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Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months, despite treatment, with most patients experiencing recurrence within 9 months of resection. The propensity of recurrence in GBM exemplifies the fatal course of the disease and remains an underlying area of study as novel instances of recurrence are encountered. The authors present a unique case of a 31-year-old male patient with a history of cerebellomedullary junction astrocytoma who later developed a supratentorial GBM followed by recurrence centered around a preexisting ventriculoperitoneal catheter and located in the hemisphere contralateral to his first GBM. Each of these lesions was initially thought to represent de novo glial neoplasms because of the absence of intervening T2 fluid-attenuated inversion recovery signal change between each lesion. However, next-generation sequencing using the GlioSeq™ platform revealed similar mutational profiles in both GBMs, suggesting an alternative method of migration of tumor cells to the shunt catheter site, and a local inflammatory environment likely triggering recurrence. This study concludes that in rare instances, in the presence of dormant glioma cells, intracranial foreign bodies may promote an inflammatory microenvironment that may activate tumorigenesis.
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The insular cortex, a critical hub in the brain's sensory, cognitive, and emotional networks, remains an intriguing subject of study. In this article, we discuss its intricate functional neuroanatomy, emphasizing its pivotal role in processing olfactory information. Through concise exploration, we delve into the insula's diverse connectivity and its involvement in sensory integration, particularly in olfaction. Stimulation studies in humans reveal compelling insights into the insula's contribution to the perception of smell, hinting at its broader implications for cognitive processing. Additionally, we explore an avenue of research in which studying olfactory processing via insular stimulation could unravel higher-level cognitive processes. This innovative approach could help give a fresh perspective on the interplay between sensory and cognitive domains, offering valuable insights into the neural mechanisms underlying cognition and emotion. In conclusion, future research efforts should emphasize a multidisciplinary approach, combining advanced imaging and surgical techniques to explore the intricate functions of the human insula. Moreover, awake craniotomies could offer a unique opportunity for real-time observation, shedding light on its neural circuitry and contributions to higher-order brain functions. Furthermore, olfaction's direct cortical projection enables precise exploration of insular function, promising insights into cognitive and emotional processes. This multifaceted approach will deepen our understanding of the insular cortex and its significance in human cognition and emotion.
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BACKGROUND: Previous research indicates that reflection can foster medical communication competence. However, best practices for embedding reflection in online medical education are missing. This study examined how reflection processes can be promoted and embedded in an e-learning course on physician-patient communication to foster learning. METHODS: We investigated three differently designed e-learning conditions featuring different proportions of reflection triggers and compared their effects on students' reflections. We had 114 medical students in their first clinical year complete one of the variants: video modelling (VM, n = 39), video reflection (VR, n = 39), or a variant merging both approaches (VMR, n = 36). Each student wrote a total of nine reflections based on the same guiding questions at three time points embedded in the course. The students' levels of reflection were measured using an adapted version of the REFLECT rubric (scale 0-18). RESULTS: Students of all course variants achieved good levels of reflection beyond the descriptive level at all three time points, with no significant differences between the variants. The mean reflection scores at the end of the course were M = 14.22 for VM (SD = 2.23), M = 13.56 for VR (SD = 2.48), and M = 13.24 for VMR (SD = 2.21). Students who completed VM showed significantly improved levels of reflection over the course, whereas we found no statistically significant development for those in VR or VMR. The reflection scores correlated significantly positively with each other, as did the text lengths of the written reflections. Reflection scores also correlated significantly positively with text length. CONCLUSIONS: Our study offers a teaching strategy that can foster good levels of reflection, as demonstrated in the three e-learning variants. The developed reflection prompts can be easily embedded in various e-learning environments and enable reflections of good quality, even in settings with limited available teaching time.
Subject(s)
Communication , Students, Medical , Humans , Students, Medical/psychology , Female , Education, Medical, Undergraduate/methods , Male , Education, Distance , Physician-Patient Relations , Computer-Assisted Instruction/methods , Clinical Competence , Video Recording , Young Adult , Adult , CurriculumABSTRACT
OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions. METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched. RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02). CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.
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BACKGROUND: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN. METHODS: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed. RESULTS: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(ß -24.9, 95%CI -39.0 to -10.7,p < 0.001). CONCLUSION: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible. LEVEL OF EVIDENCE: IV.
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BACKGROUND: Blunt traumatic abdominal wall hernias (TAWHs) are rare but require a variety of operative techniques to repair including bone anchor fixation (BAF) when tissue tears off bony structures. This study aimed to provide a descriptive analysis of BAF technique for blunt TAWH repair. Bone anchor fixation and no BAF repairs were compared, hypothesizing increased hernia recurrence with BAF repair. METHODS: A secondary analysis of the WTA blunt TAWH multicenter study was performed including all patients who underwent repair of their TAWH. Patients with BAF were compared to those with no BAF with bivariate analyses. RESULTS: 176 patients underwent repair of their TAWH with 41 (23.3%) undergoing BAF. 26 (63.4%) patients had tissue fixed to bone, with 7 of those reinforced with mesh. The remaining 15 (36.6%) patients had bridging mesh anchored to bone. The BAF group had a similar age, sex, body mass index, and injury severity score compared to the no BAF group. The time to repair (1 vs 1 days, P = .158), rate of hernia recurrence (9.8% vs 12.7%, P = .786), and surgical site infection (SSI) (12.5% vs 15.6%, P = .823) were all similar between cohorts. CONCLUSIONS: This largest series to date found nearly one-quarter of TAWH repairs required BAF. Bone anchor fixation repairs had a similar rate of hernia recurrence and SSI compared to no BAF repairs, suggesting this is a reasonable option for repair of TAWH. However, future prospective studies are needed to compare specific BAF techniques and evaluate long-term outcomes including patient-centered outcomes such as pain and quality of life.
Subject(s)
Herniorrhaphy , Surgical Mesh , Wounds, Nonpenetrating , Humans , Male , Female , Wounds, Nonpenetrating/surgery , Herniorrhaphy/methods , Adult , Middle Aged , Abdominal Injuries/surgery , Suture Anchors , Recurrence , Retrospective Studies , Treatment Outcome , Hernia, Ventral/surgery , Hernia, Abdominal/surgery , Hernia, Abdominal/etiology , Injury Severity Score , Surgical Wound Infection/etiology , Surgical Wound Infection/epidemiologyABSTRACT
BACKGROUND: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS: We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS: We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS: Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE: Level 2, Diagnostic Tests or Criteria.
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Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes. Restorative retinoic acid therapy in murine glioma models promotes clonal CD4 + T cell expansion and induces tumor regression in IDHm, but not IDH wildtype (IDHwt), gliomas. Our findings provide a mechanistic rationale for RA immunotherapy in IDHm glioma and is the basis for an ongoing investigator-initiated, single-center clinical trial investigating all-trans retinoic acid (ATRA) in recurrent IDHm human subjects.
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From its beginnings in 2018, the international elite-master program Biomedical Neuroscience of TUM School of Medicine and Health at Technical University of Munich was guided by two convictions: First, excellent research depends not only on the mediation of scientific knowledge and skills, but also on a multifaceted understanding of science itself. Second, teaching must recognize and support not only student's growing expertise but also their personal and professional development. To this end, the module Life & Science was designed. It gives students the opportunity to explore neuroscience from different angles to deepen the epistemological, sociological, and cultural understanding of their chosen profession.
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PURPOSE: Breast cancer that metastasizes to the spine is associated with low quality of life and poor survival. Radiosurgery has an increasing role in this patient population. This single-institution (2003-2023) study analyzes clinical outcomes and prognostic factors for patients who underwent spinal stereotactic radiosurgery (SSRS) for metastatic breast cancer. METHODS: Ninety patients (155 unique breast cancer spinal metastases) were treated with SSRS. The median age was 57 years (range: 35-88), and the median KPS was 80 (range: 40-100). Forty-two (27%) lesions were managed surgically prior to radiosurgery. At SSRS, 75 (48%) lesions impinged or compressed the spinal cord per the epidural spinal cord scale (ESCC). Seventy-nine (51%) lesions were categorized as potentially unstable or unstable by the Spinal Instability Neoplastic Score (SINS). RESULTS: The median follow-up was 15 months (range: 1-183). The median single-session tumor volume was 25.4 cc (range: 2-197), and the median single-fraction prescription dose was 17 Gy (range: 12-25). Seven (5%) lesions locally progressed. The 1-, 2-, and 5-year local control rates were 98%, 97%, and 92%, respectively. The median overall survival (OS) for the cohort was 32 months (range: 2-183). The 1-, 2-, and 5-year OS rates were 72%, 53%, and 30%, respectively. On univariate analysis, KPS ≥ 80 (p = 0.009, HR: 0.51, 95% CI: 0.31-0.84) was associated with improved OS. Patient-reported pain improved (68%), remained stable (29%), or worsened (3%) following radiosurgery. Fifteen (10%) radiation-induced toxicities were reported. CONCLUSIONS: Spinal radiosurgery is a safe and highly effective long-term treatment modality for metastases to the spine that originate from breast cancer.
Subject(s)
Breast Neoplasms , Radiosurgery , Spinal Neoplasms , Humans , Middle Aged , Female , Radiosurgery/adverse effects , Breast Neoplasms/surgery , Quality of Life , Spinal Neoplasms/radiotherapy , Spinal Neoplasms/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
[This corrects the article DOI: 10.4102/sajid.v37i1.363.].
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Snakes and lizards (Squamata) represent a third of terrestrial vertebrates and exhibit spectacular innovations in locomotion, feeding, and sensory processing. However, the evolutionary drivers of this radiation remain poorly known. We infer potential causes and ultimate consequences of squamate macroevolution by combining individual-based natural history observations (>60,000 animals) with a comprehensive time-calibrated phylogeny that we anchored with genomic data (5400 loci) from 1018 species. Due to shifts in the dynamics of speciation and phenotypic evolution, snakes have transformed the trophic structure of animal communities through the recurrent origin and diversification of specialized predatory strategies. Squamate biodiversity reflects a legacy of singular events that occurred during the early history of snakes and reveals the impact of historical contingency on vertebrate biodiversity.
Subject(s)
Biological Evolution , Snakes , Animals , Biodiversity , Genomics , Lizards/classification , Locomotion , Phylogeny , Snakes/classification , Snakes/geneticsABSTRACT
BACKGROUND: Preoperative symptom severity in cervical spondylotic myelopathy (CSM) can be variable. Radiomic signatures could provide an imaging biomarker for symptom severity in CSM. This study utilizes radiomic signatures of T1-weighted and T2-weighted magnetic resonance imaging images to correlate with preoperative symptom severity based on modified Japanese Orthopaedic Association (mJOA) scores for patients with CSM. METHODS: Sixty-two patients with CSM were identified. Preoperative T1-weighted and T2-weighted magnetic resonance imaging images for each patient were segmented from C2-C7. A total of 205 texture features were extracted from each volume of interest. After feature normalization, each second-order feature was further subdivided to yield a total of 400 features from each volume of interest for analysis. Supervised machine learning was used to build radiomic models. RESULTS: The patient cohort had a median mJOA preoperative score of 13; of which, 30 patients had a score of >13 (low severity) and 32 patients had a score of ≤13 (high severity). Radiomic analysis of T2-weighted imaging resulted in 4 radiomic signatures that correlated with preoperative mJOA with a sensitivity, specificity, and accuracy of 78%, 89%, and 83%, respectively (P < 0.004). The area under the curve value for the ROC curves were 0.69, 0.70, and 0.77 for models generated by independent T1 texture features, T1 and T2 texture features in combination, and independent T2 texture features, respectively. CONCLUSIONS: Radiomic models correlate with preoperative mJOA scores using T2 texture features in patients with CSM. This may serve as a surrogate, objective imaging biomarker to measure the preoperative functional status of patients.
Subject(s)
Spinal Cord Diseases , Spondylosis , Humans , Treatment Outcome , Radiomics , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , Spinal Cord Diseases/pathology , Magnetic Resonance Imaging/methods , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Cervical Vertebrae/pathology , Spondylosis/diagnostic imaging , Spondylosis/surgery , Spondylosis/complications , BiomarkersABSTRACT
OBJECTIVE: The present study investigated the efficacy of the didactic approaches of video modeling (VM, best-practice examples), video reflection (VR, problem-based approach), and the combination of both (VMR) in fostering medical communication competence in a video-based digital learning environment. METHODS: N = 126 third-year medical students who participated in the pre-post study were assigned to either the intervention groups (VM, VR, and VMR) or the wait-list control group. The efficacy of the three approaches was assessed by means of a situational judgment test (SJT) of medical communication competence. To investigate the differences between the wait-list control and the intervention groups (H1), between the single-mode and combined conditions (H2), and between VM and VR (H3), we applied planned contrast analyses. RESULTS: The planned contrasts showed that the VR condition significantly improved learning outcomes in comparison to the VM condition (H3). The decreased mean scores of the VM condition offset the increased mean scores of VR, and thus no significant differences could be found in H1 and H2. CONCLUSIONS: Our study provides promising evidence that VR fosters medical communication competence more effectively than VM. PRACTICAL IMPLICATIONS: Medical students' learning in video-based digital environments can be facilitated by the use of interactive VR.
Subject(s)
Computer-Assisted Instruction , Students, Medical , Humans , Clinical Competence , Learning , CommunicationABSTRACT
BACKGROUND: Blunt traumatic abdominal wall hernias (TAWH) occur in <1 % of trauma patients. Optimal repair techniques, such as mesh reinforcement, have not been studied in detail. We hypothesize that mesh use will be associated with increased surgical site infections (SSI) and not improve hernia recurrence. MATERIALS AND METHODS: A secondary analysis of the Western Trauma Association blunt TAWH multicenter study was performed. Patients who underwent TAWH repair during initial hospitalization (1/2012-12/2018) were included. Mesh repair patients were compared to primary repair patients (non-mesh). A logistic regression was conducted to assess risk factors for SSI. RESULTS: 157 patients underwent TAWH repair during index hospitalization with 51 (32.5 %) having mesh repair: 24 (45.3 %) synthetic and 29 (54.7 %) biologic. Mesh patients were more commonly smokers (43.1 % vs. 22.9 %, p = 0.016) and had a larger defect size (10 vs. 6 cm, p = 0.003). Mesh patients had a higher rate of SSI (25.5 % vs. 9.5 %, p = 0.016) compared to non-mesh patients, but a similar rate of recurrence (13.7 % vs. 10.5%, p = 0.742), hospital length of stay (LOS), and mortality. Mesh use (OR 3.66) and higher ISS (OR 1.06) were significant risk factors for SSI in a multivariable model. CONCLUSION: Mesh was used more frequently in flank TAWH and those with a larger defect size. Mesh use was associated with a higher incidence and risk of SSI but did not reduce the risk of hernia recurrence. When repairing TAWH mesh should be employed judiciously, and prospective randomized studies are needed to identify clear indications for mesh use in TAWH.
Subject(s)
Hernia, Ventral , Herniorrhaphy , Humans , Hernia, Ventral/etiology , Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Prospective Studies , Recurrence , Surgical Mesh/adverse effects , Surgical Wound Infection/etiologyABSTRACT
Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.
Subject(s)
Glioma , Histones , Animals , Child , Humans , Mice , Extracellular Signal-Regulated MAP Kinases , Glioma/genetics , Glycolysis , Histones/genetics , Phosphofructokinase-2 , Phosphoric Monoester Hydrolases , Signal TransductionABSTRACT
Bedside teaching (BST) is a core element of medical education. In light of a reported decrease in BST, evidence on how to use BST time most efficiently should be developed. Given that little research into the tangible quality characteristics of good BST has been reported, we investigated the influence of various teacher and structural characteristics on the perceived quality of BST. We filmed and coded 36 BSTs involving 24 lecturers and 259 students. Structural characteristics of interest were: number of students and patients, overall duration, and the proportion of clinical examination. Lecturer questionnaires provided insight into teaching experience and intrinsic motivation, and student evaluations assessed the quality of BSTs in three dimensions. Correlations are reported using the Pearson r and a linear mixed model (LMM). The intrinsic motivation of lecturers was significantly positively correlated with perceived quality, but their experience was only weakly so correlated. In the LMM, a significant association was observed for the quality dimension of clinical teaching with the number of patients and the proportion of time spent on clinical examination. Based on our findings, we recommend including multiple patients in BSTs, and providing substantial opportunities for clinical examination. Regarding lecturers, motivation matters more than experience.
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Motivation , Teaching , Humans , Students, Medical/psychology , Faculty, Medical/psychology , Video Recording , Surveys and Questionnaires , Female , Education, Medical/methods , MaleABSTRACT
Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional tissue is therefore crucial. Fluorescence-guided surgery aims to improve resection accuracy and is well studied for brain tumors, but its efficacy has not been fully assessed for spinal tumors. This meta-analysis aims to delineate the efficacy of fluorescence guidance in intradural spinal tumor resection. The authors performed a systematic review in four databases. We included studies that have utilized fluorescence agents, 5-aminolevulinic acid (5-ALA) or sodium fluorescein, for the resection of intradural spinal tumors. A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 12 studies involving 552 patients undergoing fluorescence-guided intradural spinal tumor resection were included. Meningiomas demonstrated a 98% fluorescence rate and were associated with a homogenous florescence pattern; however, astrocytomas had variable fluorescence rate with pooled proportion of 70%. There was no significant difference in gross total resection (GTR) rates between fluorescein and 5-ALA (94% vs 84%, p = .22). Pre-operative contrast enhancement was significantly associated with intraoperative fluorescence with fluorescein. Intramedullary tumors with positive intraoperative fluorescence were significantly associated with higher GTR rates (96% vs 73%, p = .03). Utilizing fluorescence guidance during intradural spinal tumor resection holds promise of improving intraoperative visualization for specific intradural spinal tumors. Meningiomas and ependymomas have the highest fluorescence rates especially with sodium fluorescein; on the other hand, astrocytomas have variable fluorescence rates with no superiority of either agent. Positive fluorescence of intramedullary tumors is associated with a higher degree of resection.
Subject(s)
Astrocytoma , Meningeal Neoplasms , Meningioma , Spinal Cord Neoplasms , Spinal Neoplasms , Humans , Spinal Neoplasms/surgery , Fluorescein , Fluorescence , Meningioma/surgery , Spinal Cord Neoplasms/surgery , Aminolevulinic Acid , Meningeal Neoplasms/surgeryABSTRACT
Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the entire organoid cytoarchitecture, while uninduced ish-TPN cerebral organoids recapitulated the normal cytoarchitecture of the brain. Transcriptomic analysis revealed a proneural GBM subtype. This proof-of-concept study offers a valuable resource for directly investigating the emergence and progression of gliomas within the context of specific genetic alterations in normal cerebral organoids.