Citations

Background: Vitamin C is a vital nutrient that functions as an antioxidant and is important as a co-factor and regulator of several immune system pathways. The role of vitamin C in the treatment of COVID-19 is largely debatable. We conducted this meta-analysis to evaluate the efficacy and safety of vitamin C in the treatment of COVID-19. Methods: We searched several electronic databases from inception to March 2023 to retrieve randomized controlled trials on the use of vitamin C for COVID-19. RevMan 5.4 was used to calculate risk ratios (RRs) and mean differences (MDs) along with confidence intervals (95% CI) using a random-effects model. Results: We included nine randomized controlled trials in our meta-analysis. Vitamin C did not reduce the all-cause mortality in patients with COVID-19 compared to the standard treatment (RR 0.92, 95% CI: 0.83–1.02; I 2 = 1%). Vitamin C was found to be associated with a similar incidence of ventilation in COVID-19 patients when compared to standard treatment (RR 0.98, 95% CI: 0.87–1.11, I 2 = 0%). There were no significant differences between both groups regarding the incidence of hospitalization (RR 1.00, 95% CI: 0.98–1.02; I 2 = 0%), incidence of recovery (RR 1.57, 95% CI: 0.45–5.50; I 2 = 52%), hospital mortality (RR 0.68, 95% CI: 0.44–1.06; I 2 = 0%) and length of hospital stay (MD −0.63, 95% CI: −3.04 to 1.78; I 2 = 81%). Conclusion: Vitamin C administration did not reduce all-cause mortality in COVID-19 patients. Additional studies are required to evaluate the role of vitamin C in the prevention and treatment of COVID-19 especially in ICU patients.

Background: Sinonasal malignancies (SNM) are rare cancers associated with poor prognosis and impaired quality of life (QOL). The 22-question Sino-Nasal Outcome Test (SNOT-22) has been used to assess QOL in patients with SNM. Objective: To determine the minimal clinically important difference (MCID) for the SNOT-22 in patients with SNM. Methods: About 264 patients with SNM were drawn from a prospective, longitudinal, multi-institutional study. SNOT-22 scores were collected at pre-treatment baseline and follow-up through 5 years post-treatment. Cronbach’s alpha was used to assess the internal consistency of the SNOT-22. Distribution-based approaches were used to estimate the MCID. Multivariable regression identified factors associated with SNOT-22 improvement exceeding the determined MCID. Results: Cronbach’s alpha was >.85. The estimated MCIDs were: 1.44 (Cohen’s effect size), 1.32 (standard error of the mean), 10.45 (1/2 of baseline standard deviation), and 3.67 (minimum detectable change). The mean MCID across methods was 4.22. Multivariable regression demonstrated higher odds of clinically meaningful improvement from baseline in patients with early-stage disease (odds ratio (OR) 3.510, P = .035), no neck irradiation (OR 11.050, P = .014), and neoadjuvant therapy (OR 16.667, P = .047). Conclusions: The SNOT-22 MCID was estimated as 4.22 in a large multi-center cohort of patients with SNM, suggesting that relatively small QOL changes are clinically relevant. When applying the MCID to the current cohort, advanced stage, treatment of neck disease, and not requiring neoadjuvant therapy were predictive of worse QOL.

Abstract Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity and plasticity. GBM tumors contain neoplastic cells within a fluid spectrum of diverse transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we develop scFOCAL (Single-Cell Framework for -Omics Connectivity and Analysis via L1000), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identify compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states, and leverage this capability to predict combination synergy. We validate the significance of these findings in vitro, ex vivo, and in vivo, and use the Olig2 inhibitor CT-179 as a reference drug to identify additional small molecules that would maximize the cell-drug discordance across the GBM transcriptional landscape. Our analysis leads to the combination of Olig2 inhibition with treatment with Depatux-M, of with which we demonstrate synergy in vivo. Our studies suggest that scFOCAL identifies cell states that are sensitive and resistant to targeted therapies in GBM using a measure of cell and drug connectivity, which can be applied to identify new synergistic combinations. Citation Format: Robert K. Suter, Anna M. Jermakowicz, Rithvik Veeramachaneni, Matthew D'Antuono, Longwei Zhang, Rishika Chowdary, Simon Kaeppeli, Madison Sharp, Pravallika Palwai, Vasileios Stathias, Grace Baker, Luz Ruiz, Winston Walters, Maria Cepero, Danielle Burgenske, Edward B. Reilly, Anatol Oleksijew, Mark G. Anderson, Sion Ll. Williams, Michael E. Ivan, Ricardo J. Komotar, Macarena I. De La Fuente, Gregory Stein, Alexandre Wojcinski, Santosh Kesari, Jann N. Sarkaria, Stephan C. Schürer, Nagi G. Ayad. Drug and single-cell gene expression integration identifies heterogeneity-aware synergistic combinations for glioblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr B032.

aims: We assessed the diagnostic accuracy of the SVEAT score in predicting 30-day major adverse cardiac events (MACE) in comparison with the well-established HEART and TIMI scores. background: Acute chest pain (ACP) is a common symptom in emergency departments. Various risk stratification tools have been developed to assess patients presenting with ACP. The Simple Vascular Event Assessment Tool (SVEAT) is the most recent scoring system introduced, based on five variables: Symptoms of chest pain, history of Vascular disease, ECG, Age, and Troponin-I. objective: We assessed the diagnostic accuracy of the SVEAT score in predicting 30-day major adverse cardiac events (MACE) in comparison with the well-established HEART and TIMI scores. method: Following PRISMA guidelines, a systematic literature search was conducted across five databases until June 22, 2024. Four studies comprising 1,520 patients were included in this meta-analysis. The predictive accuracy of the SVEAT, HEART, and TIMI scores for 30-day MACE was assessed by the area under the receiver operating characteristic curve (AUC). Heterogeneity was evaluated using the I² statistic, with values over 75% indicating significant heterogeneity. Indirect comparisons among the scores were performed using the Z-test. result: Pooled AUC for the SVEAT score was 0.92 (95% CI: 0.86-0.98), indicating superior predictive accuracy compared to the HEART (AUC: 0.86, 95% CI: 0.81-0.92) and TIMI (AUC: 0.82, 95% CI: 0.69-0.96) scores. However, significant heterogeneity (I² = 90.6%) was observed across studies, potentially due to variations in patient demographics, clinical settings, and outcome definitions. Despite the higher AUC, indirect Z-test comparisons revealed no statistically significant differences between the scoring systems. conclusion: SVEAT score demonstrates potential as an accurate tool for predicting 30-day MACE in patients with ACP. other: N/A

Abstract Radiotherapy is an established treatment for low-grade primary cutaneous B-cell lymphoma. Recommendations on its use differ internationally, which prompted our group to conduct this analysis. Twenty-two institutions participated in this international study. Patient eligibility required a diagnosis of limited (T1/T2) primary cutaneous marginal zone or follicle center lymphoma treated with radiotherapy between 1995 and 2023. Data were collected retrospectively until February 2024 within the framework of the International Lymphoma Radiation Oncology Group. Overall, 535 patients were analyzed. Predominant locations were the head (40%) and trunk (36%). Radiotherapy had a median dose of 24 Gy in fractions of 2 Gy. Complete responses were observed in 91% at a median time of 3.6 months following radiotherapy. There was no statistically significant difference between treatments ≤4 Gy and >4 Gy for complete or overall response rates (P = .077 and P = .056, respectively). However, there was an inferior duration of local control with ≤4 Gy (5-year local control 73% ± 12% vs 96% ± 2%; P< .001). Radiation dose was the main prognostic factor in the univariate and multivariable Cox analysis; however, higher doses did not translate into an overall survival benefit. Toxicities rarely exceeded grade 2 but were more frequent in the >4 Gy group. Radiotherapy remains an effective treatment option for indolent skin lymphoma with low toxicity. High response rates are observed with low doses of ≤4 Gy. In comparison to conventional doses, these treatments have a shorter duration of local control but a favorable toxicity profile.

Abstract EZHIP (EZH inhibitory protein) is a cancer-testis antigen (CTA) typically restricted to germline cells, where it inhibits Polycomb repressive complex 2 (PRC2)-mediated deposition of the repressive histone mark H3K27me3. Its aberrant expression in H3K27M mutation-negative diffuse midline gliomas (DMGs) and ependymomas leads to PRC2 inhibition and widespread epigenomic dysregulation. H3K27M-mutant gliomas are similarly characterized by global loss of H3K27me3 due to inhibition of PRC2 by the oncohistone H3K27M, positioning EZHIP as a functional epigenetic mimetic of this mutation.To explore its role in tumorigenesis, we overexpressed EZHIP in the H3K27 wild-type DMG cell lines that lack H3K27M mutations. EZHIP overexpression resulted in a significant reduction in H3K27me3 levels, indicating PRC2 inhibition. In a Nestin-TVA mouse model of DMG, the introduction of EZHIP into neural stem cells via the RCAS-EZHIP-P2A-PDGFβ vector led to the development of aggressive, high-grade diffuse gliomas. The tumorigenic potential of EZHIP was further supported by Western blot analysis of EZHIP-expressing neural stem cells, which revealed increased expression of stem cell markers, including Nanog, GFAP, and Nestin, consistent with a stem-like transcriptional state. RNA and ATAC sequencing of EZHIP-overexpressing DMG cell lines, compared to their isogenic wild-type counterparts, revealed a substantial increase in the number of upregulated genes typically repressed by PRC2, indicating widespread transcriptional activation associated with PRC2 inhibition. Comparative transcriptional analysis further showed that EZHIP-induced gene expression changes more closely resembled those in PRC2 knockout cells rather than in cells harboring the H3K27M mutation. Together, these findings highlight the complex role of EZHIP in disrupting PRC2-mediated gene silencing, promoting gliomagenesis, and altering the epigenomic landscape. While EZHIP and H3K27M mutations share some mechanistic similarities in inhibiting PRC2, key differences in their downstream effects suggest distinct contributions to tumor development. These findings advance our understanding of EZHIP-driven gliomas and reveal potential therapeutic vulnerabilities that could inform future treatments.

Most falls occur while walking, making gait quality a logical therapeutic target. Many temporo-spatial variables have been implicated in increased fall risk, but these are dependent upon kinematic parameters of the joints involved in the gait cycle. The widespread availability of wearable sensors has made the acquisition of kinematic data feasible, and those related to the ankle are most relevant, as they relate most closely to causes of falls, trips, slips, and mis-steps. The purpose of this study is to estimate the extent to which measures of ankle angular velocity (AV) during walking are associated with falls. This is a comparative study of ankle AV metrics between people who have or have not experienced a fall in the past year. Data came from experimental use of the Heel2Toe™ sensor in a variety of settings, including demonstrations and clinical research studies. The sample comprised 387 participants, of whom 68 (17.6%) self-reported falling in the past year. Logistic regression with a natural cubic spline with 3 degrees of freedom identified AV of the angle at heel strike to discriminate between fallers and non-fallers, and the regression parameters were used to propose an algorithm to estimate fall risk. Applying the algorithm to the existing data yielded a range of probabilities from 0.0480 to 0.7245 depending on age of the person assessed. Further testing of this algorithm in different samples is warranted.

ABSTRACT Background Diabetic ketoacidosis (DKA) is a severe diabetes complication managed with fluids, insulin and electrolyte correction. This review evaluates the debated effectiveness of bicarbonate therapy on DKA outcomes. Methods Following PRISMA guidelines, we systematically reviewed studies on bicarbonate therapy in DKA. We searched PubMed, Google Scholar, the Cochrane Library and ClinicalTrials.gov (as of August 2024), including studies on patients with DKA. Meta‐analysis was conducted using RevMan. Bias risk was assessed with the Newcastle‐Ottawa Scale (NOS) for cohort studies, Cochrane's ROB‐2 for RCTs and the Joanna Briggs Institute (JBI) Scale for case series. Prospero ID: CRD42024581810. Results Eight studies, including 646 patients, met the inclusion criteria. Participants' mean ages spanned from approximately 9.7 years to 45.8 years. Bicarbonate therapy did not significantly improve pH levels (mean difference = −0.02, 95% CI [−0.13, 0.09], p = 0.7), time to resolution of acidosis (mean difference = 0.09 h, 95% CI [−2.6, 2.79], p = 0.95) or potassium levels (mean difference = −0.10, 95% CI [−0.49, 0.29], p = 0.61). Bicarbonate therapy was associated with a marginally longer duration of hospital stay (mean difference = 13.63 h, 95% CI [0.23, 27.03], p = 0.05), although the overall effect size was small. No significant difference was observed in the incidence of hypoglycemia (odds ratio = 2.62, 95% CI [0.59, 11.63], p = 0.20). High heterogeneity was observed across most outcomes, mainly due to variability in study protocols and patient populations. Conclusion Bicarbonate therapy provided no meaningful clinical benefit in the routine management of DKA and was associated with potential harm, including worsened hyperglycemia. Consistent with current guidelines, its use should be restricted to cases of severe acidemia (pH < 6.9). Further high‐quality studies are needed to clarify its role in extreme acidosis and to explore alternative buffering strategies.

Abstract Purpose To develop and implement an in‑house treatment‑management platform to improve communication, data accessibility, and task tracking across a radiation oncology department. Methods We developed Capsule, a custom software platform that centralizes patient data from the ARIA oncology information system (Varian Medical Systems, Palo Alto, United States), and integrates it with data from Outlook (Microsoft, Redmond, United States), spreadsheets, and manual inputs. Built using C#, SQL, and the .NET framework, it features a graphical interface in XAML with twelve modular tools to support workflows across a large multi‐modality department. A formal validation, feedback, and maintenance cycle was established. Its impact on workflow efficiency was evaluated using average CarePath task duration before and after implementation, supplemented by user interviews and surveys. Results The Department Schedule, Treatment Planning and On‐Treatment Whiteboard, Spreadsheet, and various workload tracking modules emerged as the most frequently used among dosimetrists surveyed.The Whiteboard module consolidates planning metadata for streamlined workflows. Workload and scheduling modules help distribute tasks fairly. The Department Schedule module centralizes daily role and contact information. The Spreadsheet module allows dosimetrists to identify a reference for unique plans and provides secure access to large exportable tabulated patient data and clinical trends. Other modules support proton down‐time replanning and special procedure physics assignment. One year after Capsule's implementation, most tasks in the external beam radiation therapy workflow experienced a reduction in average duration. Discussion Capsule streamlines workflows by integrating multiple tools into a single platform, supporting urgent scenarios, and improving task hand‐off. Its modular design allows customization to local workflows, but implementation must be guided by institutional oversight and formal quality management to ensure data security and compliance. Conclusion Capsule can provide a solution for improved workflow efficiency, communication, and interdisciplinary coordination. By democratizing access to routine and retrospective data, it supports treatment planning, scheduling, and quality improvement. Ongoing updates are essential as clinical practices evolve.