Protective Role for Smooth Muscle Cell Hepcidin in Abdominal Aortic Aneurysm.

BACKGROUND: Hepcidin is a liver-derived hormone that controls systemic iron homeostasis, by inhibiting the iron exporter ferroportin in the gut and spleen, respective sites of iron absorption and recycling. Hepcidin is also expressed ectopically in the context of cardiovascular disease. However, the precise role of ectopic hepcidin in underlying pathophysiology is unknown. In patients with abdominal aortic aneurysm (AAA), hepcidin is markedly induced in smooth muscle cells (SMCs) of the aneurysm wall and inversely correlated with the expression of LCN2 (lipocalin-2), a protein implicated in AAA pathology. In addition, plasma hepcidin levels were inversely correlated with aneurysm growth, suggesting hepcidin has a potential disease-modifying role. METHODS: To probe the role of SMC-derived hepcidin in the setting of AAA, we applied AngII (Angiotensin-II)-induced AAA model to mice harbouring an inducible, SMC-specific deletion of hepcidin. To determine whether SMC-derived hepcidin acted cell-autonomously, we also used mice harboring an inducible SMC-specific knock-in of hepcidin-resistant ferroportinC326Y. The involvement of LCN2 was established using a LCN2-neutralizing antibody. RESULTS: Mice with SMC-specific deletion of hepcidin or knock-in of hepcidin-resistant ferroportinC326Y had a heightened AAA phenotype compared with controls. In both models, SMCs exhibited raised ferroportin expression and reduced iron retention, accompanied by failure to suppress LCN2, impaired autophagy in SMCs, and greater aortic neutrophil infiltration. Pretreatment with LCN2-neutralizing antibody restored autophagy, reduced neutrophil infiltration, and prevented the heightened AAA phenotype. Finally, plasma hepcidin levels were consistently lower in mice with SMC-specific deletion of hepcidin than in controls, indicating that SMC-derived hepcidin contributes to the circulating pool in AAA. CONCLUSIONS: Hepcidin elevation in SMCs plays a protective role in the setting of AAA. These findings are the first demonstration of a protective rather than deleterious role for hepcidin in cardiovascular disease. They highlight the need to further explore the prognostic and therapeutic value of hepcidin outside disorders of iron homeostasis.

Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Prediction of Abdominal Aortic Aneurysm Growth Using Geometric Assessment of Computerized Tomography Images Acquired During the Aneurysm Surveillance Period.

OBJECTIVE: We investigated the utility of geometric features for future AAA growth prediction. BACKGROUND: Novel methods for growth prediction of AAA are recognized as a research priority. Geometric feature have been used to predict cerebral aneurysm rupture, but not examined as predictor of AAA growth. METHODS: Computerized tomography (CT) scans from patients with infra-renal AAAs were analyzed. Aortic volumes were segmented using an automated pipeline to extract AAA diameter (APD), undulation index (UI), and radius of curvature (RC). Using a prospectively recruited cohort, we first examined the relation between these geometric measurements to patients' demographic features (n = 102). A separate 192 AAA patients with serial CT scans during AAA surveillance were identified from an ongoing clinical database. Multinomial logistic and multiple linear regression models were trained and optimized to predict future AAA growth in these patients. RESULTS: There was no correlation between the geometric measurements and patients' demographic features. APD (Spearman r = 0.25, P < 0.05), UI (Spearman r = 0.38, P < 0.001) and RC (Spearman r =-0.53, P < 0.001) significantly correlated with annual AAA growth. Using APD, UI, and RC as 3 input variables, the area under receiver operating characteristics curve for predicting slow growth (<2.5 mm/yr) or fast growth (>5 mm/yr) at 12 months are 0.80 and 0.79, respectively. The prediction or growth rate is within 2 mm error in 87% of cases. CONCLUSIONS: Geometric features of an AAA can predict its future growth. This method can be applied to routine clinical CT scans acquired from patients during their AAA surveillance pathway.

A Deep Learning Approach to Visualize Aortic Aneurysm Morphology Without the Use of Intravenous Contrast Agents.

BACKGROUND: Intravenous contrast agents are routinely used in CT imaging to enable the visualization of intravascular pathology, such as with abdominal aortic aneurysms. However, the injection is contraindicated in patients with iodine allergy and is associated with renal complications. OBJECTIVES: In this study, we investigate if the raw data acquired from a noncontrast CT image contains sufficient information to differentiate blood and other soft tissue components. A deep learning pipeline underpinned by generative adversarial networks was developed to simulate contrast enhanced CTA images using noncontrast CTs. METHODS AND RESULTS: Two generative models (cycle- and conditional) are trained with paired noncontrast and contrast enhanced CTs from seventy-five patients (total of 11,243 pairs of images) with abdominal aortic aneurysms in a 3-fold cross-validation approach with a training/testing split of 50:25 patients. Subsequently, models were evaluated on an independent validation cohort of 200 patients (total of 29,468 pairs of images). Both deep learning generative models are able to perform this image transformation task with the Cycle-generative adversarial network (GAN) model outperforming the Conditional-GAN model as measured by aneurysm lumen segmentation accuracy (Cycle-GAN: 86.1% ± 12.2% vs Con-GAN: 85.7% ± 10.4%) and thrombus spatial morphology classification accuracy (Cycle-GAN: 93.5% vs Con-GAN: 85.7%). CONCLUSION: This pipeline implements deep learning methods to generate CTAs from noncontrast images, without the need of contrast injection, that bear strong concordance to the ground truth and enable the assessment ofimportant clinical metrics. Our pipeline is poised to disrupt clinical pathways requiring intravenous contrast.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

A Deep Learning Pipeline to Automate High-Resolution Arterial Segmentation With or Without Intravenous Contrast.

BACKGROUND: Existing methods to reconstruct vascular structures from a computerized tomography (CT) angiogram rely on contrast injection to enhance the radio-density within the vessel lumen. However, pathological changes in the vasculature may be present that prevent accurate reconstruction. In aortic aneurysmal disease, a thrombus adherent to the aortic wall within the expanding aneurysmal sac is present in >90% of cases. These deformations prevent the automatic extraction of vital clinical information by existing image reconstruction methods. AIM: In this study, a deep learning architecture consisting of a modified U-Net with attention-gating was implemented to establish a high-throughput and automated segmentation pipeline of pathological blood vessels in CT images acquired with or without the use of a contrast agent. METHODS AND RESULTS: Seventy-Five patients with paired noncontrast and contrast-enhanced CT images were randomly selected from an ongoing study (Ethics Ref 13/SC/0250), manually annotated and used for model training and evaluation. Data augmentation was implemented to diversify the training data set in a ratio of 10:1. The performance of our Attention-based U-Net in extracting both the inner (blood flow) lumen and the wall structure of the aortic aneurysm from CT angiograms was compared against a generic 3-D U-Net and displayed superior results. Implementation of this network within the aortic segmentation pipeline for both contrast and noncontrast CT images has allowed for accurate and efficient extraction of the morphological and pathological features of the entire aortic volume. CONCLUSIONS: This extraction method can be used to standardize aneurysmal disease management and sets the foundation for complex geometric and morphological analysis. Furthermore, this pipeline can be extended to other vascular pathologies.

Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans.

OBJECTIVE: Discovery of novel biomarkers for AAA growth prediction. BACKGROUND: Novel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction. METHODS: Patients were prospectively recruited. Plasma samples were collected at baseline (n = 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n = 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10-12 weeks after surgery (n = 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n = 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers. RESULTS: We discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively. CONCLUSION: We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.

The role of dipeptidyl peptidase-IV in abdominal aortic aneurysm pathogenesis: A systematic review.

Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management relies exclusively on surgical repair as there is no effective medical therapy. A key element of AAA pathogenesis is the chronic inflammation mediated by inflammatory cells releasing proteases, including the enzyme dipeptidyl peptidase IV (DPP-IV). This review sought to recapitulate available evidence on the involvement of DPP-IV in AAA development. Further, we assessed the experimental use of currently available DPP-IV inhibitors for AAA management in murine models. Embase, Medline, PubMed, and Web of Science databases were utilised to access the relevant studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A narrative synthesis approach was used. Sixty-four studies were identified from the searched databases; a final 11 were included in the analysis. DPP-IV was reported to be significantly increased in both AAA tissue and plasma of patients and correlated with AAA growth. DPP-IV inhibitors (sitagliptin, vildagliptin, alogliptin, and teneligliptin) were all shown to attenuate AAA formation in murine models by reducing monocyte differentiation, the release of reactive oxygen species (ROS), and metalloproteinases (MMP-2 and MMP-9). DPP-IV seems to play a role in AAA pathogenesis by propagating the inflammatory microenvironment. This is supported by observations of decreased AAA formation and reduction in macrophage infiltration, ROS, matrix MMPs, and interleukins following the use of DPP-IV inhibitors in murine models. There is an existing translational gap from preclinical observations to clinical trials in this important and novel mechanism of AAA pathogenesis. This prior literature highlights the need for further research on molecular targets involved in AAA formation.

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

Palliative Surgery or Metallic Stent Positioning for Advanced Gastric Cancer: Differences in QOL.

BACKGROUND AND OBJECTIVES: Twenty percent of the patients affected with stage IV antropyloric stomach cancer are hospitalized with a gastric outlet obstruction syndrome (GOOS) requiring its resolution to improve the quality of life (QoL). We present our preliminary short- and mid-term results regarding the influence of endoscopic placement of self-expandable metal stent (SEMS) or open stomach-partitioning gastrojejunostomy in QoL. MATERIALS AND METHODS: In this prospective randomized longitudinal cohort trial, we randomly assigned 27 patients affected with stage IV antropyloric stomach cancer into two groups: Group 1 (13 patients) who underwent SEMS positioning and Group 2 (14 patients) in whom open stomach-partitioning gastrojejunostomy was performed. The Karnofsky performance scale and QoL assessment using the EQ-5D-5L™ questionnaire was administered before treatment and thereafter at 1, 3, and 6 months. Results: At 1-month, index values showed a statistically significant deterioration of the QoL in patients of Group 2 when compared to those of Group 1 (p = 0.004; CI: 0.04 to 0.21). No differences among the groups were recorded at 3-month; whereas, at 6-month, the index values showed a statistically significant deterioration of the QoL in patients of Group 1 (p = 0.009; CI: -0.25 to -0.043). CONCLUSIONS: Early QoL of patients affected with stage IV antropyloric cancer and symptoms of GOOS is significantly better in patients treated with SEMS positioning but at 6-month the QoL significantly decrease in this group of patients. We explained the reasons of this fluctuation with the higher risk of re-hospital admission in the SEMS group.

The Spatial Morphology of Intraluminal Thrombus Influences Type II Endoleak after Endovascular Repair of Abdominal Aortic Aneurysms.

INTRODUCTION: Type 2 endoleaks (T2Es) after endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) can lead to sac expansion or failure of sac regression, and often present as a management dilemma. The intraluminal thrombus (ILT) may influence the likelihood of endoleaks after EVAR and can be characterized using routine preoperative imaging. We examined the relationship between preoperative spatial morphology of ILT and the incidence of postoperative T2E. METHODS: All patients who underwent EVAR at the John Radcliffe Hospital (Oxford, UK) were prospectively entered in a clinical database. Computed tomography angiograms (CTAs) were performed as part of routine clinical care. The ILT morphology of each patient was determined using the preoperative CTA. Arterial phase cross-sectional images of the AAA were analyzed according to the presence and morphology of the thrombus in each quadrant. The overall ILT morphology was defined by measurements obtained over a 4-cm segment of the AAA. The diagnosis of T2Es during EVAR surveillance was confirmed by CTAs. The relation between the ILT morphology and T2E was assessed using logistic regression. RESULTS: Between September 2009 and July 2016, 271 patients underwent EVAR for infrarenal AAAs (male: 241, age = 79 ± 7). The ILT was present in 265 (98%) of AAAs. Mean follow-up was 1.9 ± 1.6 years. The T2E was observed in 77 cases. Sixty-one percent of T2Es were observed within the first week after surgery. The T2E was observed in 50% (3/6) of cases without the ILT (no-ILT). Compared with no-ILT, the presence of circumferential or posterolateral ILTs was protective from T2Es (odds ratio = 0.33 and 0.37; P = 0.002 and P = 0.047, respectively). CONCLUSIONS: The spatial ILT morphology on routine preoperative CTA imaging can be a biomarker for post-EVAR T2Es. ILTs that cover the posterolateral aspects of the lumen, or circumferential ILTs, are protective of T2Es. This information can be useful in the preoperative planning of EVARs.

Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study.

Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study.

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Adult IDH Wild-Type Glioblastoma Ultrastructural Investigation Suggests a Possible Correlation between Morphological Biomarkers and Ki-67 Index.

Glioblastoma is an aggressive brain tumor with an average life expectancy between 14 and 16 months after diagnosis. The Ki-67 labeling index (LI), a measure of cellular proliferation, is emerging as a prognostic marker in GBM. In this study, we investigated the ultrastructure of glioblastoma tissue from 9 patients with the same molecular profile (adult IDH wild-type glioblastoma, wild-type ATRX, and positive for TP53 expression, GFAP expression, and EGFR overexpression) to find possible ultrastructural features to be used as biomarkers and correlated with the only parameter that differs among our samples, the Ki-67 LI. Our main results were the visualization of the anatomical basis of astrocyte-endothelial cells crosstalk; the ultrastructural in situ imaging of clusters of hyperactivated microglia cells (MsEVs); the ultrastructural in situ imaging of microglia cells storing lipid vesicles (MsLVs); the ultrastructural in situ imaging of neoplastic cells mitophagy (NCsM). The statistical analysis of our data indicated that MsEVs and MsLVs correlate with the Ki-67 LI value. We can thus assume they are good candidates to be considered morphological biomarkers correlating to Ki-67 LI. The role of NCsM instead must be further evaluated. Our study findings demonstrate that by combining ultrastructural characteristics with molecular information, we can discover biomarkers that have the potential to enhance diagnostic precision, aid in treatment decision-making, identify targets for therapy, and enable personalized treatment plans tailored to each patient. However, further research with larger sample sizes is needed to validate these findings and fully utilize the potential of ultrastructural analysis in managing glioblastoma.

Role of 1p/19q Codeletion in Diffuse Low-grade Glioma Tumour Prognosis.

BACKGROUND/AIM: In the latest 2021 WHO classification of central nervous system tumours (CNS), gliomas that present isocitrate dehydrogenase (IDH) mutations are defined as diffuse low-grade gliomas (DLGGs). IDH mutations are commonly observed in this tumour type. The Extent of Resection (EOR) positively influence survival; however, it is still debated whether the predictive value of EOR is independent of the 1p/19q co-deletion. We carried out a retrospective analysis on patients operated on for DLGG at the Sant'Andrea University Hospital Sapienza University of Rome, correlating the outcome with the presence of 1p/19q co-deletion and EOR. PATIENTS AND METHODS: The study examined 66 patients with DLGG who had undergone surgery for tumour resection between 2008 and 2018. Patients with DLGG were divided into two groups; diffuse astrocytoma (DA) in which 1p/19q codeletion is absent and oligodendroglioma (OG) in which 1p/19q codeletion is present. According to EOR, both groups were divided into two subgroups: subtotal resection (STR) and gross total resection (GTR). Three end-point variables were considered: overall survival (OS), progression-free survival (PFS) and time to malignant transformation (TMT). RESULTS: In the DA group, the GTR subgroup had an average OS of 81.6 months, an average PFS of 45.9 months and an average TMT of 63.6 months. After surgery, these patients had an average Karnofsky Performance Score (KPS) of 83.4. The STR subgroup had an average OS of 60.4 months, PFS was 38.7 months, and TMT was 46.4 months, post-operative KPS was 83.4. In contrast, in the OG group, the GTR averagely had 101.7 months of OS, 64.9 months of PFS, 80.3 months of TMT and an average post-operative KPS of 84.2, and the STR subgroup had an average of OS of 73.3 months, PFS of 48.2 months, TMT of 57.3 and an average postoperative KPS of 96.2. CONCLUSION: In patients affected by DLGGs, 1p/19q codeletion is significantly associated with prolonged survival and longer time-to-malignant transformation (TMT) compared to the absence of 1p/19q codeletion. Also, the extent of surgical resection (EOR) in DLGG patients has been confirmed as one of the main prognostic factors. However, its predictive value is substantially influenced by the presence of the 1p/19q codeletion.

Cortical atrophy in chronic subdural hematoma from ultra-structures to physical properties.

Several theories have tried to elucidate the mechanisms behind the pathophysiology of chronic subdural hematoma (CSDH). However, this process is complex and remains mostly unknown. In this study we performed a retrospective randomised analysis comparing the cortical atrophy of 190 patients with unilateral CSDH, with 190 healthy controls. To evaluate the extent of cortical atrophy, CT scan images were utilised to develop an index that is the ratio of the maximum diameter sum of 3 cisterns divided by the maximum diameter of the skull at the temporal lobe level. Also, we reported, for the first time, the ultrastructural analyses of the CSDH using a combination of immunohistochemistry methods and transmission electron microscopy techniques. Internal validation was performed to confirm the assessment of the different degrees of cortical atrophy. Relative Cortical Atrophy Index (RCA index) refers to the sum of the maximum diameter of three cisterns (insular cistern, longitudinal cerebral fissure and cerebral sulci greatest) with the temporal bones' greatest internal distance. This index, strongly related to age in healthy controls, is positively correlated to the preoperative and post-operative maximum diameter of hematoma and the midline shift in CSDH patients. On the contrary, it negatively correlates to the Karnofsky Performance Status (KPS). The Area Under the Receiver Operating Characteristics (AUROC) showed that RCA index effectively differentiated cases from controls. Immunohistochemistry analysis showed that the newly formed CD-31 positive microvessels are higher in number than the CD34-positive microvessels in the CSDH inner membrane than in the outer membrane. Ultrastructural observations highlight the presence of a chronic inflammatory state mainly in the CSDH inner membrane. Integrating these results, we have obtained an etiopathogenetic model of CSDH. Cortical atrophy appears to be the triggering factor activating the cascade of transendothelial cellular filtration, inflammation, membrane formation and neovascularisation leading to the CSDH formation.