Mexican Multicenter Experience of Metastatic Spinal Disease.

Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where solid tumors metastasize. Complications involved in spinal metastasis include root or spinal cord compression, progressing to a declining quality of life as patient autonomy reduces and pain increases. The main objective of this study is to report the incidence of patients and typology of spinal metastases in three reference centers in Mexico. Methodology Retrospective cohorts of patients diagnosed with spinal metastases from January 2010 to February 2017 at the National Cancer Institute, National Rehabilitation Institute, and the Traumatology and Orthopedics Hospital "Lomas Verdes" in Mexico City were analyzed. Results A total of 326 patients (56% males) with spinal metastases were reported. The mean age was 58.06 ± 14.05 years. The main sources of spinal metastases were tumors of unknown origin in 53 (16.25%) cases, breast cancer in 67 (20.5%) cases, prostate cancer in 59 (18%) cases, myeloma in 24 (7.4%) cases, and lung cancer in 23 (7.1%) cases. Conclusions The data obtained in this analysis delivers an updated standpoint on Mexico, providing the opportunity to distinguish the current data from global references. Collecting more epidemiological information for better recording of cancer and its associated complications, as well as further studies on them, is necessary.

Intraoperative Ultrasound: An Old but Ever New Technology for a More Personalized Approach to Brain Tumor Surgery.

BACKGROUND: Although the use of transcranial ultrasound dates to the mid-20th century, the main purpose of this research work is to standardize its use in the resection of brain tumors. This is due to its wide availability, low cost, lack of contraindications, and absence of harmful effects for the patient and medical staff, along with the possibility of real-time verification of the complete resection of tumor lesions and minimization of vascular injuries or damage to adjacent structures. METHODS: A retrospective study was conducted from June to December 2022. The study included eight patients (three men and five women) aged between 32 and 76 years. Histological examination revealed two high-grade gliomas, one low-grade glioma, and five metastatic lesions. RESULTS: The low-grade glioma appeared as a homogeneously echogenic structure and easily distinguishable from brain parenchyma, whereas metastases and high-grade gliomas showed higher echogenicity, being identified as malignant lesions due to areas of low echogenicity necrosis and peritumoral edema identified as a hyperechogenic structure. CONCLUSIONS: The use of intraoperative transcranial ultrasound constitutes an important tool for neurosurgeons during tumor resection. Although it is easy to use, intraoperative ultrasound requires a relatively short learning curve and a good understanding of the fundamentals of ultrasound. Its main advantage over neuronavigation is that it is not affected by the "brain shift" phenomenon that commonly occurs during tumor resection, since the ultrasound images are updated during surgery.

Alternative molecular mechanisms for force transmission at adherens junctions via ß-catenin-vinculin interaction.

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, ß-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that ß-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and ß-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving ß-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.

Low-Cost 3D Models for Cervical Spine Tumor Removal Training for Neurosurgery Residents.

BACKGROUND AND OBJECTIVES: Spinal surgery, particularly for cervical pathologies such as myelopathy and radiculopathy, requires a blend of theoretical knowledge and practical skill. The complexity of these conditions, often necessitating surgical intervention, underscores the need for intricate understanding and precision in execution. Advancements in neurosurgical training, especially with the use of low-cost 3D models for simulating cervical spine tumor removal, are revolutionizing this field. These models provide the realistic and hands-on experience crucial for mastering complex neurosurgical techniques, filling gaps left by traditional educational methods. MATERIALS AND METHODS: This study aimed to assess the effectiveness of 3D-printed cervical vertebrae models in enhancing surgical skills, focusing on tumor removal, and involving 20 young neurosurgery residents. These models, featuring silicone materials to simulate the spinal cord and tumor tissues, provided a realistic training experience. The training protocol included a laminectomy, dural incision, and tumor resection, using a range of microsurgical tools, focusing on steps usually performed by senior surgeons. RESULTS: The training program received high satisfaction rates, with 85% of participants extremely satisfied and 15% satisfied. The 3D models were deemed very realistic by 85% of participants, effectively replicating real-life scenarios. A total of 80% found that the simulated pathologies were varied and accurate, and 90% appreciated the models' accurate tactile feedback. The training was extremely useful for 85% of the participants in developing surgical skills, with significant post-training confidence boosts and a strong willingness to recommend the program to peers. CONCLUSIONS: Continuing laboratory training for residents is crucial. Our model offers essential, accessible training for all hospitals, regardless of their resources, promising improved surgical quality and patient outcomes across various pathologies.

Surgical treatment of orbital tumors in a single center: Analysis and results.

Background: Orbital tumors, arising within the bony orbit and its contents, present diverse challenges due to their varied origins and complex anatomical context. These tumors, classified as primary, secondary, or metastatic, are further subdivided into intraconal and extraconal based on their relationship with the muscle cone. This classification significantly influences surgical approach and management. This study highlights surgical experiences with orbital tumors, underscoring the importance of tailored surgical approaches based on the lesion's site and its proximity to the optic nerve. Methods: This retrospective study at the National Institute of Cancer's Head and Neck Department (2005-2014) analyzed 29 patients with orbital tumors treated with surgery, radiotherapy, chemotherapy, or combinations of them. Patient demographics, tumor characteristics, and treatment responses were evaluated using computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT imaging. Malignant tumors often required orbital exenteration and reconstruction, highlighting the study's commitment to advancing orbital tumor treatment. Results: 29 patients (18 females and 11 males, age 18-88 years, mean 53.5 years) with orbital tumors exhibited symptoms such as decreased vision and exophthalmos. Tumors included primary lesions like choroidal melanoma and secondary types like epidermoid carcinoma. Treatments varied, involving a multidisciplinary team for surgical approaches like exenteration, with follow-up from 1 to 9 years. Radiotherapy and chemotherapy were used for specific cases. Conclusion: Our study underscores the need for a multidisciplinary approach in treating orbital tumors, involving various surgical specialists and advanced technologies like neuronavigation for tailored treatment. The integration of surgery with radiotherapy and chemotherapy highlights the effectiveness of multidimensional treatment strategies.

The Role of Ventriculocisternostomy in the Management of Hydrocephalus in Mali and the Democratic Republic of the Congo.

BACKGROUND:  Hydrocephalus continues to pose significant clinical challenges in neurosurgery. The primary goal of this study is to assess the feasibility of ventriculocisternostomy (VCS) within the provincial city of Kinshasa and Mali to optimize the management of patients afflicted with hydrocephalus. METHODS:  This investigation was hosted at two major urban healthcare facilities: the Initiative Plus Hospital Center, positioned in the bustling metropolis of Kinshasa, Democratic Republic of the Congo (DRC), and the Bamako Hospital, Republic of Mali. A prospective, analytical cohort study was executed from December 2022 to June 2023. RESULTS: In the Mali group, seven patients underwent VCS, four patients were treated with VCS and spinal surgery, and one case was treated with VCS and biopsy. Similarly, in the Kinshasa group, 25 patients underwent VCS, whereas four patients were treated with VCS and spinal surgery. The median hospital stay was eight and 10 days for the Mali and the Kinshasa groups, respectively. CONCLUSION: VCS emerges as a formidable alternative for hydrocephalus management in Mali and DRC, showcasing the potential to markedly ameliorate patient outcomes, economize healthcare expenditures, and fortify the local neurosurgical capacity.

Obesity and polycystic ovary syndrome influence on intestinal permeability at fasting, and modify the effect of diverse macronutrients on the gut barrier.

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.

Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure.

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.

Choosing T-cell sources determines CAR-T cell activity in neuroblastoma.

Introduction: The clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2. Methods: We compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines. Results: The IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h. Conclusion: CB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.

Latex vascular injection as method for enhanced neurosurgical training and skills.

Background: Tridimensional medical knowledge of human anatomy is a key step in the undergraduate and postgraduate medical education, especially in surgical fields. Training simulation before real surgical procedures is necessary to develop clinical competences and to minimize surgical complications. Methods: Latex injection of vascular system in brain and in head-neck segment is made after washing out of the vascular system and fixation of the specimen before and after latex injection. Results: Using this latex injection technique, the vascular system of 90% of brains and 80% of head-neck segments are well-perfused. Latex-injected vessels maintain real appearance compared to silicone, and more flexible vessels compared to resins. Besides, latex makes possible a better perfusion of small vessels. Conclusions: Latex vascular injection technique of the brain and head-neck segment is a simulation model for neurosurgical training based on real experiencing to improve surgical skills and surgical results.

Clivus-Cervical Stabilization through Transoral Approach in Patients with Craniocervical Tumor: Three Cases and Surgical Technical Note.

Craniocervical tumors lead to cervical pain, instability, and neurological symptoms, reducing the quality of life. Effective surgical intervention at the craniocervical junction (CCJ) is critical and complex, involving comprehensive approaches and advanced reconstructive techniques. This study, conducted at Mexico City's National Institute of Cancerology, focused on three surgical cases that occurred in 2023 involving tumors at the CCJ: two chordomas and one prostate adenocarcinoma. We utilized a specialized technique: clivus-cervical stabilization reinforced with a polymethylmethacrylate (PMMA)-filled cervical mesh. Postoperatively, patients showed marked neurological recovery and reduced cervical pain, with enhanced Karnofsky and Eastern Cooperative Oncology Group (ECOG) scores indicating improved life quality. The surgical technique provided excellent exposure and effective tumor resection, utilizing PMMA-filled cervical mesh for stability. Tumoral lesions at the CCJ causing instability can be surgically treated through a transoral approach. This type of approach should be performed with precise indications to avoid complications associated with the procedure.

The importance of social networks in neurosurgery training in low/middle income countries.

Introduction: Neurosurgery is evolving with new techniques and technologies, relies heavily on high-quality education and training. Social networks like Twitter, Facebook, Instagram and LinkedIn have become integral to this training. These platforms enable sharing of surgical experiences, fostering global knowledge-sharing and collaboration among neurosurgeons. Virtual conferences and courses are accessible, enhancing learning regardless of location. While these networks offer real-time communication and collaborative opportunities, they also pose challenges like the spread of misinformation and potential distractions. According to the PICO format, the target population (P) for the purpose of this paper are medical students, neurosurgical residents and consultants on the role of social media (I) in neurosurgery among Low-Middle income countries (C) with the main outcome to understand the collaborative domain of learning. Material and method: This cross-sectional survey, conducted in June-July 2023, involved 210 medical students, neurosurgery residents, fellows, and practicing neurosurgeons from low and middle-income countries. A structured questionnaire assessed social network usage for neurosurgery training, covering demographic details, usage frequency, and purposes like education, collaboration, and communication. Participants rated these platforms' effectiveness in training on a 1-5 scale. Data collection employed emails, social media groups, and direct messaging, assuring respondent anonymity. The survey aimed to understand and improve social networks' use in neurosurgery, focusing on professional development, challenges, and future potential in training. Results: In a survey of 210 participants from low and middle-income countries, 85.5% were male, 14.5% female, with diverse roles: 42.9% neurosurgery residents, 40% practicing neurosurgeons, 14.6% medical students, and 2.4% other healthcare professionals. Experience ranged from 0 to 35 years, with Mexico, Nigeria, and Kenya being the top participating countries. Most respondents rated neurosurgery training resources in their countries as poor or very poor. 88.7% used social media professionally, predominantly WhatsApp and YouTube. Content focused on surgical videos, research papers, and webinars. Concerns included information quality and data privacy. Interactive case discussions, webinars, and lectures were preferred resources, and most see a future role for social media in neurosurgery training. Conclusions: Our study underscores the crucial role of social media in neurosurgery training and practice in low and middle-income countries (LMICs). Key resources include surgical videos, research papers, and webinars. While social media offers a cost-effective, global knowledge-sharing platform, challenges like limited internet access, digital literacy, and misinformation risks remain significant in these regions.

Comparative Analysis of Stromal Vascular Fraction and Alternative Mechanisms in Bone Fracture Stimulation to Bridge the Gap between Nature and Technological Advancement: A Systematic Review.

BACKGROUND: Various stimulation methods, including electrical, ultrasound, mechanical, and biological interventions, are explored, each leveraging intricate cellular and molecular dynamics to expedite healing. The advent of stromal vascular fraction (SVF) marks a significant stride, offering multifarious benefits in bone healing, from enhanced bone formation to optimal vascular integration, drawing a harmonious balance between innate mechanisms and scientific advancements. METHODS: This systematic review was conducted focusing on literature from 2016 to 2023 and encompassing various bone healing stimulation mechanisms like SVF, electrical, ultrasound, and mechanical stimulation. The extracted data underwent meticulous synthesis and analysis, emphasizing comparative evaluations of mechanisms, applications, and outcomes of each intervention. RESULTS: The reviewed studies reveal the potential of SVF in bone fracture healing, with its regenerative and anti-inflammatory effects. The purification of SVF is crucial for safe therapeutic use. Characterization involves flow cytometry and microscopy. Studies show SVF's efficacy in bone regeneration, versatility in various contexts, and potential for clinical use. SVF appears superior to electrical, ultrasound, and mechanical stimulation, with low complications. CONCLUSIONS: This review compares bone healing methods, including SVF. It provides valuable insights into SVF's potential for bone regeneration. However, due to limited human studies and potential bias, cautious interpretation is necessary. Further research is essential to validate these findings and determine the optimal SVF applications in bone healing.

Analyzing the Clinical Potential of Stromal Vascular Fraction: A Comprehensive Literature Review.

Background: Regenerative medicine is evolving with discoveries like the stromal vascular fraction (SVF), a diverse cell group from adipose tissue with therapeutic promise. Originating from fat cell metabolism studies in the 1960s, SVF's versatility was recognized after demonstrating multipotency. Comprising of cells like pericytes, smooth muscle cells, and, notably, adipose-derived stem cells (ADSCs), SVF offers tissue regeneration and repair through the differentiation and secretion of growth factors. Its therapeutic efficacy is due to these cells' synergistic action, prompting extensive research. Methods: This review analyzed the relevant literature on SVF, covering its composition, action mechanisms, clinical applications, and future directions. An extensive literature search from January 2018 to June 2023 was conducted across databases like PubMed, Embase, etc., using specific keywords. Results: The systematic literature search yielded a total of 473 articles. Sixteen articles met the inclusion criteria and were included in the review. This rigorous methodology provides a framework for a thorough and systematic analysis of the existing literature on SVF, offering robust insights into the potential of this important cell population in regenerative medicine. Conclusions: Our review reveals the potential of SVF, a heterogeneous cell mixture, as a powerful tool in regenerative medicine. SVF has demonstrated therapeutic efficacy and safety across disciplines, improving pain, tissue regeneration, graft survival, and wound healing while exhibiting immunomodulatory and anti-inflammatory properties.

The effect of physical exercise on anticancer immunity.

Regular physical activity is associated with lower cancer incidence and mortality, as well as with a lower rate of tumour recurrence. The epidemiological evidence is supported by preclinical studies in animal models showing that regular exercise delays the progression of cancer, including highly aggressive malignancies. Although the mechanisms underlying the antitumorigenic effects of exercise remain to be defined, an improvement in cancer immunosurveillance is likely important, with different immune cell subtypes stimulated by exercise to infiltrate tumours. There is also evidence that immune cells from blood collected after an exercise bout could be used as adoptive cell therapy for cancer. In this Perspective, we address the importance of muscular activity for maintaining a healthy immune system and discuss the effects of a single bout of exercise (that is, 'acute' exercise) and those of 'regular' exercise (that is, repeated bouts) on anticancer immunity, including tumour infiltrates. We also address the postulated mechanisms and the clinical implications of this emerging area of research.

Factors affecting return to work following endoscopic lumbar foraminal stenosis surgery: A single-center series.

Background: This study evaluates the factors affecting the return to work of endoscopic surgery for lumbar foraminal stenosis (LFS), including symptoms, functional status, complications, and reoperation rates. Methods: The authors' retrospective cohort study included 100 consecutive patients (50 males and 50 females) diagnosed with LFS who underwent endoscopic surgery at Trotsky National Research Center of Surgery between January 2018 and December 2021. Results: There were no significant differences in age and preoperative visual analog scale and Oswestry disability index scores between the male and female groups, time to return to work for different patient groups after undergoing endoscopic lumbar foraminotomy (ELF). However, patients with more severe stenosis and comorbidities may take longer to recover. Confounding factors were patient age, preoperative physical function, and job requirements. Conclusion: This study confirms that study ELF can effectively improve symptoms associated with lumbar radiculopathy, as well as back pain, and improve patients' quality of life. Comorbidity, smoking status, and complications prolong the time to return to work following ELF surgery compared to healthy subjects.