Citations

This scientific commentary refers to ‘Common neuropathologic change drivers of hippocampal sclerosis of ageing’ by Woodworth et al. (https://doi.org/10.1093/brain/awaf158).

Abstract Background Magnetic Resonance‐guided Radiation Therapy (MRgRT) systems are increasingly used in clinical practice, necessitating a dedicated dosimetry protocol to address the challenges posed by the presence of strong magnetic fields. Purpose AAPM TG351 introduces a reference dosimetry protocol for external beam MRgRT systems, aligning with AAPM TG51 reports and incorporating elements from the IAEA TRS398 code of practice. Methods The protocol offers practical guidance on beam quality and dosimetry setup in the presence of strong magnetic fields. It reviews relevant literature to identify reference‐class chambers suitable for external beam MRgRT systems and determines their beam quality conversion and other relevant correction factors through a detailed analysis of available data and associated uncertainties. Results AAPM TG351 offers a comprehensive dosimetry protocol for external beam MRgRT systems, addressing the unique challenges posed by the presence of magnetic fields. It includes detailed guidance for measurement setups, a list of reference‐class chambers appropriate for reference dosimetry in MRgRT systems, and updated beam quality conversion and correction factors. Additionally, the protocol presents an in‐depth analysis of the uncertainty budget, identifying key contributors and providing strategies to minimize uncertainties, thereby enhancing clinical accuracy and reliability. Conclusions This protocol provides a practical, evidence‐based reference for medical physicists conducting reference dosimetry in external beam MRgRT systems.

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: To establish benchmark cutoffs for robotic liver resection (R-LR), encompassing both major and minor resections, and to determine the impact of patient selection on outcomes. Background: R-LR is a key advancement in minimally invasive liver surgery but lacks standardized benchmarks, especially for minor resections. While guidelines endorse R-LR, its role in optimizing outcomes remains unclear. This study establishes the first benchmarks for R-LR, enabling comparisons across surgical modalities and refining patient selection. Methods: This retrospective, multicenter study analyzed consecutive adult patients undergoing R-LR at 30 international centers (2020–2023). Benchmark centers had an annual case volume of ≥15 R-LR. Benchmark criteria included ASA ≤2, no major comorbidities, no prior liver resections, and Child-Pugh A status. Benchmark cutoffs for 14 key outcomes were set at the 50th and 75th percentiles of median values across benchmark centers. Multivariable logistic regression identified predictors of textbook outcomes. Results: Eighteen high-volume centers contributed 4028 cases with 2632 (65.3%) meeting benchmark criteria. Malignancy was the indication in 29.6%, most commonly hepatocellular carcinoma followed by colorectal liver metastases. Major liver resection was performed in 42.6%. The distribution of Iwate difficulty scores was low (25.4%), intermediate (53.9%), advanced (15.9%), and expert (4.9%). Benchmark cutoffs were established for minor and major resection, and stratified by Iwate low (0-3), intermediate (4-6) and high (7-12): Open conversion (≤6.5% minor, ≤10.5% major), major complications within 90 days (≤5.2% minor, ≤16.7% major), R1 resection (≤9.2% minor, ≤6.7% major). Benchmark cases performed at low-volume centers were able to achieve outcomes within the corresponding benchmark cutoffs. In fact, patient selection reflected by the proportion of benchmark patients, rather than case volume, was associated with textbook outcomes. Conclusions: This study defines R-LR benchmarks, emphasizing patient selection over center volume for optimal outcomes. Benchmark cutoffs guide training and support the expansion of R-LR.

Abstract Background Robotic Whipple holds the promise to overcome safety concerns associated with laparoscopy, paving the way for widespread implementation of minimal-invasive surgery in this complex procedure. However, randomized data comparing robot vs. open Whipple demonstrate more pancreas-specific complications and R1-resections in the robotic arm. Recent international consensus identified establishing benchmarks as critical to ensure safe adoption of the robot. Benchmarking is a validated quality improvement tool, enabling comparison of surgical performance. Aims The aim was to define benchmarks for outcome parameters in robotic Whipple. Methods We analyzed consecutive patients undergoing robotic Whipple from January 2020 until December 2023 in 11 centers across 4 continents, with a minimum one-year follow-up. Centers had to perform ≥15 cases/year and have mounted their learning curve. Benchmark criteria included benign or resectable malignant disease without neoadjuvant therapy, arterial resection, major co-morbidities, or significant previous abdominal surgery. Medians across centers represented benchmark cutoffs. Results Eleven centers performed 1’037 Whipple procedures, of which 603 (58%) were benchmark cases. One third (n=192) were pancreatic ductal adenocarcinoma (PDAC) patients. Key benchmarks at 6 months included ≤1.2% mortality, ≤24.2% major complications, and ≤ 8.7 points Comprehensive Complication Index®. Pancreas-specific cutoffs included ≤13.0% postoperative pancreatic fistula (POPF) B/C and ≤3.4% post-pancreatectomy hemorrhage B/C, with 100% R0-resection and ≥19 harvested lymph nodes in PDAC patients. One-year actuarial overall and recurrence-free survival was 87% and 77%. In the entire cohort POPF B/C occurred in 16% (n=195). Independent POPF predictors included duct diameter ≤4mm (OR 1.79 95%CI [1.27-2.55]), anticoagulation (OR 3.68 95%CI [2.14-6.24]), and indication other than PDAC (OR 3.17, 95%CI [2.13-4.85]). Conclusion This study establishes benchmarks for key outcomes in robotic Whipple, demonstrating oncologic adequacy and morbidity comparable to open surgery. Risk factors for POPF in open surgery also hold true in the robotic approach.

Abstract Rationale: The D'Nerva Targeted Lung Denervation (TLD) System uses radiofrequency energy delivered bronchoscopically to the main bronchi to disrupt parasympathetic nerve innervation to the lung. AIRFLOW-3 clinical trial was a randomized, double blind, sham controlled study to determine the impact of TLD on COPD exacerbations. Methods: AIRFLOW-3 patients had symptomatic COPD (CAT ≥10) with moderate to very severe airflow obstruction (GOLD stage II-IV: 25% ≤ FEV1 ≤ 80% predicted, FEV1/FVC<0.70) and GOLD E status (≥2 moderate or ≥1 severe exacerbation in the prior 12 months) despite optimal medical therapy. The primary endpoint was a time-to-first event comparison of the probability of subjects having a moderate or severe exacerbation, between the Treatment arm (TLD + optimal medical therapy) and the Sham Control arm (optimal medical therapy). Results: 388 patients were randomized 1:1 at 32 clinical sites across the US, EU, and UK. Patients were 67.8 (SD 7.1) years of age, ex-smokers with a 46.7 (22.0) pack-year smoking history, and 41.0 (11.8) post bronchodilator FEV1% pred. SGRQ-C and CAT scores were 62.5 (17.0) and 23.6 (6.3), respectively. Over 90% of patients were on triple therapy (LAMA+LABA+ICS) at baseline and through 1 year of follow up. 42% of patients had prior-year COPD hospitalization(s). There was no difference between groups in the analysis of the primary endpoint. At 1 year, the sham arm exhibited a statistical decline in lung function (decrease in FEV1 and FVC) and worsening of gas trapping (increase in RV). Lung function and gas trapping were stable in the treatment arm. The treatment arm exhibited a statistically significant improvement in dyspnea at one year compared to sham (mMRC, and TDI). These observations led to the identification of a subgroup of TLD treatment responders corresponding to an airway predominant phenotype (lung hyperinflation in the absence of significant emphysema) that demonstrated clinically and statistically significant improvements in lung function and exacerbation frequency and severity (Table). Conclusions: The AIRFLOW-3 clinical trial failed to meet its prespecified primary endpoint. Post-hoc analysis of this robust dataset led to the identification of a responder profile that achieved significant and sustained improvements in lung function, and exacerbation reduction. A future clinical study is being designed to confirm these findings.

ABSTRACTThe incidence of ischemic cholangiopathy (IC) is expected to remain significant due to rising rates of transplants performed with livers donated after circulatory death (DCD), despite the use of machine perfusion. Absent established pharmacologic interventions against this progressive etiology of allograft dysfunction and failure, we describe the use of fenofibrate—a cheap and widely‐accessible peroxisome proliferator‐activated receptor agonist that downregulates bile acid production—to impede IC progression in 15 DCD liver recipients who were not responding to reactive, standard‐of‐care management. All patients were undergoing serial endoscopic retrograde cholangiopathy (ERC) to maintain biliary patency but demonstrated progressive cholestasis, with serum alkaline phosphatase (ALP) rising 70.3% over the 90 days preceding fenofibrate. Cholestasis improved in all patients after fenofibrate initiation, with a 63.9% reduction in mean ALP at 90 days, maintained at 270 days (p = 0.02) and 360 days (p = 0.06). ALP improvement was associated with reduced ERC frequency during and after fenofibrate treatment, and this improvement was independent of concurrent ERC or ursodeoxycholic acid use during fenofibrate treatment. In patients who stopped treatment, ALP increased. No fenofibrate‐associated adverse events were seen. These preliminary data support the further study of agents that downregulate bile acid production as a means of impeding IC in DCD livers.

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Background The Woven EndoBridge (WEB) device is a prevalent treatment for intracranial aneurysms. While many studies have assessed the obliteration rate post-WEB embolization, few have focused on long-term outcomes in partially thrombosed aneurysms. Objective To assess whether partially thrombosed aneurysms are at higher risk of recurrence or retreatment following WEB embolization compared with non-thrombosed aneurysms. Methods We evaluated data from 22 academic institutions, focusing on previously untreated cerebral aneurysms treated with the WEB device. Logistic regression was utilized to analyze factors predicting long-term aneurysm obliteration and retreatment necessity. Results Among 1303 patients, 26 presented with a partially thrombosed aneurysm. In the partially thrombosed group, the mean aneurysm maximal diameter was 10.7±4 mm with a neck ratio of 1.99±1.19 mm, larger than in the control group where the mean aneurysm maximal diameter was 6.81±2.37 mm with a neck ratio of 1.64±0.51 mm (P<0.001 for both maximal diameter and neck ratio). At the final follow-up, partially thrombosed aneurysms treated by the WEB device had a 38.5% retreatment rate, compared with 7.0% for non-thrombosed aneurysms (P<0.001). Among partially thrombosed aneurysms, the Raymond-Roy type IIIa/b occlusion rate was higher (38.5% vs 9.9%, P<0.001). On multivariate analysis, partially thrombosed aneurysms compared with non-thrombosed aneurysms had an increased rate of retreatment (OR 3.64, 95% CI 1.28 to 10.1). Conclusion Partially thrombosed aneurysms are associated with a poorer occlusion rate and a higher rate of retreatment following WEB embolization. For partially thrombosed aneurysms, the WEB device appears suboptimal as a first-line treatment, and therefore alternative techniques should be prioritized.

ABSTRACTIndividuals with primary progressive apraxia of speech (PPAOS) often develop parkinsonism and dysphagia. To evaluate the clinical correlates and impact of dysphagia in this population, we compared enrollment visit data between individuals with (n = 12) versus individuals without (n = 44) dysphagia symptoms. The group with dysphagia had more motor speech symptoms and parkinsonism. Longitudinal analysis revealed that almost everyone developed dysphagia before dying; the average time to death after developing dysphagia was 5.43 years and complications of dysphagia resulted in mortality for 35% of the individuals for whom data were available. These results emphasize the need for dysphagia management and provide useful prognostic estimates.