Tenebrio molitor beetles.

The functional properties of edible insects can be explored by a joint use of novel technologies. This work applied varied pre-treatments (ultra-sound-assisted extraction, UAE; microwave-assisted extraction, MAE; temperature-assisted extraction, TAE; CO2-assisted extraction) and solvents (water, ethanol, water:ethanol) in Tenebrio molitor beetles to enhance the extraction of phenolic compounds with antioxidant activity. An enzymatic hydrolysis (EH) was performed in wet and treated biomasses to determine the protein hydrolysis. Higher phenolic compounds and antioxidant activity was released after MAE using water as solvent compared to the other treatments and solvents. Treatments decreased 32 %, 19 % and 30 % the protein, chitin and lipids content. EH improved protein and amino acids hydrolysis in the MAE-treated insects, followed by UAE and TAE treatments. In conclusion, MAE was the most effective to release phenolics and antioxidant activity from T. molitor beetles, while using MAE followed by EH improved protein and amino acids hydrolysis, envisioning valuable applications for this insect biomass.

Bilateral pulvinar responsive neurostimulation for bilateral multifocal posteriorly dominant drug resistant epilepsy.

OBJECTIVE: To describe four cases of Responsive Neurostimulation (RNS) in the bilateral pulvinar nuclei (PUL) in individuals with drug resistant epilepsy (DRE). This will show that due to widespread PUL connectivity, bilateral PUL RNS may be an option for some individuals with bilateral multifocal epilepsy. METHODS: This study comprises two centers' experience with bilateral PUL RNS for DRE. Patients treated with bilateral PUL RNS at Westchester Medical Center (Valhalla, NY) and Corewell Health (Grand Rapids, MI) between the years 2019 and 2022 were analyzed and described. Presented here are methods for target selection, device programming, and clinical outcomes. RESULTS: Two patients with Lennox-Gastaut phenotype (aged 13 and 21 years) with posteriorly dominant discharges were implanted with bilateral PUL electrodes. Additionally, two patients (aged 20 and 31 years) with independent left and right occipital bilateral multifocal seizure onsets were implanted with bilateral RNS devices targeting the ipsilateral PUL and ipsilateral occipital cortex. Subclinical and clinical seizures were captured by RNS electrocorticography (ECoG) in all patients. RNS implantation and treatment was well-tolerated without adverse effects in all patients. Relative to baseline, two patients had 25% and 50% reduction in disabling seizures, and two patients had 71% and 100% reduction in disabling seizures. Stimulation paradigms utilized high frequency stimulation in both Lennox-Gastaut phenotype patients. Low frequency (individualized to the terminal ictal frequencies) stimulation was effective in the two bioccipital patients. SIGNIFICANCE: RNS with electrode placement targeting bilateral PUL is safe, and no adverse effects have been attributable to the pulvinar electrode placement. PUL responsive neurostimulation is potentially effective for patients with bilateral multifocal, posteriorly dominant DRE. Both high and low frequency responsive stimulation are treatment options. Longer follow-up will shed light on the ultimate reduction of seizure burden. PLAIN LANGUAGE SUMMARY: We describe four cases where stimulation devices were placed in the Pulvinar area of the thalamus (central sensory area in the brain). This is very unique and different location than where these devices are typically placed. These patients all had great outcomes with marked seizure reduction, demonstrating that this placement is both safe and effective.

Intensive care unit patients' experiences of receiving music therapy sessions during invasive procedures: A qualitative phenomenological study.

BACKGROUND: Excessive noise in intensive care units poses a significant challenge, impacting both patients and staff by elevating stress, disrupting recovery, and impeding effective communication among healthcare professionals. Despite the World Health Organization recommending noise levels below 35 dB, alarms in these units often surpass these limits, contributing to consistently high noise levels. OBJECTIVES: The aim of this study is to explore intensive care unit patients' experiences with music therapy sessions during invasive procedures. METHODS: This study was conducted using a qualitative hermeneutic phenomenological methodology grounded in Heideggerian philosophy. Interventions were conducted with a music therapist, and 14 in-depth interviews were collected. Reflexive inductive thematic analysis was performed. RESULTS/FINDINGS: From the thematic analysis extracted from the 14 personal interviews, three themes were described that represent the bulk of the experiences and emotions of the study participants following the completion of the music therapy sessions. The most noteworthy results are described in the following, organised according to each theme: (i) music therapy against noise, sounds, and light; (ii) music therapy in the face of invasive tests and techniques; and (iii) music therapy as a strategy and tool. CONCLUSIONS: Music therapy has significant potential to enhance the quality of life for patients in the intensive care unit. Music therapy can promote relaxation, reduce stress and anxiety, alleviate pain and discomfort, and improve emotional and physical wellbeing during patients' stay and invasive procedures.

Inpatient Outcomes of Cerebral Venous Thrombosis in Patients With Malignancy Throughout the United States.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is associated with a high degree of morbidity and mortality. Our objective is to elucidate characteristics, treatments, and outcomes of patients with cancer and CVT (CA-CVT). METHODS: The 2016-2019 National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of CVT. Patients with a currently active diagnosis of malignancy (CA-CVT) were then identified. Demographics and comorbidities were compared between CA-CVT and CVT patients. Subgroup analyses explored patients with hematopoietic cancer and non-hematopoietic cancers. Stroke severity and treatment were explored. Inpatient outcomes studied were discharge disposition, length of stay, and mortality. RESULTS: Between 2016 and 2019, 6,140 patients had a primary diagnosis code of CVT, and 370 (6.0%) patients had a coexisting malignancy. The most common malignancy was hematopoietic (n=195, 52.7%), followed by central nervous system (n=40, 10.8%), respiratory (n=40, 10.8%), and breast (n=40, 10.8%). These patients tended to be older than non-CA-CVT and were more likely to have coexisting comorbidities. CA-CVT patients had higher severity scores on the International Study of Cerebral Vein and Dural Sinus Thrombosis Risk Score (ISCVT-RS) and increased complications. In a propensity-score matched cohort, there were no differences in inpatient outcomes. CONCLUSION: Malignancy occurs in 6% of patients presenting with CVT and should be considered a potential comorbidity in instances where clear causes of hypercoagulabilty have not been identified. Malignancy was linked to higher mortality rates. Nonetheless, after adjusting for the severity of CVT, the outcomes for inpatients with cancer-associated CVT were comparable to those without cancer, indicating that the increased mortality associated with malignancy is probably due to more severe CVT conditions.

Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Does serum neurofilament light chain measurement influence therapeutic decisions in multiple sclerosis?

BACKGROUND: The assessment of serum neurofilament light chain (sNfL) concentration in multiple sclerosis (MS) is a useful tool for predicting clinical outcomes and assessing treatment response. However, its use in clinical practice is still limited. We aimed to assess how measurement of sNfL influences neurologists' treatment decisions in MS. METHODS: We conducted a cross-sectional, web-based study in collaboration with the Spanish Society of Neurology. Neurologists involved in MS care were presented with different simulated case scenarios of patients experiencing either their first demyelinating MS event or a relapsing-remitting MS. The primary outcome was therapeutic inertia (TI), defined as the absence of treatment initiation or intensification despite elevated sNfL levels. Nine cases were included to estimate the TI score (range 0-9, where higher values represented a higher degree of TI). RESULTS: A total of 116 participants were studied. Mean age (standard deviation-SD) was 41.9 (10.1) years, 53.4 % male. Seventy-eight (67.2 %) were neurologists fully dedicated to the care of demyelinating disorders. Mean (SD) TI score was 3.65 (1.01). Overall, 92.2 % of participants (n = 107) presented TI in at least 2/9 case scenarios. The lack of full dedication to MS care (p = 0.014), preference for taking risks (p = 0.008), and low willingness to adopt evidence-based innovations (p = 0.009) were associated with higher TI scores in the multivariate analysis after adjustment for confounders. CONCLUSION: TI was a common phenomenon among neurologists managing MS patients when faced with the decision to initiate or escalate treatment based on elevated sNfL levels. Identifying factors associated with this phenomenon may help optimize treatment decisions in MS care.

Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center.

INTRODUCTION: Pediatric thyroid nodules exhibit higher malignancy rates compared to adults and are associated with increased incidences of metastases and recurrences. The American Thyroid Association recommends surgery for indeterminate thyroid biopsies in children based on these higher malignancy risks, though this approach may lead to overtreatment. However, there remains a lack of comprehensive pediatric data to inform clinical decisions. This study examines the risk of malignancy (ROM) in pediatric thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and assesses the diagnostic accuracy of fine-needle aspiration (FNA) biopsy compared to histological outcomes. METHODS: A retrospective cross-sectional analysis was performed on patients under 19 years with thyroid nodules who underwent FNA and thyroidectomy at a tertiary care center. The sensitivity, specificity, positive predictive value, negative predictive value, and ROM of cytological biopsies were evaluated using TBSRTC criteria, with histology serving as the gold standard. Two analyses were conducted to assess diagnostic accuracy: (a) TBSRTC II as negative and TBSRTC VI as positive and (b) TBSRTC II as negative with TBSRTC V and VI as positive. For neoplasia detection, TBSRTC II was deemed negative, while TBSRTC IV, V, and VI were considered positive. TBSRTC categories III and I were excluded from the performance analysis and evaluated separately. Follicular neoplasm or lesions suspicious for follicular neoplasm (FN/SFN) were treated as positive outcomes, correlated with the presence of adenoma or carcinoma in the surgical specimen. RESULTS: Of 75 nodules from 73 patients, 28 (37.3%) were benign and 47 (62.6%) malignant. No significant differences in gender or age were noted between groups. The ROM in each TBSRTC was Bethesda I 0/2, 0%; II 0/13, 0%; III 2/7, 29%: IV 6/14, 43%; V 10/10, 100%, and VI 29/29, 100%. A sensitivity of 78.38% and specificity of 100% for FNA in detecting malignancy was found, with an even higher sensitivity (100%) for detecting neoplasia in TBSRTC IV. CONCLUSIONS: This study reveals that indeterminate thyroid nodules in pediatric patients exhibit a higher rate of malignancy compared to adults, yet align with rates previously reported in the pediatric population. These findings highlight the critical need for guidelines tailored specifically to the management of thyroid nodules and thyroid cancer in children.

A Multi-Target Pharmacological Correction of a Lipoyltransferase LIPT1 Gene Mutation in Patient-Derived Cellular Models.

Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.

Smouldering-Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions.

Despite therapeutic suppression of relapses, multiple sclerosis (MS) patients often experience subtle deterioration, which extends beyond the definition of "progression independent of relapsing activity." We propose the concept of smouldering-associated-worsening (SAW), encompassing physical and cognitive symptoms, resulting from smouldering pathological processes, which remain unmet therapeutic targets. We provide a consensus-based framework of possible pathological substrates and manifestations of smouldering MS, and we discuss clinical, radiological, and serum/cerebrospinal fluid biomarkers for potentially monitoring SAW. Finally, we share considerations for optimizing disease surveillance and implications for clinical trials to promote the integration of smouldering MS into routine practice and future research efforts. ANN NEUROL 2024;96:826-845.

Exploring Synthesis Strategies and Interactions between MOFs and Drugs for Controlled Drug Loading and Release, Characterizing Interactions through Advanced Techniques.

This study explores various aspects of Metal-Organic Frameworks (MOFs), focusing on synthesis techniques to adjust pore size and key ligands and metals for crafting carrier MOFs. It investigates MOF-drug interactions, including hydrogen bonding, van der Waals, and electrostatic interactions, along with kinetic studies. The multifaceted applications of MOFs in drug delivery systems are elucidated. The morphology and structure of MOFs are intricately linked to synthesis methodology, impacting attributes like crystallinity, porosity, and surface area. Hydrothermal synthesis yields MOFs with high crystallinity, suitable for catalytic applications, while solvothermal synthesis generates MOFs with increased porosity, ideal for gas and liquid adsorption. Understanding MOF-drug interactions is crucial for optimizing drug delivery, affecting charge capacity, stability, and therapeutic efficacy. Kinetic studies determine drug release rates and uniformity, vital for controlled drug delivery. Overall, comprehending drug-MOF interactions and kinetics is essential for developing effective and controllable drug delivery systems.

The role of duty, gender and intergenerational care in grandmothers' parenting of grandchildren: a phenomenological qualitative study.

OBJECTIVES: The aim of this study was to describe grandmothers' experiences of taking care of their grandchildren in terms of their care-giving tasks, motivations and emotions. METHODS: A qualitative phenomenological study was conducted. Purposive sampling was used, based on the relevance of the research question. Seventeen participants were included, women ≥ 65 years old, grandmothers who care for their grandchildren at least 10 h per week and who attended the Nursing units of the Primary Care Health Centers (Madrid Public Health Service). Seventeen in-depth interviews were conducted. The interviews were audio-recorded, transcribed verbatim and thematic analysis was carried out from the perspective of hermeneutic phenomenology. For the analysis, the Excel program was used to organize and share the coding process. Also, we followed COREQ guidelines. RESULTS: Four main themes were identified: (a) Care out of obligation, where participants feel an obligation to help their children by caring for grandchildren, regardless of their number, and prefer to do so voluntarily; (b) Care out of responsibility, where grandmothers see their role as a responsibility that includes saving costs by caring for grandchildren and facilitating their children's work life balance; (c) Care as a social duty, reflecting a moral commitment inherited from their mothers to help future generations; and (d) Construction of care from a gender perspective, where grandmothers, as women, primarily assume the care and upbringing of grandchildren. DISCUSSION: Our results contribute to increase knowledge about childcare provided by grandmothers to their grandchildren. Grandmothers become fundamental pillars of families by helping their children balance family and work. Behind this care there is a strong sense of obligation, duty and generational responsibility. Grandmothers' help presents differences in the distribution of tasks and care by sex. Identifying factors that motivate grandmothers to care for their grandchildren helps nurses to perform higher quality comprehensive care.

Rheumatoid meningitis: a case series report and review of modern therapeutic schemes and outcome.

INTRODUCTION: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. METHODS: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. RESULTS: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. CONCLUSIONS: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended.

Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer.

The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan-Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11-3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11-3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials.

Establishing Normal Serum Values of Neurofilament Light Chains and Glial Fibrillary Acidic Protein Considering the Effects of Age and Other Demographic Factors in Healthy Adults.

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

Impact of nirsevimab immunization on RSV infections attended in the pediatric emergency department: First results in a tertiary hospital in Madrid.

INTRODUCTION: Human respiratory syncytial virus (RSV) is the most commonly identified virus associated with lower respiratory tract infections. The monoclonal antibody nirsevimab immunization campaign began in our country in October 2023. METHODS: This study was conducted in the Pediatric Emergency Department (PED) of a tertiary care center in Madrid, Spain. The aim was to compare PED visits of patients eligible for immunization with nirsevimab who attended between weeks 40 and 52 of 2022 and 2023 and who had a confirmed diagnosis of RSV infection. RESULTS: During the study period, 264 out of 765 patients with confirmed RSV infection who attended the PED were eligible for immunization with nirsevimab and were selected for our analysis. The PED attendance was 80.3% in 2022 and 19.7% in 2023. The number of RSV-positive cases increased from week 42 in both analyzed periods, with a peak of maximum incidence between weeks 46 and 48. In 2022, the morphology of the case curve in the group of children eligible for immunization was similar to the overall curve. However, in 2023, we did not observe a similar increase in cases among patients eligible for immunization. CONCLUSION: Immunization with nirsevimab during the 2023 RSV epidemic season had a beneficial effect, reducing the number of PED consultations for RSV infection.

Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.