Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Unraveling the Intricate Link: Deciphering the Role of the Golgi Apparatus in Breast Cancer Progression

Breast cancer represents a paramount global health challenge, warranting intensified exploration of the molecular underpinnings influencing its progression to facilitate the development of precise diagnostic instruments and customized therapeutic regimens. Historically, the Golgi apparatus has been acknowledged for its primary role in protein sorting and trafficking within cellular contexts. However, recent findings suggest a potential link between modifications in Golgi apparatus function and organization and the pathogenesis of breast cancer. This review delivers an exhaustive analysis of this correlation. Specifically, we examine the consequences of disrupted protein glycosylation, compromised protein transport, and inappropriate oncoprotein processing on breast cancer cell dynamics. Furthermore, we delve into the impacts of Golgi-mediated secretory routes on the release of pro-tumorigenic factors during the course of breast cancer evolution. Elucidating the nuanced interplay between the Golgi apparatus and breast cancer can pave the way for innovative therapeutic interventions and the discovery of biomarkers, potentially enhancing the diagnostic, prognostic, and therapeutic paradigms for afflicted patients. The advancement of such research could substantially expedite the realization of these objectives

Successful Surgical Treatment of a Giant Intraventricular Meningioma: A Case Report and Literature Review

In our study, we document the case of a 48-year-old patient who presented at our clinic with various neurological disturbances. Magnetic Resonance Imaging revealed the presence of an intraventricular meningioma located in the body of the left lateral ventricle measuring 60 mm in diameter. This tumor was classified as a giant meningioma, accompanied by a significant amount of digitiform-type edema. A surgical procedure was conducted, resulting in a gross total resection of the tumor. Histopathological analysis identified the tumor as a fibrous meningioma. Postoperative assessments, as well as follow-ups conducted at 3 months and 1 year post-surgery, indicated considerable neurological improvement. The patient exhibited a remission of hemiparesis and gait disturbances along with a marginal improvement in the status of expressive aphasia. This case report underscores the significance of achieving total and safe resection of the tumor and includes an analysis of various cases from the literature, particularly focusing on those that describe minimally invasive surgical approaches and highlight the benefits of radiosurgery in the treatment of giant intraventricular meningiomas

Case Study of a Complex Neurovascular Disorder: Choroidal Arteriovenous Malformation

This study conducts an in-depth analysis of the management of a complex arteriovenous malformation (AVM) in a 44-year-old individual, who initially manifested with acute left hemiparesis and progressively declined into a comatose state. Diagnostic neuroimaging identified a substantial right fronto-temporal intraparenchymal hematoma via a CT scan. Cerebral angiography further elucidated a choroidal AVM originating from the anterior choroidal artery, accompanied by intranidal aneurysms. The elected treatment strategy was the surgical excision of the AVM. The procedure achieved complete removal of the intracranial AVM, situated in a neurologically sensitive region, leading to notable neurological recovery. This study thoroughly explores and critically evaluates a wide spectrum of treatment approaches for intracranial arteriovenous malformations, including novel endovascular therapies. Despite extensive discourse on AVM in contemporary literature, this report is among the few documenting the treatment of a choroidal AVM via a microsurgical technique, and highlights various therapeutic options

Unmet needs in the diagnosis and treatment of Romanian patients with bilio-pancreatic tumors: results of a prospective observational multicentric study

Background. Biliopancreatic tumors (BPT) are among the most aggressive solid malignancies, and their incidence is rising. Good patient outcome relies heavily on a multidisciplinary approach to therapy, including timely access to endoscopy, surgery and chemo/radiotherapy. We aimed to evaluate current practices as reflected in the management and outcome of patients diagnosed with BPT in the setting of a low-resource medical system in order to identify areas suitable for improvement

Mind, Mood and Microbiota—Gut–Brain Axis in Psychiatric Disorders

Psychiatric disorders represent a primary source of disability worldwide, manifesting as disturbances in individuals’ cognitive processes, emotional regulation, and behavioral patterns. In the quest to discover novel therapies and expand the boundaries of neuropharmacology, studies from the field have highlighted the gut microbiota’s role in modulating these disorders. These alterations may influence the brain’s processes through the brain–gut axis, a multifaceted bidirectional system that establishes a connection between the enteric and central nervous systems. Thus, probiotic and prebiotic supplements that are meant to influence overall gut health may play an insightful role in alleviating psychiatric symptoms, such as the cognitive templates of major depressive disorder, anxiety, or schizophrenia. Moreover, the administration of psychotropic drugs has been revealed to induce specific changes in a microbiome’s diversity, suggesting their potential utility in combating bacterial infections. This review emphasizes the intricate correlations between psychiatric disorders and the gut microbiota, mentioning the promising approaches in regard to the modulation of probiotic and prebiotic treatments, as well as the antimicrobial effects of psychotropic medication

A Comprehensive Review on Neuroimmunology: Insights from Multiple Sclerosis to Future Therapeutic Developments

This review delves into neuroimmunology, focusing on its relevance to multiple sclerosis (MS) and potential treatment advancements. Neuroimmunology explores the intricate relationship between the immune system and the central nervous system (CNS). Understanding these mechanisms is vital for grasping the pathophysiology of diseases like MS and for devising innovative treatments. This review introduces foundational neuroimmunology concepts, emphasizing the role of immune cells, cytokines, and blood–brain barrier in CNS stability. It highlights how their dysregulation can contribute to MS and discusses genetic and environmental factors influencing MS susceptibility. Cutting-edge research methods, from omics techniques to advanced imaging, have revolutionized our understanding of MS, offering valuable diagnostic and prognostic tools. This review also touches on the intriguing gut–brain axis, examining how gut microbiota impacts neuroimmunological processes and its potential therapeutic implications. Current MS treatments, from immunomodulatory drugs to disease-modifying therapies, are discussed alongside promising experimental approaches. The potential of personalized medicine, cell-based treatments, and gene therapy in MS management is also explored. In conclusion, this review underscores neuroimmunology’s significance in MS research, suggesting that a deeper understanding could pave the way for more tailored and effective treatments for MS and similar conditions. Continued research and collaboration in neuroimmunology are essential for enhancing patient outcomes

Decoding Neurodegeneration: A Comprehensive Review of Molecular Mechanisms, Genetic Influences, and Therapeutic Innovations

Neurodegenerative disorders often acquire due to genetic predispositions and genomic alterations after exposure to multiple risk factors. The most commonly found pathologies are variations of dementia, such as frontotemporal dementia and Lewy body dementia, as well as rare subtypes of cerebral and cerebellar atrophy-based syndromes. In an emerging era of biomedical advances, molecular–cellular studies offer an essential avenue for a thorough recognition of the underlying mechanisms and their possible implications in the patient’s symptomatology. This comprehensive review is focused on deciphering molecular mechanisms and the implications regarding those pathologies’ clinical advancement and provides an analytical overview of genetic mutations in the case of neurodegenerative disorders. With the help of well-developed modern genetic investigations, these clinically complex disturbances are highly understood nowadays, being an important step in establishing molecularly targeted therapies and implementing those approaches in the physician’s practice

From Homeostasis to Pathology: Decoding the Multifaceted Impact of Aquaporins in the Central Nervous System

Aquaporins (AQPs), integral membrane proteins facilitating selective water and solute transport across cell membranes, have been the focus of extensive research over the past few decades. Particularly noteworthy is their role in maintaining cellular homeostasis and fluid balance in neural compartments, as dysregulated AQP expression is implicated in various degenerative and acute brain pathologies. This article provides an exhaustive review on the evolutionary history, molecular classification, and physiological relevance of aquaporins, emphasizing their significance in the central nervous system (CNS). The paper journeys through the early studies of water transport to the groundbreaking discovery of Aquaporin 1, charting the molecular intricacies that make AQPs unique. It delves into AQP distribution in mammalian systems, detailing their selective permeability through permeability assays. The article provides an in-depth exploration of AQP4 and AQP1 in the brain, examining their contribution to fluid homeostasis. Furthermore, it elucidates the interplay between AQPs and the glymphatic system, a critical framework for waste clearance and fluid balance in the brain. The dysregulation of AQP-mediated processes in this system hints at a strong association with neurodegenerative disorders such as Parkinson’s Disease, idiopathic normal pressure hydrocephalus, and Alzheimer’s Disease. This relationship is further explored in the context of acute cerebral events such as stroke and autoimmune conditions such as neuromyelitis optica (NMO). Moreover, the article scrutinizes AQPs at the intersection of oncology and neurology, exploring their role in tumorigenesis, cell migration, invasiveness, and angiogenesis. Lastly, the article outlines emerging aquaporin-targeted therapies, offering a glimpse into future directions in combatting CNS malignancies and neurodegenerative diseases