ABSTRACT
PURPOSE: To investigate differences in sociodemographic characteristics and short-term outcomes between patients undergoing prenatal versus postnatal myelomeningocele repair. METHODS: Patients who underwent myelomeningocele repair at our institution were stratified based on prenatal or postnatal timing of repair. Baseline characteristics and outcomes were compared. Multivariate analysis was performed to identify whether prenatal repair was a predictor of outcomes independent of socioeconomic measures. RESULTS: 49 patients underwent postnatal repair, and 30 underwent prenatal repair. Patients who underwent prenatal repair were more likely to have private insurance (73.3% vs. 42.9%, p = 0.03) and live farther from the hospital where they received their repair (251.5 ± 447.4 vs. 72.5 ± 205.6 miles, p = 0.02). Patients who underwent prenatal repair had shorter hospital stays (14.3 ± 22.7 days vs. 25.3 ± 20.1 days, p = 0.03), fewer complications (13.8% vs. 42.9%, p = 0.01), fewer 30-day ED visits (0.0% vs. 34.0%, p < 0.001), lower CSF diversion rates (13.8% vs. 38.8%, p = 0.02), and better functional status at 3-months (13.3% vs. 57.1% delayed, p = 0.009), 6-months (20.0% vs. 56.7% delayed, p = 0.03), and 1-year (29.4% vs. 70.6% delayed, p = 0.007). On multivariate analysis, prenatal repair was an independent predictor of inpatient complication (OR(95%CI): 0.19(0.05-0.75), p = 0.02) and 3-month (OR(95%CI): 0.14(0.03-0.80) p = 0.03), 6-month (OR(95%CI): 0.12(0.02-0.73), p = 0.02), and 1-year (OR(95%CI): 0.19(0.05-0.80), p = 0.02) functional status. CONCLUSION: Prenatal repair for myelomeningocele is associated with better outcomes and developmental functional status. However, patients receiving prenatal closure are more likely to have private health insurance and live farther from the hospital, suggesting potential barriers to care.
Subject(s)
Hydrocephalus , Meningomyelocele , Pregnancy , Female , Humans , Meningomyelocele/surgery , Hydrocephalus/surgery , Neurosurgical Procedures/adverse effects , Insurance, Health , Socioeconomic FactorsABSTRACT
We report a unique case of a huge malignant peripheral nerve sheath tumor with probable smooth muscle differentiation.
Subject(s)
Nerve Sheath Neoplasms , Neurilemmoma , Humans , Neurilemmoma/diagnostic imaging , Neurilemmoma/surgery , Neurilemmoma/pathology , Buttocks/surgery , Buttocks/pathology , Diagnosis, Differential , Peripheral Nerves , Nerve Sheath Neoplasms/diagnostic imaging , Nerve Sheath Neoplasms/surgery , Nerve Sheath Neoplasms/pathologyABSTRACT
Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.
Subject(s)
Brain Neoplasms , Glioblastoma , Animals , Mice , Humans , Glioblastoma/pathology , Brain Neoplasms/therapy , Brain Neoplasms/drug therapy , Disease Models, AnimalABSTRACT
Background: Infliximab (IFX) biosimilar was the first biosimilar approved in Jordan in 2014, with limited evidence of its safety and effectiveness from the Middle East and North Africa (MENA) region. Thus, this study aimed to evaluate the safety and effectiveness of IFX biosimilar in active rheumatoid arthritis (RA) patients over 34 weeks by investigating (1) the adverse events (AEs), serious adverse events (SAEs), and therapy discontinuation and (2) the score changes of the 28-Joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Methods: This multicenter prospective cohort study collected clinical parameters within hospital settings every four weeks. The numbers and percentages of observed AEs and SAEs were informed. The DAS28 utilizing Erythrocyte Sedimentation Rate (ESR), HAQ-DI, and ESR were reported at baseline and 14th and 30th weeks; thus, they were reported as means (SD). Results: A total of 22 RA patients were enrolled and initiated IFX biosimilar, of which nine (41.0%) discontinued the study, but their data were analyzed up to the point of withdrawal. A total of 35 AEs were reported in 14 patients, including two (5.7%) SAEs. None of the participants discontinued treatment due to AEs. The mean (SD) score of DAS28-ESR significantly decreased from 6.55 (1.16) at baseline to 4.59 (1.45) at week 14 (p < 0.0001) and to 4.77 (1.09) at week 30 (p < 0.0001). Similarly, the mean (SD) HAQ-DI score significantly decreased from 0.95 (0.74) at baseline to 0.48 (0.62) at week 14 (p=0.008) and to 0.71 (0.78) at week 30 (p=0.483). The mean (SD) value of ESR decreased from 58.75 (26.94) at baseline to 47.92 (33.89) at week 14 (p=0.082) and to 39.83 (17.38) at week 30 (p=0.005). Conclusion: IFX biosimilar demonstrated safety and effectiveness in managing RA patients bringing real-world clinical support for biosimilars' role in rheumatology.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Humans , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/adverse effects , Infliximab/adverse effects , Jordan , Prospective StudiesABSTRACT
Aneurysms arising in the spinal circulation are rare and underreported. The objective of this study was to systematically review the English literature on different aspects of isolated spinal aneurysms using the PubMed, Ovid MEDLINE, and Google Scholar databases. Eighty-two papers reporting 107 individual patient cases were included. Most isolated spinal aneurysms have a fusiform morphology, and are most commonly found in the anterior spinal artery at the thoracic or cervical levels. Subarachnoid hemorrhage is the most common form of presentation, and sudden onset back pain is the most common initial symptom. The diagnosis of spinal aneurysms requires a high degree of clinical suspicion. Because of their small size, they can be missed on CT/MR angiography and spinal angiogram may be employed. Treatment of spinal aneurysms should be individualized on a case-by-case basis. Conservative management can be a valid option in spinal aneurysms where the risk of treatment is high. Surgical or endovascular intervention may be indicated in cases of significant or progressive neurologic decline due aneurysmal mass effect, or progressive growth of the aneurysm despite conservative treatment.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Subarachnoid Hemorrhage , Aneurysm, Ruptured/surgery , Humans , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/surgery , Spinal Cord/blood supply , Spine , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/etiology , Subarachnoid Hemorrhage/surgery , Treatment Outcome , Vertebral Artery/surgeryABSTRACT
BACKGROUND AND OBJECTIVE: Comparative effectiveness research plays a vital role in health care delivery. Specialty training is one of these variables; surgeons who are trained in different specialties may have different outcomes performing the same procedure. The objective of this study was to investigate the impact of spine surgeon specialty (neurosurgery vs orthopedic surgery) on early perioperative outcome measures of elective posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective, 1:4 propensity score-matched cohort study. 5520 AIS patients were reviewed from ACS-NSQIP pediatric database. Propensity score matching was utilized. RESULTS: Patients operated on by orthopedic surgeons were more likely to have shorter operation time (263 min vs 285 min), shorter total hospital stay (95 h vs 118 h), lower rate of return to operating room within the same admission (1.2% vs 3.8%), lower discharge rates after postoperative day 4 (23.8% vs 30.9%), and lower unplanned readmission rate (1.6% vs 4.1%), (p < 0.05). On the other hand, patients operated on by neurosurgeons had lower perioperative blood transfusion rate (62.1% vs 69.8%), (p < 0.05). Other outcome measures and mortality rates were not significantly different between the two cohorts. CONCLUSIONS: This retrospective study found significant differences in early perioperative outcomes of patients undergoing PSF for AIS by neurosurgeons and orthopedic surgeons. Further studies are recommended to corroborate this finding which may trigger changes in the educational curriculum for neurosurgery residents.
Subject(s)
Kyphosis , Scoliosis , Spinal Fusion , Surgeons , Adolescent , Child , Cohort Studies , Humans , Kyphosis/etiology , Retrospective Studies , Scoliosis/etiology , Scoliosis/surgery , Spinal Fusion/methods , Treatment OutcomeABSTRACT
Significant advancements in the treatment of spinal cord injury (SCI) were developed in the setting of military conflicts, partly due to the large numbers of injuries sustained by service members. No effective SCI treatment options existed into the early 20th century, and soldiers who sustained these injuries were usually considered untreatable. Extensive progress was made in SCI treatment during and after World War II, as physical therapy was increasingly encouraged for patients with SCI, multidisciplinary teams oversaw care, pathophysiology was better understood, and strategies were devised to prevent wound infection and pressure sores. Recent conflicts in Iraq and Afghanistan have caused a substantial rise in the proportion of SCIs among causes of casualties and wounds, largely due to new forms of war and weapons, such as improvised explosive devices. Modern military SCIs resulting from blast mechanisms are substantively different from traumatic SCIs sustained by civilians. The treatment paradigms developed over the past 100 years have increased survival rates and outcomes of soldiers with SCI. In this paper, the authors review the role of military conflicts in the development of therapeutic interventions for SCI and discuss how these interventions have improved outcomes for soldiers and civilians alike.
Subject(s)
Military Medicine , Military Personnel , Spinal Cord Injuries , Spinal Injuries , Afghanistan , Humans , Spinal Cord Injuries/etiology , Spinal Cord Injuries/therapy , Survival RateABSTRACT
The blood-brain barrier (BBB) constitutes a microvascular network responsible for excluding most drugs from the brain. Treatment of brain tumors is limited by the impermeability of the BBB and, consequently, survival outcomes for malignant brain tumors remain poor. Nanoparticles (NPs) represent a potential solution to improve drug transport to brain tumors, given their small size and capacity to target tumor cells. Here, we review the unique physical and chemical properties of NPs that aid in BBB transport and discuss mechanisms of NP transport across the BBB, including paracellular transport, carrier-mediated transport, and adsorptive- and receptor-mediated transcytosis. The major types of NPs investigated for treatment of brain tumors are detailed, including polymeric NPs, liposomes, solid lipid NPs, dendrimers, metals, quantum dots, and nanogels. In addition to their role in drug delivery, NPs can be used as imaging contrast agents and can be conjugated with imaging probes to assist in visualizing tumors, demarcating lesion boundaries and margins, and monitoring drug delivery and treatment response. Multifunctional NPs can be designed that are capable of targeting tumors for both imaging and therapeutic purposes. Finally, limitations of NPs for brain tumor treatment are discussed.
Subject(s)
Brain Neoplasms , Nanoparticles , Blood-Brain Barrier , Brain , Brain Neoplasms/drug therapy , Drug Delivery Systems , Humans , Nanoparticles/chemistry , TechnologyABSTRACT
Aortic injury is a rare, yet underreported and underestimated complication of spine surgery. Anatomical relation between the aorta and the spine changes under physiological (positional) as well as pathological (deformity) conditions, which puts the aorta at risk of injury during spine surgery. Clinical presentation of aortic injury ranges from asymptomatic perforation of the aorta to acute fatal bleeding. Although several diagnostic methods have been reported, CT-angiography remains an important diagnostic study. Several advancements in the open and the endovascular surgical management have been reported to be successfully used in the management of aortic injury following spine surgery. Management approach of malpositioned screws abutting the aorta is still controversial. Anatomical knowledge and understanding of the previously reported mechanisms of aortic injury are important to be integrated in the preoperative planning process. If the complication occurs, time-to- recognition and to-appropriate-management are important factors for predicting mortality. If unrecognized and untreated in the acutely injured patients, mortality can approach 100%.
Subject(s)
Surgeons , Vascular System Injuries , Humans , Spine , Vascular System Injuries/diagnosis , Vascular System Injuries/etiology , Vascular System Injuries/surgeryABSTRACT
Most of the debilitating conditions following aneurysmal subarachnoid hemorrhage result from symptomatic cerebral vasospasm and delayed cerebral ischemia. Several scales are being used, but they still lack objectivity and fail to quantify complications considered essential for prognostication routine use of biomarkers to predict complications and outcomes after aneurysmal rupture is still experimental. Degradomics were studied extensively in traumatic brain injury, but there is no discussion of these biomarkers related to aneurysmal subarachnoid hemorrhage. Degradomics involve the activation of proteases that target specific substrates and generate specific protein fragments called degradomes. While the proteolytic activities constitute the pillar of development, growth, and regeneration of tissues, dysregulated proteolysis resulting from pathological conditions like aneurysmal subarachnoid hemorrhage ends up in apoptotic processes and necrosis. To our knowledge, this is the first overview that lists a panel of degradomics with cut-off values in serum and cerebrospinal fluid, where specificity and sensitivity are only found in Kallikrein 6, Ubiquitin C Terminal Hydrolase 1 and Alpha-II-Spectrin.
Subject(s)
Biomarkers/metabolism , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/metabolism , Peptide Hydrolases/metabolism , Proteomics , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/metabolism , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Humans , Intracranial Aneurysm/complications , Subarachnoid Hemorrhage/complicationsABSTRACT
Meningiomas are amongst the most commonly encountered intracranial tumors. The majority of these tumors arise intracranially, and the remaining incidents occur along the spinal cord. Meningiomas tend to grow gradually, with many tumors arising in inaccessible locations. Such sporadic behavior poses a therapeutic challenge to clinicians, causing incomplete tumor resections that often lead to recurrence. Therefore, ongoing research seeks to find alternative systematic treatments for meningiomas, with gene-based therapeutics of high interest. Subsequently, genetic studies characterized frequent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA. These genes are communally exhibited in 80% of sporadic meningiomas. In addition, other genes such as the DUSP family, the NR4 family, CMKOR, and FOSL2, have been identified as key players in spinal meningiomas. In this perspective, we aim to investigate current genetic-based studies, with the ongoing research mainly focused on the above NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA genes and their involved pathways. In addition, this perspective can serve as a potential cornerstone for future genetic analyses of meningioma cases.
Subject(s)
Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/genetics , Meningioma/drug therapy , Meningioma/genetics , HumansABSTRACT
Aneurysmal subarachnoid hemorrhage is a devastating condition, often leading to a debilitating outcome. Delayed ischemic neurological deficits are considered the feared sequelae. Proteomics is a large-scale study of proteins incorporating structural and functional properties in complex biological fluids. Analysis of proteomes has led to identifying relevant complex proteins related to specific pathophysiological processes reflecting the severity and extent of diseases. Proteomics has evolved in the past few years; more biomarkers are deemed clinically relevant to diagnose, monitor, and define prognosis in patients with aneurysmal subarachnoid hemorrhage. Despite the absence of candidate biomarkers in the clinical routine, many have shown promising results. The complexity of proteins implicated in aneurysmal subarachnoid hemorrhage rendered these biomarkers' clinical use paved with various pitfalls and technical difficulties, especially when data about the perfect timing and values are lacking. We review the latest literature concerning serum proteomics and their clinical utility regarding the prediction of cerebral vasospasm and other complications of aneurysmal subarachnoid hemorrhage, as well as the clinical outcome. Future prospective studies will allow changing the disease's course, label patients according to their prognosis to provide earlier and better management and improve outcomes.
Subject(s)
Biomarkers/blood , Intracranial Aneurysm/blood , Proteome/metabolism , Proteomics , Subarachnoid Hemorrhage/blood , Humans , Intracranial Aneurysm/complications , Intracranial Aneurysm/diagnosis , Proteomics/methods , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/etiologyABSTRACT
OBJECTIVE: The differential diagnosis for postoperative back pain is broad, and conventional imaging modalities are not always conclusive. Therefore, we performed a systematic review of the literature and present case studies describing the use of single-photon emission CT (SPECT)/CT or positron emission tomography (PET)/CT in the diagnosis of back pain following spine surgery. METHODS: A systematic review was conducted according to PRISMA guidelines across 5 databases. Relevant keywords included PET/CT, bone SPECT/CT, and pseudarthrosis. The studies were assessed for diagnostic accuracy of the imaging technologies. RESULTS: A total of 2,444 studies were screened, 91 were selected for full-text review, and 21 were ultimately included. Six retrospective studies investigated the use of SPECT/CT with a total sample size of 309 patients. Two of these studies used SPECT/CT to predict screw loosening in over 50% of patients. Eight studies examined the use of 18-fluoride sodium fluoride (18F-NaF) PET/CT. Among these studies, measures of diagnostic accuracy varied but overall demonstrated the ability of 18F-NaF PET/CT to detect screw loosening and pseudarthrosis. Seven studies examined 18F-fluorodeoxyglucose (FDG) PET/CT and supported its utility in the diagnosis of postoperative infections in the spine. CONCLUSIONS: PET/CT and SPECT/CT are useful in the evaluation of postoperative pain of the spine, especially in patients for whom conventional imaging modalities yield inconclusive results. More diagnostic accuracy studies with strong reference standards are needed to compare hybrid imaging to conventional imaging.
Subject(s)
Positron Emission Tomography Computed Tomography , Pseudarthrosis , Humans , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies , Positron-Emission Tomography/methods , Pain, Postoperative/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Back Pain , Fluorodeoxyglucose F18 , Sensitivity and SpecificityABSTRACT
OBJECTIVE: Pedicle screw placement guidance is critical in spinal fusions, and spinal surgery robots aim to improve accuracy and reduce complications. Current literature has yet to compare the relative merits of available robotic systems. In this review, the authors aimed to 1) assess the current state of spinal robotics literature; 2) conduct a meta-analysis of robotic performance based on accuracy, speed, and safety; and 3) offer recommendations for robotic system selection. METHODS: Following PRISMA guidelines, the authors conducted a systematic literature review across PubMed, Embase, Cochrane Library, Web of Science, and Scopus as of April 28, 2022, for studies on approved robots for placing lumbar pedicle screws. Three reviewers screened and extracted data relating to the study characteristics, accuracy rate, intraoperative revisions, and reoperations. Secondary performance metrics included operative time, blood loss, and radiation exposure. The authors statistically compared the performance of the robots using a random-effects model to account for variation within and between the studies. Each robot was also compared with performance benchmarks of traditional techniques including freehand, fluoroscopic, and CT-navigated insertion. Finally, we performed a Duval and Tweedie trim-and-fill test to assess for the presence of publication bias. RESULTS: The authors identified 46 studies, describing 4670 patients and 25,054 screws, that evaluated 4 different robotic systems: Mazor X, ROSA, ExcelsiusGPS, and Cirq. The weighted accuracy rates of Gertzbein-Robbins classification grade A or B screws were as follows: ExcelsiusGPS, 98.0%; ROSA, 98.0%; Mazor, 98.2%; and Cirq, 94.2%. No robot was significantly more accurate than the others. However, the accuracy of the ExcelsiusGPS was significantly higher than that of traditional methods, and the accuracies of the Mazor and ROSA were significantly higher than that of fluoroscopy. The intraoperative revision rates were Cirq, 0.55%; ROSA, 0.91%; Mazor, 0.98%; and ExcelsiusGPS, 1.08%. The reoperation rates were Cirq, 0.28%; ExcelsiusGPS, 0.32%; and Mazor, 0.76% (no reoperations were reported for ROSA). Operative times were similar for all robots. Both the ExcelsiusGPS and Mazor were associated with significantly less blood loss than the ROSA. The Cirq had the lowest radiation exposure. Robots tended to be more accurate and generally their use was associated with fewer reoperations and less blood loss than freehand, fluoroscopic, or CT-navigated techniques. CONCLUSIONS: Robotic platforms perform comparably based on key metrics, with high accuracy rates and low intraoperative revision and reoperation rates. The spinal robotics publication rate will continue to accelerate, and choosing a robot will depend on the context of the practice.
ABSTRACT
Glioblastoma (GBM) represents a profoundly aggressive and heterogeneous brain neoplasm linked to a bleak prognosis. Hypoxia, a common feature in GBM, has been linked to tumor progression and therapy resistance. In this study, we aimed to identify hypoxia-related differentially expressed genes (DEGs) and construct a prognostic signature for GBM patients using multi-omics analysis. Patient cohorts were collected from publicly available databases, including the Gene Expression Omnibus (GEO), the Chinese Glioma Genome Atlas (CGGA), and The Cancer Genome Atlas-Glioblastoma Multiforme (TCGA-GBM), to facilitate a comprehensive analysis. Hypoxia-related genes (HRGs) were obtained from the Molecular Signatures Database (MSigDB). Differential expression analysis revealed 41 hypoxia-related DEGs in GBM patients. A consensus clustering approach, utilizing these DEGs' expression patterns, identified four distinct clusters, with cluster 1 showing significantly better overall survival. Machine learning techniques, including univariate Cox regression and LASSO regression, delineated a prognostic signature comprising six genes (ANXA1, CALD1, CP, IGFBP2, IGFBP5, and LOX). Multivariate Cox regression analysis substantiated the prognostic significance of a set of three optimal signature genes (CP, IGFBP2, and LOX). Using the hypoxia-related prognostic signature, patients were classified into high- and low-risk categories. Survival analysis demonstrated that the high-risk group exhibited inferior overall survival rates in comparison to the low-risk group. The prognostic signature showed good predictive performance, as indicated by the area under the curve (AUC) values for one-, three-, and five-year overall survival. Furthermore, functional enrichment analysis of the DEGs identified biological processes and pathways associated with hypoxia, providing insights into the underlying mechanisms of GBM. Delving into the tumor immune microenvironment, our analysis revealed correlations relating the hypoxia-related prognostic signature to the infiltration of immune cells in GBM. Overall, our study highlights the potential of a hypoxia-related prognostic signature as a valuable resource for forecasting the survival outcome of GBM patients. The multi-omics approach integrating bulk sequencing, single-cell analysis, and immune microenvironment assessment enhances our understanding of the intricate biology characterizing GBM, thereby potentially informing the tailored design of therapeutic interventions.
ABSTRACT
Serpins are serine proteinase inhibitors, with several serpins being overexpressed in cancer cells. Thus, we aim to analyze the single-nucleotide polymorphism (SNP) of Serpinb11 and its association with GBM survival. A cohort of 63 GBM patients recruited from King Abdullah University Hospital in Jordan underwent polymorphism analysis and overall survival (OS) assessments. The Cancer Genome Atlas (GBM) cohort was useful for validation. We constructed a risk score using the principal component analysis for the following Serpin genes: Serpinb3, Serpinb5, Serpinb6, Serpinb11, and Serpinb12, and patients were grouped into high- vs. low-risk groups based on the median cutoff. Univariable Cox models were used to study the survival outcomes. We identified a significant association between rs4940595 and survival. In the TCGA cohort, Serpinb3 alterations showed worse OS. Univariable Cox showed worse PFS outcomes with higher SERPINB5 and SERPINB6 expression. A Serpin B 5-gene risk score showed a trend towards worse PFS in the high-risk group. Upregulated DEGs showed GO enrichment in cytokine regulation and production, positive regulation of leukocyte activation, and the MAPK cascade. The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.
ABSTRACT
Novel therapeutic and diagnostic methods are sorely needed for gliomas, which contribute yearly to hundreds of thousands of cancer deaths worldwide. Despite the outpouring of research efforts and funding aimed at improving clinical outcomes for patients with glioma, the prognosis for high-grade glioma, and especially glioblastoma, remains dire. One of the greatest obstacles to improving treatment efficacy and destroying cancer cells is the safe delivery of chemotherapeutic drugs and biologics to the tumor site at a high enough dose to be effective. Over the past few decades, a burst of research has leveraged nanotechnology to overcome this obstacle. There has been a renewed interest in adapting previously understudied dendrimer nanocarriers for this task. Dendrimers are small, highly modifiable, branched structures featuring binding sites for a variety of drugs and ligands. Recent studies have demonstrated the potential for dendrimers and dendrimer conjugates to effectively shuttle therapeutic cargo to the correct tumor location, permeate the tumor, and promote apoptosis of tumor cells while minimizing systemic toxicity and damage to surrounding healthy brain tissue. This review provides a primer on the properties of dendrimers; outlines the mechanisms by which they can target delivery of substances to the site of brain pathology; and delves into current trends in the application of dendrimers to drug and gene delivery, and diagnostic imaging, in glioma. Finally, future directions for translating these in vitro and in vivo findings to the clinic are discussed.
ABSTRACT
Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized challenges of surgery for adult spinal deformity (ASD). Multiple risk factors have been identified for PJK/PJF, including osteoporosis, frailty, neurodegenerative disease, obesity, and smoking. Several surgical techniques to mitigate risk of PJK/PJF have been identified; however, patient optimization is also critical. This review summarizes the data behind these 5 risk factors (osteoporosis, frailty, neurodegenerative disease, obesity, and smoking) and details the related recommendations for patients undergoing surgery for ASD.
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Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors.
ABSTRACT
BACKGROUND: Microvascular decompression (MVD) using a retrosigmoid approach is a highly effective, open-surgical procedure for neurovascular conflict in the posterior fossa, although there is a risk of postoperative cerebrospinal fluid (CSF) leak. OBJECTIVE: To identify factors associated with postoperative CSF leakage after MVD. METHODS: We retrospectively reviewed all patients who underwent MVDs at our institution from 2007 to 2020. Patient demographics, clinical diagnoses, and procedural characteristics were recorded and compared. Factors leading to CSF leak were analyzed using χ 2 , univariate, and multivariate regression. RESULTS: Of 1011 patients who underwent MVDs, 37 (3.7%) presented with postoperative CSF leaks. In univariate analysis, the use of Cranios/Norian to obliterate the air cells was protective against CSF leak ( P = .01). Craniotomies ( P = .002), the use of dural substitutes such as Durepair ( P = .04), dural onlays such as DuraGen ( P = .04), muscle/fascia ( P = .03), and titanium mesh cranioplasty >5 cm ( P = .03) were associated with CSF leak. On multivariate analysis, only the presence of craniotomies ( P = .04) and nonprimary dural closure ( P = .03) were significant risk factors for CSF leak. When excluding the 34 (3.4%) patients who underwent a craniotomy, the lack of primary dural closure still remained significantly associated with postoperative CSF leak ( P = .04). CONCLUSION: Our results represent one of the largest series of posterior fossa surgeries for a uniform indication in North America. Our study demonstrates increased risk for postoperative CSF leak when craniotomies are performed and when primary dural closure is not established. Given the small sample of patients who received a craniotomy, however, future studies corroborating this finding should be performed.