Surgery versus endovascular treatment for spinal dural arteriovenous fistulas: a multicenter experience and systematic literature review.

Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications.

The tiny giant of the sea, Ostreococcus's unique adaptations.

Ostreococcus spp. are unicellular organisms with one of the simplest cellular organizations. The sequencing of the genomes of different Ostreococcus species has reinforced this status since Ostreococcus tauri has one most compact nuclear genomes among eukaryotic organisms. Despite this, it has retained a number of genes, setting it apart from other organisms with similar small genomes. Ostreococcus spp. feature a substantial number of selenocysteine-containing proteins, which, due to their higher catalytic activity compared to their selenium-lacking counterparts, may require a reduced quantity of proteins. Notably, O. tauri encodes several ammonium transporter genes, that may provide it with a competitive edge for acquiring nitrogen (N). This characteristic makes it an intriguing model for studying the efficient use of N in eukaryotes. Under conditions of low N availability, O. tauri utilizes N from abundant proteins or amino acids, such as L-arginine, similar to higher plants. However, the presence of a nitric oxide synthase (L-arg substrate) sheds light on a new metabolic pathway for L-arg in algae. The metabolic adaptations of O. tauri to day and night cycles offer valuable insights into carbon and iron metabolic configuration. O. tauri has evolved novel strategies to optimize iron uptake, lacking the classic components of the iron absorption mechanism. Overall, the cellular and genetic characteristics of Ostreococcus contribute to its evolutionary success, making it an excellent model for studying the physiological and genetic aspects of how green algae have adapted to the marine environment. Furthermore, given its potential for lipid accumulation and its marine habitat, it may represent a promising avenue for third-generation biofuels.

The Role of Magnetic Resonance Imaging in Cardiomyopathies in the Light of New Guidelines: A Focus on Tissue Mapping.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review.

Background: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results: Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral (n = 8, 44.4%), followed by clivus (n = 7, 38.9%) and lumbar spine (n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery (n = 10, 55.6%), RT (n = 9, 50.0%), and systemic treatments (n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions: This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.

Bloodless Gynecological Surgery in Blood Products Refusing Patients: Experience of a Single Institution.

Propose: This pilot study aimed to apply the central tenets of bloodless surgery and to analyze the effectiveness of specific preoperative, intraoperative, and postoperative strategies to minimize the risk for blood transfusion after gynecological surgery in a specific group of patients who refused blood products. Methods: A total of 83 patients undergoing gynecological surgery were included in the study. Forty-two patients received preoperatively oral iron, acid folic, and vitamin B12 supplementation in the 30 days before surgery, and 41 patients did not receive therapy. Results: No significant differences were found when comparing the two study groups. The implementation of all procedures to maintain a bloodless surgery has been helpful, in association with the other available procedures, in achieving optimal management and maintenance of hemoglobin levels, even in the most critical situations. Conclusion: In conclusion, implementing the bloodless approach as much as possible could guarantee the patient better and safer clinical and care management. Furthermore, well-designed research is required to clarify further the effects of bloodless surgery in gynecological patients.

Current status and future perspectives on stem cell transplantation for spinal cord injury.

BACKGROUND: Previous assessments of stem cell therapy for spinal cord injuries (SCI) have encountered challenges and constraints. Current research primarily emphasizes safety in early-phase clinical trials, while systematic reviews prioritize effectiveness, often overlooking safety and translational feasibility. This situation prompts inquiries regarding the readiness for clinical adoption. AIM: To offer an up-to-date systematic literature review of clinical trial results con cerning stem cell therapy for SCI. METHODS: A systematic search was conducted across major medical databases [PubMed, Embase, Reference Citation Analysis (RCA), and Cochrane Library] up to October 14, 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "spinal cord", "injury", "clinical trials", "stem cells", "functional outcomes", and "adverse events". Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI. RESULTS: In a comprehensive review of 66 studies on stem cell therapies for SCI, 496 papers were initially identified, with 237 chosen for full-text analysis. Among them, 236 were deemed eligible after excluding 170 for various reasons. These studies encompassed 1086 patients with varying SCI levels, with cervical injuries being the most common (42.2%). Bone marrow stem cells were the predominant stem cell type used (71.1%), with various administration methods. Follow-up durations averaged around 84.4 months. The 32.7% of patients showed functional impro vement from American spinal injury association Impairment Scale (AIS) A to B, 40.8% from AIS A to C, 5.3% from AIS A to D, and 2.1% from AIS B to C. Sensory improvements were observed in 30.9% of patients. A relatively small number of adverse events were recorded, including fever (15.1%), headaches (4.3%), muscle tension (3.1%), and dizziness (2.6%), highlighting the potential for SCI recovery with stem cell therapy. CONCLUSION: In the realm of SCI treatment, stem cell-based therapies show promise, but clinical trials reveal potential adverse events and limitations, underscoring the need for meticulous optimization of transplantation conditions and parameters, caution against swift clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before gradual and careful adoption in clinical practice.

Current and Future Applications of Arterial Spin Labeling MRI in Cerebral Arteriovenous Malformations.

Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment.

Comparative Efficacy of Transsphenoidal and Transcranial Approaches for Treating Tuberculum Sellae Meningiomas: A Systematic Review and Meta-Analysis.

Background/Objectives: Tuberculum sellae meningiomas (TSMs) constitute 5-10% of intracranial meningiomas, often causing visual impairment. Traditional microsurgical transcranial approaches (MTAs) have been effective, but the emergence of innovative surgical trajectories, such as endoscopic endonasal approaches (EEAs), has sparked debate. While EEAs offer advantages like reduced brain retraction, they are linked to higher cerebrospinal fluid leak (CSF leak) risk. This meta-analysis aims to comprehensively compare the efficacy and safety of EEAs and MTAs for the resection of TSMs, offering insights into their respective outcomes and complications. Methods: A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on TSMs treated with either EEA or MTA until 2024. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications. Results: A total of 291 papers were initially identified, of which 18 studies spanning from 2000 to 2024 met the inclusion criteria. The exclusion of 180 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and a lack of details on method/results. The 18 studies comprised a total sample of 1093 patients: 444 patients who underwent EEAs and 649 patients who underwent MTAs for TSMs. Gross total resection (GTR) rates ranged from 80.9% for EEAs to 79.8% for MTAs. The rate of visual improvement was 86.6% in the EEA group and 65.4% in the MTA group. The recurrence rate in the EEA group was 6.9%, while it was 5.1% in MTA group. The postoperative complications analyzed were CSF leak, infections, dysosmia, intracranial hemorrhage (ICH), and endocrine disorders. The rate of CSF leak was 9.8% in the EEA group and 2.1% in MTA group. The rate of infections in the EEA group was 5.7%, while it was 3.7% in the MTA group. The rate of dysosmia ranged from 10.3% for MTAs to 12.9% for EEAs. The rate of ICH in the EEA group was 0.9%, while that in the MTA group was 3.8%. The rate of endocrine disorders in the EEA group was 10.8%, while that in the MTA group was 10.2%. No significant difference was detected in the rate of GTR between the EEA and MTA groups (OR 1.15, 95% CI 0.7-0.95; p = 0.53), while a significant benefit in visual outcomes was shown in EEAs (OR 3.54, 95% CI 2.2-5.72; p < 0.01). There was no significant variation in the recurrence rate between EEA and MTA groups (OR 0.92, 95% CI 0.19-4.46; p = 0.89). While a considerably increased chance of CSF leak from EEAs was shown (OR 4.47, 95% CI 2.52-7.92; p < 0.01), no significant difference between EEA and MTA groups was detected in the rate of infections (OR 1.92, 95% CI 0.73-5.06; p = 0.15), the rate of dysosmia (OR 1.25, 95% CI 0.31-4.99; p = 0.71), the rate of ICH (OR 0.61, 95% CI 0.20-1.87; p = 0.33), and the rate of endocrine disorders (OR 1.16, 95% CI 0.69-1.95; p = 0.53). Conclusions: This meta-analysis suggests that both EEAs and MTAs are viable options for TSM resection, with distinct advantages and drawbacks. The EEAs demonstrate superior visual outcomes in selected cases while GTR and recurrence rates support the overall effectiveness of MTAs and EEAs. Endoscopic endonasal approaches had a higher chance of CSF leaks, but there are no appreciable variations in other complications. These results provide additional insights regarding patient outcomes in the intricate clinical setting of TSMs.

Size-tunable silicon nanoparticles synthesized in solution via a redox reaction.

A current challenge in silicon chemistry is to perform liquid-phase synthesis of silicon nanoparticles, which would permit the use of colloidal synthesis techniques to control size and shape. Herein we show how silicon nanoparticles were synthesized at ambient temperature and pressure in organic solvents through a redox reaction. Specifically, a hexacoordinated silicon complex, bis(N,N'-diisopropylbutylamidinato)dichlorosilane, was reduced by a silicon Zintl phase, sodium silicide (Na4Si4). The resulting silicon nanoparticles were crystalline with sizes tuned from a median particle diameter of 15 nm to 45 nm depending on the solvent. Photoluminescence measurements performed on colloidal suspensions of the 45 nm diameter silicon nanoparticles indicated a blue emission signal, attributed to the partial oxidation of the Si nanocrystals or to the presence of nitrogen impurities.

Milk and Lacticaseibacillus casei BL23 effects on intestinal responses in a murine model of colitis.

Probiotic-containing fermented dairy foods have the potential to benefit human health, but the importance of the dairy matrix for efficacy remains unclear. We investigated the capacity of Lacticaseibacillus casei BL23 in phosphate-buffered saline (BL23-PBS), BL23-fermented milk (BL23-milk), and milk to modify intestinal and behavioral responses in a Dextran Sodium Sulfate (DSS, 3% w/v) mouse model of colitis. Significant sex-dependent differences were found such that female mice exhibited more severe colitis, greater weight loss, and higher mortality rates. Sex differences were also found for ion transport ex vivo, colonic cytokine and tight junction gene expression, and fecal microbiota composition. Measurements of milk and BL23 effects showed BL23-PBS consumption improved weight recovery in females, while milk resulted in better body weight recovery in males. Occludin and Claudin-2 gene transcript levels indicated barrier function was impaired in males, but BL23-milk was still found to improve colonic ion transport in those mice. Pro-inflammatory and anti-inflammatory gene expression levels were increased in both male and female mice fed BL23, and to a more variable extent, milk, compared to controls. The female mouse fecal microbiota contained high proportions of Akkermansia (average of 18.1%) at baseline, and females exhibited more changes in gut microbiota composition following BL23 and milk intake. Male fecal microbiota harbored significantly more Parasutterella and less Blautia and Roseburia after DSS treatment, independent of BL23 or milk consumption. These findings show the complex interplay between dietary components and sex-dependent responses in mitigating inflammation in the digestive tract.

Laparoscopic right colectomy: correct technique based on key anatomical principles.

Since the early1990s, laparoscopic right colon resections have been the most performed advanced laparoscopic procedures just after laparoscopic left colectomies and sigmoid resections. Indications for laparoscopic right colectomies are either benign or malignant diseases. Despite its many indications, a laparoscopic right or extended right colectomy is mostly performed for cancer of the caecum, the ascending colon, the hepatic flexure or the proximal transverse colon. Worldwide, colorectal cancer is the third most diagnosed cancer: an estimated 1,880,725 people were diagnosed with colorectal cancer in 2020, out of which 1,148,515 were colon cancer cases and 40% were located in the right colon. These figures make an oncologic sound surgery for right colon cancer of the utmost relevance. More recently, complete mesocolic excision has been advocated as the optimal choice in term of radicality, especially in node-positive patients with right colon cancer. Laparoscopic standard right colectomy and extended right colectomy with or without CME should be performed according to defined principles based on a close knowledge of key anatomical landmarks. This knowledge will allow to trace anatomical structures and drive instruments along the correct surgical planes and has its foundations in teachings from surgeons and scientists of past and present time.

Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies.

BACKGROUND: Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance. METHODS: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects. RESULTS: Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-ß) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%). CONCLUSIONS: The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.

Failure to reduce benzodiazepine prescriptions through the implementation of a psychological intervention for insomnia in an Italian mental health service.

PURPOSE: Despite the evidence of higher effectiveness of psychological interventions for insomnia compared to pharmacological ones, drug prescriptions for insomnia remain frequent. This study has assessed patterns of prescriptions of BZDs for insomnia before and after the delivery of a training in psychological interventions to professionals working in the services of a Department of Mental Health in northern Italy. METHODS: The intervention consisted in two training sessions about psychological interventions for insomnia delivered to professionals of the participating services. The prevalence of users with a prescription of BZDs for insomnia in an index period after the delivery of the training was compared to the prevalence in an index period before the training. RESULTS: Among 727 people assessed for BZDs prescription at pre-intervention, 306 (42.1%, 95% CI 0.39-0.46) had a prescription, and 344 (49.2%, 95% CI 0.45-0.53) had a prescription among 699 people assessed at post-intervention, corresponding to a significant odds ratio of 1.33 to be prescribed with BZDs in the second index period compared to the first one. Psychological interventions were offered to a small group of patients. CONCLUSION: Prescribing attitudes of BZDs for insomnia were not modified after the training and delivery of a psychological intervention in a mental healthcare outpatient setting. Prescribing habits should be addressed more directly in training, and professionals should be more aware of risks of BZDs assumption. The failure in changing drug prescriptions in this study should prompt more real-world studies of the application of evidence-based strategies, particularly in outpatient mental health settings.

Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.

BACKGROUND: The blood-brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery. METHODS: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases. RESULTS: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications. CONCLUSIONS: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial.

'ALL ABOUT MY IDEAL MENTAL HEALTH SERVICE': Users, family members and experts by experience discussing a co-designed service.

INTRODUCTION: Many studies have investigated patients' understandings of how to optimise mental health services. However, only a few studies in the Italian context have involved experts by experience (EbEs), who can be ex-users, family members of ex-users or current service collaborators. Their role is crucial in implementing collaborative service quality assessment projects. METHOD: The study investigated the experience of 35 EbEs,  users, and family members who carried out a 9-month fortnightly project aimed at imagining an 'ideal service'. The facilitators of the discussion groups (two EbEs) were interviewed; written reports of each meeting were produced with relevant comments, notes and specific suggestions; and content analysis was applied. RESULTS: The most important result concerns the effectiveness of the project management method and group leadership carried out by the two EbEs. This approach allowed for complete autonomy of the work, without professional gaze or power imbalance. Also, the ideas and specific contents focused on by the two groups offer strategies to facilitate users' entry and reception in health care centres, to reduce the stigma of mental illness, to improve the centres' physical environment, to improve organisational aspects, to keep family members actively involved and to network mental health services with other territorial services. CONCLUSIONS: EbEs have proven to be key figures in ensuring equity of role in the service co-design process. This also concerns a context, the Italian one, where their role has not yet been recognised and legalised. Their contribution and ideas to improve services could be fundamental not only in mental health centres, but also in other health facilities, and could concern the entire service delivery process rather than being limited to quality assurance, according to a virtuous circle based on active participation and transformation of the role of users. PATIENT OR PUBLIC CONTRIBUTION: This work resulted from close collaboration between the two EbEs who conducted the groups, users and family members, the university, and the psychiatrist in charge of the service. All of them contributed to the research. The EbEs, researchers and psychiatrist participated in the interpretation of the data and are the co-authors of this paper.

High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Intensive training programme for ultrasound-guided minimally invasive synovial tissue biopsy on knees and wrists in different phases of inflammation.

OBJECTIVES: To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees' expectations. METHODS: Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees' expectations and perceptions were collected. RESULTS: 328 ST biopsy procedures were included. The rate of trainees' informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees' expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult. CONCLUSIONS: This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases.

Emergency crisis resource management: a simulation-based course developed by the Spanish Society of Emergency Medicine (SEMES) for health sciences students. / Emergency Crisis Resource Management de la Sociedad Española de Medicina de Urgencias y Emergencias: curso de gestión en crisis basado en simulación para estudiantes de ciencias de la salud.

OBJECTIVES: Educational programs based on high-fidelity simulation training aim to promote students' acquisition of nontechnical competencies such as understanding crisis resource management (CRM). This study evaluated the efficacy of a CRM course for students in their last year of university studies in health sciences. The course was developed by the Spanish Society of Emergency Medicine (SEMES). MATERIAL AND METHODS: Quasi-experimental study of a high-fidelity simulation course to teach emergency CRM (E-CRM) using preand postcourse measures of achievement in a single student cohort. A total of 209 students completed 2 selfadministered self-efficacy evaluations of their acquisition of nontechnical competencies and resilience. External observers also assessed the students' nontechnical competencies with objective measurement scales. RESULTS: Scores on resilience and self-efficacy assessments improved through the intervention (F = 25.90 and F = 68.02, respectively; P .001, for both pre-post comparisons). Statistically significant differences were found between students in different health sciences at baseline (t = 2.67; P = .008). Scores improved significantly on the Mayo High Performance Teamwork Scale (F = 6.18, P .001, eta2 = 0.20) and the Ottawa CRM Global Rating Scale (F = 5.58; P .005, eta2 = 0.19). CONCLUSION: The E-CRM course developed by a coordinated multiprofessional team based on high-fidelity simulations improved self-efficacy assessments of resilience and all nontechnical competencies.

OBJETIVO: Los programas educativos dirigidos a la adquisición de competencias no técnicas, tales como el Crisis Resource Management (CRM), basado en simulación de alta fidelidad, implican un aumento de las competencias del alumno en el manejo de situaciones de crisis. El objetivo del presente trabajo es evaluar la eficacia del programa Emergency CRM (E-CRM) de la Sociedad Española de Medicina de Urgencias y Emergencias, dirigido a estudiantes de último año de los grados de ciencias de la salud. METODO: Se llevó a cabo un estudio cuasiexperimental con medidas pre y posintervención, que consistió en un programa de E-CRM con simulación de alta fidelidad, en un único grupo. Participaron un total de 209 estudiantes que completaron dos instrumentos autoadministrados sobre la autoeficacia hacia las competencias no técnicas y la resiliencia. Además, a través de observadores externos se evaluó sus competencias no técnicas con instrumentos de evaluación objetivos. RESULTADOS: El alumnado mejoró las puntuaciones de resiliencia (F = 25,90; p < 0,001) y autoeficacia (F = 68,02; p 0,001) tras la intervención, con diferencias estadísticamente significativas para la resiliencia en la línea basal en función del grupo de estudios (t = 2,67; p = 0,008). Por otro lado, se encontraron mejoras de las puntuaciones obtenidas tanto para el instrumento Mayo High Performance Teamwork Scale (F = 6,18; p 0,001; eta2 = 0,20) como para el Ottawa Global Rating Scale Crisis Resource Management (F = 5,58; p 0,005; eta2 = 0,19). CONCLUSIONES: El programa de E-CRM, basado en simulación de alta fidelidad, con un equipo interprofesional coordinado, mejora la autoeficacia en todas las competencias no técnicas medidas y aumenta la resiliencia.

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.