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Background: Historically, there have been perceptions that engagement with palliative care (PC) services may preclude potentially curative but high-risk operations. As such, we sought to investigate the relationship between specialty PC consultation and the care trajectory of surgical patients. We hypothesized that PC consultation would be associated with increased frequency of nonoperative treatments being chosen among surgical inpatients. Design: All general surgery and general surgery subspecialty patients receiving PC consultation at a single tertiary academic medical center from 2020 to 2021 were identified. Surgical operations were stratified as "elevated risk" in accordance with 2014 American Heart Association guidelines. Retrospective chart review was performed, and comparisons were made with univariable statistics. Results: We identified a total of 729 patients who received specialty PC consultation, 159 of whom were admitted to a surgical service. PC was actively involved in consultation for surgical decision making in 27% (43/159) of these encounters. PC assistance with surgical decision making was associated with a greater incidence of elevated-risk operative procedures during admission compared with patients without presurgical PC consultation (OR 3.29 [2.51, 7.16]). There was no association between PC involvement with surgical decision making and odds of discharge to hospice (OR 0.42 [0.18, 1.51]) nor death during admission (OR 0.66 [0.21, 2.10]). Conclusions: We found that specialty PC involvement in surgical decision making does not preclude the pursuit of disease-directed surgical treatment. Contrary to our hypothesis, our single institutional data demonstrate that early PC consultation can be synergistic with surgical disease management and does not preclude elevated-risk operative care.

Background: While REIMS technology has successfully been demonstrated for the histological identification of ex-vivo breast tumor tissues, questions regarding the robustness of the approach and the possibility of tumor molecular diagnostics still remain unanswered. In the current study, we set out to determine whether it is possible to acquire cross-comparable REIMS datasets at multiple sites for the identification of breast tumors and subtypes., Methods: A consortium of four sites with three of them having access to fresh surgical tissue samples performed tissue analysis using identical REIMS setups and protocols. Overall, 21 breast cancer specimens containing pathology-validated tumor and adipose tissues were analyzed and results were compared using uni- and multivariate statistics on normal, WT and PIK3CA mutant ductal carcinomas., Results: Statistical analysis of data from standards showed significant differences between sites and individual users. However, the multivariate classification models created from breast cancer data elicited 97.1% and 98.6% correct classification for leave-one-site-out and leave-one-patient-out cross validation. Molecular subtypes represented by PIK3CA mutation gave consistent results across sites., Conclusions: The results clearly demonstrate the feasibility of creating and using global classification models for a REIMS-based margin assessment tool, supporting the clinical translatability of the approach., (© 2024. Waters Technologies Corporation and The Author(s).)

Forest fragmentation is a grave threat to biodiversity. Forests are becoming increasingly fragmented with more than 70% now < 1 km from forest edge. Although much is known about the effects of forest fragmentation on individual species, much less is understood about its effects on species interactions (i.e., mutualisms, antagonisms, etc.). In 2014, a previous meta-analysis assessed the impacts of forest fragmentation on different species interactions, across 82 studies. We pooled the previous data with data published in the last 10 years (combined total 104 studies and 168 effect sizes). We compared the new set of publications (22 studies and 32 effect sizes) with the old set to evaluate potential changes in species interactions over time given the global increase in fragmentation rates. Mutualisms were more negatively affected by forest fragmentation than antagonisms (p < 0.0001). Edge effects, fragment size, and degradation negatively affected mutualisms, but not antagonisms, a different finding from the original meta-analysis. Parasitic interactions increased as fragment size decreased (p < 0.0001)-an intriguing result at variance with earlier studies. New publications showed a more negative mean effect size of forest fragmentation on mutualisms than old publications. Although research is still limited for some interactions, we identified an important scientific trend: current research tends to focus on antagonisms. We concluded that forest fragmentation disrupts important species interactions and that this disruption has increased over time., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Background: Soft tissue sarcomas (STS) constitute a heterogeneous group of rare tumor entities. Treatment relies on challenging patient-tailored surgical resection. Real-time intraoperative lipid profiling of electrosurgical vapors by rapid evaporative ionization mass spectrometry (REIMS) may aid in achieving successful surgical R0 resection (i.e., microscopically negative-tumor margin resection). Here, we evaluate the ex vivo accuracy of REIMS to discriminate and identify various STS from normal surrounding tissue., Methods: Twenty-seven patients undergoing surgery for STS at Maastricht University Medical Center+ were included in the study. Samples of resected STS specimens were collected and analyzed ex vivo using REIMS. Electrosurgical cauterization of tumor and surrounding was generated successively in both cut and coagulation modes. Resected specimens were subsequently processed for gold standard histopathological review. Multivariate statistical analysis (principal component analysis-linear discriminant analysis) and leave-one patient-out cross-validation were employed to compare the classifications predicted by REIMS lipid profiles to the pathology classifications. Electrosurgical vapors produced during sarcoma resection were analyzed in vivo using REIMS., Results: In total, 1200 histopathologically-validated ex vivo REIMS lipid profiles were generated from 27 patients. Ex vivo REIMS lipid profiles classified STS and normal tissues with 95.5% accuracy. STS, adipose and muscle tissues were classified with 98.3% accuracy. Well-differentiated liposarcomas and adipose tissues could not be discriminated based on their respective lipid profiles. Distinction of leiomyosarcomas from other STS could be achieved with 96.6% accuracy. In vivo REIMS analyses generated intense mass spectrometric signals., Conclusion: Lipid profiling by REIMS is able to discriminate and identify STS with high accuracy and therefore constitutes a potential asset to improve surgical resection of STS in the future., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Optical neuronavigation systems using infrared light to create a virtual reality image of the brain allow the surgeon to track instruments in real time. Due to the high vulnerability of the brain, neurosurgical interventions must be performed with a high precision. The aim of the experimental cadaveric study was to determine the application accuracy of a frameless optical neuronavigation system as guide for craniotomies by determining the target point deviation of predefined target points at the skull surface in the area of access to the cerebrum, cerebellum and the pituitary fossa. On each of the five canine cadaver heads ten target points were marked in a preoperative computed tomography (CT) scan. These target points were found on the cadaver skulls using the optical neuronavigation system. Then a small drill hole (1.5 mm) was drilled at these points. Subsequently, another CT scan was made. Both CT data sets were fused into the neuronavigation software, and the actual target point coordinates were identified. The target point deviation was determined as the difference between the planned and drilled target point coordinates. The calculated deviation was compared between two observers., Results: The analysis of the target point accuracies of all dogs in both observers taken together showed a median target point deviation of 1.57 mm (range: 0.42 to 5.14 mm). No significant differences were found between the observers or the different areas of target regions., Conclusion: The application accuracy of the described system is similar to the accuracy of other optical neuronavigation systems previously described in veterinary medicine, in which mean values of 1.79 to 4.3 mm and median target point deviations of 0.79 to 3.53 mm were determined., (© 2023. The Author(s).)

The need to integrate palliative care (PC) training into surgical education has been increasingly recognized. Our aim is to describe a set of PC educational strategies, with a range of requisite resources, time, and prior expertise, to provide options that surgical educators can tailor for different programs. Each of these strategies has been successfully employed individually or in some combination at our institutions, and components can be generalized to other training programs. Asynchronous and individually paced PC training can be provided using existing resources published by the American College of Surgeons and upcoming SCORE curriculum modules. A multiyear PC curriculum, with didactic components of increasing complexity for more advanced residents, can be applied based on available time in the didactic schedule and local expertise. Simulation-based training in PC skills can be developed to provide objective competency-based training. Finally, a dedicated rotation on a surgical palliative care service can provide the most immersive experience with steps toward clinical entrustment of PC skills for trainees., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this paper, we discuss surgical palliative care for patients with cancer through the lens of frailty and the preoperative context. Historically, palliative care principles such as complex symptom management, high-risk decision-making and communication have played an important role in preoperative discussions of oncologic surgery for both palliative and curative intent. There is increasing motivation among surgeons to integrate palliative care into the perioperative period in order to more effectively and comprehensively address potential adverse functional and quality of life outcomes. We discuss how the concept of frailty, and various instruments to measure frailty, have impacted perioperative decision-making, review the roots of surgical risk stratification and counseling on acceptable perioperative risk, and explore the preoperative setting as a possible avenue by which primary and specialty palliative care integration may have beneficial impact for patients considering oncologic resections., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rationale: Isomeric separation of prostanoids is often a challenge and requires chromatography and time-consuming sample preparation. Multiple prostanoid isomers have distinct in vivo functions crucial for understanding the inflammation process, including prostaglandins E 2 (PGE 2 ) and D 2 (PGD 2 ). High-resolution ion mobility spectrometry (IMS) based on linear ion transport in low-to-moderate electric fields and nonlinear ion transport in strong electric fields emerges as a broad approach for rapid separations prior to mass spectrometry., Methods: Derivatization with Girard's reagent T (GT) was used to overcome inefficient ionization of prostanoids in negative ionization mode due to poor deprotonation of the carboxylic acid group. Three high-resolution IMS techniques, namely linear cyclic IMS, linear trapped IMS, and nonlinear high-field asymmetric waveform IMS, were compared for the isomeric separation and endogenous detection of prostanoids present in intestinal tissue., Results: Direct infusion of GT-derivatized prostanoids proved to increase the ionization efficiency in positive ionization mode by a factor of >10, which enabled detection of these molecules in endogenous concentration levels. The high-resolution IMS comparison revealed its potential for rapid isomeric analysis of biologically relevant prostanoids. Strengths and weaknesses of both linear and nonlinear IMS are discussed. Endogenous prostanoid detection in intestinal tissue extracts demonstrated the applicability of our approach in biomedical research., Conclusions: The applied derivatization strategy offers high sensitivity and improved stereoisomeric separation for screening of complex biological systems. The high-resolution IMS comparison indicated that the best sensitivity and resolution are achieved by linear and nonlinear IMS, respectively., (© 2022 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Objective: National guidelines have suggested that quality surgical care should incorporate effective palliative care (PC). Numerous barriers to surgeon participation remain and the domains of optimal surgeon participation are unclear., Design: Eight semi-structured and multi-professional focus groups with 34 total participants. Discussion was transcribed, and qualitative approaches were used to encode, identify, and categorize emergent themes., Setting: Oregon Health & Science University, Portland Oregon. A tertiary care teaching hospital., Participants: 34 multi-disciplinary participants in eight focus groups, identified on a volunteer basis., Results: Key themes defining domains of optimal surgeon/palliative practice include: (1) "primary/secondary PC" which detailed conflict between the surgeon's desire to be part of palliative discussions and competing clinical/time demands. (2) "role/responsibility" described the tension surgeons feel around a desire to provide honest and goal concordant care (3) "teamwork/conflict" detailed the approach to disagreement among multidisciplinary teams., Conclusions: In this qualitative analysis, emergent themes suggest that surgeons want to be involved in the PC of their patients but are limited by available time and competing for ethical obligations. Tension between competing communication and care obligations and PC goals is common, and discord around patient goals remains an issue. This work highlights the need for a standardized curriculum to improve the PC of surgical patients., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Rapid evaporative ionization mass spectrometry (REIMS) is a direct tissue metabolic profiling technique used to accurately classify tissues using pre-built mass spectral databases. The reproducibility of the analytical equipment, methodology and tissue classification algorithms has yet to be evaluated over multiple sites, which is an essential step for developing this technique for future clinical applications. In this study, we harmonized REIMS methodology using single-source reference material across four sites with identical equipment: Imperial College London (UK); Waters Research Centre (Hungary); Maastricht University (The Netherlands); and Queen's University (Canada). We observed that method harmonization resulted in reduced spectral variability across sites. Each site then analyzed four different types of locally-sourced food-grade animal tissue. Tissue recognition models were created at each site using multivariate statistical analysis based on the different metabolic profiles observed in the m/z range of 600-1000, and these models were tested against data obtained at the other sites. Cross-validation by site resulted in 100% correct classification of two reference tissues and 69-100% correct classification for food-grade meat samples. While we were able to successfully minimize between-site variability in REIMS signals, differences in animal tissue from local sources led to significant variability in the accuracy of an individual site's model. Our results inform future multi-site REIMS studies applied to clinical samples and emphasize the importance of carefully-annotated samples that encompass sufficient population diversity.

Background: A shortage of palliative care (PC) sub-specialists highlights the need for quality PC provided by treating surgeons, although no established curriculum exists to teach surgical residents PC skills. To guide curriculum development, we sought to determine what modifiable factors contribute to surgical residents successfully providing PC., Methods: Eight focus groups with 34 participants were conducted. Semi-structured interviews were recorded, transcribed, and de-identified. Inductive thematic analysis was utilized to encode, identify, and categorize emergent themes., Results: Barriers to resident involvement in PC included: Limited Knowledge/Inexperience, Communication Difficulties, Time Constraints, and Burnout. Factors supporting resident involvement included: Patient Relationship/Rapport, Expertise Guiding PC Discussions, and Institutional Support. Communication skills that support successful PC delivery include establishing rapport, managing conflicts, avoiding bias, and acknowledging personal/scientific limitations., Discussion: This work identifies modifiable factors that support surgical residents providing PC. Faculty and institutional support, resident education on PC principles, and expanding clinical experience with PC may be the most modifiable from a programmatic perspective. Curriculum and process development focused on these areas will help optimize surgical resident's success delivering PC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Primary palliative care (PPC) is provided by the primary team and is essential for high-quality surgical care. There is a recognized PPC clinical and research need but little work on the optimal way to teach PPC to general surgery residents. We sought to define important factors of PPC pedagogy (i.e. nature and practice of teaching)., Methods: Eight semi-structured and multi-professional focus groups (n = 34) were performed. Discussion was transcribed, and de-identified. Qualitative approaches were used to encode, identify, and categorize emergent themes., Results: Emergent themes included: establishing a baseline knowledge, use of existing resources, simulation and debriefings, and emphasis on authentic clinical opportunities with graduated responsibility. A tension between resident entrustability and hesitancy of faculty to entrust was identified., Conclusions: PPC must be taught in surgical residency and the themes identified here will inform development and implementation of a PPC curriculum., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OSCC) challenges the ability of REIMS to detect low amounts of tumor cells. We evaluate REIMS sensitivity to determine the minimal amount of detected tumors cells during oral cavity cancer surgery. A total of 11 OSCC patients were included in this study. The tissue classification based on 185 REIMS ex vivo metabolic profiles from five patients was compared to histopathology classification using multivariate analysis and leave-one-patient-out cross-validation. Vapors were analyzed in vivo by REIMS during four glossectomies. Complementary desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to map tissue heterogeneity on six oral cavity sections to support REIMS findings. REIMS sensitivity was assessed with a new cell-based assay consisting of mixtures of cell lines (tumor, myoblasts, keratinocytes). Our results depict REIMS classified tumor and soft tissues with 96.8% accuracy. In vivo REIMS generated intense mass spectrometric signals. REIMS detected 10% of tumor cells mixed with 90% myoblasts with 83% sensitivity and 82% specificity. DESI-MSI underlined distinct metabolic profiles of nerve features and a metabolic shift phosphatidylethanolamine PE(O-16:1/18:2))/cholesterol sulfate common to both mucosal maturation and OSCC differentiation. In conclusion, the assessment of tissue heterogeneity with DESI-MSI and REIMS sensitivity with cell mixtures characterized sensitive metabolic profiles toward in vivo tissue recognition during oral cavity cancer surgeries.

Bile acids are steroid compounds involved in biological mechanisms of neurodegenerative diseases making them potential biomarkers for diagnosis or treatment. These compounds exist as structural and conformational isomers, which hinder distinguishing them in physiological processes. We aimed to develop tandem mass spectrometry-ion mobility spectrometry (MS/MS-IMS) methodologies to explore and understand the behaviour of isomeric steroids in the gas-phase and rapidly separate them. Unlike previously published ion mobility data, various isomers were investigated in mixtures to better mimic complex (pre-) clinical samples. The experimental collision cross sections (CCS)s were compared to the theoretical CCS values for an in-depth analysis of isomeric ions' behaviour in the gas-phase. Based on density-functional theory, we identified the impact of adduct positioning on the 3D conformation of enantiomers, diastereomers and structural isomers. The curling of the large side chains hedged the small differences among the isomers and lowered the CCS values. On the other hand, fragmenting off the identical side branches as well as imposing the bending of the steroid ring resulted in ion mobility differentiation. Careful data evaluation revealed the tendency of isomers to form homo-cluster in the mixture solutions and assist the separation. Our fundamental and experimental findings enable the ion mobility separation of isomeric steroids to be predicted. The introduced rapid and optimal MS/MS-IMS analytical methodology can be applied to distinguish isomeric bile acids both in a solution and potentially in patients' tissue samples, and consequently, reveal their molecular pathways., Competing Interests: Declaration of competing interest 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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fracture healing is a complex process, involving cell-cell interactions, various cytokines, and growth factors. Although fracture treatment improved over the last decades, a substantial part of all fractures shows delayed or absent healing. The fracture hematoma (fxh) is known to have a relevant role in this process, while the exact mechanisms by which it influences fracture healing are poorly understood. To improve strategies in fracture treatment, regulatory pathways in fracture healing need to be investigated. Lipids are important molecules in cellular signaling, inflammation, and metabolism, as well as key structural components of the cell. Analysis of the lipid spectrum in fxh may therefore reflect important events during the early healing phase. This study aims to develop a protocol for the determination of lipid signals over time, and the identification of lipids that contribute to these signals, with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in fxh in healthy fracture healing. Methods: Twelve fxh samples (6 porcine; 6 human) were surgically removed, snap frozen, sectioned, washed, and analyzed using MALDI-MSI in positive and negative ion mode at different time points after fracture (porcine: 72 h; human samples: range 1-19 days). A tissue preparation protocol for lipid analysis in fxh has been developed with both porcine and human fxh. Data were analyzed through principal component- and linear discriminant analyses. Results: A protocol for the preparation of fxh sections was developed and optimized. Although hematoma is a heterogeneous tissue, the intra-variability within fxh was smaller than the inter-variability between fxh. Distinctive m/ z values were detected that contributed to the separation of three different fxh age groups: early (1-3 days), middle (6-10 days), and late (12-19 days). Identification of the distinctive m/ z values provided a panel of specific lipids that showed a time dependent expression within fxh. Conclusion: This study shows that MALDI-MSI is a suitable analytical tool for lipid analysis in fxh and that lipid patterns within fxh are time-dependent. These lipid patterns within fxh may serve as a future diagnostic tool. These findings warrant further research into fxh analysis using MALDI-MSI and its possible clinical implications in fracture treatment., 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 © 2022 Groven, Nauta, Gruisen, Claes, Greven, van Griensven, Poeze, Heeren, Porta Siegel, Cillero-Pastor and Blokhuis.)