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The Saudi Thoracic Society (STS) developed an updated evidence-based guideline for diagnosing and managing chronic obstructive pulmonary disease (COPD) in Saudi Arabia. This guideline aims to provide a comprehensive and unbiased review of current evidence for assessing, diagnosing, and treating COPD. While epidemiological data on COPD in Saudi Arabia are limited, the STS panel believes that the prevalence is increasing due to rising rates of tobacco smoking. The key objectives of the guidelines are to facilitate accurate diagnosis of COPD, identify the risk for COPD exacerbations, and provide recommendations for relieving and reducing COPD symptoms in stable patients and during exacerbations. A unique aspect of this guideline is its simplified, practical approach to classifying patients into three classes based on symptom severity using the COPD Assessment Test and the risk of exacerbations and hospitalizations. The guideline provides the reader with an executive summary of recommended COPD treatments based on the best available evidence and also addresses other major aspects of COPD management and comorbidities. This guideline is primarily intended for use by internists and general practitioners in Saudi Arabia.

Abstract Background Age-related macular degeneration (AMD) affects quality of life and independence, and its incidence and prevalence are increasing due to ageing of the population. Access to effective timely treatment can improve vision and reduce incidence of blindness. This study aimed to explore the perspectives of ophthalmologists in the Israeli public healthcare system regarding timely treatment of AMD patients. Methods Qualitative semi-structured interviews were conducted in 2020-2021 with 22 senior ophthalmologists, from 10 general hospitals and from two HMOs, representing different geographic regions. All interviewees specialize in retinal diseases and work with AMD patients. Interviews discussed patient pathways involved in the diagnosis and treatment of AMD, access to care, and obstacles to timely care. Thematic analysis was conducted. Results Based on the interviews, we describe the usual referral and treatment pathways. Themes included regional disparities, long wait times in some areas, a lack of retina specialists, differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second-line treatment not fully covered by insurance, most affecting the weakest segments of the population. Conclusions Loss of vision incurs high health and societal costs. In the context of insufficient medical manpower in Israel, the healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population. Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. Awareness of AMD symptoms and the importance of early intervention could be highlighted by campaigns, particularly among high-risk groups. Highlights • Interviews with hospital-based and community ophthalmologists showed regional disparities in AMD treatment, with long wait times and a lack of retina specialists in some areas. • Differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second line treatment not fully covered by insurance were highlighted. • The healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population • Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. • Awareness of AMD symptoms and the importance of early intervention should be emphasized in high-risk groups.

Background: Understanding the characteristics and outcomes of cancer patients with unplanned ICU admission is imperative for therapeutic decisions and prognostication purposes. Objective: To describe the clinical characteristics of patients with hematological and non-hematological malignancies (NHM) who require unplanned ICU admission and to determine the predictors of mortality and long-term survival. Methods: This retrospective study included all patients with cancer who had an unplanned ICU admission between 2011 and 2016 at a tertiary hospital in Saudi Arabia. The following variables were collected: age, gender, ICU length of stay (LOS), APACHE II score, type of malignancy, febrile neutropenia, source and time of admission, and need for mechanical ventilation (MV), renal replacement therapy (RRT), and treatment with vasopressors (VP). Predictors of mortality and survival rates at 28 days and 3, 6, and 12 months were calculated. Results: The study included 410 cancer patients with 466 unplanned ICU admissions. Of these, 52% had NHM. The average LOS in the ICU was 9.6 days and the mean APACHE score was 21.9. MV was needed in 73% of the patients, RRT in 15%, and VP in 24%, while febrile neutropenia was present in 24%. There were statistically significant differences between survivors and non-survivors in the APACHE II score (17.7 ± 8.0 vs. 25.6 ± 9.2), MV use (52% vs. 92%), need for RRT (6% vs. 23%), VP use (42% vs. 85%), and presence of febrile neutropenia (18% vs. 30%). The predictors of mortality were need for MV (OR = 4.97), VP (OR = 3.43), RRT (OR = 3.31), and APACHE II score (OR = 1.10). Survival rates at 28 days, 3, 6, and 12 months were 52%, 28%, 22%, and 15%, respectively. Conclusion: The survival rate of cancer patients with an unplanned admission to the ICU remains low. Predictors of mortality include need for MV, RRT, and VP and presence of febrile neutropenia. About 85% of cancer patients died within 1 year after ICU admission.

# Background COVID-19 pandemic curfew made it difficult for families to communicate with their loved ones while hospitalized in the intensive care unit (ICU). A hybrid telephone and video conferencing model (VC) was created as a method of communication. This study aims to assess the satisfaction of critically ill non-COVID-19 patients and their families with VC as a mean of communication during the curfew. # Methods A prospective observational study was conducted in two academic hospitals. Family visits were replaced by VC during the curfew and visitation restriction. To assess the satisfaction with VC, families were surveyed twice while patients were surveyed once during the ICU admission. # Results Among 81 family representatives initially surveyed, 26 (32.1%) underwent a follow-up survey. On a scale of 1-10, high general satisfaction was reported by family representatives in the initial and follow-up surveys (8.68 ± 1.66 and 8.31 ± 1.89, respectively). General satisfaction of 9.64 ± 0.67 was reported by the patients who were surveyed during their ICU admission (n=11). Higher patient's Glasgow Coma Scale at the time of VC and increased number of VC sessions were associated with higher family satisfaction (*P*=0.001 and *P*=0.019, respectively). Among family representatives, more than 70% preferred video conferencing over traditional means of communication during the curfew. # Conclusions Family representatives and their critically ill non-COVID-19 patients were highly satisfied with video conferencing as a mean of communication during the curfew and visiting restriction. Video conferencing offers a great way of communication during pandemics, such as COVID-19.

Abstract Background This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality. Methods This was a post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4–7 (at least active standing), 1–3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables. Results Of 1708 patients, only 85 (5.0%) had early mobility level 4–7 and 356 (20.8%) level 1–3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4–7 and 1–3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4–7 group, 7/348 (2.0%) patients in mobility 1–3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4–7 and 1–3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4–7 and 1–3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p

ARL2 regulates the dynamics of cytological components and is highly expressed in colon cancer tissues. Here, we report novel roles of ARL2 in the cell nucleus and colon cancer stem cells (CSCs). ARL2 is expressed at relatively low levels in K‐RAS active colon cancer cells, but its expression is induced in CSCs. Depletion of ARL2 results in M phase arrest exclusively in non‐CSC cultured cells; in addition, DNA break stress accumulates in CSCs leading to apoptosis. ARL2 expression is positively associated with the expression of all six RAD51 family genes, which are essential for homologous recombination repair (HRR). Furthermore, ARL2 is required for HRR and detected within chromatin compartments. These results demonstrate the requirement of ARL2 in colon CSC maintenance, which possibly occurs through mediating double‐strand break DNA repair in the nucleus.

Abstract There are contradictory data regarding the effect of intermittent pneumatic compression (IPC) on the incidence of deep-vein thrombosis (DVT) and heart failure (HF) decompensation in critically ill patients. This study evaluated the effect of adjunctive use of IPC on the rate of incident DVT and ventilation-free days among critically ill patients with HF. In this pre-specified secondary analysis of the PREVENT trial (N = 2003), we compared the effect of adjunctive IPC added to pharmacologic thromboprophylaxis (IPC group), with pharmacologic thromboprophylaxis alone (control group) in critically ill patients with HF. The presence of HF was determined by the treating teams according to local practices. Patients were stratified according to preserved (≥ 40%) versus reduced (

Purpose: To examine the differences in the peripapillary vascular parameters and foveal-avascular-zone (FAZ) vascularity parameters between primary open-angle-glaucoma (POAG) patients versus exfoliation-glaucoma (XFG) patients versus healthy subjects. Methods: This is cross-sectional study and a comparative clinical study. POAG and XFG patients and healthy subjects underwent a comprehensive ophthalmic examination, including visual field optical coherence tomography (OCT) and OCT angiography (OCTA) of the optic disc and FAZ. Differences in peripapillary vessel density (VD), perfusion density (PD), and FAZ area and circularity were examined between all groups, as well as correlations between clinical parameters and vascularity parameters for each glaucoma group. Results: A total of 109 subjects (one eye for each patient) were analyzed, including 45 with POAG, 30 with XFG, and 34 controls. The average peripapillary VDs were the lowest among the XFG patients and the highest among the controls (P < 0.05, ANOVA). The average peripapillary PD of the central ring was the lowest in the XFG group and the highest in the control group (P = 0.02, ANOVA). A significant negative correlation was found between the average peripapillary VDs and PDs of the inner ring and full ring and disease severity of the POAG patients. There was a significant positive correlation between the average peripapillary PDs of the central rings and full ring and the central macular thickness of the XFG patients (P < 0.01 and P < 0.04, respectively, Pearson correlation). Conclusion: The peripapillary vascular parameters of the POAG and XFG patients were lower compared to those of normal participants. A correlation between clinical characteristics of POAG and XFG patients and PD was found. This may hint to a vascular mechanism in glaucoma either primary or secondary to intra-ocular pressure/OAG damage.

Chronic inflammatory airway diseases, including asthma, chronic rhinosinusitis, eosinophilic COPD and allergic rhinitis are a global health concern. Despite the coexistence of these diseases and their common pathophysiology, they are often managed independently, resulting in poor asthma control, continued symptoms and poor quality of life. Understanding disease pathophysiology is important for best treatment practice, reduced disease burden and improved patient outcomes. The pathophysiology of type 2 inflammation is driven by both the innate immune system triggered by pollutants, viral or fungal infections involving type 2 innate lymphoid cells (ILC2) and the adaptive immune system, triggered by contact with an allergen involving type 2 T-helper (Th2) cells. Both ILC2 and Th2 cells produce the type-2 cytokines (interleukin (IL)-4, IL-5 and IL-13), each with several roles in the inflammation cascade. IL-4 and IL-13 cause B-cell class switching and IgE production, release of pro-inflammatory mediators, barrier disruption and tissue remodelling. In addition, IL-13 causes goblet-cell hyperplasia and mucus production. All three interleukins are involved in trafficking eosinophils to tissues, producing clinical symptoms characteristic of chronic inflammatory airway diseases. Asthma is a heterogenous disease; therefore, identification of biomarkers and early targeted treatment is critical for patients inadequately managed by inhaled corticosteroids and long-acting β-agonists alone. The Global Initiative for Asthma guidelines recommend add-on biological (anti IgE, IL-5/5R, IL-4R) treatments for those not responding to standard of care. Targeted therapies, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab, were developed on current understanding of the pathophysiology of type 2 inflammation. These therapies offer hope for improved management of type 2 inflammatory airway diseases.

The Soil and Water Assessment Tool (SWAT) was used to simulate monthly runoff in the Yarmouk River Basin (YRB). The objectives were to assess the performance of this model in simulating the hydrological responses in arid watersheds then utilized to study the impact of YRB agricultural development project on transport of sediments in the YRB. Nine and three years of input data, namely from 2005 to 2013, were used to calibrate the model, whereas data from 2014 to 2015 were used for model validation. Time series plots as well as statistical measures, including the coefficient of determination (R 2) and the Nash–Sutcliffe coefficient of efficiency (NSE) that range between 0 to 1 and −∞ to 1, respectively, between observed and simulated monthly runoff values were used to verify the SWAT simulation capability for the YRB. The SWAT model satisfactorily predicted mean monthly runoff values in the calibration and validation periods, as indicated by R 2 = 0.95 and NSE = 0.96 and R 2 = 0.91 and NSE = 0.63, respectively. The study confirmed the positive impact of soil conservation measures implemented in the YRB development project and confirmed that contouring can reduce soil loss from 15 to 44% during the study period. This study showed that the SWAT model was capable of simulating hydrologic components in the drylands of Jordan.

Various studies have been conducted to conceive the factors of regional economic growth and its nature in order to obtain the right formulation of regional development policy. The main aim of this research is exploring the spatial influence of economic growth in East Java Province. The result of Lagrange Multiplier test shows that the regencies/cities economic growth affects each other in the long term. Parameters estimation on spatial lag model shows that the spatial influence of economic growth inter regencies/cities is negative. These indicate that development activities in East Java Province have not been get synergistic yet.

Abstract Background The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. Methods/design In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is “incident” proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Discussion Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. Trial registration ClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013.

Abstract Objectives To utilize cumulative evaluation data of the pediatric airway management simulation-based learning course on knowledge and practical skills of residents in the Saudi Commission for Health Speciality (SCFHS) in order to measure its efficacy and areas for improvement. Methods The evaluation is a retrospective cohort study that compares pre- and post-test (knowledge and skills) of a pediatric airway management simulation course. The 2-day course has been conducted four times annually at CRESENT and is comprised of interactive lectures on airway management and crew resource management, a demonstration of fundamentals of intubation, three skill stations, and six case scenarios with debriefing. Our evaluation data includes all pediatric residents who attended the course between January and December 2015. Results Forty-six residents participated, of whom 30 (65.2%) are male and 16 (34.78%) are female. Overall, there is statistically significant improvement between the pre-test and post-test knowledge and practical skill scores. The pre-test scores are significantly different between the four different resident levels with p values of 0.003 and

The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.

Vision incapacitation and blindness associated with incurable retinal degeneration affect millions of people worldwide. In this study, 0.25 × 106 human bone marrow stem cells (hBM-MSCs) were transplanted epiretinally in the right eye of Royal College Surgeons (RCS) rats at the age of 28 days. Epiretinally transplanted cells were identified as a thin layer of cells along vitreous cavity, in close proximity to the retina or attached to the lens capsule, up to 6 weeks following transplantation. Epiretinal transplantation delayed photoreceptor degeneration and rescued retinal function up to 20 weeks following cell transplantation. Visual functions remained close to normal levels in epiretinal transplantation rats. No inflammation or any other adverse effects were observed in transplanted eyes. Our findings suggest that transplantation of hBM-MSCs as a thin epiretinal layer is effective for treatment of retinal degeneration in RCS rats, and that transplanting the cells in close proximity to the retina enhances hBM-MSC therapeutic effect compared with intravitreal injection.

BACKGROUND: Dyspnea is a distressing symptom experienced by people with chronic obstructive pulmonary disease (COPD). The dyspnea-12 (D-12) questionnaire comprises of 12 items and assesses the quality of this symptom, its severity and the emotional response. The original (English) version of the D-12 is reliable and valid for the measurement of dyspnea in pulmonary diseases. AIM: To translate the D-12 into Arabic and determine whether this version is reliable and valid in Saudi nationals with COPD. METHODS: The D-12 was translated into Arabic version and reviewed by an expert panel before being back-translated into English. The Arabic version was administered to five patients with COPD to test whether it was easily understood after which a final Arabic version was produced. Thereafter, 40 patients with COPD (aged 63 ΁ 9 years; 33 [82.5%] males; forced expiratory volume in one second (FEV 1 ) 47 ΁ 16% predicted) completed the D-12, the COPD Assessment Test (CAT) and the Chronic Respiratory Disease Questionnaire (CRDQ). Lung function and 6-minute walk distance were also measured. The D-12 was re-administered two weeks later. RESULTS: The Arabic version of the D-12 demonstrated good reliability over the two administration (intraclass correlation coefficient = 0.94, P = 0.01). Strong associations were demonstrated between the (1) total score for the D-12 and the CAT, (2) quality sub-score of the D-12 and the CAT and (3) emotional response sub-score of the D-12 and emotional function domain of the CRDQ (r ≥ 0.6, all P < 0.01). CONCLUSION: The Arabic version of the D-12 is a reliable and valid instrument in Saudi nationals with COPD.

Among the many stilbenoids found in a variety of berries, resveratrol and pterostilbene are of particular interest given their potential for use in cancer therapeutics and prevention. We purified four stilbenoids from R. undulatum and found that pterostilbene inhibits cancer cell proliferation more efficiently than rhapontigenin, piceatannol and resveratrol. To investigate the underlying mechanism of this superior action of pterostilbene on cancer cells, we utilized a reverse-phase protein array followed by bioinformatic analysis and found that the ATM/CHK pathway is modified by pterostilbene in a lung cancer cell line. Given that ATM/CHK signaling requires p53 for its biological effects, we hypothesized that p53 is required for the anticancer effect of pterostilbene. To test this hypothesis, we used two molecularly defined precancerous human bronchial epithelial cell lines, HBECR and HBECR/p53i, with normal p53 and suppressed p53 expression, respectively, to represent premalignant states of squamous lung carcinogenesis. Pterostilbene inhibited the cell cycle more efficiently in HBECR cells compared to HBECR/p53i cells, suggesting that the presence of p53 is required for the action of pterostilbene. Pterostilbene also activated ATM and CHK1/2, which are upstream of p53, in both cell lines, though pterostilbene-induced senescence was dependent on the presence of p53. Finally, pterostilbene more effectively inhibited p53-dependent cell proliferation compared to the other three stilbenoids. These results strongly support the potential chemopreventive effect of pterostilbene on p53-positive cells during early carcinogenesis.

Background and Objectives: In patients with spontaneous intracranial hypotension (SIH), microsurgical repair is recommended in Type 1 (ventral) dural leaks, when conservative measures fail. However, there is lacking consensus on the optimal surgical technique for permanent and safe closure of ventral leaks., Methods: We performed a retrospective analysis of surgically treated SIH patients with Type 1 leaks at our institution between 2013 and 2023. Patients were analyzed according to the type of surgical technique: (1) Microsurgical suture vs (2) extradural and intradural patching (sealing technique). End points were resolution of spinal longitudinal epidural cerebrospinal fluid collection (SLEC), change in brain SIH-Score (Bern-Score), headache resolution after 3 months, surgery time, complications, and reoperation rates., Results: In total, 85 (66% women) patients with consecutive SIH (mean age 47 ± 11 years) underwent transdural microsurgical repair. The leak was sutured in 53 (62%) patients (suture group) and patch-sealed in 32 (38%) patients (sealing group). We found no significant difference in the rates of residual SLEC and resolution of headache between suture and sealing groups (13% vs 22%, P = .238 and 89% vs 94%, P = .508). No changes were found in the postoperative Bern-Score between suture and sealing groups (1.4 [±1.6] vs 1.7 [±2.1] P = 1). Mean surgery time was significantly shorter in the sealing group than in the suture group (139 ± 48 vs 169 ± 51 minutes; P = .007). Ten patients of the suture and 3 of the sealing group had a complication (23% vs 9%, P = .212), whereas 6 patients of the suture and 2 patients of the sealing group required reoperation (11% vs 6%, P = .438)., Conclusion: Microsurgical suturing and patch-sealing of ventral dural leaks in patients with SIH are equally effective. Sealing alone is a significantly faster technique, requiring less spinal cord manipulation and may therefore minimize the risk of surgical complications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Background: Post-dural puncture headache (PDPH) is still mostly regarded a minor complication after lumbar puncture. In the International Classification of Headache Disorders (ICHD)-3 headaches lasting longer than 14 days or persisting after epidural blood patch (EBP) are not even considered. We illustrate that there may be many patients with persisting headaches and a large disease burden., Methods: In a retrospective, single center analysis from 04/2018 to 03/2022 we assessed patients with a dural puncture and orthostatic headache of >14 days duration, resistant to one or more EBPs. Socioeconomic factors and individual patient history were assessed by a specifically designed questionnaire., Results: We included 30 patients with a mean age of 36.4 (±10.6) years. The median duration of acute inpatient care was 31 (Interquartile ratio (IQR) = 32) days and of sick leave 381 (IQR = 666.3) days. Patients consulted a median of 5 (IQR = 6.5) different physicians/ institutions due to chronic post-dural puncture headache (cPDPH). All patients reported major negative impact of cPDPH on their social and work life., Conclusion: Despite long hospitalizations and a profound impairment of social and work lives cPDPH was neglected and underrated in all patients. We conclude that cPDPH needs to be considered and might be an underreported, severe condition which requires further prospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kraus, Häni, El Rahal, Vasilikos, Fariña Nuñez, Volz, Urbach, Lützen, Ulrich, Beck and Fung.)

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool., Methods: The RANO resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model was prognostically verified in a separate external validation cohort., Results: Our training cohort compromised 1003 patients with newly diagnosed isocitrate dehydrogenase-wildtype glioblastoma. Residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, age, and postoperative KPS were prognostic for survival and incorporated into regression tree analysis. By individually weighting the prognostic factors, an additive score (range, 0-9 points) integrating these four variables distinguished patients with low (0-2 points), intermediate (3-5 points), and high risk (6-9 points) for inferior survival. The prognostic value of our risk model was retained in treatment-based subgroups and confirmed in an external validation cohort of 258 patients with glioblastoma. Compared to previously postulated models, goodness-of-fit measurements were superior for our model., Conclusions: The novel RANO risk model serves as an easy-to-use, yet highly prognostic tool for postoperative patient stratification prior to further therapy. The model may serve to guide patient management and reduce imbalances between study arms in prospective trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background and Objectives: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of clinical symptoms, the most common being orthostatic headache. Lateral leaks (Type II) and direct CSF-venous fistulas (Type III) are a subgroup of spinal CSF leaks, representing about 1/3 of spinal CSF leaks. This study aimed to analyze the risk and efficacy of nerve root clipping in patients with Type II and Type III CSF leaks., Methods: All consecutive patients with Type II and Type III CSF fistulas treated with nerve root clipping at our institution from May 2018 to December 2022 were included. Patients were evaluated for postoperative sensory motor deficits and neuropathic pain using the "Douleur Neuropathique 4" questionnaire, and the outcome was evaluated using the "Patient Global Impression of Change" and the return-to-work rate., Results: A total of 40 patients were included, and the mean follow-up time was 22 months. According to the Patient Global Impression of Change, significant symptoms improvement was reported in 85% of patients. Over 87% of patients returned to work fully or partially. One patient experienced a low-grade motor deficit after T1-nerve root clipping. 2.5% of patients developed postoperative neuropathic pain requiring medical treatment under which they fully improved. Over 80% of patients developed dermatomal hypoesthesia, with no reported effect on quality of life., Conclusion: The surgical strategy of noneloquent nerve root clipping shows favorable outcomes and return-to-work rates. There are instances of neuropathic pain and dermatomal hypoesthesia with no significant morbidity. Despite the favorable outcome and low recurrence rate, nerve root-sparing surgical techniques should be further explored., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Introduction: Spontaneous intracranial hypotension (SIH) is an important cause of devastating headaches and caused by CSF-leaks in the spine., Research Question: The aim of this analysis was to gain an overview of the progress of research on SIH over time. The global publication landscape relating to SIH was analyzed and comparisons between regions were made., Material and Methods: A bibliometric analysis was performed by searching for research articles on SIH in PubMed published between 1983 and 2022. Countries responsible for the publications were ranked by the sum of citations. An average annual growth rate was calculated and the density of SIH publications per 100 000 physicians was determined., Results: We identified 974 articles. In 1983 only one SIH patient was reported; in 2021 the number of patients had increased to 4230. The average annual growth rate of SIH publications during this period was 12.7%. The most common publication type were case reports (n = 570). The most common medical specialty of the first author was neurology (n = 251) followed by neurosurgery (n = 250) and radiology (n = 191). Although most publications originated from the United States of America (USA), South Korea had the highest density of SIH investigators (37.86 publications per 100 000 medical doctors). The most cited paper (296 citations) was published in 2006 in JAMA (USA)., Discussion and Conclusion: Research on SIH has increased exponentially over the past four decades. The international community of SIH researchers is growing, and with it the opportunities for global networks involved in research, treatment, and patient education., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: The authors' aim was to assess the velocity and pattern of growth of meningiomas and to correlate the kinetics of tumor growth with their previously reported two-item radiological risk stratification and CNS WHO grade (5th edition, 2021)., Methods: The authors performed a serial volumetric analysis of meningiomas diagnosed radiologically at their institution between 2003 and 2015. The primary endpoint was velocity of diametric expansion (VDE), which represents the slope of the linear regression of the mean tumor diameter against time. For the secondary analysis, they categorized the growth patterns as linear or exponential by fitting time-volume curves to a linear and exponential function. Three radiological risk categories based on T2-weighted iso/hyperintensity and absence of calcifications were compared: low risk (T2-weighted hypointense), intermediate-risk (T2-weighted iso/hyperintense with calcifications), and high-risk (T2-weighted iso/hyperintense without calcifications) tumors., Results: For the entire cohort of 240 meningiomas, the median (IQR) VDE was 0.33 (0.00-0.71) mm/year. Distribution of VDE differed significantly among radiological risk categories (0.49 vs 0.35 vs 0.05 mm/year, p < 0.001). High-risk and intermediate-risk tumors more frequently tended to grow exponentially compared to low-risk tumors (43.8% vs 37.0% vs 8.3%, p = 0.067). The authors found no correlation of growth velocity with CNS WHO grade in their cohort (1.30 mm/year for CNS WHO grade 1 vs 4.01 mm/year for CNS WHO grade 2, p = 0.185)., Conclusions: A radiological risk assessment using two parameters-T2-weighted signal iso/hyperintensity and absence of calcifications-allows estimation of growth velocity and characteristics of untreated intracranial meningiomas. Only high-risk tumors exhibit the potential for rapid growth. However, rapid tumor growth does not indicate a higher CNS WHO grade per se.

Purpose: Spontaneous spinal epidural hematoma (SSEH) is a rare pathology characterized by a hemorrhage in the spinal epidural space without prior surgical or interventional procedure. Recent literature reported contradictory findings regarding the clinical, radiological and surgical factors determining the outcome, hence the objective of this retrospective analysis was to re-assess these outcome-determining factors., Methods: Patients surgically treated for SSEH at our institution from 2010 - 2022 were screened and retrospectively assessed regarding management including the time-to-treatment, the pre-and post-treatment clinical status, the radiological findings as well as other patient-specific parameters. The outcome was assessed using the modified McCormick Scale. Statistical analyses included binary logistic regression and Fisher's exact test., Results: In total, 26 patients (17 men [65%], 9 women [35%], median age 70 years [interquartile range 26.5]) were included for analysis. The SSEHs were located cervically in 31%, cervicothoracically in 42% and thoracically in 27%. Twenty-four patients (92%) improved after surgery. Fifteen patients (58%) had a postoperative modified McCormick Scale grade of I (no residual symptoms) and 8 patients (31%) had a grade of II (mild symptoms). Only 3 (12%) patients remained with a modified McCormick Scale grade of IV or V (severe motor deficits / paraplegic). Neither time-to-treatment, craniocaudal hematoma expansion, axial hematoma occupation of the spinal canal, anticoagulation or antiplatelet drugs, nor the preoperative clinical status were significantly associated with the patients' outcomes., Conclusion: Early surgical evacuation of SSEH generally leads to favorable clinical outcomes. Surgical hematoma evacuation should be indicated in all patients with symptomatic SSEH., (© 2024. The Author(s).)

Objective: Spontaneous intracranial hypotension (SIH) is an important cause of orthostatic headaches caused by spinal CSF leaks. It has a strong negative impact on patients' socioeconomic status and health-related quality of life (HRQOL). This study aimed to analyze the impact of surgical and endovascular treatments on patients' HRQOL., Methods: The authors conducted a prospective, observational cohort study that included all patients treated for SIH with microsurgery or embolization, depending on the type of CSF leak, at their institution between April 2022 and May 2023. Patients were asked to complete a specifically designed questionnaire, as well as the 15D HRQOL questionnaire, before and 3 months after treatment., Results: A total of 21 patients (14 female; mean age 51.7 years) were treated in the study period. There were 12 (57%) type 1 leaks, 3 (14%) type 2, and 6 (29%) type 3. While 20 (95.2%) leaks were localized in the thoracic spine, only 1 (4.8%) was found in the lumbar spine. All patients completed the questionnaires. Fifteen (71.4%) patients underwent microsurgery and 6 (28.6%) endovascular embolization. The mean 15D score improved from 0.802 before to 0.889 after treatment (p = 0.013). Compared with an age- and sex-matched general population, HRQOL was significantly impaired in patients with SIH before treatment. After treatment, the authors found no significant difference in the overall HRQOL between patients and the healthy population. Mean headache intensity on a numeric rating scale improved from 8.1 before treatment to 2.3 after treatment (p = 0.003). Patients reported that SIH had a notable impact on their social and working life., Conclusions: SIH has a considerable negative impact on HRQOL. Microsurgery or embolization can dramatically improve HRQOL, subjective perception of health, and headache intensity. Therefore, surgical or endovascular treatment should be considered given the improvement observed in HRQOL for patients with SIH.

Objective: Glioblastomas are the most common primary central nervous system (CNS) tumors. Although modern management strategies have modestly improved overall survival, the prognosis remains dismal, with treatment side effects often impinging on the clinical course. Glioblastomas cause neurological dysfunction by infiltrating CNS tissue and via perifocal oedema formation. The administration of steroids such as dexamethasone is thought to alleviate symptoms by reducing oedema. However, despite its widespread use, the evidence for the administration of dexamethasone is limited and conflicting. Therefore, we aimed to review the current evidence concerning the use and outcomes of dexamethasone in patients with glioblastoma., Methods: We performed a systematic review and meta-analysis according to the PRISMA-P guidelines. We performed a restricted search using the keywords "Dexamethasone" and "Glioblastoma" on PubMed, Web of Science, Cochrane Library, and Academic Search Premier. We included studies reporting on overall survival (OS) and progression-free survival (PFS) in glioblastoma patients receiving higher or lower dexamethasone doses. The risk of bias was assessed using ROBINS-I. We performed a meta-analysis using a random effects model for OS and PFS., Results: Twenty-two retrospective studies were included. Higher doses of dexamethasone were associated with poorer OS (hazard ratio 1.62, confidence interval 1.40-1.88) and PFS (1.49, 1.23-1.81). OS remained worse even when studies corrected for clinical status (1.52, 1.38-1.67)., Conclusion: Despite the widespread use of dexamethasone in glioblastoma patients, its use is correlated with worse long-term outcomes. Consequently, Dexamethasone administration should be restricted to selected symptomatic patients. Future prospective studies are crucial to confirm these findings.

Background and Purpose: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of symptoms, most common being orthostatic headache. In addition, ventral spinal CSF leaks are a possible etiology of superficial siderosis (SS), a rare condition characterized by hemosiderin deposits in the central nervous system (CNS). The classical presentation of SS involves ataxia, bilateral hearing loss, and myelopathy. Unfortunately, treatment options are scarce. This study was undertaken to evaluate whether microsurgical closure of CSF leaks can prevent further clinical deterioration or improve symptoms of SS., Methods: This cohort study was conducted using data from a prospectively maintained database in two large spontaneous intracranial hypotension (SIH) referral centers in Germany and Switzerland of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. Patients with spinal CSF leaks were screened for the presence of idiopathic infratentorial symmetric SS of the CNS., Results: Twelve patients were included. The median latency between the onset of orthostatic headaches and symptoms attributed to SS was 9.5 years. After surgical closure of the underlying spinal CSF leak, symptoms attributed to SS improved in seven patients and remained stable in three. Patients who presented within 1 year after the onset of SS symptoms improved, but those who presented in 8-12 years did not improve. We could show a significant association between patients with spinal longitudinal extrathecal collections and SS., Conclusions: Long-standing untreated ventral spinal CSF leaks can lead to SS of the CNS, and microsurgical sealing of spinal CSF leaks might stop progression and improve symptoms in patients with SS in a time-dependent manner., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement., Methods: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement., Results: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables., Conclusions: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objective: Although orthostatic headache is the hallmark symptom of spontaneous intracranial hypotension (SIH), patients can present with a wide range of different complaints and thereby pose a diagnostic challenge for clinicians. Our aim was to describe and group the different symptoms associated with SIH and their course over time., Methods: We retrospectively surveyed consecutive patients diagnosed and treated for SIH at our institution from January 2013 to May 2020 with a specifically designed questionnaire to find out about their symptomatology and its course., Results: Of 112 eligible patients, 79 (70.5%) returned the questionnaire and were included in the analysis. Of those, 67 (84.8%) reported initial orthostatic headaches, whereas 12 (15.2%) denied having this initial symptom. All except one (98.7%) patients reported additional symptoms: most frequently cephalic pressure (69.6%), neck pain (68.4%), auditory disturbances (59.5%), nausea (57%), visual disturbances (40.5%), gait disturbance (20.3%), confusion (10.1%) or sensorimotor deficits (21.5%). Fifty-seven (72.2%) patients reported a development of the initial symptoms predominantly in the first three months after symptom onset. Age and sex were not associated with the symptomatology or its course (p > 0.1)., Conclusion: Although characteristic of SIH, a relevant amount of patients present without orthostatic headaches. In addition, SIH can manifest with non-orthostatic headaches at disease onset or during the course of the disease. Most patients report a wide range of associated complaints. A high degree of suspicion is crucial for an early diagnosis and targeted treatment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)