Pre-exercise hot water immersion increased circulatory heat shock proteins but did not alter muscle damage markers or endurance capacity after eccentric exercise.

Pre-exercise passive heating attenuates muscle damage caused by eccentric exercise in rats where the induction of heat shock proteins (HSPs) confers a myoprotective effect. We investigated whether pre-exercise hot water immersion (HWI) confers similar benefits in humans. Eleven recreational male athletes were immersed in 41°C water up to 60 min or until rectal temperatures reached 39.5°C. After a 6 h rest, the participants performed an eccentric downhill run for 1 h at -4% gradient to induce muscle damage. An endurance capacity test at 75% VO2max was conducted 18 h later. The control trial was similar except that participants were immersed at 34°C. Blood samples were collected to assess HSPs levels, creatine kinase, and lactate dehydrogenase activities. Plasma eHSP70 was higher post-immersion in HWI trials (1.3 ± 0.4 vs 1.1 ± 0.4; p = 0.005). Plasma eHSP27 was higher before (p = 0.049) and after (p = 0.015) endurance test in HWI. Leukocytic p-HSP27 was increased 18 h after HWI (0.97 ± 0.14 vs 0.67 ± 0.11; p = 0.04). Creatine kinase and lactate dehydrogenase activities were increased by 3-fold and 1.5-fold, respectively, after endurance test in HWI but did not differ across trials (p > 0.05). Mean heart rates were higher during eccentric run and endurance test in HWI as compared to control (p < 0.05). Endurance capacity was similar between trials (57.3 ± 11.5 min vs 55.0 ± 13.5 min; p = 0.564). Pre-exercise heating increased the expression of plasma eHSPs and leukocytic p-HSP27 but did not reduce muscle damage nor enhance endurance capacity.

Impact of early surgical complications on kidney transplant outcomes.

BACKGROUND: Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions. METHODS: We conducted a single-centre, observational cohort study examining adult patients (≥ 18 years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31st, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT. RESULTS: The cumulative probability of SC within 30 days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 [95% CI: 1.11, 2.86]), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 [95% CI: 1.37, 2.77]). CONCLUSIONS: Early SC following KT are common and have a significant influence on long-term patient outcomes.

Diagnosis and management of thoracic outlet syndrome in athletes.

The physical demands of sports can place patients at elevated risk of use-related pathologies, including thoracic outlet syndrome (TOS). Overhead athletes in particular (eg, baseball and football players, swimmers, divers, and weightlifters) often subject their subclavian vessels and brachial plexuses to repetitive trauma, resulting in venous effort thrombosis, arterial occlusions, brachial plexopathy, and more. This patient population is at higher risk for Paget-Schroetter syndrome, or effort thrombosis, although neurogenic TOS (nTOS) is still the predominant form of the disease among all groups. First-rib resection is almost always recommended for vascular TOS in a young, active population, although a surgical benefit for patients with nTOS is less clear. Practitioners specializing in upper extremity disorders should take care to differentiate TOS from other repetitive use-related disorders, including shoulder orthopedic injuries and nerve entrapments at other areas of the neck and arm, as TOS is usually a diagnosis of exclusion. For nTOS, physical therapy is a cornerstone of diagnosis, along with response to injections. Most patients first undergo some period of nonoperative management with intense physical therapy and training before proceeding with rib resection. It is particularly essential for ensuring that athletes can return to their baselines of flexibility, strength, and stamina in the upper extremity. Botulinum toxin and lidocaine injections in the anterior scalene muscle might predict which patients will likely benefit from first-rib resection. Athletes are usually satisfied with their decisions to undergo first-rib resection, although the risk of rare but potentially career- or life-threatening complications, such as brachial plexus injury or subclavian vessel injury, must be considered. Frequently, they are able to return to the same or a higher level of play after full recovery.

Pure-Water-Fed Forward-Bias Bipolar Membrane CO2 Electrolyzer.

Coupling renewable electricity to reduce carbon dioxide (CO2) electrochemically into carbon feedstocks offers a promising pathway to produce chemical fuels sustainably. While there has been success in developing materials and theory for CO2 reduction, the widespread deployment of CO2 electrolyzers has been hindered by challenges in the reactor design and operational stability due to CO2 crossover and (bi)carbonate salt precipitation. Herein, we design asymmetrical bipolar membranes assembled into a zero-gap CO2 electrolyzer fed with pure water, solving both challenges. By investigating and optimizing the anion-exchange-layer thickness, cathode differential pressure, and cell temperature, the forward-bias bipolar membrane CO2 electrolyzer achieves a CO faradic efficiency over 80% with a partial current density over 200 mA cm-2 at less than 3.0 V with negligible CO2 crossover. In addition, this electrolyzer achieves 0.61 and 2.1 mV h-1 decay rates at 150 and 300 mA cm-2 for 200 and 100 h, respectively. Postmortem analysis indicates that the deterioration of catalyst/polymer-electrolyte interfaces resulted from catalyst structural change, and ionomer degradation at reductive potential shows the decay mechanism. All these results point to the future research direction and show a promising pathway to deploy CO2 electrolyzers at scale for industrial applications.

Bilateral Atypical Femoral Fracture in a Bisphosphonate-Naïve Patient with Prior Long-Term Denosumab Therapy: A Case Report of the Management Strategy and a Literature Review.

The benefits of denosumab as an antiresorptive therapy and in reducing fragility fractures are well documented. However, its association with atypical femur fractures (AFFs), especially in the absence of prior bisphosphonate use, remains poorly understood and warrants further investigation. This case report presents a rare instance of bilateral AFFs in a 78-year-old bisphosphonate-naïve patient with a history of long-term denosumab therapy for previous metastatic breast cancer. Management involved intramedullary nail fixation after initial presentation with a unilateral AFF and a recommendation to cease denosumab therapy. However, the patient subsequently experienced a contralateral periprosthetic AFF below a total hip implant 5 months thereafter and was treated with open reduction internal fixation. This case report highlights the critical need for orthopedic surgeons to maintain a high level of suspicion and vigilance in screening for impending AFFs, especially in patients with a prolonged history of denosumab therapy without prior bisphosphonate use. Furthermore, the growing report of such cases emphasizes the urgent need for comprehensive research aimed at refining treatment protocols that balance the therapeutic benefits of denosumab and its associated risks of AFFs.

The Role of Momentum Partitioning in Covariance Ion Imaging Analysis.

We present results from a covariance ion imaging study, which employs extensive filtering, on the relationship between fragment momenta to gain deeper insight into photofragmentation dynamics. A new data analysis approach is introduced that considers the momentum partitioning between the fragments of the breakup of a molecular polycation to disentangle concurrent fragmentation channels, which yield the same ion species. We exploit this approach to examine the momentum exchange relationship between the products, which provides direct insight into the dynamics of molecular fragmentation. We apply these techniques to extensively characterize the dissociation of 1-iodopropane and 2-iodopropane dications prepared by site-selective ionization of the iodine atom using extreme ultraviolet intense femtosecond laser pulses with a photon energy of 95 eV. Our assignments are supported by classical simulations, using parameters largely obtained directly from the experimental data.

What Faculty and Students Value When Evaluating Human Digital Anatomy Platforms: A Mixed-Methods Study.

OBJECTIVES: There is an increasing availability of digital technologies for teaching and learning of human anatomy. Studies have shown that such applications allow for better spatial awareness than traditional methods. These digital human anatomy platforms offer users myriad features, such as the ability to manipulate 3D models, conduct prosection, investigate anatomical regions through virtual reality, or perform knowledge tests on themselves. This study examined what faculty members' value when using digital human anatomy platforms for teaching and what students value when using these platforms for learning. METHODS: Six anatomy faculty members and 21 students were selected to participate in this study. After using the three digital anatomy platforms for at least 1 week, a survey was conducted to record their feedback in 4 categories: usability, interactive features, level of detail, and learning support. Respondents' Qualitative feedback within each category was also analyzed to strengthen the study's findings. RESULTS: The study's findings showed that faculty members and students have different priorities when evaluating digital anatomy platforms. Faculty members valued platforms that provided better accuracy and detailed anatomical structures, while students prioritized usability above the rest of the features. CONCLUSION: Given that faculty and students have different preferences when selecting digital anatomy platforms, this article proposed that educators maximize the specific affordances offered by the technology by having a clear pedagogy and strategy on how the technology will be incorporated into the curriculum to help students achieve the desired learning outcomes.

Effects of Heat Exposure and Ice Slurry Ingestion on Risk-Taking Behavior in Healthcare Workers.

PURPOSE: Healthcare workers (HCWs) wearing personal protective equipment (PPE) experience physiological strain that can impair motor and psychological functions, potentially affecting patient care. We assessed the effects of heat exposure on maximal strength and risk-taking behavior amongst PPE-wearing HCWs and the efficacy of ice slurry to alleviate adverse effects. METHODS: 17 HCWs completed two experimental trials in a crossover design, consuming 5 g × kg-1 of body mass of ambient drink (AMB) or ice slurry (ICE) before donning PPE and undergoing 2-h of simulated decontamination exercise (wet-bulb globe temperature (WBGT): 25.9 ± 0.8 °C, PPE microenvironment WBGT: 29.1 ± 2.1 °C). Body core temperature (Tc), heart rate (HR), chest skin temperature (Tsk), ratings of perceived exertion (RPE), thermal sensation (RTS), maximal voluntary contraction (MVC), risk-taking behavior (Balloon Analogue Risk-Taking task; BART) and salivary cortisol were assessed. RESULTS: Pre- to post-drinking ∆Tc was greater in ICE (-0.2 ± 0.1 °C) than AMB (-0.0 ± 0.1 °C, P = 0.003). Post-drinking RTS was lower in ICE (2.7 ± 1.2) than AMB (4.1 ± 0.4, P < 0.001). ICE and AMB had similar Tc and HR (both P > 0.05), but Tsk was lower in ICE than AMB (P = 0.049). A lower MVC (30.3 ± 6.7 kg vs 27.4 ± 4.9 kg, P = 0.001) and higher BART adjusted total pump count (472 ± 170 pumps vs 615 ± 174 pumps, P = 0.017) was observed pre- to post-trial in AMB but absent in ICE (both P > 0.05). Salivary cortisol was similar between trials (P = 0.42). CONCLUSIONS: Heat-exposed PPE-wearing HCWs had impaired maximal strength and elevated risk-taking behavior. This may increase the risk of avoidable workplace accidents that can jeopardize HCWs and patient care. Ice slurry ingestion alleviated these heat-related impairments, suggesting its potential as an ergogenic aid.

The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials.

OBJECTIVES: To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes. METHODS: A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥ 65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method. RESULTS: Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5 %, [95 %CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3 %, [95 %CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6 % ([95 %CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥ 100 events, and random-effects models provided comparable estimates for all outcomes. CONCLUSIONS: HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥ 65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.

Evaluation of Age and Sex Differences in Contemporary versus High-Sensitivity Troponin I Measurement in Hospitalized Patients.

Background: With the transition from the contemporary (cTnI) to high-sensitivity troponin assay (hs-cTnI), concerns have arisen regarding the diagnostic differences between these two assays due to analytical distinctions. This study aims to evaluate the age and sex differences between these two assays, as well as the differences resulting from using two different 99th percentile values of the high-sensitivity troponin assay. Method: A retrospective observational study was conducted at an academic medical center, encompassing a total of 449 lithium heparin plasma samples included in the dataset. Both contemporary and high-sensitivity troponin were simultaneously measured using Siemens ADVIA Centaur analyzers. Two sets of sex-specific 99th percentile URLs from the Siemens study (cutoff-1) and Universal Sample Bank data (cutoff-2) were used for the data analysis. Results: The use of cutoff-1 or cutoff-2 had a negligible impact on troponin classification. Troponin elevation significantly increased in individuals > 50 years old for males and >40 years old for females, with both troponin assays. A receiver operating characteristic analysis did not find significant differences between the two assays. The Kaplan-Meier curves showed no differences in survival in cTnI according to the non-sex-specific 99th URL or hs-cTnI (cutoff-2) but showed a slight difference in survival in hs-cTnI (cutoff-1). Conclusions: Overall, there were no significant differences in age and sex in the diagnostic performance between the contemporary and high-sensitivity troponin assays. Selection criteria for the establishment of the 99th percentile URL should be standardized to avoid the misinterpretation of the troponin results.

Vascular In-person for Students In the match Trial: An investigation of postinterview site visits to address the limitations of virtual interviews.

PURPOSE: The graduate medical education community implemented virtual residency interviews in response to travel restrictions during the COVID-19 pandemic, and this approach has persisted. Although many residency applicants wish to visit in-person prospective training sites, such opportunities could bias programs toward those who are able to meet this financial burden, exacerbating equity concerns. One proposed solution is to offer applicants the opportunity to visit only after a program's rank list is "locked," avoiding favoritism to applicants who visit, but allowing applicants to experience some of the camaraderie, geography, and local effects of an in-person visit. As debate about the optimal format of residency interviews continues, it is important to investigate whether in-person program visits, completed after program rank list certification, provide meaningful benefits to applicants in the residency match process. METHODS: All vascular programs entering the 2023 integrated vascular surgery residency match were invited to participate. Programs agreed to certify their National Resident Matching Program rank lists by February 1, 2023. Applicants then had the opportunity to visit the programs at which they interviewed. The particulars of the visit were determined by the individual programs. Applicants completed their standard rank list and locked on the standard date: March 1, 2023. Applicants then completed a survey regarding the impact of the visits on their rank order list decision-making. Program directors (PDs) completed a survey regarding their experiences as well. Data were collected using REDCap. RESULTS: Twenty-one of the 74 (28%) programs participated. Nineteen PDs completed the postinterview site visit survey (response rate 90%). Applicants interviewing at the participating programs (n = 112) were informed of the study, offered the opportunity to attend postinterview site visits, and received the survey. Forty-seven applicants responded (response rate 42%). Eighty-six percent of applicants stated that the visit impacted their rank list. Most important factors were esprit de corps of the program (86%), the faculty/trainees/staff (81%), and the physical setting (62%). Seventy-one percent of those participating spent ≤$800 on their visit. Eighty-one percent were satisfied with the process. Twenty-one percent of PDs would have changed their rank list if they could have based on the applicants' in-person visit. Sixty-three percent of the visit sessions cost the programs ≤$500, and 63% were satisfied with the process. CONCLUSIONS: This study is the first to document the impact of in-person site visits by applicants on a graduate medical education match process in one specialty. Our results suggest that this process provides meaningful data to applicants that helped them with their decision-making evidenced by most altering their rank lists, while avoiding some of the critical equity issues that accompany traditional in-person interviews. This may provide a model for future interview processes for residency programs.

'Spin' in urology non-randomised studies comparing therapeutic interventions: a temporal analysis.

OBJECTIVE: To determine the prevalence of 'spin' (i.e., reporting practices that distort the interpretation of results by positively reflecting negative findings or downplaying potential harms) strategies and level of spin in urological observational studies and whether the use of spin has changed over time. MATERIALS AND METHODS: MEDLINE and Embase were searched to identify observational studies comparing therapeutic interventions in the top five urology journals and major urological subspecialty journals, published between 2000 and 2001, 2010 and 2011, and 2020 and 2021. RESULTS: A total of 235 studies were included. Spin was identified in 81% of studies, with a median of two strategies per study. The most commonly used strategies were inadequate implication for clinical practice (30%), causal language or causal claim (29%), and use of linguistic spin (29%). Moderate to high levels of spin were found in 55% of conclusions. From 2000 to 2020, the average number of strategies used has significantly decreased each decade (H = 27.459, P < 0.001), and the median level of spin in conclusions was significantly lower in studies published in the 2020s and 2010s than in the 2000s (H = 11.649, P = 0.003). CONCLUSIONS: Our results suggest that 81% of urological observational studies comparing therapeutic interventions contained spin. Over the past two decades, the use of spin has significantly declined, but this remains an area for improvement, with 70% of included studies published in the 2020s employing spin. Medical writing should scrupulously avoid words or phrases that are not supported by data in the manuscript.

Poor personal protective equipment practices were associated with heat-related symptoms among Asian healthcare workers: a large-scale multi-national questionnaire survey.

BACKGROUND: It is pertinent to understand the perceptions of healthcare workers (HCWs) with their associated personal protective equipment (PPE) usage and heat strain symptoms experienced to effectively combat the negative effects of heat stress during treatment and care activities. METHODS: We evaluated the associated heat stress perceived by HCWs across Asia and validated a questionnaire on perceptions of heat stress, associated PPE usage, and heat strain symptoms experienced. The questionnaire was administered to 3,082 HCWs in six Asian regions. Factor analyses, including Cronbach's alpha, assessed the questionnaire's validity and reliability. Structural equation modelling analysed the effects of knowledge, attitudes and practices, and heat strain symptoms. RESULTS: The questionnaire was found to be reliable in assessing HCWs' knowledge, and attitudes and practices towards heat stress and PPE usage (both Cronbach's alpha = 0.9), but not heat strain symptoms (Cronbach's alpha = 0.6). Despite knowledge of heat stress, HCWs had negative attitudes and practices regarding PPE usage (ß1 = 0.6, p < 0.001). Knowledge (path coefficient = 0.2, p < 0.001), and negative attitudes and practices (path coefficient = 0.2, p < 0.001) of HCWs towards heat stress and PPE usage adversely affected symptoms experienced. CONCLUSIONS: The questionnaire was not reliable in assessing symptoms. HCWs should, nevertheless, still self-assess their symptoms for early detection of heat strain. To effectively attenuate heat strain, understanding HCWs' attitudes and practices towards PPE usage should guide policymakers in implementing targeted heat management strategies.

Text Report Analysis to Identify Opportunities for Optimizing Target Selection for Chest Radiograph Artificial Intelligence Models.

Our goal was to analyze radiology report text for chest radiographs (CXRs) to identify imaging findings that have the most impact on report length and complexity. Identifying these imaging findings can highlight opportunities for designing CXR AI systems which increase radiologist efficiency. We retrospectively analyzed text from 210,025 MIMIC-CXR reports and 168,949 reports from our local institution collected from 2019 to 2022. Fifty-nine categories of imaging finding keywords were extracted from reports using natural language processing (NLP), and their impact on report length was assessed using linear regression with and without LASSO regularization. Regression was also used to assess the impact of additional factors contributing to report length, such as the signing radiologist and use of terms of perception. For modeling CXR report word counts with regression, mean coefficient of determination, R2, was 0.469 ± 0.001 for local reports and 0.354 ± 0.002 for MIMIC-CXR when considering only imaging finding keyword features. Mean R2 was significantly less at 0.067 ± 0.001 for local reports and 0.086 ± 0.002 for MIMIC-CXR, when only considering use of terms of perception. For a combined model for the local report data accounting for the signing radiologist, imaging finding keywords, and terms of perception, the mean R2 was 0.570 ± 0.002. With LASSO, highest value coefficients pertained to endotracheal tubes and pleural drains for local data and masses, nodules, and cavitary and cystic lesions for MIMIC-CXR. Natural language processing and regression analysis of radiology report textual data can highlight imaging targets for AI models which offer opportunities to bolster radiologist efficiency.

The comprehensive English National Lynch Syndrome Registry: development and description of a new genomics data resource.

Background: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. Methods: For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). Findings: A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40-62), compared to 73 years (IQR 64-80) in the general population (p < 0.0001). Interpretation: The ENLSR represents the first comprehensive national registry of PV carriers in England and one of the largest cohorts of MMR PV carriers worldwide. The establishment of a secure, centralised infrastructure and mechanism for routine registration of newly identified carriers ensures sustainability of the data resource. Funding: This work was funded by the Wellcome Trust, Cancer Research UK and Bowel Cancer UK. The funder of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

89Zr-ImmunoPET for the Specific Detection of EMP2-Positive Tumors.

Epithelial membrane protein-2 (EMP2) is upregulated in a number of tumors and therefore remains a promising target for mAb-based therapy. In the current study, image-guided therapy for an anti-EMP2 mAb was evaluated by PET in both syngeneic and immunodeficient cancer models expressing different levels of EMP2 to enable a better understanding of its tumor uptake and off target accumulation and clearance. The therapeutic efficacy of the anti-EMP2 mAb was initially evaluated in high- and low-expressing tumors, and the mAb reduced tumor load for the high EMP2-expressing 4T1 and HEC-1-A tumors. To create an imaging agent, the anti-EMP2 mAb was conjugated to p-SCN-Bn-deferoxamine (DFO) and radiolabeled with 89Zr. Tumor targeting and tissue biodistribution were evaluated in syngeneic tumor models (4T1, CT26, and Panc02) and human tumor xenograft models (Ramos, HEC-1-A, and U87MG/EMP2). PET imaging revealed radioactive accumulation in EMP2-positive tumors within 24 hours after injection, and the signal was retained for 5 days. High specific uptake was observed in tumors with high EMP2 expression (4T1, CT26, HEC-1-A, and U87MG/EMP2), with less accumulation in tumors with low EMP2 expression (Panc02 and Ramos). Biodistribution at 5 days after injection revealed that the tumor uptake ranged from 2 to approximately 16%ID/cc. The results show that anti-EMP2 mAbs exhibit EMP2-dependent tumor uptake with low off-target accumulation in preclinical cancer models. The development of improved anti-EMP2 Ab fragments may be useful to track EMP2-positive tumors for subsequent therapeutic interventions.

Incidence and trends in the treatment of kidney stones in Canada: A population-based cohort study.

INTRODUCTION: Our objective was to assess the incidence of kidney stones requiring acute care, trends in the surgical treatment of stones, and the demographics of stone formers in Canada. METHODS: We conducted a population-based, retrospective cohort study using administrative data from the Canadian Institute for Health Information. We included Canadian residents age >18, outside of Quebec, who presented between January 1, 2013, and December 31, 2018, with a kidney stone episode. This was defined as a kidney stone resulting in hospital admission, emergency department visit, or stone intervention, specifically shockwave lithotripsy (SWL), ureteroscopy (URS), or percutaneous nephrolithotomy (PCNL). RESULTS: There were 471 824 kidney stone episodes, including 184 373 interventions. The number of kidney stone episode increased from 277/100 000 in 2013 to 290/100 000 in 2018. The median age was 53 (interquartile range 41-65) and 59.9% were male. The crude rate for stone intervention was 877/100 000. The age- and gender-standardized rate for interventions was highest in Nova Scotia and Newfoundland and Labrador and lowest in Prince Edward Island. The most common intervention in Canada was URS (73.5%), followed by SWL (19.8%) and PCNL (6.7%). The percent utilization of SWL was highest in Manitoba, whereas for URS, it was highest in Prince Edward Island and Alberta. CONCLUSIONS: Our study provides the first population-based data on the demographics of stone formers and treatment trends across Canada. There has been a 4.7% increase in kidney stone episodes over the study period. Those presenting to hospital or requiring intervention for a kidney stone are more likely to be male, age 41-65, and undergo URS.

Patient-specific computational flow simulation reveals significant differences in paravisceral aortic hemodynamics between fenestrated and branched endovascular aneurysm repair.

Background: Endovascular aneurysm repair with four-vessel fenestrated endovascular aneurysm repair (fEVAR) or branched endovascular aneurysm repair (bEVAR) currently represent the forefront of minimally invasive complex aortic aneurysm repair. This study sought to use patient-specific computational flow simulation (CFS) to assess differences in postoperative hemodynamic effects associated with fEVAR vs bEVAR. Methods: Patients from two institutions who underwent four-vessel fEVAR with the Cook Zenith Fenestrated platform and bEVAR with the Jotec E-xtra Design platform were retrospectively selected. Patients in both cohorts were treated for paravisceral and extent II, II, and V thoracoabdominal aortic aneurysms. Three-dimensional finite element volume meshes were created from preoperative and postoperative computed tomography scans. Boundary conditions were adjusted for body surface area, heart rate, and blood pressure. Pulsatile flow simulations were performed with equivalent boundary conditions between preoperative and postoperative states. Postoperative changes in hemodynamic parameters were compared between the fEVAR and bEVAR groups. Results: Patient-specific CFS was performed on 20 patients (10 bEVAR, 10 fEVAR) with a total of 80 target vessels (40 renal, 20 celiac, 20 superior mesenteric artery stents). bEVAR was associated with a decrease in renal artery peak flow rate (-5.2% vs +2.0%; P < .0001) and peak pressure (-3.4 vs +0.1%; P < .0001) compared with fEVAR. Almost all renal arteries treated with bEVAR had a reduction in renal artery perfusion (n = 19 [95%]), compared with 35% (n = 7) treated with fEVAR. There were no significant differences in celiac or superior mesenteric artery perfusion metrics (P = .10-.27) between groups. Time-averaged wall shear stress in the paravisceral aorta and branches also varied significantly depending on endograft configuration, with bEVAR associated with large postoperative increases in renal artery (+47.5 vs +13.5%; P = .002) and aortic time-averaged wall shear stress (+200.1% vs -31.3%; P = .001) compared with fEVAR. Streamline analysis revealed areas of hemodynamic abnormalities associated with branched renal grafts which adopt a U-shaped geometry, which may explain the observed differences in postoperative changes in renal perfusion between bEVAR and fEVAR. Conclusions: bEVAR may be associated with subtle decreases in renal perfusion and a large increase in aortic wall shear stress compared with fEVAR. CFS is a novel tool for quantifying and visualizing the unique patient-specific hemodynamic effect of different complex EVAR strategies. Clinical Relevance: This study used patient-specific CFS to compare postoperative hemodynamic effects of four-vessel fenestrated endovascular aneurysm repair (fEVAR) and branched endovascular aneurysm repair (bEVAR) in patients with complex aortic aneurysms. The findings indicate that bEVAR may result in subtle reductions in renal artery perfusion and a significant increase in aortic wall shear stress compared with fEVAR. These differences are clinically relevant, providing insights for clinicians choosing between these approaches. Understanding the patient-specific hemodynamic effects of complex EVAR strategies, as revealed by CFS, can aid in future personalized treatment decisions, and potentially reduce postoperative complications in aortic aneurysm repair.

Preoperative proteinuria is independently associated with mortality after fenestrated endovascular aneurysm repair.

OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) has become a mainstay in treating complex aortic aneurysms, though baseline patient factors predicting long-term outcomes remain poorly understood. Proteinuria is an early marker for chronic kidney disease and associated with adverse cardiovascular outcomes, but its utility in patients with aortic aneurysms is unknown. We aimed to determine whether preoperative proteinuria impacts long-term survival after FEVAR. METHODS: A single-institution, retrospective review of all elective FEVAR was performed. Preoperative proteinuria was assessed by urinalysis: negative (0-29 mg/dL), 1+ (30-100 mg/dL), 2+ (101-299 mg/dL), and 3+ (≥300 mg/dL). The cohort was stratified by patients with proteinuria (≥30 mg/dL) vs those without (<30 mg/dL). Baseline, perioperative, and long-term outcomes were compared. The primary outcome, all-cause mortality, was evaluated by Kaplan-Meier analysis and independent predictors with Cox proportional hazards modeling. RESULTS: Among 181 patients who underwent standard FEVAR from 2012 to 2022 (mean follow-up 33 months), any proteinuria was noted in 30 patients (16.6%). Patients with proteinuria were more likely to be Black (10.0% vs 1.3%) with a lower estimated glomerular filtration rate (eGFR) (52.7 ± 24.7 vs 67.7 ± 20.5 mL/min/1.73 m2), higher Society for Vascular Surgery comorbidity score (10.9 ± 4.3 vs 8.2 ± 4.7) and calcium channel blocker therapy (50.0% vs 29.1%), and larger maximal aneurysm diameter (67.2 ± 16.9 vs 59.8 ± 9.8 mm) (all P < .05). Thirty-day mortality was higher in the proteinuria group (10.0% vs 1.3%; P = .03). Overall survival at 1 and 5 years was significantly lower for those with proteinuria (71.5% vs 92.3% and 29.5% vs 68.1%; log-rank P < .001). On multivariable analysis, preoperative proteinuria was independently associated with over threefold higher hazard of mortality (hazard ratio [HR]: 3.21, 95% confidence interval [CI]: 1.66-6.20; P < .001), whereas preoperative eGFR was not predictive (HR: 0.99, 95% CI: 0.98-1.01; P = .28). Additional significant predictors included chronic obstructive pulmonary disease (HR: 2.04), older age (HR: 1.05), and larger maximal aneurysm diameter (HR: 1.03; all P < .05). CONCLUSIONS: In our 10-year experience with FEVAR, preoperative proteinuria was observed in 17% of patients and was significantly associated with worse survival. In this cohort, proteinuria was independently associated with all-cause mortality, whereas eGFR was not, suggesting that urinalysis may provide an additional simple metric for risk-stratifying patients before FEVAR.