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PURPOSE External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery is a popular intervention for small vestibular schwannomas in patients with preserved hearing. Gamma Knife radiosurgery (GKRS) and CyberKnife radiosurgery (CKRS) represent 2 alternative modalities, with CKRS potentially allowing for the delivery of higher doses over multiple sessions. However, the optimal dosing and hearing outcomes of CKRS remain unclear. This study systematically reviewed all literature describing outcomes following treatment of vestibular schwannomas with CKRS, with a focus on tumor control, hearing preservation, and dosing schema. METHODS: The PubMed, Scopus, and Embase databases were queried to identify primary retrospective studies reporting local tumor control and hearing preservation rates following CKRS for vestibular schwannoma. Studies were reviewed, and the systematic review and meta-analysis were performed according to PRISMA and meta-analysis guidelines. RESULTS: Fifteen studies with study periods ranging from 1998 to 2018 were included. These studies comprised 2018 patients (mean age, 60.2 years; range, 11-91 years; 52% female), of whom 64 had neurofibromatosis type 2. The mean follow-up was 40 (range, 6-120) months, and 309 patients had undergone prior treatment (surgery and/or stereotactic radiosurgery). In aggregate, local control at the last follow-up was 96% (95% CI, 95%-98%), and 73% (95% CI, 66%-81%) of patients had preserved hearing. The most common major complications after CKRS were facial neuropathy (1.4%), trigeminal neuralgia (1.3%), and hydrocephalus (0.5%). CKRS provides a high rate of short-term and mid-term tumor control with hearing preservation comparable with GKRS, but long-term outcomes remain under investigated. CONCLUSION: This systematic review and meta-analysis found that CKRS offers high rates of tumor control and hearing preservation in patients undergoing stereotactic radiosurgery for vestibular schwannomas. Current data suggest that CKRS is a reasonable, safe therapeutic option for patients with small tumors and preserved hearing. Further exploration in larger cohorts and direct comparison with GKRS is merited.

Background & objectives Antimicrobial resistance has steadily become a grave public health problem worldwide, making carbapenems, often the last choice of antibiotic, for treating infections involving multidrug-resistant Gram-negative organisms. The production of carbapenemases is one of the primary mechanisms responsible for the development of resistance. KPC, NDM, VIM, IMP, and OXA-48-like are the most prevalent carbapenemases. Identification of CROs is based on the resistance phenotype or requires molecular assays, which are not widely available. A lateral flow assay (LFA) has been developed to enable rapid identification of carbapenemase production in cultured bacteria. Methods A total of 87 isolates characterised by Whole Genome Sequence (WGS) were tested. Five ATCC strains were used for quality control. LFA was performed according to the kit literature, and the results were compared with those by WGS. The assay was assessed for its sensitivity and specificity for the detection of five major carbapenemases. Results A total of 87 isolates of Enterobacterales and Pseudomonas aeruginosa, characterised by WGS, were tested. Of these, 52 were positive for the big five carbapenemases (IMP, VIM, KPC, NDM, and OXA-48-like), and 35 were negative. ATCC strains were run for quality control with each batch of tests. Overall sensitivity of the assay was 98.07 per cent (51/52), with no false positives, having 100 per cent specificity (35/35). The assay correctly detected strains producing KPC, OXA-48-like, VIM, and IMP, being 100 per cent sensitive (n=33/33) when compared with WGS results; whereas, it showed delayed positivity (>15 min) to identify one strain producing NDM-1 (thus considered false negative), accounting to sensitivity of 92.3 per cent (n=12/13) for detection of NDM. It correctly identified six strains simultaneously producing OXA-48-like and NDM, and one strain producing NDM-1 and KPC. Interpretation & conclusions The assay, being robust and cost-effective, with a short turn-around-time, will prove to be a great addition to the diagnostic armamentarium, helping in implementing antimicrobial stewardship and preventing AMR.

ABSTRACT Contrast‐enhanced ultrasound (CEUS) utilizes microbubble contrast agents to improve imaging clarity during surgeries, offering real‐time visualization of anatomy and perfusion without ionizing radiation. CEUS has demonstrated feasibility in congenital heart defect repairs for monitoring procedures and cerebral perfusion, in developmental dysplasia of hip surgeries for assessing hip perfusion, in neurosurgery for delineating tumor margins, and in urogenital surgeries for guiding interventions. Intraoperative CEUS improves precision, reduces reliance on postoperative imaging, and enhances safety. While it is a safe and effective tool for intraoperative decision‐making in pediatric surgeries, further studies are needed to expand its applications and standardize its use.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

OBJECTIVE Blister aneurysms of the internal carotid artery (ICA) have high associated mortality rates and are challenging due to their friable wall and poorly defined neck. Microsurgical and endovascular treatment options have been suggested, including bypass of the parent vessel to exclude the aneurysm. The goal of this study was to evaluate the safety and efficacy of microsurgical versus endovascular interventions. Additionally, for patients treated with open surgery, the outcomes of bypass were compared to nonbypass techniques. METHODS Three databases were systematically queried for primary studies comparing microsurgery to endovascular therapy and assessing bypass versus nonbypass treatment modalities for blister aneurysms of the ICA. All relevant studies published between 2000 and 2023 were eligible for inclusion. All articles were screened against title and abstract by 2 authors, as were those eligible for full-text assessment. Ultimately, relevant data from all included studies were pooled for meta-analysis in which the Mantel-Haenszel method with random-effects modeling was used. RESULTS Among the 504 cases reported across 24 studies, 182 (35.1%) blister aneurysms of the ICA were surgically treated, whereas 337 (64.9%) involved endovascular treatment. There were 235 (46.6%) female patients in the cohort. Functional outcomes were comparable between groups, with 83% of surgically treated patients and 85% of endovascularly treated patients achieving a favorable outcome (p > 0.05). Among the 7 studies (178 patients) comparing bypass to nonbypass microsurgery, rates of postoperative bleeding, ischemic infarct, vasospasm, recurrence, favorable outcomes, and mortality were comparable for bypass (n = 54, 30.3%) and nonbypass groups (n = 124, 69.7%). CONCLUSIONS Blister aneurysms of the ICA are rare intracranial aneurysms that are difficult to treat with microsurgical and endovascular techniques. Considering only patients treated with open surgery, there appears to be no significant difference in complication profile or functional outcomes between patients undergoing bypass or alternative microsurgical techniques. However, it must be noted that the complex nature of bypass procedures means that much of the data granularity is lost on meta-analysis, suggesting that additional investigations comparing bypass to other open microsurgical techniques may be merited. Similarly, future studies should determine the limitations of dual antiplatelet therapy in endovascular treatment and the efficacy of different numbers and types of overlapping, flow-diverting devices.

Abstract Background Celiac disease (CeD) is a T-cell mediated enteropathy driven by gluten in genetically susceptible individuals. Mucosal inflammation persists for years even when treated with a gluten-free diet (GFD). Although patients may be advised to increase dietary fibre, some fibres are poorly tolerated leading, potentially, to suboptimal fibre intake and hampering dietary recommendations. Aims Our project aims to investigate whether and how the supplementation of two fibre types with distinct functional profiles affects the recovery of gluten-immunopathology in a mouse model of gluten-sensitivity. We hypothesize that: (1) HylonVII, but not inulin, accelerates mucosal recovery by increasing microbial carbolytic activity and production of short-chain fatty acids (SCFA); (2) fibre intake is decreased in CeD patients, leading to decreased SCFA production. Methods NOD-DQ8 mice were immunized to gliadin and then placed on a gluten-containing diet. Three weeks later, mice were returned to GFD supplemented with or without HylonVII or inulin to 15% total fibre, for 6, 10, or 12 weeks. Recovery from gluten-induced pathology was evaluated by counting CD3+ intraepithelial lymphocytes (IELs) in villi tips and measuring villus-to-crypt (V/C) ratios in the small intestine. Adult CeD patients (newly diagnosed n=6 and GFD-treated n=7) and healthy controls (n=5) completed a food frequency questionnaire (Victoria DQES v2) and provided fecal samples for evaluation of SCFA production. Fecal SCFA were measured with targeted single ion monitoring gas-chromatography/mass-spectrometry (Agilent) as markers of fibre metabolism. Results In gluten immunized mice, 3 weeks of wheat diet led to increased CD3+ IEL counts and decreased V/C ratios (pampersand:003C0.01), which remained abnormal after 6 weeks of GFD. Mice consuming GFD+inulin, but not HylonVII, normalized CD3+ IELs and V/C ratios, had higher fecal SCFAs (pampersand:003C0.05) (primarily acetate), and a higher carbolytic-proteolytic metabolite ratio (pampersand:003C0.05) compared with mice consuming a GFD alone for six weeks. Only 1/7 patients with CeD on GFD met the minimum recommendation for fibre intake (25 g/day, Health Canada), compared with 5/11 participants on gluten-containing diets. SCFA production was impaired in active but not in treated CeD patients (2563 vs 3744 μg/g, pampersand:003C0.01). Conclusions In gluten-immunized NOD-DQ8 mice, GFD+inulin accelerates mucosal recovery, which is associated with increased fecal SCFA. In our pilot clinical data, patients on a GFD did not meet the recommendation for fibre intake although they were capable of metabolizing fibre to produce SCFA that could facilitate mucosal recovery. Together these results suggest that CeD on GFD may benefit from increasing fibre, such as inulin, during the GFD. Funding Agencies CIHRCeliac Canada