Clinical Risk Factors Affecting Survival of Primary Cerebral Malignant Astrocytoma at a University Hospital in Western Saudi Arabia

Objective: Malignant astrocytomas are the most aggressive tumors affecting the brain. The natural history of survival of malignant astrocytomas differs significantly between anaplastic astrocytoma and glioblastoma multiforme (1). The clinical risk factors affecting the survival of malignant astrocytomas are scarcely studied (2). The aim of this study is to describe the clinical risk factors affecting the survival of malignant astrocytomas at king abdulaziz university hospital in Jeddah.Materials and Method: From January 2004 to December 2008, medical files of patients with a diagnosis of anaplastic astrocytoma and glioblastoma multiforme were retrospectively reviewed. Only those with characteristic pathologic findings suggestive of malignant astrocytomas were enrolled. Demographic data and clinical manifestations with outcome were analyzed. All data were processed using SPSS 16 software (SPSS Inc., Chicago Illinois).The data were analysed for age, symptoms, signs and clinical risk factors influencing the survival of both tumours. Differences with p < 0.05 were considered significant.Results: Forty eight cases were evaluated. The number of anaplastic astrocytoma was 15 (31.25%) and the number of GBM was 33 (68.75%). The mean age for glioblastoma multiforme was 55.3 ± 27.5 years. The mean age of anaplastic astrocytoma was 27.4 ± 21.3 years. Risk factors that worsen the prognosis were: A- old age p = .00002, B- Vomiting p < .02, C- Numbness p < .0001, D- Cranial nerves abnormalities p < .0004 and E- Abnor-mal mental status p < .003.Conclusion: Clinical risk factors affecting the survival negatively of patients with malignant astrocytomas are age, presentation with vomiting, numbness, abnormal mental status and abnormal cranial nerves examination

Gut-Spine Connection: Unexplored Pathways to Improving Outcomes in Spinal Health and Disease

Introduction: Lumbar spinal fusion is among the most expensive procedures in the Medicare system, with costs exceeding $33 billion annually. Improving recovery outcomes for these procedures is critical, and emerging research suggests that microbiome-targeted therapies could play a key role. There is growing evidence linking spinal health with gut microbiota alterations, particularly through the gut-spine axis, which involves the gut-disc, gut-bone, and gut-immune interactions. This bidirectional relationship between gut microbiota and spinal health offers a novel approach for understanding recovery mechanisms. Additionally, magnesium deficiency, which is prevalent, may exacerbate both gut dysbiosis and poor bone health, contributing to chronic skeletal catabolic conditions such as osteoporosis. According to epidemiological studies, more than 50% of the U.S. population consumes less magnesium than the recommended dietary allowance (RDA). This widespread inadequate intake has resulted in a high prevalence of magnesium deficiency across the country. We have analyzed how gut microbiome-targeted therapies, including magnesium supplementation, may improve spinal health and recovery outcomes. Methods: Using publications from 2010 to 2024, we conducted a comprehensive literature review focusing on PubMed and Google Scholar, searching for key terms such as gut microbiome, gut dysbiosis, spinal injury, probiotics, bone health, “magnesium,” and surgical outcomes. We selected studies that investigated the relationship between the gut microbiome and spinal health, as well as potential interventions to improve recovery. Results: Spinal injuries significantly disrupt gut microbiota, leading to dysbiosis, delayed recovery, and increased systemic inflammation. This disruption affects nutrient absorption, inflammatory cytokine activity, and short-chain fatty acid production, all of which are critical for good bone health. Pre-existing conditions like osteoporosis and inflammatory bowel disease exacerbate these effects, while perioperative antibiotic use worsens microbiota imbalances. Animal studies have demonstrated that interventions like fecal microbiota transplantation (FMT) and probiotics can restore gut homeostasis, enhance functional recovery, and reduce inflammation in spinal injury models. Furthermore, magnesium supplementation has potential for modulating dysbiosis and supporting bone healing. Conclusion: Gut microbiome-targeted interventions, including probiotics, FMT, and magnesium supplementation, offer promising strategies to improve recovery outcomes in spinal injury care. Given the widespread magnesium deficiency in the population and its anabolic effects on bone health, integrating nutrient supplementation into recovery plans is crucial. Future research should focus on incorporating these therapies into holistic spinal injury management to optimize patient outcomes

The anterior gradient homologue 2 (AGR2) co‑localises with the glucose‑regulated protein 78 (GRP78) in cancer stem cells, and is critical for the survival and drug resistance of recurrent glioblastoma: in situ and in vitro analyses

open access articleBackground: Glioblastomas (GBs) are characterised as one of the most aggressive primary central nervous system tumours (CNSTs). Single-cell sequencing analysis identified the presence of a highly heterogeneous population of cancer stem cells (CSCs). The proteins anterior gradient homologue 2 (AGR2) and glucose-regulated protein 78 (GRP78) are known to play critical roles in regulating unfolded protein response (UPR) machinery. The UPR machinery influences cell survival, migration, invasion and drug resistance. Hence, we investigated the role of AGR2 in drug-resistant recurrent glioblastoma cells. Methods: Immunofluorescence, biological assessments and whole exome sequencing analyses were completed under in situ and in vitro conditions. Cells were treated with CNSTs clinical/preclinical drugs taxol, cisplatin, irinotecan, MCK8866, etoposide, and temozolomide, then resistant cells were analysed for the expression of AGR2. AGR2 was repressed using single and double siRNA transfections and combined with either temozolomide or irinotecan. Results: Genomic and biological characterisations of the AGR2-expressed Jed66_GB and Jed41_GB recurrent glioblastoma tissues and cell lines showed features consistent with glioblastoma. Immunofluorescence data indicated that AGR2 co-localised with the UPR marker GRP78 in both the tissue and their corresponding primary cell lines. AGR2 and GRP78 were highly expressed in glioblastoma CSCs. Following treatment with the aforementioned drugs, all drug-surviving cells showed high expression of AGR2. Prolonged siRNA repression of a particular region in AGR2 exon 2 reduced AGR2 protein expression and led to lower cell densities in both cell lines. Co-treatments using AGR2 exon 2B siRNA in conjunction with temozolomide or irinotecan had partially synergistic effects. The slight reduction of AGR2 expression increased nuclear Caspase-3 activation in both cell lines and caused multinucleation in the Jed66_GB cell line. Conclusions: AGR2 is highly expressed in UPR-active CSCs and drug-resistant GB cells, and its repression leads to apoptosis, via multiple pathways

Acute liver failure following paracetamol overdose

Background Acute liver failure is a rare syndrome comprising a coagulopathy of liver origin, jaundice and encephalopathy in a patient with no prior history of liver disease. Paracetamol overdose is the leading cause of acute liver failure in the United Kingdom and often presents with extrahepatic organ dysfunction requiring critical care. Presentation: We present the case of a patient with hyper acute liver failure secondary to paracetamol overdose. Management and discussion: Management focused on ensuring the correct diagnosis had been made, administering N-acetyl cysteine, fluid resuscitation and broad spectrum antimicrobials. Early intubation and transfer to a transplant centre were undertaken following development of hepatic encephalopathy. Neuroprotective measures and hypertonic saline were instituted to reduce the risk of intracranial hypertension. High dose haemofiltration was also started to help reduce ammonia levels. Aggressive critical care therapies with specialised input results in good outcomes for patients admitted with paracetamol induced hyper acute liver failure. Liver transplant is reserved for those patients unlikely to survive with medical treatment alone. </jats:sec