Extracellular vesicle-mediated drug delivery in breast cancer theranostics.

Breast cancer (BC) continues to be a significant global challenge due to drug resistance and severe side effects. The increasing prevalence is alarming, requiring new therapeutic approaches to address these challenges. At this point, Extracellular vesicles (EVs), specifically small endosome-released nanometer-sized EVs (SEVs) or exosomes, have been explored by literature as potential theranostics. Therefore, this review aims to highlight the therapeutic potential of exosomes in BC, focusing on their advantages in drug delivery and their ability to mitigate metastasis. Following the review, we identified exosomes' potential in combination therapies, serving as miRNA carriers and contributing to improved anti-tumor effects. This is evident in clinical trials investigating exosomes in BC, which have shown their ability to boost chemotherapy efficacy by delivering drugs like paclitaxel (PTX) and doxorubicin (DOX). However, the translation of EVs into BC therapy is hindered by various challenges. These challenges include the heterogeneity of EVs, the selection of the appropriate parent cell, the loading procedures, and determining the optimal administration routes. Despite the promising therapeutic potential of EVs, these obstacles must be addressed to realize their benefits in BC treatment.

Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research.

Gastric cancer (GC) represents a major global health burden and is responsible for a significant number of cancer-related fatalities. Its complex nature, characterized by heterogeneity and aggressive behaviour, poses considerable challenges for effective diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as an important technique, offering unprecedented precision and depth in gene expression profiling at the cellular level. By facilitating the identification of distinct cell populations, rare cells and dynamic transcriptional changes within GC, scRNA-seq has yielded valuable insights into tumour progression and potential therapeutic targets. Moreover, this technology has significantly improved our comprehension of the tumour microenvironment (TME) and its intricate interplay with immune cells, thereby opening avenues for targeted therapeutic strategies. Nonetheless, certain obstacles, including tumour heterogeneity and technical limitations, persist in the field. Current endeavours are dedicated to refining protocols and computational tools to surmount these challenges. In this narrative review, we explore the significance of scRNA-seq in GC, emphasizing its advantages, challenges and potential applications in unravelling tumour heterogeneity and identifying promising therapeutic targets. Additionally, we discuss recent developments, ongoing efforts to overcome these challenges, and future prospects. Although further enhancements are required, scRNA-seq has already provided valuable insights into GC and holds promise for advancing biomedical research and clinical practice.

Exoscope-assisted spine surgery: Current applications and future directions.

Spine surgery is continually evolving, with the application of new technologies often serving as a catalyst for improved clinical outcomes. Exoscope-assisted spinal surgery has recently emerged as a notable technological advancement offering a refined approach to visualisation, thereby potentially contributing to improved surgical precision, reduced complication rates, and optimised patient outcomes. The application of exoscopes have improved spine surgeries such as spinal fusion procedures, decompression surgeries, instrumentation surgeries, minimally invasive and complex surgeries. These improvements include enhanced visualisation, improved ergonomics, improved surgical precision, reduced operation times and postoperative infection rates. The integration of robotics in exoscope-assisted spine surgery enables autofocus function, ensuring the integrity of the sterile field, providing superior image quality, resolution, and three-dimensional perception. However, challenges such as decrease in depth perception and the lack of long-term follow-up data hinder its widespread adoption. Ethical considerations regarding patient safety, technology dependency, and health inequity add another dimension to these challenges. Despite these challenges, exoscope-assisted spine surgery holds significant potential for transforming clinical practice and improving patient outcomes. This review seeks to provide a concise overview of the benefits and limits of exoscope-assisted spine surgeries, while highlighting its challenges and ethical considerations. Addressing these limitations by conducting large-scale clinical trials and exploring the integration of artificial intelligence (AI) could assist in realising the potential of exoscopes in spine surgery."

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review.

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

Current trends and challenges: The landscape of perioperative mortality in intracranial surgeries in low- and middle-income settings: A narrative review.

Background and Aims: Intracranial surgeries are pivotal in treating cerebral pathologies, particularly in resource-limited contexts, utilizing techniques such as craniotomy, transsphenoidal approaches, and endoscopy. However, challenges in low and middle income countries (LMICs), including resource scarcity, diagnostic delays, and a lack of skilled neurosurgeons, lead to elevated perioperative mortality (POM). This review seeks to identify major contributors to these challenges and recommend solutions for improved patient outcomes in neurosurgical care within LMICs. Methods: This review examines POM in LMICs using a detailed literature search, focusing on studies from these regions. Databases like PubMed, EMBASE, and Google Scholar were utilized using specific terms related to "intracranial surgery," "perioperative mortality," "traumatic brain injuries," and "LMICs." Inclusion criteria covered various study designs and both pediatric and adult populations while excluding stand-alone abstracts and case reports. Results: POM rates for intracranial surgeries differ widely across many low and middle-income regions: Africa sees rates from 2.5% to 39.1%, Asia between 3.6% and 34.8%, and Latin America and the Caribbean have figures ranging from 1.3% to 12%. The POM rates in LMICs were relatively higher compared to most first-world countries. The high POM rates in LMICs can be attributed to considerable delays and compromises in neurosurgical care delivery, exacerbated by late diagnoses and presentations of neurosurgical pathologies. This, coupled with limited resources, underdeveloped infrastructure, and training gaps, complicates intracranial disease management, leading to elevated POM. Conclusion: Intracranial POM is a pronounced disparity within the neurosurgical field in LMICs. To mitigate intracranial POM, it is imperative to bolster healthcare infrastructure, amplify personnel training, foster global partnerships, and harness technologies like telemedicine. Tackling socioeconomic obstacles and prioritizing early detection through sustained funding and policy shifts can substantially enhance patient outcomes.

Non-colloid-cyst primary brain tumors: A systematic review of unexpected fatality.

OBJECTIVE: Primary brain tumors have the potential to present a substantial health hazard, ultimately resulting in unforeseen fatalities. Despite the enhanced comprehension of many diseases, the precise prediction of disease progression continues to pose a significant challenge. The objective of this study is to investigate cases of unexpected mortality resulting from primary brain tumors and analyze the variables that contribute to such occurrences. METHODS: This systematic review explores research on individuals diagnosed with primary brain tumors who experienced unexpected deaths. It uses PRISMA standards and searches PubMed, Google Scholar, and Scopus. Variables considered include age, gender, symptoms, tumor type, WHO grade, postmortem findings, time of death - time taken from first medical presentation or hospital admission to death, comorbidity, and risk factors. RESULTS: This study examined 46 studies to analyze patient-level data from 76 individuals with unexpected deaths attributed to intracranial lesions, deliberately excluding colloid cysts. The cohort's age distribution showed an average age of 37 years, with no significant gender preference. Headache was the most common initial symptom. Astrocytomas, meningiomas, and glioblastoma were the most common lesions, while the frontal lobe, temporal lobe, and cerebellum were common locations. Meningiomas and astrocytomas showed faster deaths within the first hour of hospital admission. CONCLUSION: The etiology of unforeseen fatalities resulting from cerebral tumors elucidates an intricate and varied phenomenon. Although unexpected deaths account for a very tiny proportion of total fatalities, it is probable that their actual occurrence is underestimated as a result of underreporting and misdiagnosis.

Exploring the advances of single-cell RNA sequencing in thyroid cancer: a narrative review.

Thyroid cancer, a prevalent form of endocrine malignancy, has witnessed a substantial increase in occurrence in recent decades. To gain a comprehensive understanding of thyroid cancer at the single-cell level, this narrative review evaluates the applications of single-cell RNA sequencing (scRNA-seq) in thyroid cancer research. ScRNA-seq has revolutionised the identification and characterisation of distinct cell subpopulations, cell-to-cell communications, and receptor interactions, revealing unprecedented heterogeneity and shedding light on novel biomarkers for therapeutic discovery. These findings aid in the construction of predictive models on disease prognosis and therapeutic efficacy. Altogether, scRNA-seq has deepened our understanding of the tumour microenvironment immunologic insights, informing future studies in the development of effective personalised treatment for patients. Challenges and limitations of scRNA-seq, such as technical biases, financial barriers, and ethical concerns, are discussed. Advancements in computational methods, the advent of artificial intelligence (AI), machine learning (ML), and deep learning (DL), and the importance of single-cell data sharing and collaborative efforts are highlighted. Future directions of scRNA-seq in thyroid cancer research include investigating intra-tumoral heterogeneity, integrating with other omics technologies, exploring the non-coding RNA landscape, and studying rare subtypes. Overall, scRNA-seq has transformed thyroid cancer research and holds immense potential for advancing personalised therapies and improving patient outcomes. Efforts to make this technology more accessible and cost-effective will be crucial to ensuring its widespread utilisation in healthcare.

The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery.

Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.

Utilizing indocyanine green video angiography to bridge intracranial aneurysm treatment gaps in low- and middle-income countries: a mini-review.

Intracranial aneurysms, affecting 2%-5% of the population, pose a significant challenge to neurosurgeons due to their potential to cause subarachnoid haemorrhage and high mortality rates. Intraoperative angiography is necessary for effective surgical planning and indocyanine green video angiography (ICG-VA) has emerged as a useful tool for real-time visualization of aneurysmal blood flow, aiding in better planning for potential blood flow and detection of aneurysm remnants. This mini narrative review explores the application of ICG-VA in intracranial aneurysm surgery. Compared with conventional dye-based angiography, ICG-VA is safer, more effective and more cost-effective. It can assess haemodynamic parameters, cerebral flow during temporary artery occlusion, completeness of clipping and patency of branch vessels. However, implementing ICG-VA in low- and middle-income countries presents challenges such as financial constraints, limited access to training and expertise, patient selection and consent issues. Addressing these obstacles requires capacity-building, training programmes for neurosurgeons and multidisciplinary teams, technology transfer, equipment donations, public-private partnerships, continued research and development, reducing conventional dye usage, reducing ICG wastage, exploring mechanisms to reuse ICG dyes and advocating for increased government funding and healthcare budgets.

The unmet surgical needs of global refugee populations: A perspective review.

The global refugee community, including those forced to flee due to persecution, conflict, or violence, faces significant challenges in accessing healthcare, resulting in a higher prevalence of surgical disease. These challenges have a profound impact on morbidity and mortality rates, particularly in low- and middle-income countries where many immigrants seek refuge. Limited availability of medical facilities, an inadequate surgical workforce, financial constraints and linguistic and cultural barriers all contribute to reduced access to healthcare. Limited access to competent healthcare leads to poor health outcomes, increased morbidity and mortality rates and suboptimal surgical results for refugees. To address these challenges, a multifaceted approach is necessary. This includes increased funding for healthcare initiatives, workforce recruitment and training and improved coordination between aid organisations and local healthcare systems. Strategies for managing surgical conditions in the global refugee community encompass the development of targeted public health programmes, removing legal barriers, establishing healthcare facilities to enhance surgical access and prioritising disease prevention among refugees.

Challenges and opportunities in prostate cancer surgery in South America: Insights into robot-assisted radical prostatectomies-A perspective.

Background and Aims: Prostate cancer imposes a significant health burden, particularly in South America with its high incidence and mortality rates. This article explores the emergence of robot-assisted radical prostatectomy (RARP) as a potential solution in the region. Methods: This study relies on a comprehensive review of relevant literature. The analysis highlights the advantages of RARP, identifies impediments to its implementation, and proposes strategies to overcome these barriers. Results: RARP demonstrates notable benefits, including improved functional outcomes, reduced complications, and minimized incisions. However, the integration of RARP in South America is hindered by challenges such as regional disparities, financial limitations, and data gaps. Limited healthcare infrastructure and a scarcity of skilled professionals further compound the issues. Conclusion: Despite its potential, RARP faces obstacles to widespread adoption in South America. Strategic solutions encompassing technology investment, healthcare infrastructure enhancement, and workforce training are imperative. Overcoming these challenges can establish RARP as a crucial tool in managing prostate cancer in the region, ultimately enhancing patient care and treatment outcomes.

ER and COX2 expression in endometrial hyperplasia processes.

Endometrial hyperplastic processes (EHPs) encompass various morphological changes, characterized by an increased ratio of endometrial glands to stroma. These changes manifest as endometrial hyperplasia (EH) and endometrial polyps. The objective of this study was to investigate the expressions of ER and Cyclooxygenase-2 (COX2) in EH and endometrial polyps, and determine their correlation with histological and anthropometric parameters. Tissue samples were obtained during hysteroresectoscopy and divided into 3 groups: non-atypical EH, glandular EP, and glandular-fibrous EP. We examined the immunoprofile of epithelial and stromal cells using rabbit polyclonal anti-COX2 antibodies and rabbit monoclonal anti-ER antibodies (clone SP1). Our results indicate that there is no association between the expressions of ER and COX2 and the type of EHP. Furthermore, the expression levels of ER and COX2 are not influenced by the patients anthropometric parameters. However, tissues with EHPs exhibited significantly higher COX2 expression compared to intact tissues. We also observed a direct correlation between ER and COX2 expression in the endometrial epithelium. The variability in ER and COX2 expressions observed in hyperplastic processes of the endometrium potentially suggests their synergistic involvement in the initiation and progression of EHPs, as well as their potential role in subsequent tumor transformation.

Craniomaxillofacial trauma in war-torn nations: Incidence, management gaps, and recommendations.

Craniomaxillofacial trauma (CMFT) is a type of injury that affects the face, neck, and scalp, and includes facial bone fractures, dentoalveolar trauma, and soft tissue injuries. Work, traffic accidents, sports, and daily activities commonly cause these injuries. However, they are widespread in war-torn countries where armed conflict leads to a high incidence of CMFT. The lack of resources, health care infrastructure, and surgical personnel in these areas result in subpar treatment and poor patient outcomes, contributing to the high mortality and morbidity rates among war victims. The importance of a multidisciplinary approach to CMFT management cannot be overstated, but current obstacles, such as a lack of access to proper medical care and rehabilitation services, impede the development of effective treatments. CMFT treatment is complex and prohibitively expensive for war-torn nations to afford, necessitating international intervention to provide life-saving surgical procedures for those suffering from CMFT in conflict zones. Despite efforts to improve CMFT treatments in war-torn countries, more must be done to improve treatment outcomes. Data collection and research must also be improved in order to develop effective evidence-based treatment methods.

A reflection of Africa's cardiac surgery capacity to manage congenital heart defects: a perspective.

Congenital heart defects (CHDs) are birth abnormalities that may drastically alter the structure and functionality of the heart. For 70% of infants with congenital disorders to survive or maintain a better quality of life, surgery is necessary. Over 500 000 of the 1.5 million CHD cases reported annually, or 1% of all live births, occur in Africa, according to the WHO. A surmounted 90% of these patients are from Africa, and as a consequence, 300 000 infants die annually as a result of poor care or difficulty accessing adequate healthcare. However, the high prevalence of CHDs, precipitated by a plethora of aetiologies worldwide, is particularly pronounced in Africa due to maternal infectious diseases like syphilis and rubella amongst the pregnant populace. In low- and middle-income countries, especially in Africa, where foreign missions and organizations care for the majority of complicated cardiac surgical patients, access to secure and affordable cardiac surgical therapy is a substantial issue. Interventions for CHDs are very expensive in Africa as many of the continent's domiciles possess low expenditures and funding, thereby cannot afford the costs indicated by associated surgical treatments. Access to management and healthcare for CHDs is further hampered by a lack of trained surgical personnel, specialized tools, infrastructure, and diagnostic facilities in Africa.

Stress-induced menstrual disorders in adolescents during the Ukrainian war: cross-sectional study.

The objective was to investigate the peculiarities of menstrual cycle changes in teenagers exposed to a devastating war for an extended period. Methods: A cross-sectional study of 120 Ukrainian girls aged 9-18 asked to complete a survey about their menstrual cycle status 3-6 months after the war began. Other examination methods used included anthropometry, laboratory, and instrumental studies. Results: The frequency of menstrual cycle disorders in the study group was 65.8% (n=79). The following menstrual cycle disorders were most frequently reported; dysmenorrhea 45.6% (n=36), excessive menstruation during puberty 27.8% (n=22), and secondary amenorrhea 26.6% (n=21). The 52.5% (n=63) of those examined had pathological menarche. The 81.7% (n=63) of respondents reported a change in eating habits in the previous few months. The 61.9% (n=39) of these children had dyshormonal disorders or met the criteria for metabolic syndrome. Conclusion: Adolescent females under stress warrant a quick assessment of their psychoemotional and metabolic conditions. The protection from future menstruation and reproductive illnesses depends on this tactic. By diagnosing these conditions promptly and well-managed, adolescent females may maintain good physical and emotional health.

Relationship of microvascular density on histological and immunohistochemical features in endometrioid adenocarcinomas of the uterus: experimental study.

The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells and their stroma. The neovascularization of EA tissues and level of microvascular density (MVD) influence tumor progression. Our study aims to establish the relationship between MVD in EA tissue and the histological and immunohistochemical features of tumors. Materials and methods: The authors studied 30 cases of endometrial ЕА and compared their histological and immunohistochemical characteristics with the MVD of tumor tissues. Results: Our study indicated that MVD in EA tissue depends on the grade of the tumors and their FIGO stage. Increased MVD was correlated with a depression of E-cadherin and PR expression and enhanced expression of VEGF and Ki-67. MVD enhancement during VEGF overexpression is a manifestation of the functional activity of these proteins. The increase in MVD was accompanied by more frequent metastasis of the EA to the lymph nodes. Conclusion: EA progression is accompanied by qualitative and quantitative variations of parenchymal and stromal patterns of tumors. Dedifferentiation of EA leads to overexpression of VEGF, which becomes diffuse in tumors cells, resulting in an increase of adenocarcinomas' MVD and their metastatic potential. Correlations between histological and immunohistochemical features of EAs indicate the synchronicity of the occurrence and progression of morphological and immunological anaplasia, which can be used in predicting the course of the disease.