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Chlorpyrifos is an organophosphorus insecticide that elicits acute toxicity through inhibition of acetylcholinesterase (AChE), leading to acetylcholine accumulation and prolonged stimulation of cholinergic receptors throughout the central and peripheral nervous systems. Previous studies have indicated that neurodevelopment may also be impaired through alternative pathways, including reduction of cAMP catalyzed downstream events. The upstream initiating events that underlie non-cholinergic neurological actions of chlorpyrifos and other organophosphorus compounds remain unclear. To investigate the potential role of disruption of fatty acid signaling as a mechanism of toxicity, lipid metabolism and fatty acid profiles were examined to identify alterations that may play a critical role in upstream signaling in the CNS. Juvenile rainbow trout were treated for 7 days with nominal chlorpyrifos concentrations previously reported to diminish olfactory responses (10, 20, and 40 μg/L). While lethality was noted higher doses, measured chlorpyrifos concentrations of 1.38 μg/L (nominal concentration 10 μg/L) significantly reduced the activity of AChE and two serine lipases, monoacylglycerol lipase and fatty acid amide hydrolase in the brain. Reductions in lysophosphatidylethanolamines (16:0; 18:0, 18:1, and 22:6) derived from the phosphatidylethanolamines and free fatty acids (Palmitic acid16:0; Linolenic acid18:3; Eicosadienoic acid 20:2; Arachidonic acid 20:4; and Docosahexaenoic acid 22:6) were also noted, suggesting that chlorpyrifos inhibited the metabolism of selected phospholipid signaling precursors at sublethal concentrations. These results indicate that in addition to AChE inhibition, environmentally relevant chlorpyrifos exposure alters serine lipase activity and lipid metabolites in the trout brain, which may compromise neuronal signaling and impact neurobehavioral responses in aquatic animals.

Competing Interests: Disclosure. Nolan M. Winicki, Fabian M. Johnston, and Jonathan B. Greer have no conflicts of interest to declare that may be relevant to the contents of this article.

Background: No guidelines exist regarding the management of the uninvolved uterus or adnexa (fallopian tubes and/or ovaries) in patients with peritoneal metastases (PM) from non-gynecologic malignancies. It is unclear whether salpingo-oophorectomy, hysterectomy, or both should be performed when a complete pelvic peritonectomy is otherwise warranted., Methods: A 25-item electronic survey was sent to 225 surgeons worldwide who routinely perform cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Participants were recruited through listservs of expert groups. Individual surgeon approaches to the management of the grossly uninvolved uterus and adnexa in pre- and post-menopausal women with PM from low- and high-grade appendiceal neoplasms, colorectal cancer, and peritoneal mesothelioma were collected using a 5-point Likert scale., Results: A total of 135 complete responses (60% response rate) were obtained from surgeons practicing in 27 countries. Respondents reported a median practice of 10 years (interquartile range [IQR] 6-15 years) and a median performance of 20 (IQR 12-30) CRS/HIPEC operations per year. Rates of salpingo-oophorectomy differed by histology and a woman's menopausal status, ranging from 29 to 42% in pre-menopausal women to 71-77% in post-menopausal women (P < 0.001). Notably, the number of surgeons who would perform a hysterectomy was lower, ranging from 12 to 27% for pre-menopausal women and from 32 to 44% for post-menopausal women, dependent on histology (P < 0.001)., Conclusions: Surgeons are overall more aggressive with adnexal resection than with hysterectomy in both pre- and post-menopausal women with PM from non-gynecologic malignancies. Further prospective studies are required to determine the best approach to optimize surgical and oncologic outcomes while also accounting for the fertility and hormonal impact., Competing Interests: Disclosure: Shannon N. Radomski received financial support from the National Cancer Institute (NCI) grant 5T32CA126607-12 and the American College of Surgeons Resident Research Scholarship. Stephanie Wethington - In the 36 months prior to publication, I had 6 weeks of employment by Astrazeneca. Olivier Glehen - consultant for GAMIDA., (© 2024. Society of Surgical Oncology.)

Background: Hematologic changes after splenectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) can complicate postoperative assessment of infection. This study aimed to develop a machine-learning model to predict postoperative infection after cytoreductive surgery (CRS) and HIPEC with splenectomy., Methods: The study enrolled patients in the national TriNetX database and at the Johns Hopkins Hospital (JHH) who underwent splenectomy during CRS/HIPEC from 2010 to 2024. Demographics, comorbidities, vital signs, daily laboratory values, and documented infections were collected. The patients were divided into infected and non-infected cohorts within 14 days postoperatively. Extreme gradient boost (XGBoost) machine-learning was used to predict postoperative infection. An initial model was generated using the TriNetX dataset and externally validated in the JHH cohort., Results: From TriNetX, 1016 patients were included: 802 in the non-infected group (79%) and 214 (21%) in the postoperative infection group. The mean age was 61 ± 13 years, and 597 (56%) of the patientswere female. Most of the patients underwent CRS/HIPEC with splenectomy for appendiceal cancer (n = 590, 56%), followed by colorectal malignancy (n = 299, 29%). The remainder (n = 127, 15%) underwent CRS/HIPEC with splenectomy for gastric, pancreatic, ovarian, and small bowel malignancies or peritoneal mesothelioma. In detecting any infection, XGBoost exhibited excellent prediction accuracy (area under the receiver operating characteristic curve [AUC], 0.910 ± 0.073; F1 score, 0.915 ± 0.040) and retained high accuracy upon external validation with 96 demographically similar JHH patients (AUC, 0.823 ± 0.08; F1 score, 0.864 ± 0.03)., Conclusion: A novel machine-learning algorithm was developed to predict postoperative infection after CRS/HIPEC with splenectomy that could aid in the early diagnosis and initiation of treatment., Competing Interests: Disclosure: There are no conflicts of interest., (© 2025. Society of Surgical Oncology.)

Competing Interests: Disclosure: Albert Leng, Vrinda Madan, Manuj Shah, Andrei Gurau, Fabian M. Johnston, and Jonathan B. Greer declare no conflicts of interest that may be relevant to the contents of this study. Informed consent: Not applicable.

Background and Objectives: Neuroblastoma, the most common extracranial solid tumor in children, is rare in adults. This study compares patient characteristics, disease patterns, and treatments among adults, adolescents, and children with neuroblastoma., Methods: We queried the National Cancer Database (2004-2019) for neuroblastoma cases. Patient and tumor characteristics, treatments, and 5-year overall survival (5-OS) were compared between adults (≥ 18 years), adolescents (10-17 years), and children (0-9 years). Kaplan-Meier curves and Cox regression assessed survival differences., Results: Among 6350 neuroblastoma patients, 256 (4.0%) were adults, 222 (3.5%) were adolescents, and 5872 (92.5%) were children. Tumors were largest in adolescents (9.7 cm), followed by adults (8.0 cm) and children (6.7 cm) (p < 0.001). Adults were less likely to have tumors in the adrenal glands (34.0% vs. children: 54.7%, adolescents: 43.2%, p < 0.001) and had lower rates of metastasis (10.9% vs. 19.3% and 19.4%, p < 0.001). Compared to children, adults received less chemotherapy, immunotherapy, and bone marrow transplants (p < 0.001). 5-OS was worse in adults (65.8%), followed by adolescents (70.4%) and children (78.2%) (p < 0.001). After adjustment, adults (aHR: 2.27; 95% CI, 1.71-3.01) and adolescents (aHR: 2.02; 95% CI, 1.54-2.64) had higher hazards of death compared to children., Conclusions: Adults and adolescents with neuroblastoma have distinct clinical features and lower survival than children, underscoring the need for tailored treatment approaches for older patients., Level of Evidence: III., (© 2025 Wiley Periodicals LLC.)

Individual ion mass spectrometry (I 2 MS) is the Orbitrap-based extension of the niche mass spectrometry technique known as charge detection mass spectrometry (CDMS). While traditional CDMS analysis is performed on in-house-built instruments such as the electrostatic linear ion trap, I 2 MS extends CDMS analysis to Orbitrap analyzers, allowing charge detection analysis to be available to the scientific community at large. I 2 MS simultaneously measures the mass-to-charge ratios (m/z) and charges (z) of hundreds to thousands of individual ions within one acquisition event, creating a spectral output directly into the mass domain without the need for further spectral deconvolution. A mass distribution or 'profile' can be created for any desired sample regardless of composition or heterogeneity. To assist in reducing I 2 MS analysis to practice, we developed this workflow for data acquisition and subsequent data analysis, which includes (i) protein sample preparation, (ii) attenuation of ion signals to obtain individual ions, (iii) the creation of a charge-calibration curve from standard proteins with known charge states and finally (iv) producing a meaningful mass spectral output from a complex or unknown sample by using the STORIboard software. This protocol is suitable for users with prior experience in mass spectrometry and bioanalytical chemistry. First, the analysis of protein standards in native and denaturing mode is presented, setting the foundation for the analysis of complex mixtures that are intractable via traditional mass spectrometry techniques. Examples of complex mixtures included here demonstrate the relevant analysis of an intact human monoclonal antibody and its intricate glycosylation patterns., Competing Interests: Competing interests: The authors declare the following competing financial interest(s): P.F.Y., V.Z., K.S. and M.W.S. are employees of Thermo Fisher Scientific, a provider of MS systems. R.T.F., K.R.D., J.B.G. and N.L.K. are involved in commercialization of MS informatics software including STORIboard. N.L.K. is a paid consultant for Thermo Fisher Scientific., (© 2025. Springer Nature Limited.)

Competing Interests: Disclosure: Shannon N. Radomski received salary support from National Cancer Institute (NCI) grant 5T32CA126607-12 and the American College of Surgeons Resident Research Scholarship

Competing Interests: Disclosure: There are no conflicts of interest.

Introduction: Racial disparities in minimally invasive surgery (MIS) utilization across gastrointestinal (GI) cancers are not well characterized. We evaluated racial/ethnic disparities in the use of MIS approaches and associated outcomes., Methods: We analyzed a cohort of patients with GI cancer in the National Cancer Database (2010-2020). Multinomial logistic regression was used to evaluate associations between race/ethnicity and approach. Logistic regression was used to assess 30-day readmission and 90-day mortality. Cox regression was used to analyze overall survival. Models were adjusted for demographics, clinical characteristics, cancer factors, and facility features., Results: Of the 839 398 patients included, 76.9% were White, 11.6% Black, 6.6% Hispanic/Latino, 4.0% Asian, and 0.3% Indigenous. Compared with patients of White race, the odds of robotic surgery were lower for Black (OR 0.89, 95% CI 0.86-0.93) and Indigenous patients (OR 0.72, 95% CI 0.59-0.89), but higher for Hispanic/Latino (OR 1.12, 95% CI 1.08-1.17) and Asian patients (OR 1.27, 95% CI 1.21-1.34). Indigenous patients had higher odds of readmission (OR 1.41, 95% CI 1.23-1.62), 90-day mortality (OR 1.31, 95% CI 1.11-1.54), and worse overall survival (HR 1.11, 95% CI 1.05-1.18)., Conclusion: Indigenous and Black patients have lower utilization of minimally invasive approaches and worse outcomes in GI cancer care., (© 2024 Wiley Periodicals LLC.)

Crude oil toxicity to early life stage fish is commonly attributed to polycyclic aromatic hydrocarbons (PAHs). However, it remains unclear how the polar unresolved complex mixture (UCM), which constitutes the bulk of the water-soluble fraction of crude oil, contributes to crude oil toxicity. Additionally, the role of photomodification-induced toxicity in relation to the polar UCM is not well understood. This study addresses these knowledge gaps by assessing the toxicity of two laboratory generated polar UCMs from Cook Inlet crude oil, representing the readily water-soluble fraction of crude oil and photoproduced hydrocarbon oxidation products (HOPs), to Pacific herring (Clupea pallasii) embryos. A small-scale semi-static exposure design was utilized with a range of polar UCM concentrations (0.5-14 mg/L) in nonvolatile dissolved organic carbon (NVDOC) units, quantifying the entire polar UCM. Compositional analyses revealed a photochemical-driven shift toward more complex aromatic compositions, naphthenic acids, and no detectable levels of PAHs (above 0.3 μg/L). Exposure to the dark polar UCM resulted in higher mortality than exposure to the light polar UCM. Both dark and light polar UCMs induced developmental abnormalities commonly attributed to the PAH fraction, including edema, reduced heart rate, body axis defects, and decreased body lengths, with these effects observed at the lowest dose group (0.5 mg/L NVDOC). These responses suggest photomodification-induced toxicity is driven by exposure to increased concentrations of dissolved HOPs rather than photochemical induced compositional changes. Gene expression analyses focusing on xenobiotic metabolism and cardiac morphogenesis yielded results consistent with previous studies examining the biological mechanisms of crude oil toxicity. In summary, these phenotypic and genotypic responses in Pacific herring embryos indicate that the polar UCM is a significant driver of crude oil toxicity. These findings emphasize the importance of considering the polar UCM in future studies, metric reporting, and risk assessments related to crude oil toxicity., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures: Shannon N. Radomski received financial support from the National Cancer Institute (NCI) grant 5T32CA126607-12 and the American College of Surgeons Resident Research Scholarship. During the 36 months prior to publication, Stephanie Wethington was employed for 6 weeks by AstraZeneca. Olivier Glehen is a consultant for GAMIDA.

The tire-rubber-derived ozonation product of N -(1,3-dimethylbutyl)- N '-phenyl- p -phenylenediamine (6PPD), N -(1,3-dimethylbutyl)- N '-phenyl- p -phenylenediamine-quinone (6PPD-Q), was recently discovered to cause acute mortality in coho salmon ( Oncorhynchus kisutch ). para -Phenylenediamines (PPDs) with variable side chains distinct from 6PPD have been identified as potential replacement antioxidants, but their toxicities remain unclear under environmentally relevant ozone conditions. We herein tested the multiphase gas-surface ozone reactivity of four select PPDs [6PPD, N -isopropyl- N '-phenyl- p -phenylenediamine (IPPD), N , N '-diphenyl- p -phenylenediamine (DPPD), and N -phenyl- N '-cyclohexyl- p -phenylenediamine (CPPD)] and evaluated the toxicity of their reaction mixtures in coho salmon, rainbow trout ( Oncorhynchus mykiss ), and fathead minnow ( Pimephales promelas ). 6PPD and IPPD were found to rapidly react with ozone, while no significant multiphase ozone reactivity was observed for DPPD or CPPD. The viability of coho salmon CSE-119 cells was strongly affected by the ozonolysis products of 6PPD but not by those of the other three PPDs. Acute mortality was only observed in juvenile rainbow trout that were exposed to oxidized 6PPD, suggesting a common mechanism of toxic action in the two salmonid fish species. This study reports the structurally selective ozone reactivity of PPDs and the unique toxicity of 6PPD ozonolysis mixtures, which demonstrates that other PPDs are potential alternative antioxidants.

Introduction: Minimally invasive surgery (MIS) is increasingly used in the surgical management of gastric cancer; however, its adoption lags that of other cancers. Most randomized controlled trials comparing MIS to open gastrectomy have been conducted in Asia, with limited data from the United States. This study aimed to compare perioperative, oncologic, and survival outcomes between open, laparoscopic, and robotic gastrectomy in a large US cohort., Methods: Using the National Cancer Database, we identified patients with gastric adenocarcinoma who underwent open, laparoscopic, or robotic gastrectomy between 2010 and 2020. Multivariate regression models were used to examine the association between surgical approach and various outcomes, including 30-d readmission, length of stay (LOS), surgical margin status, lymph node yield, 30- and 90-d mortality, and overall survival (OS). The interaction between surgical approach and tumor location (distal versus proximal or gastroesophageal junction [GEJ]) was also assessed., Results: Of the 34,937 included patients, 64.8% underwent open gastrectomy, 25.7% underwent laparoscopic surgery, and 9.5% underwent robotic surgery. MIS was associated with lower odds of 30-d readmission (laparoscopic: odds ratio [OR] 0.78, 95% confidence interval [CI] 0.67-0.89; robotic: OR 0.75, 95% CI 0.60-0.92), positive margins (laparoscopic: OR 0.83, 95% CI 0.74-0.93; robotic: OR 0.75, 95% CI 0.62-0.90), 30-d mortality (laparoscopic: OR 0.69, 95% CI 0.55-0.85; robotic: OR 0.66, 95% CI 0.44-0.95), and 90-d mortality (laparoscopic: OR 0.74, 95% CI 0.63-0.87; robotic: OR 0.63, 95% CI 0.47-0.84), as well as improved OS (laparoscopic: hazard ratio 0.83, 95% CI 0.79-0.87; robotic: hazard ratio 0.76, 95% CI 0.69-0.83) compared to open surgery. Considering the interaction of approach with tumor location, for proximal/GEJ tumors, the associated outcome improvements with MIS were attenuated. We observe that the odds for 30-d readmission, 90-d mortality, and OS are similar to those for open operations. However, regardless of tumor location, robotic gastrectomy was associated with decreased LOS and yielded a higher lymph node count than laparoscopic or open approaches., Conclusions: In this large US cohort, MIS gastrectomy was associated with improved perioperative, oncologic, and survival outcomes compared to open surgery for distal gastric cancers. However, the associated benefits of MIS were attenuated for proximal/GEJ tumors, with higher odds of readmission, mortality, and worse OS. Notably, robotic gastrectomy was associated with superior lymph node yield and LOS compared to laparoscopic and open approaches, even for proximal/GEJ tumors. These findings underscore the need for further research, especially randomized controlled trials conducted in Western populations, to definitively determine the efficacy of MIS for distal and proximal/GEJ tumors and guide surgical decision-making for gastric adenocarcinoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The standard of care for gastric cancer in the United States involves perioperative chemotherapy. While most post-therapy pathologic staging results are concordant (i.e. ypT + N + or ypT0N0), patients occasionally display discordant results, such as ypT0N1. Herein, we characterized the survival of patients with ypT0N1 staging to better determine their categorization within the American Joint committee on Cancer (AJCC) staging system., Methods: Using the National Cancer Database (NCDB), we queried all patients diagnosed with gastric adenocarcinoma from 2004 to 2021 who received neoadjuvant chemotherapy. Patients were stratified by their ypTNM stage: (1) ypT0N0; (2) ypT+N0; (3) ypT+N1; and (4) ypT0N1. Multivariable Cox proportional hazard regression was used to assess 5- and 10-year survival between ypTNM stages., Results: A total of 28,985 patients received neoadjuvant chemotherapy, of whom 2378 (8.2%) had ypT0N0, 9402 (32.4%) had ypT+N0, 5339 (18.4%) had ypT+N1, and 318 (1.1%) had ypT0N1 staging. Overall, patients had a median age of 64 years, with the majority being male (74.9%) or White (82.2%). Additionally, 50.2% received care from an academic center, and 53.3% received neoadjuvant chemotherapy and radiotherapy. On multivariable analysis, patients with ypT0N1 had a 105% higher risk for mortality within 5 years (adjusted hazards ratio [aHR] 2.05, 95% confidence interval [CI] 1.69-2.50) and 86% increased risk within 10 years (aHR 1.86, 95% CI 1.54-2.23) when compared with ypT0N0., Conclusion: Patients with stage ypT0N1 disease have worse 5- and 10-year outcomes than those with node-negative disease. Thus, their survival pattern most closely matches patients with ypstage IIB and III disease., Competing Interests: Disclosures: Albert Leng, Vrinda Madan, Manuj Shah, Andrei Gurau, Fabian M. Johnston, and Jonathan B. Greer declare no conflicts of interest that may be relevant to the contents of this study. Informed Consent: Not applicable., (© 2024. Society of Surgical Oncology.)

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective but costly procedure for select patients with peritoneal malignancies. The impact of progression along a learning curve on the cost of these procedures is unknown., Patients and Methods: We performed a retrospective cohort study of patients undergoing CRS-HIPEC from 2016 to 2022 at a single quaternary center. Our study cohort was temporally divided into four equally sized volume quartiles (A, B, C, and D). We utilized cumulative sum plots and split-group analysis to characterize the institutional learning curve based on cost, operative time, length of stay, and morbidity. Multivariable linear regression was performed to estimate costs after adjusting for covariates. Bivariate analysis was performed using a Kruskal-Wallis test to compare continuous variables and a χ 2 test to compare categorical variables., Results: Of 201 patients, the median age [interquartile range (IQR)] was 57 (47-65) years, 113 (56%) patients were female, 143 (71%) were white, and 107 (53%) had private insurance. Median operating room charge [US$42,639 (US$32,477-54,872), p < 0.001] varied between volume quartiles, peaking in quartile C. Stabilization was achieved for 86 cases for operating room cost, 88 cases for routine cost, 96 cases for length of stay, 103 cases for operative time, 120 cases for intensive care unit length of stay, and 150 cases for overall and serious morbidity. The actual operating room and routine costs were similar to predicted costs at the end of the study period., Conclusions: The CRS-HIPEC learning curve is triphasic, with cost stability achieved relatively early compared with other markers of surgical proficiency., (© 2024. Society of Surgical Oncology.)

Introduction: Advanced retroperitoneal sarcoma (RPS) can include unresectable locoregional disease, systemic or multifocal intra-abdominal metastasis, or abdominal sarcomatosis, all of which are associated with high morbidity and may be addressed through palliative therapy. Current trends in the use of palliative therapy and factors associated with its use in patients with advanced RPS remain largely unexplored. The objectives of this study are to (1) describe the temporal trend in the use of palliative therapy and (2) identify factors associated with its use in patients with advanced RPS in the United States from 2004 to 2020., Methods: This study is a retrospective cohort study using the National Cancer Database. We identified adult patients who were diagnosed with advanced RPS (American Joint Committee on Cancer stages III and IV) from 2004 to 2020. We performed a trend analysis to describe the use of palliative therapy over time, followed by univariable and multivariable logistic regression analyses to identify predictors of palliative therapy use in this patient population., Results: A total of 6149 patients with advanced RPS were identified, of which only 383 used palliative therapy, including surgery (n = 28), radiation therapy (n = 87), systemic therapy (n = 115), pain management (n = 61), combination therapy (n = 55), or other palliative therapy (n = 37). The proportion of patients using palliative therapy increased significantly from 2.6% in 2004 to 6.5% in 2020 (P trend < 0.001). On multivariable logistic regression, age (odds ratio [OR] 1.03, 95 confidence interval [CI] 1.01-1.04), year of diagnosis (OR 1.05, 95 CI 1.02-1.08), lack of insurance (OR 2.18, 95 CI 1.17-4.04), community cancer program status (OR 1.83, 95 CI 1.05-3.19), stage IV disease (OR 5.19, 95 CI 4.49-7.79), and rhabdomyosarcoma (OR 2.75, 95 CI 1.32-5.72) histology were found to be predictors of palliative therapy use., Conclusions: This study sheds light on the evolving landscape of palliative therapy use for patients with advanced RPS in the United States from 2004 to 2020. The observed gradual increase in the use of palliative therapy underscores the growing recognition of its importance in managing the unique challenges associated with this complex disease. Despite this positive trend, the persistently low overall rates highlight the need for further efforts to enhance awareness and accessibility of palliative therapy for this patient population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Anesthesiologists transition patient care to combat clinician fatigue and accommodate shift limitations. Studies exploring the association of increased handovers with patient outcomes have conflicting findings. Here, we investigate the association of anesthesia handovers with perioperative outcomes in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy., Methods: Patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a single institution from 2017 to 2022 were stratified by the number of anesthesia attending and nonattending (nurse anesthetist/resident) handovers (0-1 or ≥2). Primary outcomes were intensive care unit and hospital length of stay, in addition to 30-day serious morbidity. Logistic and negative binomial regression models were adjusted for covariates related to patient and case complexity., Results: A total of 182 patients were included. Median operative time was 720 minutes (interquartile range, 540-900 minutes). Most cases had fewer than 2 attending handovers (n = 147, 81% vs ≥2 handovers n = 35, 19%) and 2 nonattending handovers (n = 120, 71% vs ≥2 handovers n = 53, 29%). In adjusted models, there were no differences in 30-day serious morbidity and intensive care unit or hospital length of stay between the attending handover groups (0-1 vs ≥2). Patients with ≥2 non-attending handovers had similar odds of 30-day serious morbidity compared with the 0-1 group (odds ratio, 1.613, 95% confidence interval, 0.733-3.550, P = .235), but a longer total hospital (incidence rate ratio, 1.301, 95% confidence interval, 1.071-1.579, P = .008) and intensive care unit length of stay (incidence rate ratio 1.548, 95% confidence interval, 1.038-2.049, P = .030)., Conclusions: Multiple anesthesia handovers were not associated with an increased risk of serious morbidity for patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. However, increased handovers (≥2) between nonattending providers was associated with longer hospital and intensive care unit length of stays., Competing Interests: Conflict of Interest/Disclosure The authors have no related conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) with peritoneal metastases is a complex disease and its management presents significant clinical challenges. In well-selected patients at experienced centers, CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed with acceptable morbidity and is associated with prolonged survival. Based on the results of recent randomized controlled trials, HIPEC using oxaliplatin after CRS with shortened perfusion periods (30 minutes) is no longer recommended. There is a movement toward utilizing mitomycin C as a first-line intraperitoneal agent with extended perfusion times (90-120 minutes); however, there is currently little prospective evidence to support its widespread use., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The environmental ubiquity of tire and road wear particles (TRWP) underscores the need to understand the occurrence, persistence, and environmental effects of tire-related chemicals in aquatic ecosystems. One such chemical is 6PPD-quinone (6PPD-Q), a transformation product of the tire antioxidant 6PPD. In urban stormwater runoff 6PPD-Q can exceed acute toxicity thresholds for several salmonid species and is being implicated in significant coho salmon losses in the Pacific Northwest. There is a critical need to understand the prevalence of 6PPD-Q across watersheds to identify habitats heavily affected by TRWPs. We conducted a reconnaissance of 6PPD and 6PPD-Q in surface waters across the United States from sites (N = 94) with varying land use (urban, agricultural, and forested) and streamflow to better understand stream exposures. A rapid, low-volume direct-inject, liquid chromatography mass spectrometry method was developed for the quantitation of 6PPD-Q and screening for 6PPD. Laboratory holding times, bottle material, headspace, and filter materials were investigated to inform best practices for 6PPD-Q sampling and analysis. Glass bottles with PTFE-lined caps minimized sorption and borosilicate glass fiber filters provided the highest recovery. 6PPD-Q was stable for at least 5 months in pure laboratory solutions and for 75 days at 5 °C with minimal headspace in the investigated surface water and stormwaters. Results also indicated samples can be frozen to extend holding times. 6PPD was not detected in any of the 526 analyzed samples and there were no detections of 6PPD-Q at agricultural or forested sites. 6PPD-Q was frequently detected in stormwater (57%, N = 90) and from urban impacted sites (45%, N = 276) with concentrations ranging from 0.002 to 0.29 μg/L. The highest concentrations, above the lethal level for coho salmon, occurred during stormwater runoff events. This highlights the importance of capturing episodic runoff events in urban areas near ecologically relevant habitat or nursery grounds for sensitive species., 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., (Published by Elsevier Ltd.)

Introduction: Up to half of patients with leiomyosarcoma (LMS) present with distant metastases, most commonly in the lungs. Despite guidelines around managing metachronous oligometastatic disease, limited evidence exists for synchronous isolated lung metastases (SILMs). Our histology-specific study describes management patterns and outcomes for patients with LMS and SILM across disease sites., Methods: We used the National Cancer Database to analyze patients with LMS of the retroperitoneum, extremity, trunk/chest/abdominal wall, and pelvis with SILM. Patients with extra-pulmonary metastases were excluded. We identified factors associated with primary tumor resection and receipt of metastasectomy. Outcomes included median, 1-year, and 5-year overall survival (OS) across treatment approaches using log-rank tests, Kaplan-Meier curves, and Cox proportional hazard models., Results: We identified 629 LMS patients with SILM from 2004 to 2017. Patients were more likely to have resection of their primary tumor or lung metastases if treated at an academic center compared to a community cancer center. Five year OS for patients undergoing both primary tumor resection and metastasectomy was 20.9% versus 9.2% for primary tumor resection alone, and 2.6% for nonsurgical patients. Median OS for all-comers was 15.5 mo. Community treatment site, comorbidity score, and larger primary tumors were associated with worse survival. Chemotherapy, primary resection, and curative intent surgery predicted improved survival on multivariate Cox regression., Conclusions: An aggressive surgical approach to primary LMS with SILM was undertaken for select patients in our population and found to be associated with improved OS. This approach should be considered for suitable patients at high-volume centers., (Copyright © 2024. Published by Elsevier Inc.)

Background: Enhanced recovery after surgery (ERAS) protocols have been shown to reduce length of stay (LOS) and complications. The impact of ERAS protocols on the cost of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has not been studied., Patients and Methods: We performed a retrospective cohort analysis of patients undergoing CRS-HIPEC from 2016-2022 at a single quaternary center. Propensity score matching was used to create pre-and post-ERAS cohorts. Cost, overall and serious complications, and intensive care unit (ICU) length of stay (LOS) between the two cohorts were compared using the Mann-Whitney U-test for continuous variables and χ2 test for categorical variables., Results: Our final matched cohort consisted of 100 patients, with 50 patients in both the pre- and post-ERAS groups. After adjusting for patient complexity and inflation, the median total cost [$75,932 ($67,166-102,645) versus $92,992 ($80,720-116,710), p = 0.02] and operating room cost [$26,817 ($23,378-33,121) versus $34,434 ($28,085-$41,379), p < 0.001] were significantly higher in the post-ERAS cohort. Overall morbidity (n = 22, 44% versus n = 17, 34%, p = 0.40) and ICU length of stay [2 days (IQR 1-3) versus 2 days (IQR 1-4), p = 0.70] were similar between the two cohorts. A total cost increase of $22,393 [SE $13,047, 95% CI (-$3178 to $47,965), p = 0.086] was estimated after implementation of ERAS, with operating room cost significantly contributing to this increase [$8419, SE $1628, 95% CI ($5228-11,609), p < 0.001]., Conclusions: CRS-HIPEC ERAS protocols were associated with higher total costs due to increased operating room costs at a single institution. There was no significant difference in ICU LOS and complications after the implementation of the ERAS protocol., (© 2024. Society of Surgical Oncology.)

We introduce single cell Proteoform imaging Mass Spectrometry ( scPiMS ), which realizes the benefit of direct solvent extraction and MS detection of intact proteins from single cells dropcast onto glass slides. Sampling and detection of whole proteoforms by individual ion mass spectrometry enable a scalable approach to single cell proteomics. This new scPiMS platform addresses the throughput bottleneck in single cell proteomics and boosts the cell processing rate by several fold while accessing protein composition with higher coverage.

Background: Accurately predicting survival in patients with cancer is crucial for both clinical decision-making and patient counseling. The primary aim of this study was to generate the first machine-learning algorithm to predict the risk of mortality following the diagnosis of an appendiceal neoplasm., Methods: Patients with primary appendiceal cancer in the Surveillance, Epidemiology, and End Results database from 2000 to 2019 were included. Patient demographics, tumor characteristics, and survival data were extracted from the Surveillance, Epidemiology, and End Results database. Extreme gradient boost, random forest, neural network, and logistic regression machine learning models were employed to predict 1-, 5-, and 10-year mortality. After algorithm validation, the best-performance model was used to develop a patient-specific web-based risk prediction model., Results: A total of 16,579 patients were included in the study, with 13,262 in the training group (80%) and 3,317 in the validation group (20%). Extreme gradient boost exhibited the highest prediction accuracy for 1-, 5-, and 10-year mortality, with the 10-year model exhibiting the maximum area under the curve (0.909 [±0.006]) after 10-fold cross-validation. Variables that significantly influenced the predictive ability of the model were disease grade, malignant carcinoid histology, incidence of positive regional lymph nodes, number of nodes harvested, and presence of distant disease., Conclusion: Here, we report the development and validation of a novel prognostic prediction model for patients with appendiceal neoplasms of numerous histologic subtypes that incorporate a vast array of patient, surgical, and pathologic variables. By using machine learning, we achieved an excellent predictive accuracy that was superior to that of previous nomograms., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes., Methods: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients., Results: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008)., Conclusions: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians., Plain Language Summary: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes., (© 2023 American Cancer Society.)

Introduction: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC., Methods: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome., Results: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125., Conclusions: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association., (© 2024. Society of Surgical Oncology.)

Background: Select patients with peritoneal metastases are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We assayed for intra- and interpatient drug response heterogeneity through testing of patient-derived tumor organoids (PDTOs)., Methods: PDTOs were generated from CRS/HIPEC patients from December 2021 to September 2022 and subjected to an in vitro HIPEC drug screen. Drug response was assessed with a cell viability assay and cleaved caspase-3 staining., Results: A total of 31 patients were consented for tissue collection. Viable tissue was harvested from 23, and PDTO generation was successful in 13 (56%). PDTOs were analyzed from six appendiceal, three colorectal, two small bowel, one gastric, and one adrenal tumor. Drug screen results were generated in as few as 7 days (62%), with an average time of 12 days. Most patients received mitomycin-C (MMC) intraoperatively (n = 9); however, in only three cases was this agent considered the optimal choice in vitro. Three sets of PDTOs were resistant (defined as > 50% PDTO viability) to all agents tested and two were pan-sensitive (defined as 3 or more agents with < 50% PDTO viability). In three patients, organoids were generated from multiple metastatic sites and intrapatient drug response heterogeneity was observed., Conclusions: Both intra- and interpatient drug response heterogeneity exist in patients undergoing CRS/HIPEC for nongynecologic abdominal cancers. Caution must be used when interpreting patient response to chemotherapeutic agents based on a single site of testing in those with metastatic disease., (© 2024. Society of Surgical Oncology.)

Objective: The primary objective of this study was to determine the effects of temperature on viral erythrocytic necrosis (VEN) progression under controlled conditions. Secondarily, this study was intended to evaluate the combined effects of temperature and VEN on the Pacific Herring Clupea palasii transcriptome., Methods: The effects of temperature on VEN progression were assessed by waterborne exposure of laboratory-reared, specific-pathogen-free Pacific Herring to tissues homogenates containing erythrocytic necrosis virus (ENV) at 6.9, 9.0, or 13.5°C., Result: Exposure of Pacific Herring to ENV resulted in the establishment of infections characterized by high infection prevalence (89%; 40/45) and mean viral loads (5.5 log 10 [gene copies/μg genomic DNA]) in kidney tissues at 44 days postexposure. Mean viral loads were significantly higher in fish from the ambient (mean = 9.0°C) and warm (mean = 13.5°C) treatments (6.1-6.2 log 10 [gene copies/total genomic DNA]) than in fish from the cool (mean = 6.9°C) treatment (4.3 log 10 [gene copies/μg genomic DNA]). Similarly, the peak proportion of diseased fish was directly related to temperature, with cytoplasmic inclusion bodies detected in 21% of fish from the cool treatment, 52% of fish from the ambient treatment, and 60% of fish from the warm treatment. The mean VEN load in each fish (enumerated as the percentage of erythrocytes with cytoplasmic inclusions) at 44 days postexposure increased with temperature from 15% in the cool treatment to 36% in the ambient treatment and 32% in the warm treatment. Transcriptional analysis indicated that the number of differentially expressed genes among ENV-exposed Pacific Herring increased with temperature, time postexposure, and viral load. Correlation network analysis of transcriptomic data showed robust activation of interferon and viral immune responses in the hepatic tissue of infected individuals independent of other experimental variables., Conclusion: Results from this controlled laboratory study, combined with previous observations of natural epizootics in wild populations, support the conclusion that temperature is an important disease cofactor for VEN in Pacific Herring., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the preferred treatment for select patients with peritoneal malignancies. However, the procedure is resource intensive and costly. This study aimed to determine the risk of financial toxicity for patients undergoing CRS-HIPEC., Patients and Methods: We performed a retrospective cohort study of patients undergoing CRS-HIPEC at a single institution from 2016 to 2022. We utilized insurance status, out-of-pocket expenditures, and estimated post-subsistence income to determine risk of financial toxicity. A multivariable logistic regression was used to determine risk factors for financial toxicity., Results: Our final study cohort consisted of 163 patients. Average age was 58 [standard deviation 10] years, and 52.8% (n = 86) were male. A total of 52 patients (31.9%) were at risk of financial toxicity. A total of 36 patients (22.1%) were from the lower income quartiles (first or second) and 127 patients (77.9%) were from the higher income quartiles (third or fourth). A total of 47 patients (29%) were insured by Medicare, and 116 patients (71%) had private insurance. The median out-of-pocket expenditure across the study cohort was $3500, with a median of $5000 ($3341-$7350) for the at-risk group and $3341 ($2500-$4022) for the not at-risk group (p < 0.001). Risk factors for financial toxicity included high out-of-pocket expenditures and a lower income quartile., Conclusions: An estimated one-third of patients undergoing CRS-HIPEC at our institution were at risk for financial toxicity. Several preoperative factors were associated with an increased risk and could be utilized to identify patients who might benefit from interventions., (© 2023. Society of Surgical Oncology.)

Introduction: We explored the association between weekend discharge and 30- and 90-d readmission rates in patients undergoing hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis., Methods: The US HIPEC Collaborative database, comprised of a longitudinal cohort of patients undergoing CRS/HIPEC for peritoneal carcinomatosis at twelve academic institutions between 2000 and 2017, was queried for date of discharge information. Patients were retrospectively divided into weekday and weekend/holiday discharge groups. Patients <18 y old, lacking day of discharge information, or who experienced intraoperative/in-hospital mortality were excluded. Comparisons were made between patients discharged on a weekday versus those discharged on a weekend or major holiday., Results: 1415 patients met inclusion criteria for the study: 1108 (78%) patients with a weekday discharge and 308 (22%) with a weekend/holiday discharge. Median age at time of surgery was 55 y (Interquartile Range: 46-63); 59% (n = 841) patients were female, 25% (n = 328) of patients had high volume disease (defined as a peritoneal cancer index >20 intraoperatively), and 92% (n = 1210) of patients had a complete cytoreduction (defined as a completeness of cytoreduction score of 0 or 1). Overall, 15% (n = 218) of patients were readmitted within 30 d and 19% (n = 265) within 90 d. In a linear mixed effects model, weekend discharge was not associated with higher 30- or 90-d readmissions (P = 0.291, P = 0.743)., Conclusions: Weekend discharges are safe following CRS/HIPEC. Length of stay initiatives should focus on discharging the patient when medically ready, rather than avoiding weekend discharge out of an abundance of caution., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: One third of patients with uterine leiomyosarcomas (uLMS) present with distant metastases. Current guidelines do not include recommendations around surgery for metastatic uLMS. Patients with distant metastases commonly receive primary tumor resection for symptoms and so oncologic outcomes after surgery warrant exploration. We describe treatment patterns and outcomes for uLMS patients with synchronous isolated lung metastases (SILM)., Methods: This retrospective analysis of the National Cancer Database identified patients with uLMS and SILM. Patients with non-pulmonary metastases were excluded. We collected demographic, disease, and treatment characteristics and assessed clinicopathologic factors associated with the receipt of surgery on multivariate regression. Median, 1-year, and 5-year overall survival (OS) across treatment approaches were compared using Kaplan-Meier curves and log-rank tests. Multivariate Cox proportional hazard regressions identified independent predictors of survival., Results: We identified 905 patients with uLMS and SILM between 2004 and 2017. 600 patients had primary tumor resection; 63 also had curative intent surgery with metastasectomy. Patients who did not receive chemotherapy were older (p<0.01) with a higher comorbidity index (p<0.05). Women with private health insurance were more likely to receive chemotherapy (p<0.01) and primary tumor resection (p<0.01). Patients who underwent curative intent surgery had 1-year OS of 71.2% and 5-year survival of 18% compared to 1-year survival of 35.6 % and 5-year survival of 5.16 % for patients who had no surgery. Black women had poorer survival on multivariate regression., Conclusions: Primary tumor resection and curative intent surgery are associated with improved OS in uLMS with SILM and may be a reasonable treatment option in appropriately selected patients., Competing Interests: 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., (© 2023 The Authors.)

Blood serum and plasma are arguably the most commonly analyzed clinical samples, with dozens of proteins serving as validated biomarkers for various human diseases. Top-down proteomics may provide additional insights into disease etiopathogenesis since this approach focuses on protein forms, or proteoforms, originally circulating in blood, potentially providing access to information about relevant post-translational modifications, truncations, single amino acid substitutions, and many other sources of protein variation. However, the vast majority of proteomic studies on serum and plasma are carried out using peptide-centric, bottom-up approaches that cannot recapitulate the original proteoform content of samples. Clinical laboratories have been slow to adopt top-down analysis, also due to higher sample handling requirements. In this study, we describe a straightforward protocol for intact proteoform sample preparation based on the depletion of albumin and immunoglobulins, followed by simplified protein fractionation via polyacrylamide gel electrophoresis. After molecular weight-based fractionation, we supplemented the traditional liquid chromatography-tandem mass spectrometry (LC-MS 2 ) data acquisition with high-field asymmetric waveform ion mobility spectrometry (FAIMS) to further simplify serum proteoform mixtures. This LC-FAIMS-MS 2 method led to the identification of over 1000 serum proteoforms < 30 kDa, outperforming traditional LC-MS 2 data acquisition and more than doubling the number of proteoforms identified in previous studies.

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear., Patients and Methods: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS)., Results: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS., Conclusions: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies., (© 2023. Society of Surgical Oncology.)

Analysis of intact proteins by mass spectrometry enables direct quantitation of the specific proteoforms present in a sample and is an increasingly important tool for biopharmaceutical and academic research. Interpreting and quantifying intact protein species from mass spectra typically involves many challenges including mass deconvolution and peak processing as well as determining optimal spectral averaging parameters and matching masses to theoretical proteoforms. Each of these steps can present informatic hurdles, as parameters often need to be tailored specifically to the data sets. To reduce intact mass deconvolution data analysis burdens, we built upon the widely used "sliding window" mass deconvolution technique with several additional concepts. First, we found that how spectra are averaged and the overlap in spectral windows can be tuned to favor either sensitivity or speed. A multiple window averaging approach was found to be the most effective way to increase mass detection and yielded a >2-fold increase in the number of masses detected. We also developed a targeted feature-finding routine that boosted sensitivity by >2-fold, decreased coefficient of variation across replicates by 50%, and increased the quality of mass elution profiles through 3-fold more detected time points. Lastly, we furthered existing approaches for annotating detected masses with potential proteoforms through spectral fitting for possible proteoform family modifications and network viewing. These proteoform annotation approaches ultimately produced a more accurate way of finding related, but previously unknown proteoforms from intact mass-only data. Together, these quantitation workflow improvements advance the information obtainable from intact protein mass spectrometry analyses.

Purpose: Patients with pancreatic and periampullary cancers may experience significant reduction in their quality of life and often rely on family and unpaid caregivers for assistance after surgery. However, as caregivers are not systematically identified, little is known about the nature, difficulty, and personal demands of assistance they provide. We aim to assess the frequency and difficulty of specific assistance caregivers provide and identify potential interventions that could alleviate the caregiving demands., Methods: This was a prospective, multi-institutional study of caregivers accompanying patients with periampullary and pancreatic cancer at their 1-month postpancreatectomy office visit. An instrument that drew heavily on the National Study of Caregiving was administered to caregivers., Results: Of 240 caregivers, more than half (58.3%) of caregivers were the patients' spouse, a quarter (25.8%) were daughters or sons, 12.9% other relatives, and 2.9% nonrelatives. Caregivers least frequently provided assistance with transportation (14.6% every day) and most frequently provided assistance with housework (65.0% every day, P = .003) and diet (56.5% every day, P = .004). Caregivers reported the least difficulty helping patients with exercise (1.5% somewhat difficult). Caregivers reported significantly more difficulty with assisting with housework (14.5% somewhat difficult, P < .001) and diet (14.9% somewhat difficult, P < .001). Caregivers identified the immediate postpancreatectomy and early discharge periods as the most stressful phases. They also reported having received very little information about available services that could have supported their efforts., Conclusion: Caregivers of patients with periampullary or pancreatic cancer provide considerable assistance in the postoperative period and many reported difficulty in assisting with housework and diet. Work is needed to better prepare and support caregivers to better enable them to adequately care for patients with pancreas and periampullary cancer.

Urban stormwater runoff frequently contains the car tire transformation product 6PPD-quinone, which is highly toxic to juvenile and adult coho salmon ( Onchorychus kisutch ). However, it is currently unclear if embryonic stages are impacted. We addressed this by exposing developing coho salmon embryos starting at the eyed stage to three concentrations of 6PPD-quinone twice weekly until hatch. Impacts on survival and growth were assessed. Further, whole-transcriptome sequencing was performed on recently hatched alevin to address the potential mechanism of 6PPD-quinone-induced toxicity. Acute mortality was not elicited in developing coho salmon embryos at environmentally measured concentrations lethal to juveniles and adults, however, growth was inhibited. Immediately after hatching, coho salmon were sensitive to 6PPD-quinone mortality, implicating a large window of juvenile vulnerability prior to smoltification. Molecularly, 6PPD-quinone induced dose-dependent effects that implicated broad dysregulation of genomic pathways governing cell-cell contacts and endothelial permeability. These pathways are consistent with previous observations of macromolecule accumulation in the brains of coho salmon exposed to 6PPD-quinone, implicating blood-brain barrier disruption as a potential pathway for toxicity. Overall, our data suggests that developing coho salmon exposed to 6PPD-quinone are at risk for adverse health events upon hatching while indicating potential mechanism(s) of action for this highly toxic chemical.

The high-throughput quantification of intact proteoforms using a label-free approach is typically performed on proteins in the 0-30 kDa mass range extracted from whole cell or tissue lysates. Unfortunately, even when high-resolution separation of proteoforms is achieved by either high-performance liquid chromatography or capillary electrophoresis, the number of proteoforms that can be identified and quantified is inevitably limited by the inherent sample complexity. Here, we benchmark label-free quantification of proteoforms of Escherichia coli by applying gas-phase fractionation (GPF) via field asymmetric ion mobility spectrometry (FAIMS). Recent advances in Orbitrap instrumentation have enabled the acquisition of high-quality intact and fragmentation mass spectra without the need for averaging time-domain transients prior to Fourier transform. The resulting speed improvements allowed for the application of multiple FAIMS compensation voltages in the same liquid chromatography-tandem mass spectrometry experiment without increasing the overall data acquisition cycle. As a result, the application of FAIMS to label-free quantification based on intact mass spectra substantially increases the number of both identified and quantified proteoforms without penalizing quantification accuracy in comparison to traditional label-free experiments that do not adopt GPF.

Background and Objectives: Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients., Methods: A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage., Results: A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31)., Conclusions: In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HR counterparts. Alternative strategies for surveillance and treatment should be considered., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)