A case of pneumomediastinum complicating immunotherapy associated pneumonitis.

We describe the case of an 87-year-old gentleman referred to a metropolitan hospital in Sydney with pneumomediastinum complicating immunotherapy associated pneumonitis and recent bronchoscopic intervention. The contribution of pneumonitis in the setting of interstitial lung disease has been well described to developing pneumomediastinum however this is less clear in the setting of immunotherapy associated pneumonitis and to what extent bronchoscopic intervention compounds this risk.

Use of a novel device for intraoperative wire management during fenestrated endovascular type 4 thoracoabdominal aortic aneurysm repair.

Endovascular procedures are minimally invasive approaches to treat conditions affecting blood vessels without the need for large incisions. The benefits are less blood loss and faster recovery. One condition commonly treated endovascularly is aortic aneurysmal disease often secondary to atherosclerosis or chronic hypertension. As endovascular aneurysm repair becomes increasingly complex and sophisticated, the intraoperative organization and management of wires from multiple access sites becomes paramount. Often, the physician selects visceral or great vessels for delivery of stent grafts to maintain vessel patency. Loss of wire in critical target vessels and wire contamination pose significant patient risks. WireWatch (BioTex Inc. Houston, Texas, USA) is a novel device designed for intraoperative wire management to improve surgical field organization, provide wire stabilization, and prevent dropped wires. This case describes its use in a 73-year-old female undergoing a fenestrated endovascular aneurysm repair of 5.6 cm types IV thoracoabdominal aortic aneurysm.

The Management of Aneurysmal Degeneration of Lower Extremity Cryopreserved Saphenous Vein Bypass Grafts.

BACKGROUND: The use of cryopreserved saphenous veins (CSVs) for the treatment of lower extremity peripheral arterial disease is an attractive option when there is no available autogenous vein. Prior studies found CSVs are at risk for aneurysmal degeneration requiring reoperation. As the management of these complications and patient outcomes is not well described, the objective of this case series is to describe the open and endovascular management of degenerative CSVs at a tertiary community center. METHODS: All CSVs implanted for lower extremity bypass at our institution between 2001 and 2021 were retrospectively reviewed. All CSVs with evidence of aneurysmal change were included in this study. CSVs with evidence of active infection were excluded. The decision to intervene was left to the discretion of the operating surgeon. Demographic data, indications for the index operation, and details about subsequent interventions for degenerative CSVs were recorded. Study end points included limb salvage and continued patency. Demographic data, indications for the index operation, and details about subsequent interventions for degenerative CSVs were recorded. RESULTS: Seventeen bypasses were identified to have aneurysmal degeneration in 13 patients in the absence of infection between 2001 and 2021. Nine of the 13 patients were male, and the average age and body mass index during the index procedure were 72 and 28, respectively. Indications for the index bypass included acute limb ischemia (9), popliteal aneurysm (2), and chronic limb threatening ischemia with Rutherford's class IV (5) and V (1). The mean time between the index procedure and first graft revision due to aneurysmal changes was 4 years. Most of the aneurysms did not occur at the site of anastomosis with 13 occurring in the body of the graft. Thirteen grafts were managed with open surgery and 3 were managed with endovascular techniques. All endovascular repairs were managed via covered stenting. Patients were followed for an average duration of 7 years from the initial bypass and 2 years from their last aneurysmal repair. Limb salvage in this cohort was 87% with 2 limbs requiring amputation, all of whom underwent open reconstruction. The mortality rate in this series was 54% and no patients died due to complications from their graft. Continued patency on Kaplan Meier survival curve analysis was 79% at 6 months, 65% at 1 year, 54% at 3 years, and 27% at 5 years. CONCLUSIONS: In our experience, aneurysmal degeneration of CSV grafts was mostly managed with standard open surgical techniques, although endovascular therapy also proved acceptable. Limb salvage rates and continued patency of repair at 1 year in this cohort were acceptable. This case series highlights the importance of diligent surveillance for patients with CSVs.

Disparities in Access to Robotic Knee Arthroplasty: A Geospatial Analysis.

BACKGROUND: The utilization of robotic knee arthroplasty (RKA) continues to increase across the United States. The aim of this geospatial analysis was to elucidate if RKA is distributed uniformly across the United States or if disparities exist in patient access. METHODS: Publicly available provider-finding functions for 5 major manufacturers of RKA systems were used to obtain the practice locations of surgeons performing RKA along with their associated RKA system manufacturer. The average travel distance for each county to the nearest RKA surgeon was calculated and Moran's index clustering analysis was used to find hotspots and coldspots of RKA access. A logistic regression model was used to identify the predictive odds ratios between robotic hotspots and coldspots with county-level sociodemographic variables. Of the 34,216 currently practicing orthopedic surgeons in 2022, 2,571 have access to robotic assistance for knee arthroplasty. RESULTS: Hotspots of increased travel time were predominantly in West South Central and West North Central census regions. Hotspots were significantly more rural and consisted of predominantly White populations, with lower median income and health insurance coverage. CONCLUSIONS: The results of the current study align with existing literature, demonstrating absolute geographic access disparities for rural and economically disadvantaged populations. Additionally, relative access disparities persist for minority populations and individuals with high comorbidity burdens residing in urban areas.

Recurrence-Free Survival in Patients With Surgically Resected Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Standard treatment for early-stage or locoregionally advanced non-small cell lung cancer (NSCLC) includes surgical resection. Recurrence after surgery is commonly reported, but a summary estimate for postsurgical recurrence-free survival (RFS) in patients with NSCLC is lacking. RESEARCH QUESTION: What is the RFS after surgery in patients with stage I-III NSCLC at different time points, and what factors are associated with RFS? STUDY DESIGN AND METHODS: A systematic search was performed in MEDLINE, EMBASE, and Cochrane databases between January 2011 and June 2021. The primary outcome was RFS at 1, 2, 3, and 5 years postresection. Single-arm, random-effects meta-analyses were done to calculate effect estimates and 95% CIs. Analyses were stratified by stage/substage as per the AJCC Cancer Staging Manual, and RFS was estimated (1) after pooling studies, using seventh or eighth edition staging criteria; and (2) among studies using only the eighth edition. Meta-regressions were performed to assess associations between RFS and patient demographic/clinical characteristics of interest. RESULTS: Data from 471 studies comprising 1,060 surgical study arms were extracted. RFS estimates from 60,695 patients staged with the seventh or eighth edition were analyzed. RFS ranged from 96% at 1 year postresection to 82% at 5 years for stage I, and from 68% at 1 year to 34% at 5 years for stage III. Estimates for patients staged using only eighth edition criteria were slightly higher. Older age, higher percentage of male patients, advancing stage, larger tumor size, and geographic region (North America/Europe vs Asia) were significantly associated with worse RFS. INTERPRETATION: This study presents a comprehensive assessment of reported RFS from published clinical literature, offering estimates at multiple postsurgical time points and by geographic region. Findings can inform treatment decisions, clinical trial design, and future research to improve outcomes among patients with NSCLC.

Explainable Artificial Intelligence to Identify Dosimetric Predictors of Toxicity in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Secondary Analysis of RTOG 0617.

PURPOSE: Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. METHODS AND MATERIALS: A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. RESULTS: The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P = .038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P = .043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P < .001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P = .014) were identified. No significant thresholds were identified for cardiac toxicity. CONCLUSIONS: In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated.

Mechanical thrombectomy of inferior vena cava filter-associated caval thrombosis using FlowTriever and ClotTriever systems.

OBJECTIVE: Chronically indwelling inferior vena cava filters (IVCFs) can have multiple adverse sequelae, including IVCF-associated thrombosis. The Inari ClotTriever and FlowTriever mechanical and aspiration thrombectomy systems (Inari Medical) can be used for acute caval thrombosis associated with IVCFs if appropriate proximal IVCF protection is used intraprocedurally. The present study reports a single institution's outcomes after ClotTriever and FlowTriever thrombectomy of acute IVCF-associated iliocaval thrombus. METHODS: A retrospective review was conducted of all patients who underwent ClotTriever or FlowTriever thrombectomy for IVCF-associated caval thrombosis. The patient demographics, clinical characteristics, and postprocedural outcomes of a 15-patient cohort were compiled and described. RESULTS: A total of 15 patients were identified as presenting with acute IVCF-associated caval thrombosis and having undergone intervention with either the ClotTriever or FlowTriever system from 2019 to 2022. Of the 15 patients in the cohort, 3 (20%) had presented with a threatened extremity (phlegmasia cerulea dolens), and 12 had presented with severe, debilitating, but non-limb-threatening, lower extremity edema. The preprocedural clot burden was significant and involved the cava, iliac veins, and femoropopliteal veins in 7 of 15 patients (47%) in the cohort. The procedure was technically successful in 11 patients (73.33%). Resolution of acute symptoms was noted in 100% of the technically successful procedures. The 30-day mortality rate was 13% (2 of 15 patients). One intraprocedural death occurred from pulmonary embolism, and one patient died of malignancy complications. The surviving patients not lost to follow-up experienced stable or improving venous disease, with only one patient presenting with post-phlebitic syndrome. CONCLUSIONS: Mechanical and aspiration thrombectomy of IVCF-associated thrombus with the FlowTriever and ClotTriever systems have good technical success and resulted in significant improvement in acute symptoms with adequate clot clearance. Proximal embolic protection maneuvers for pulmonary embolism prophylaxis and preexisting filter protection are required intraprocedurally.

Society for Vascular Surgery duplex ultrasound surveillance guidelines are safe and cost effective for transcarotid artery revascularization.

BACKGROUND: Carotid duplex ultrasound (CDUS) examination is used in the long-term surveillance after transcarotid artery revascularization (TCAR). The objective of this study was to evaluate the usefulness and cost effectiveness of post-TCAR CDUS surveillance regimens in monitoring for in-stent restenosis (ISR) and associated stroke risk at a single-center community institution. METHODS: CDUS data were collected retrospectively from patients who had undergone TCAR between January 2017 and January 2023. ISR >50% was defined as a peak systolic velocity (PSV) of >220 cm/s and an internal carotid artery (ICA) to common carotid velocity ratio of >2.7. ISR >80% was defined as a PSV of >340 cm/s and an ICA/common carotid artery ratio of >4.15. Study outcomes included incidences of ISR, reintervention, transient ischemic attacks (TIAs), strokes, and mortality. A Kaplan-Meier survival analysis was done to calculate the rates of freedom from ISR. RESULTS: During the study period, 108 TCAR stents were deployed in 104 patients. Eight patients were excluded in analysis or lost to follow-up. Preoperatively, 62% of patients had >80% stenosis, and 39% were symptomatic. No intraprocedural complications were noted. One patient suffered an immediate postoperative dissection. Eight stents (8%) experienced ISR progression from <50% to >50%. Three of the eight had further ISR progression to >80%. One patient had high-grade ISR and a contralateral ICA occlusion that warranted reintervention. There were no occurrences of postoperative TIAs, strokes, or TCAR-related deaths. Rates of freedom from ISR progression from <50% to >50% were 97.4%, 95.9%, 90.9%, 88.2%, and 88.2% at 6, 12, 24, 36, and 42 months, respectively. Rates of freedom from ISR >80% were 100%, 100%, 98.5%, 95.5%, and 95.5% at the same time points. Patients with >50% ISR tended to be females with hyperlipidemia. In addition, they had higher average lesion lengths and lower rates of postdilation balloon angioplasty. The 5-year estimated surveillance cost in this cohort using the Society for Vascular Surgery 2022, and 2018 guidelines, as well as our current protocol would be $113,853, $221,382, and $193,207, respectively. CONCLUSIONS: This study revealed a low incidence of ISR progression, as well as no TIA, stroke, or TCAR-related deaths, highlighting the safety and efficacy of TCAR. Post-TCAR CDUS examination using the updated Society for Vascular Surgery guidelines are safe and cost effective. Patients with contralateral occlusion or stenosis, or who have significant risk factors, should have more frequent surveillance regimens.

In Vitro Proof of Concept of a First-Generation Growth-Accommodating Heart Valved Conduit for Pediatric Use.

Currently available heart valve prostheses have no growth potential, requiring children with heart valve diseases to endure multiple valve replacement surgeries with compounding risks. This study demonstrates the in vitro proof of concept of a biostable polymeric trileaflet valved conduit designed for surgical implantation and subsequent expansion via transcatheter balloon dilation to accommodate the growth of pediatric patients and delay or avoid repeated open-heart surgeries. The valved conduit is formed via dip molding using a polydimethylsiloxane-based polyurethane, a biocompatible material shown here to be capable of permanent stretching under mechanical loading. The valve leaflets are designed with an increased coaptation area to preserve valve competence at expanded diameters. Four 22 mm diameter valved conduits are tested in vitro for hydrodynamics, balloon dilated to new permanent diameters of 23.26 ± 0.38 mm, and then tested again. Upon further dilation, two valved conduits sustain leaflet tears, while the two surviving devices reach final diameters of 24.38 ± 0.19 mm. After each successful dilation, the valved conduits show increased effective orifice areas and decreased transvalvular pressure differentials while maintaining low regurgitation. These results demonstrate concept feasibility and motivate further development of a polymeric balloon-expandable device to replace valves in children and avoid reoperations.

Evaluating a Novel, Portable, Self-Administrable Device ("Beacon") That Measures Critical Flicker Frequency as a Test for Hepatic Encephalopathy.

INTRODUCTION: We compared critical flicker frequency (CFF) thresholds obtained using a novel portable device "Beacon" with thresholds from the commercially available Lafayette Flicker Fusion System (Lafayette-FFS) in patients with cirrhosis. METHODS: One hundred fifty-three participants with chronic liver disease underwent CFF testing using Beacon and Lafayette-FFS with a method-of-limits and/or forced-choice protocol. RESULTS: Beacon demonstrated excellent test-retest reliability (intraclass correlation 0.91-0.97) and good correlation with the Lafayette-FFS values (intraclass correlation 0.77-0.84). Forced-choice CFF were on average 4.1 Hz higher than method-of-limits descending CFFs. DISCUSSION: Beacon can be self-administered by patients with chronic liver disease and cirrhosis to measure CFF, a validated screening test for minimal hepatic encephalopathy.

Loneliness and social support as key contributors to burnout among Canadians workers in the third wave of the COVID-19 pandemic: A cross-sectional study.

OBJECTIVE: COVID-19 has dramatically affected Western Society's relationship with work and contributed to increased worker burnout. Existing studies on burnout have mostly emphasized workplace culture, leadership, and employee engagement as key contributors to burnout. In this cross-sectional study, we examine the associations between Malach-Pines Short Burnout Measure (MPSBM) scores and participant's self reported personal characteristics, financial strain, workplace conditions, work-life balance, and social inclusion among Canadians living during the third wave of the COVID-19 pandemic. METHODS: To identify the most salient correlates of burnout, Canadian residents, aged 16+, were recruited using paid social media advertisements in French and English to complete a cross-sectional study. Multivariable linear regression and dominance analysis identified the most salient correlates of MPSBM scores. Exposure variables included demographic factors, financial strain, workplace conditions, work-life balance, social support, and loneliness. RESULTS: Among 486 participants, family social support (adjusted ß = -0.14, 95%CI = -0.23, -0.05), emotional loneliness (adjusted ß = 0.26, 95% CI = 0.18, 0.35), insufficient sleep (adjusted ß = 0.38, 95% CI = 0.16, 0.60) and "me time" (adjusted ß = 0.22, 95% CI = 0.03, 0.42), and indicators of financial security (e.g., owning vs renting; adjusted ß = -0.36, 95% CI = -0.54, -0.17; insufficient pay: adjusted ß = -0.36, 95% CI = -0.54, -0.17) were key burnout indicators. People with a bachelor's degree (vs ≤high school diploma; adjusted ß = 0.29, 95% CI = 0.01, 0.58) also had higher burnout scores. CONCLUSION: Interventions addressing workplace culture, leadership, and other proximal workplace stressors, while important, are likely insufficient to meet the needs of workers. Our findings suggest that broader, holistic multicomponent approaches that address multiple upstream dimensions of health-including mental health-are likely necessary to prevent and reduce burnout.

Evaluation of Regional Geospatial Clusters in Inguinal Hernia Repair.

Introduction There is significant variation in how inguinal hernia repairs are conducted across the United States (US). This study seeks to utilize national public data on inguinal hernia repair to determine regional differences in the use of ambulatory surgical centers (ASC) and in the choice of laparoscopic or open technique. Methods Medicare provider billing and enrollee demographic data were merged with US census and economic data to create a county-level database for the years 2014-2019. Location, technique, and total count of all inguinal hernia repair billing were recorded for 1286 counties. Moran's I cluster analysis for inguinal hernia repairs, percent laparoscopic technique, and percent ACS were conducted. Subsequent hotspot and coldspot clusters identified in geospatial analysis were compared using ANOVA across 50 socioeconomic variables with a significance threshold of 0.001.  Results  There were 292,870 inguinal hernia repairs, of which 39.8% were conducted laparoscopically and 21.3% of which were in an ACS. Inguinal hernia repair coldspots were in the Mid-Atlantic and Northern Midwest, while hotspots were in Nebraska, Kansas, and Maryland (3.85 and 36.53 repairs per 1000 beneficiaries, respectively). Compared to coldspots, hotspot areas of repair were less obese, had less tobacco use, older, and less insured; there were no differences in gender, white population, or county urbanization (p<0.001). Laparoscopic technique coldspots were in the Mid-Atlantic, Michigan, and Great Plains, while hotspots were in the Rocky Mountains and contiguous states from Florida to Wisconsin (6.14% and 75.39%, respectively). ACS coldspots were diffusely scattered between Oklahoma and New Hampshire, while hotspots were in California, Colorado, Maryland, Tennessee, and Indiana (0.51% and 48.71%, respectively). Conclusions Inguinal hernia repair, the surgical setting, and the choice of technique demonstrated interesting geospatial trends in our population of interest that have not been previously characterized.

A biomimetic multilayered polymeric material designed for heart valve repair and replacement.

Materials currently used to repair or replace a heart valve are not durable. Their limited durability related to structural degeneration or thrombus formation is attributed to their inadequate mechanical properties and biocompatibility profiles. Our hypothesis is that a biostable material that mimics the structure, mechanical and biological properties of native tissue will improve the durability of these leaflets substitutes and in fine improve the patient outcome. Here, we report the development, optimization, and testing of a biomimetic, multilayered material (BMM), designed to replicate the native valve leaflets. Polycarbonate urethane and polycaprolactone have been processed as film, foam, and aligned fibers to replicate the leaflet's architecture and anisotropy, through solution casting, lyophilization, and electrospinning. Compared to the commercialized materials, our BMMs exhibited an anisotropic behavior and a closer mechanical performance to the aortic leaflets. The material exhibited superior biostability in an accelerated oxidization environment. It also displayed better resistance to protein adsorption and calcification in vitro and in vivo. These results will pave the way for a new class of advanced synthetic material with long-term durability for surgical valve repair or replacement.

Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities.

Cutaneous metastases (CM) are neoplastic lesions involving the dermis or subcutaneous tissues, originating from another primary tumor. Breast cancer is commonest primary solid tumor, representing 24%-50% of CM patients. There is no "standard of care" on management. In particular, the role of surgery in the treatment of cutaneous metastases from breast carcinoma (CMBC) remains controversial. This systematic review evaluates the role of cutaneous metastasectomy in breast cancer and provides an overview of existing treatment types.

Stakeholder engagement to inform the risk assessment and governance of gene drive technology to manage spotted-wing drosophila.

Emerging biotechnologies, such as gene drive technology, are increasingly being proposed to manage a variety of pests and invasive species. As one method of genetic biocontrol, gene drive technology is currently being developed to manage the invasive agricultural pest spotted-wing drosophila (Drosophila suzukii, SWD). While there have been calls for stakeholder engagement on gene drive technology, there has been a lack of empirical work, especially concerning stakeholder engagement to inform risk assessment. To help address this gap and inform future risk assessments and governance decisions for SWD gene drive technology, we conducted a survey of 184 SWD stakeholders to explore how they define and prioritize potential benefits and potential adverse effects from proposed SWD gene drive technology. We found that stakeholders considered the most important potential benefits of SWD gene drive technology to be: 1) Decrease in the quantity or toxicity of pesticides used, and 2) Decrease in SWD populations. Stakeholders were most concerned about the potential adverse effects of: 1) Decrease in beneficial insects, 2) Increase in non-SWD secondary pest infestations, and 3) Decrease in grower profits. Notably, we found that even stakeholders who expressed support for the use of SWD gene drive technology expressed concerns about potential adverse effects from the technology, emphasizing the need to move past simplistic, dichotomous views of what it means to support or oppose a technology. These findings suggest that instead of focusing on the binary question of whether stakeholders support or oppose SWD gene drive technology, it is more important to identify and assess the factors that are consequential to stakeholder decision making - including, for example, exploring whether and under what conditions key potential adverse effects and potential benefits would result from the use of SWD gene drive technology.

Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort.

The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 "critical" (in the intensive care unit under mechanical ventilation) and 25 "non-critical" (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease ADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified ADAM9 as a driver of disease severity and a candidate therapeutic target.

Characterizing impact of positive lymph node number in endometrial cancer using machine-learning: A better prognostic indicator than FIGO staging?

BACKGROUND: Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. PATIENTS AND METHODS: Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. RESULTS: We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). CONCLUSION: Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Pyrolyzed Ultrasharp Glassy Carbon Microneedles.

Polymeric microneedles fabricated via two-photon polymerization (2PP) lithography enable safe medical access to the inner ear. Herein, the material class for 2PP-lithography-based microneedles is expanded by pyrolyzing 2PP-fabricated polymeric microneedles, resulting in glassy carbon microneedles. During pyrolysis the microneedles shrink up to 81% while maintaining their complex shape when the exposed surface-area-to-volume ratio (SVR) is 0.025 < SVR < 0.04, for the temperature history protocol used herein. The derived glassy carbon is confirmed with energy-dispersive X-ray spectroscopy and Raman spectroscopy. The pyrolyzed glassy carbon has Young's modulus 9.0 GPa. As a brittle material, the strength is stochastic. Using the two-parameter Weibull distribution, the glassy carbon has Weibull modulus of 3.1 and characteristic strength of 710 MPa. The viscoelastic response has characteristic time scale of about 10000 s. In vitro experiments demonstrate that the glassy carbon microneedles introduce controlled perforations across the guinea pig round window membrane (RWM) from the middle ear space into the inner ear, without damaging the microneedle. The resultant controlled perforation of RWM is known to enhance diffusion of therapeutics across the RWM in a predictable fashion. Hence, the glassy carbon microneedles can be deployed for mediating inner ear delivery.

A cloud-based toolbox for the versatile environmental annotation of biodiversity data.

A vast range of research applications in biodiversity sciences requires integrating primary species, genetic, or ecosystem data with other environmental data. This integration requires a consideration of the spatial and temporal scale appropriate for the data and processes in question. But a versatile and scale flexible environmental annotation of biodiversity data remains constrained by technical hurdles. Existing tools have streamlined the intersection of occurrence records with gridded environmental data but have remained limited in their ability to address a range of spatial and temporal grains, especially for large datasets. We present the Spatiotemporal Observation Annotation Tool (STOAT), a cloud-based toolbox for flexible biodiversity-environment annotations. STOAT is optimized for large biodiversity datasets and allows user-specified spatial and temporal resolution and buffering in support of environmental characterizations that account for the uncertainty and scale of data and of relevant processes. The tool offers these services for a growing set of near global, remotely sensed, or modeled environmental data, including Landsat, MODIS, EarthEnv, and CHELSA. STOAT includes a user-friendly, web-based dashboard that provides tools for annotation task management and result visualization, linked to Map of Life, and a dedicated R package (rstoat) for programmatic access. We demonstrate STOAT functionality with several examples that illustrate phenological variation and spatial and temporal scale dependence of environmental characteristics of birds at a continental scale. We expect STOAT to facilitate broader exploration and assessment of the scale dependence of observations and processes in ecology.