Evaluating the Effectiveness of Nirsevimab in Reducing Pediatric RSV Hospitalizations in Spain.

Background/Objectives: Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Nirsevimab has demonstrated to be a promising tool for preventing severe RSV disease. Although clinical trials have demonstrated the efficacy of Nirsevimab in preventing severe RSV disease, evidence regarding its performance in real-world clinical settings is still limited due to its recent introduction. This study aims to fill this knowledge gap by evaluating the impact of Nirsevimab in a cohort of infants and determining its effectiveness in reducing the burden of RSV disease. Methods: A retrospective study of RSV hospitalizations was conducted in children under six months of age, between 1 October and 31 March, across four seasons: pre-COVID (2018-2019), COVID (2019-2020), post-COVID pre-Nirsevimab (2022-2023), and Nirsevimab season (2023-2024). Results: Nirsevimab demonstrated significant efficacy in reducing RSV-related hospitalizations in infants under six months of age. During the 2023/2024 season, following the introduction of Nirsevimab, there was a substantial reduction in RSV-related lower respiratory tract infection (LRTI) hospitalizations. Among infants under 3 months of age, hospitalizations decreased by 79.3% (IRR: 0.21, 95% CI: 0.12-0.34). In infants aged 3 to 6 months, there was a 66.9% reduction (IRR: 0.33, 95% CI: 0.15-0.64). Additionally, Nirsevimab decreased the severity of RSV cases with LRTI who required the support of equipment for sanitary use, further reducing overall healthcare burden. Conclusions: These results underscore Nirsevimab's vital role in preventing severe RSV infections and hospitalizations, especially among the most vulnerable infants, positioning it as a critical advancement in pediatric respiratory care.

Virulence of Burkholderia pseudomallei ATS2021 Unintentionally Imported to United States in Aromatherapy Spray.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimABm allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

Synergistic antifungal activity against Candida albicans between voriconazole and cyclosporine a loaded in polymeric nanoparticles.

The goal of this work is to investigate if the synergistic antifungal activity between cyclosporine A, CsA, and voriconazole, VRZ, increases when both drugs are encapsulated in a nanocarrier as compared when they are free. The preparation and characterization of blank and VRZ and CsA loaded polymeric based PLGA nanoparticles (PLGA, PLGA-PEG, and PLGA+PEG) was a necessary previous step. Using the more suitable NPs, those of PLGA, the antifungal susceptibility tests performed with VRZ-loaded PLGA NPs, show no significant increase of the antifungal activity in comparison to that of free VRZ. However, the synergistic behavior found for the (VRZ+CsA)-loaded PLGA NPs was fourfold stronger than that observed for the two free drugs together. On the other hand, the investigation into the suppression of C. albicans biofilm formation showed that blank PLGA NPs inhibit the biofilm formation at high NPs concentrations. However, a minor effect or even a slight biofilm increase formation was observed at low and moderate NPs concentrations. Therefore, the enhancement of the biofilm inhibition found for the three tested treatments (CsA alone, VRZ alone, and VRZ+CsA) when comparing free and encapsulated drugs, within the therapeutic window, can be attributed to the drug encapsulation approach. Indeed, polymeric PLGA NPs loaded with CsA, VRZ, or VRZ+CsA are more effective at inhibiting the C. albicans biofilm growth than their free counterparts.

The Madrid Posterior Component Separation: An Anatomical Approach for Effective Reconstruction of Complex Midline Hernias.

Introduction: In recent years, Posterior Component Separation (PCS) with the Madrid modification (Madrid PCS) has emerged as a surgical technique. This modification is believed to enhance the dissection of anatomical structures, offering several advantages. The study aims to present a detailed description of this surgical technique and to analyse the outcomes in a large cohort of patients. Materials and Methods: This study included all patients who underwent the repair of midline incisional hernias, with or without other abdominal wall defects. Data from patients at three different centres specialising in abdominal wall reconstruction was analysed. All patients underwent the Madrid PCS, and several variables, such as demographics, perioperative details, postoperative complications, and recurrences, were assessed. Results: Between January 2015 and June 2023, a total of 223 patients underwent the Madrid PCS. The mean age was 63.4 years, with a mean BMI of 33.3 kg/m2 (range 23-40). According to the EHS classification, 139 patients had a midline incisional hernia, and 84 had a midline incisional hernia with a concomitant lateral incisional hernia. According to the Ventral Hernia Working Group (VHWG) classification, 177 (79.4%) patients had grade 2 and 3 hernias. In total, 201 patients (90.1%) were ASA II and III. The Carolinas Equation for Determining Associated Risks (CeDAR) was calculated preoperatively, resulting in 150 (67.3%) patients with a score between 30% and 60%. A total of 105 patients (48.4%) had previously undergone abdominal wall repair surgery. There were 93 (41.7%) surgical site occurrences (SSO), 36 (16.1%) surgical site infections (SSI), including 23 (10.3%) superficial and 7 (3.1%) deep infections, and 6 (2.7%) organ/space infections. Four (1.9%) recurrences were assessed by CT scan with an average follow-up of 23.9 months (range 6-74). Conclusion: The Madrid PCS appears to be safe and effective, yielding excellent long-term results despite the complexity of abdominal wall defects. A profound understanding of the anatomy is crucial for optimal outcomes. The Madrid modification contributes to facilitating a complete retromuscular preperitoneal repair without incision of the transversus abdominis. The extensive abdominal wall retromuscular dissection obtained enables the placement of very large meshes with minimal fixation.

Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis.

OBJECTIVE: To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis. METHODS: We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. RESULTS: We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12-0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11-0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. CONCLUSIONS: NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs.

Bridge bronchus and pulmonary artery sling: Case report and literature review.

We present the case of a 14-year-old adolescent boy with a history of poorly controlled asthma and a final diagnosis of a bridge bronchus associated with sling of the left pulmonary artery. Regarding the case report, we describe the characteristic findings in computerized tomography multidetector of the thorax, its classification, and the most relevant information about this malformation. Congenital malformations of the tracheobronchial tree may occur in the context of asymptomatic or symptomatic respiratory patients. These malformations may be associated with other vascular, tracheal, and syndromes with multiorgan involvement. Although most patients are asymptomatic, some of them will have nonspecific symptoms without a clear etiology or will be diagnosed incidentally during the diagnostic evaluation of other pathologies. It is important to know and recognize the normal anatomy and its variations, since radiology undoubtedly plays a fundamental role in the diagnosis and preoperative assessment of these malformations, which although they have low incidence, must be identified in a timely manner by the specialist in diagnostic images.

An atlas of cells in the human tonsil.

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.

Spatial-temporal risk factors in the occurrence of rabies in Mexico.

Rabies is a zoonotic disease that affects livestock worldwide. The distribution of rabies is highly correlated with the distribution of the vampire bat Desmodus rotundus, the main vector of the disease. In this study, climatic, topographic, livestock population, vampire distribution and urban and rural zones were used to estimate the risk for presentation of cases of rabies in Mexico by co- Kriging interpolation. The highest risk for the presentation of cases is in the endemic areas of the disease, i.e. the States of Yucatán, Chiapas, Campeche, Quintana Roo, Tabasco, Veracruz, San Luis Potosí, Nayarit and Baja California Sur. A transition zone for cases was identified across northern Mexico, involving the States of Sonora, Sinaloa, Chihuahua, and Durango. The variables topography, vampire distribution, bovine population and rural zones are the most important to explain the risk of cases in livestock. This study provides robust estimates of risk and spread of rabies based on geostatistical methods. The information presented should be useful for authorities responsible of public and animal health when they plan and establish strategies preventing the spread of rabies into rabies-free regions of México.

Recurrence after retromuscular repair or posterior components separation: How to address them. A retrospective multicentre cohort study.

Abdominal wall hernias are common entities that represent important issues. Retromuscular repair and component separation for complex abdominal wall defects are considered useful treatments according to both short and long-term outcomes. However, failure of surgical techniques may occur. The aim of this study is to analyze results of surgical treatment for hernia recurrence after prior retromuscular or posterior components separation. We have retrospectively reviewed patient charts from a prospectively maintained database. This study was conducted in three different hospitals of the Madrid region with surgical units dedicated to abdominal wall reconstruction. We have included in the database 520 patients between December 2014 and December 2021. Fifty-one patients complied with the criteria to be included in this study. We should consider offering surgical treatment for hernia recurrence after retromuscular repair or posterior components separation. However, the results might be associated to increased peri-operative complications.

SARS-CoV-2 Aerosol and Intranasal Exposure Models in Ferrets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the worldwide COVID-19 pandemic. Animal models are extremely helpful for testing vaccines and therapeutics and for dissecting the viral and host factors that contribute to disease severity and transmissibility. Here, we report the assessment and comparison of intranasal and small particle (~3 µm) aerosol SARS-CoV-2 exposure in ferrets. The primary endpoints for analysis were clinical signs of disease, recovery of the virus in the upper respiratory tract, and the severity of damage within the respiratory tract. This work demonstrated that ferrets were productively infected with SARS-CoV-2 following either intranasal or small particle aerosol exposure. SARS-CoV-2 infection of ferrets resulted in an asymptomatic disease course following either intranasal or small particle aerosol exposure, with no clinical signs, significant weight loss, or fever. In both aerosol and intranasal ferret models, SARS-CoV-2 replication, viral genomes, and viral antigens were detected within the upper respiratory tract, with little to no viral material detected in the lungs. The ferrets exhibited a specific IgG immune response to the SARS-CoV-2 full spike protein. Mild pathological findings included inflammation, necrosis, and edema within nasal turbinates, which correlated to positive immunohistochemical staining for the SARS-CoV-2 virus. Environmental sampling was performed following intranasal exposure of ferrets, and SARS-CoV-2 genomic material was detected on the feeders and nesting areas from days 2-10 post-exposure. We conclude that both intranasal and small particle aerosol ferret models displayed measurable parameters that could be utilized for future studies, including transmission studies and testing SARS-CoV-2 vaccines and therapeutics.

Glioblastoma cell fate is differentially regulated by the microenvironments of the tumor bulk and infiltrative margin.

Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states. However, bulk and margin have distinct biology. Injury-like programs associated with immune infiltration dominate in the bulk, leading to the generation of lowly proliferative injured neural progenitor-like cells (iNPCs). iNPCs account for a significant proportion of dormant GBM cells and are induced by interferon signaling within T cell niches. In contrast, developmental-like trajectories are favored within the immune-cold margin microenvironment resulting in differentiation toward invasive astrocyte-like cells. These findings suggest that the regional tumor microenvironment dominantly controls GBM cell fate and biological vulnerabilities identified in the bulk may not extend to the margin residuum.

Contextual fear response is modulated by M-type K+ channels and is associated with subtle structural changes of the axon initial segment in hippocampal GABAergic neurons.

Background: In the fear memory network, the hippocampus modulates contextual aspects of fear learning while mutual connections between the amygdala and the medial prefrontal cortex are widely involved in fear extinction. G-protein-coupled receptors (GPCRs) are involved in the regulation of fear and anxiety, so the regulation of GPCRs in fear signaling pathways can modulate the mechanisms of fear memory acquisition, consolidation and extinction. Various studies suggested a role of M-type K+ channels in modulating fear expression and extinction, although conflicting data prevented drawing of clear conclusions. In the present work, we examined the impact of M-type K+ channel blockade or activation on contextual fear acquisition and extinction. In addition, regarding the pivotal role of the hippocampus in contextual fear conditioning (CFC) and the involvement of the axon initial segment (AIS) in neuronal plasticity, we investigated whether structural alterations of the AIS in hippocampal neurons occurred during contextual fear memory acquisition and short-time extinction in mice in a behaviorally relevant context. Results: When a single systemic injection of the M-channel blocker XE991 (2 mg/kg, IP) was carried out 15 minutes before the foot shock session, fear expression was significantly reduced. Expression of c-Fos was increased following CFC, mostly in GABAergic neurons at day 1 and day 2 post-fear training in CA1 and dentate gyrus hippocampal regions. A significantly longer AIS segment was observed in GABAergic neurons of the CA1 hippocampal region at day 2. Conclusions: Our results underscore the role of M-type K + channels in CFC and the importance of hippocampal GABAergic neurons in fear expression.

Human Metapneumovirus Infections during COVID-19 Pandemic, Spain.

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.

Incisions in Hepatobiliopancreatic Surgery: Surgical Anatomy and its Influence to Open and Close the Abdomen.

Incisions performed for hepato-pancreatic-biliary (HPB) surgery are diverse, and can be a challenge both to perform correctly as well as to be properly closed. The anatomy of the region overlaps muscular layers and has a rich vascular and nervous supply. These structures are fundamental for the correct functionality of the abdominal wall. When performing certain types of incisions, damage to the muscular or neurovascular component of the abdominal wall, as well as an inadequate closure technique may influence in the development of long-term complications as incisional hernias (IH) or bulging. Considering that both may impair quality of life and that are complex to repair, prevention becomes essential during these procedures. With the currently available evidence, there is no clear recommendation on which is the better incision or what is the best method of closure. Despite the lack of sufficient data, the following review aims to correlate the anatomical knowledge learned from posterior component separation with the incisions performed in hepato-pancreatic-biliary (HPB) surgery and their consequences on incisional hernia formation. Overall, there is data that suggests some key points to perform these incisions: avoid vertical components and very lateral extensions, subcostal should be incised at least 2 cm from costal margin, multilayered suturing using small bites technique and consider the use of a prophylactic mesh in high-risk patients. Nevertheless, the lack of evidence prevents from the possibility of making any strong recommendations.