Nuclear rupture induced by capillary constriction forces promotes differential effects on metastatic and normal breast cells.

During metastatic dissemination, circulating tumour cells (CTCs) enter capillary beds, where they experience mechanical constriction forces. The transient and persistent effects of these forces on CTCs behaviour remain poorly understood. Here, we developed a high-throughput microfluidic platform mimicking human capillaries to investigate the impact of mechanical constriction forces on malignant and normal breast cell lines. We observed that capillary constrictions induced nuclear envelope rupture in both cancer and normal cells, leading to transient changes in nuclear and cytoplasmic area. Constriction forces transiently activated cGAS/STING and pathways involved in inflammation (NF-κB, STAT and IRF3), especially in the non-malignant cell line. Furthermore, the non-malignant cell line experienced transcriptional changes, particularly downregulation of epithelial markers, while the metastatic cell lines showed minimal alterations. These findings suggest that mechanical constriction forces within capillaries may promote differential effects in malignant and normal cell lines.

Discharge within 1 day following elective single-level transforaminal lumbar interbody fusion: a propensityscore-matched analysis of predictors, complications, and readmission.

STUDY DESIGN: This was a retrospective case-control study using 8 years of data from a nationwide database of surgical outcomes in the United States. PURPOSE: This study aimed to improve our understanding of the risk factors associated with a length of stay (LOS) >1 day and aid in reducing postoperative hospitalization and complications. OVERVIEW OF LITERATURE: Despite the proven safety of transforaminal lumbar interbody fusion (TLIF), some patients face prolonged postoperative hospitalization. METHODS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program dataset from 2011 to 2018. The cohort was divided into patients with LOS up to 1 day (LOS ≤1 day), defined as same day or next-morning discharge, and patients with LOS >1 day (LOS >1 day). Univariable and multivariable regression analyses were performed to evaluate predictors of LOS >1 day. Propensity-score matching was performed to compare pre- and postdischarge complication rates. RESULTS: A total of 12,664 eligible patients with TLIF were identified, of which 14.8% had LOS ≤1 day and 85.2% had LOS >1 day. LOS >1 day was positively associated with female sex, Hispanic ethnicity, diagnosis of spondylolisthesis, American Society of Anesthesiologists classification 3, and operation length of >150 minutes. Patients with LOS >1 day were more likely to undergo intraoperative/postoperative blood transfusion (0.3% vs. 4.5%, p<0.001) and reoperation (0.1% vs. 0.6%, p=0.004). No significant differences in the rates of postdischarge complications were found between the matched groups. CONCLUSIONS: Patients with worsened preoperative status, preoperative diagnosis of spondylolisthesis, and prolonged operative time are more likely to require prolonged hospitalization and blood transfusions and undergo unplanned reoperation. To reduce the risk of prolonged hospitalization and associated complications, patients indicated for TLIF should be carefully selected.

Apneustic anesthesia ventilation improves pulmonary function in anesthetized bottlenose dolphins (Tursiops truncatus).

Introduction: Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. Methods: To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. Results: During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Discussion: Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.

Circulating tumor cells shed large extracellular vesicles in capillary-sized bifurcations.

Circulating tumor cells (CTCs) and their clusters are the drivers of metastasis, but their interactions with capillary beds are poorly understood. Using microfluidic models mimicking human capillary bifurcations, we observed cell size- and bifurcation-dependent shedding of nuclei-free fragments by patient CTCs, CTC-derived explant cells and numerous cancer cell lines. Shedding reduced cell sizes up to 61%, facilitating their transit through bifurcations. We demonstrated that shed fragments were a novel class of large extracellular vesicles (LEVs), whose proteome was associated with immune-related and signaling pathways. LEVs were internalized by endothelial and immune cells, disrupted endothelial barrier integrity and polarized monocytes into M2 tumor-promoting macrophages. Cumulatively, these findings suggest that CTCs shed LEVs in capillary beds that drive key processes involved in the formation of pre-metastatic niches.

Validation of the Spanish translation Sheffield Profile for Assessment and Referral for Care (SPARC-Sp) at the Hospital Universitario San Jose of Popayan, Colombia.

OBJECTIVES: We determined the validity and reliability of the Spanish translation Sheffield Profile for Assessment and Referral for Care (SPARC-Sp) questionnaire to identify the palliative care (PC) needs of patients with chronic noncommunicable diseases (NCDs) in Colombia. METHODS: We developed a cross-sectional observational study of scale assessment in adults with the aim of determining the validity and reliability of the SPARC-Sp questionnaire to identify the PC needs of patients with NCDs receiving outpatient or inpatient care at the Hospital Universitario San Jose of Popayan - ESE, Colombia, from 2021 to 2022. RESULTS: We applied a questionnaire consisting of demographic, clinical data, and SPARC-Sp to 507 participants. The constructed model explained 75% of the variance with an adequate fit according to the root mean square residual (0.03), the comparative fit index (0.98), and acceptable reliability (McDonald's total omega 0.4-0.9). Opportunities for improvement are the reformulation and inclusion of particular words to improve the representativeness and clarity of the domains of communication and information, religious, and spiritual issues. SIGNIFICANCE OF RESULTS: This research represents the first validation of SPARC in Spanish. SPARC-Sp is an instrument that allows initiating a conversation of the patient's main needs through a systematic assessment of the patients' main needs. Its psychometric validation demonstrated good fit and acceptable reliability.

Calculations of Absolute Free Energies, Enthalpies, and Entropies for Drug Binding.

Computer simulation methods can aid in the rational design of drugs aimed at a specific target, typically a protein. The affinity of a drug for its target is given by the free energy of binding. Binding can be further characterized by the enthalpy and entropy changes in the process. Methods exist to determine exact free energies, enthalpies, and entropies that are dependent only on the quality of the potential model and adequate sampling of conformational degrees of freedom. Entropy and enthalpy are roughly an order of magnitude more difficult to calculate than the free energy. This project combines a replica exchange method for enhanced sampling, designed to be efficient for protein-sized systems, with free energy calculations. This approach, replica exchange with dynamical scaling (REDS), uses two conventional simulations at different temperatures so that the entropy can be found from the temperature dependence of the free energy. A third replica is placed between them, with a modified Hamiltonian that allows it to span the temperature range of the conventional replicas. REDS provides temperature-dependent data and aids in sampling. It is applied to the bromodomain-containing protein 4 (BRD4) system. We find that for the force fields used, the free energies are accurate but the entropies and enthalpies are not, with the entropic contribution being too positive. Reproducing the entropy and enthalpy of binding appears to be a more stringent test of the force fields than reproducing the free energy.

First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors.

PURPOSE: TPST-1120 is a first-in-class oral inhibitor of peroxisome proliferator-activated receptor α (PPARα), a fatty acid ligand-activated transcription factor that regulates genes involved in fatty acid oxidation, angiogenesis, and inflammation, and is a novel target for cancer therapy. TPST-1120 displayed antitumor activity in xenograft models and synergistic tumor reduction in syngeneic tumor models when combined with anti-PD-1 agents. EXPERIMENTAL DESIGN: This phase I, open-label, dose-escalation study (NCT03829436) evaluated TPST-1120 as monotherapy in patients with advanced solid tumors and in combination with nivolumab in patients with renal cell carcinoma (RCC), cholangiocarcinoma (CCA), or hepatocellular carcinoma. Objectives included evaluation of safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity (RECIST v1.1). RESULTS: A total of 39 patients enrolled with 38 treated (20 monotherapy, 18 combination; median 3 prior lines of therapy). The most common treatment-related adverse events (TRAE) were grade 1-2 nausea, fatigue, and diarrhea. No grade 4-5 TRAEs or dose-limiting toxicities were reported. In the monotherapy group, 53% (10/19) of evaluable patients had a best objective response of stable disease. In the combination group, 3 patients had partial responses, for an objective response rate of 20% (3/15) across all doses and 30% (3/10) at TPST-1120 ≥400 mg twice daily. Responses occurred in 2 patients with RCC, both of whom had previously progressed on anti-PD-1 therapy, and 1 patient with late-line CCA. CONCLUSIONS: TPST-1120 was well tolerated as monotherapy and in combination with nivolumab and the combination showed preliminary evidence of clinical activity in PD-1 inhibitor refractory and immune compromised cancers. SIGNIFICANCE: TPST-1120 is a first-in-class oral inhibitor of PPARα, whose roles in metabolic and immune regulation are implicated in tumor proliferation/survival and inhibition of anticancer immunity. This first-in-human study of TPST-1120 alone and in combination with nivolumab supports proof-of-concept of PPARα inhibition as a target of therapeutic intervention in solid tumors.

Translation and linguistic validation of the Sheffield Profile for Assessment and Referral for Care (SPARC) to Colombian Spanish.

OBJECTIVES: We aimed to translate and linguistically and cross-culturally validate Sheffield Profile for Assessment and Referral for Care (SPARC) in Spanish for Colombia (SPARC-Sp). METHODS: The linguistic validation of SPARC followed a standard methodology. We conducted focus groups to assess the comprehensibility and feasibility. The acceptability was assessed using a survey study with potential users. RESULTS: The comprehensibility assessment showed that additional adjustments to those made during the translation-back-translation process were required to apply SPARC-Sp in rural and low-schooled populations. It also identified the need for alternative administration mechanisms for illiterate people. The acceptability survey showed that potential users found SPARC-Sp as not only acceptable but also highly desirable. However, they desired to expand the number of items in all domains. SIGNIFICANCE OF RESULTS: Beyond the semantic and conceptual validity attained through the back-translation process, actual cultural validity could be acquired thanks to the comprehensibility tests. Although extending the instrument is something potential users would like to do, it would make it less feasible to utilize the SPARC-Sp in clinical settings. Nonetheless, the instrument might benefit from the inclusion of a domain that evaluates challenges encountered when accessing the health-care system. For communities lacking literacy, alternate administration methods must also be considered.

Surgical Outcomes in Octogenarians with Central Cord Syndrome: A Propensity-Score Matched Analysis.

OBJECTIVE: Central cord syndrome (CCS) is a traumatic cervical spine injury that is treated with surgical decompression. In octogenarians (80-89), surgeons often opt for conservative management instead due to fears of postoperative complications and prolonged recovery times. This study aims to assess the in-hospital complications and outcomes in octogenarians undergoing surgery compared to those undergoing nonsurgical management for CCS. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for octogenarians with CCS. Patients who received surgical fusion or decompression were divided into the surgery group and the remaining into the nonsurgical group. The surgery group was sampled and propensity score matched with the non-surgery group. Student t tests and Pearson χ2 tests were used to test for group differences. RESULTS: A total of 759 octogenarians with CCS were identified. Following sampling and propensity score matching, 225 patients were identified in each group. The surgery group experienced longer intensive care unit (6.8 days vs. 3.21 days, P < 0.001) and hospital (13.79 days vs. 7.8 days, P < 0.001) lengths of stay and higher rates of deep vein thrombosis (4.89% vs. 0.44%, P = 0.02) and ventilator-associated pneumonia (4% vs. 0%, P = 0.02). Patients did not otherwise differ in mortality rate, other hospital complications, and discharge disposition. CONCLUSIONS: Octogenarians undergoing surgery for CCS experience longer length of stay and complications consistent with prolonged hospitalization but otherwise have similar mortality, hospital complications, and discharge disposition compared to non-surgical treatment. Given the relative lack of short-term drawbacks, surgery should be considered first-line management when the long-term benefits are substantive.

Neurometabolic alterations in children and adolescents with functional neurological disorder.

OBJECTIVES: In vivo magnetic resonance spectroscopy (MRS) was used to investigate neurometabolic homeostasis in children with functional neurological disorder (FND) in three regions of interest: supplementary motor area (SMA), anterior default mode network (aDMN), and posterior default mode network (dDMN). Metabolites assessed included N-acetyl aspartate (NAA), a marker of neuron function; myo-inositol (mI), a glial-cell marker; choline (Cho), a membrane marker; glutamate plus glutamine (Glx), a marker of excitatory neurotransmission; γ-aminobutyric acid (GABA), a marker of inhibitor neurotransmission; and creatine (Cr), an energy marker. The relationship between excitatory (glutamate and glutamine) and inhibitory (GABA) neurotransmitter (E/I) balance was also examined. METHODS: MRS data were acquired for 32 children with mixed FND (25 girls, 7 boys, aged 10.00 to 16.08 years) and 41 healthy controls of similar age using both short echo point-resolved spectroscopy (PRESS) and Mescher-Garwood point-resolved spectroscopy (MEGAPRESS) sequences in the three regions of interest. RESULTS: In the SMA, children with FND had lower NAA/Cr, mI/Cr (trend level), and GABA/Cr ratios. In the aDMN, no group differences in metabolite ratios were found. In the pDMN, children with FND had lower NAA/Cr and mI/Cr (trend level) ratios. While no group differences in E/I balance were found (FND vs. controls), E/I balance in the aDMN was lower in children with functional seizures-a subgroup within the FND group. Pearson correlations found that increased arousal (indexed by higher heart rate) was associated with lower mI/Cr in the SMA and pDMN. CONCLUSIONS: Our findings of multiple differences in neurometabolites in children with FND suggest dysfunction on multiple levels of the biological system: the neuron (lower NAA), the glial cell (lower mI), and inhibitory neurotransmission (lower GABA), as well as dysfunction in energy regulation in the subgroup with functional seizures.

Women in Neurosurgery: Trends in the United States.

OBJECTIVE: We sought to identify trends in the number of female neurosurgeons across each state and identify state characteristics that affect such values. METHODS: The Physician Compare National Downloadable File was queried from the Center for Medicare & Medicaid Services for 2017 and 2023. Physicians indicating "neurosurgery" as their primary specialty were extracted and duplicates were removed. States were ranked based on the number of female neurosurgeons. The percent growth in the number of female neurosurgeons from 2017 to 2023 was calculated for each state. Univariable and multivariable regressions were used to identify the association between state characteristics and the number of female neurosurgeons. RESULTS: The number of female neurosurgeons was higher in urban states while rural states saw a greater increase compared to five years ago. Univariable regression showed significant differences in the number of neurosurgery residency programs, neurosurgery hospitals ranked in U.S. News & World Report, paid parental leave law, number and percentage of female physicians, and diversity index score (P < 0.05). The diversity index score independently affected the number of female neurosurgeons (P < 0.05). CONCLUSIONS: States with more training programs, female physicians, and paid parental leave policies saw a large number of female neurosurgeons. Diversity in the general population is also crucial to improving the equity in gender representation of neurosurgeons in each state. The increase in female neurosurgery representation in rural states shows that the shortage of neurosurgeons in underserved areas is creating a unique niche for female neurosurgeons to excel.

Validation of traditional Chinese version of Sheffield Profile for Assessment and Referral for Care Questionnaire in Taiwanese patients.

BACKGROUND: Holistic health care considers all aspects of patient care, namely the physical, psychological, spiritual, and social aspects. To assess which patient needs are unmet, a screening questionnaire covering the four aforementioned aspects is required. Therefore, the Sheffield Profile for Assessment and Referral for Care (SPARC), a multidimensional, self-reported questionnaire designed to screen patients regardless of diagnosis, was developed. This study developed a translated and validated traditional Chinese version of the SPARC for patients in Taiwan. METHODS: The original English version of the SPARC was translated into a traditional Chinese version (SPARC-T) through forward-backward translation. Semistructured debriefing interviews were conducted with participants to evaluate the SPARC-T. The reliability and validity of the SPARC-T were assessed through Cronbach's alpha coefficients and a correlation analysis conducted using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. RESULTS: Fifty-three patients were enrolled from our hospital: 22 had cancer but the majority had nonmalignant chronic conditions. About internal consistency, the Cronbach's alpha values for all domains of the SPARC-T were favorable. A correlation analysis of the SPARC-T and FACT-G revealed significant correlations for the domains of physical symptoms, independence and activity, family and social issues, sleep, and treatment issues; no significant correlation was identified for the "psychological issues" domain. CONCLUSION: This study revealed that the SPARC-T is an effective tool for screening Mandarin-speaking patients. Thus, it can be used in hospitals to holistically screen and identify the needs of patients to ensure they can receive appropriate professional support and holistic health care.

A High-Throughput Experimental Approach to Screening Gas Sorption by Liquids and Solids.

High-precision measurement of gas uptake from single or mixed feeds in solid and liquid sorbents traditionally requires time-consuming experimental procedures and/or complex and costly equipment. A simple and cost-effective headspace gas chromatography (HS-GC) approach for the fast, universal experimental screening of sorbents for gas uptake and/or determination of their real gas separation selectivity has been developed and is demonstrated for pressures up to 2500 mbar and temperatures above 30 °C. This method allows screening of solids and both volatile and nonvolatile liquid materials, physisorbents, and chemisorbents using both single and mixed permanent gases that can include CO2, CH4, H2, and NH3, for gas uptakes as low as 0.04 mmol or 1.8 mg of CO2. We estimate that this method allows for the screening of at least 30-96 sorbents (in triplicate) or 90-264 sorbents (singles) per day, representing at least a 90-3000 times reduction in the time required for equivalent analysis.

Co-Designing a Strategy for Implementing the SPARC Holistic Needs Assessment Tool in the Colombian Clinical Context.

In Colombia, timely access to palliative care (PC) is hampered by difficulties in identifying and referring to necessary services. The SPARC (Sheffield Profile for Assessment and Referral for Care) instrument provides a holistic needs assessment to improve referrals for different forms of care. SPARC was recently validated in Colombian Spanish (SPARC-Sp) but has not yet been implemented in clinical practice. We undertook workshops that aimed to co-design an implementation strategy to inform a future trial testing SPARC-Sp in the Colombian healthcare system. Workshop attendees included patients, informal caregivers, healthcare professionals, volunteers, administrative staff and decision makers. Discussions within the workshops refined implementation and dissemination strategies for SPARC-Sp in practical scenarios. Results include the need for education, clarification and demystification of PC and the lack of time and skills of professionals to identify patients' needs. Attendees recognized SPARC-Sp as a valuable tool for highlighting patients' concerns, whose adaptations are needed in Colombia to address the low literacy of the population and specificities of the healthcare system. We proposed local adaptations to SPARC-Sp and produced five educational videos aimed at health professionals, patients and caregivers to strengthen understanding of holistic needs in PC while building a strategy for SPARC-Sp implementation in the Colombian context.

Racial disparities in incidence, treatment, and survival in adult brain metastases: a 10-year national database analysis.

OBJECTIVE: The aim of this study was to assess demographic and racial disparities in incidence, treatment, and survival of adults with metastatic malignancy to the brain. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) Program database, the authors identified adults with nonprimary brain metastases between 2010 and 2019. Incidence was calculated for all 10 years while data from 2010 to 2014 were used for survival analysis. The primary outcome measure was all-cause mortality within 5 years, assessed by 6-month, 1-year, 2-year, and 5-year survival rates. Chi-square tests of independence and one-way ANOVA were used to compare categorical and continuous measures, respectively, between non-Hispanic White (NHW), Hispanic White (HW), Black, and Asian/Pacific Islander (API) patients. A multivariable Cox proportional hazards model was developed to evaluate the risk of death within 5 years. RESULTS: A total of 64,690 patient records were identified and analyzed following exclusion based on age (patients > 84 years or < 18 years were excluded), missing race data, and missing survival data. Incidences are reported per 100,000 adults. The incidence of brain metastases increased from 2.59 in 2010 to 2.78 in 2019, with an average 10-year incidence of 2.72. API patients had the highest population-adjusted incidence (3.52), followed by NHW (2.99), Black (2.32), and HW (1.59) patients. Black patients were the most likely to have low income and single status, while API patients were the most likely to have high income and married status. Subsequently, Black patients had the shortest survival time (9.05 months vs 9.19 months for NHW vs 12.93 months for HW vs 15.89 months for API patients, p < 0.001). After controlling for the effect of socioeconomic factors on survival, the multivariable analysis showed that Black (HR 0.91, 95% CI 0.88-0.94), HW (HR 0.73, 95% CI 0.69-0.76), and API (HR 0.69, 95% CI 0.66-0.73) patients all had a survival advantage compared with NHW patients. Surgery also conferred a strong survival advantage (HR 0.47, 95% CI 0.44-0.49). CONCLUSIONS: The incidence of brain metastases has increased slightly between 2010 and 2019, with the highest rate in API patients. Black patients had the lowest survival, potentially due to poor socioeconomic status and lower rates of surgery and chemotherapy. Black patients were the most likely to not be recommended surgery, suggesting a discrepancy in services offered to these patients. More research is warranted to understand the underlying causes of these disparities.

Sharing Medical Big Data While Preserving Patient Confidentiality in Innovative Medicines Initiative: A Summary and Case Report from BigData@Heart.

Sharing individual patient data (IPD) is a simple concept but complex to achieve due to data privacy and data security concerns, underdeveloped guidelines, and legal barriers. Sharing IPD is additionally difficult in big data-driven collaborations such as Bigdata@Heart in the Innovative Medicines Initiative, due to competing interests between diverse consortium members. One project within BigData@Heart, case study 1, needed to pool data from seven heterogeneous data sets: five randomized controlled trials from three different industry partners, and two disease registries. Sharing IPD was not considered feasible due to legal requirements and the sensitive medical nature of these data. In addition, harmonizing the data sets for a federated data analysis was difficult due to capacity constraints and the heterogeneity of the data sets. An alternative option was to share summary statistics through contingency tables. Here it is demonstrated that this method along with anonymization methods to ensure patient anonymity had minimal loss of information. Although sharing IPD should continue to be encouraged and strived for, our approach achieved a good balance between data transparency while protecting patient privacy. It also allowed a successful collaboration between industry and academia.

Perioperative Chemotherapy and Chemoradiotherapy for Patients With Resectable and Borderline Resectable Pancreatic Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS. METHODS: A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS). RESULTS: Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR). CONCLUSIONS: Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.

Effect of perioperative anticoagulant prophylaxis in patients with traumatic subdural hematoma and a history of anticoagulant use: a propensity-matched National Trauma Data Bank analysis.

OBJECTIVE: The use of anticoagulation to prevent venous thromboembolism (VTE) is controversial in the setting of neurosurgical decompression for traumatic subdural hematoma (SDH). In these patients, there is concern that anticoagulation may cause secondary hemorrhage, increasing the risk of death and other complications. Patients with a history of anticoagulant use are at further risk of VTE, but the effect of VTE prophylaxis (VTEP) following neurosurgery for SDH has not been thoroughly investigated in this population. This study aims to investigate the differences in in-hospital outcomes in patients with SDH and preexisting anticoagulant use who received VTEP following neurosurgical intervention compared with those who did not. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all patients with preexisting anticoagulant use presenting with an SDH who subsequently underwent neurosurgical intervention. Patients who received VTEP were propensity score matched with patients who did not based on demographics, insurance type, injury severity, and comorbidities. Paired Student t-tests, Pearson's chi-square tests, and Benjamini-Hochberg multiple comparisons correction were used to compare differences in in-hospital complications, length of stay (LOS), and mortality rate between the two groups. A logistic regression model was developed to identify risk factors for in-hospital mortality. RESULTS: Two thousand seven hundred ninety-four patients matching the inclusion criteria were identified, of whom 950 received VTEP. Following one-to-one matching and multiple comparisons correction, the VTEP group had a lower mortality rate (18.53% vs 34.53%, p < 0.001) but longer LOS (14.09 vs 8.57 days, p < 0.001) and higher rates of pressure ulcers (2.11% vs 0.53%, p = 0.01), unplanned intensive care unit admission (9.05% vs 3.47%, p < 0.001), and unplanned intubation (9.47% vs 6.11%, p = 0.021). The multivariable logistic regression showed that use of unfractionated heparin (UH; OR 0.36, p < 0.001) and low-molecular-weight heparin (LMWH; OR 0.3, p < 0.001) were associated with lower odds of in-hospital mortality. CONCLUSIONS: In patients with traumatic SDH and a history of anticoagulant use, perioperative VTEP was associated with increased LOS but provided a mortality benefit. LMWH and UH use were the strongest predictors of survival.

Characteristics of work-related spine injury in the USA: a National Trauma Data Bank analysis.

PURPOSE: Workplace injury is a commonplace occurrence in the USA. Spine injuries are especially devastating as they can cause chronic pain and limit mobility which prevents patients from returning to work. Gaining a better understanding of the patients, mechanisms, and treatments associated with these injuries can aid in improving outcomes. The purpose of this study is to characterize the nature of work-related spine injuries. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all diagnoses involving the cervical, thoracic, lumbar, and sacral spine. Patient demographics, comorbidities, injury characteristics, spinal diagnoses, and procedures were identified for each occupation. Occupational industries, patient demographics, mechanisms of injury, diagnoses, and spinal procedures were characterized. RESULTS: A total of 100,842 work-related injuries were identified between 2017 and 2019. Of those, 19,002 (19%) were spine injuries, and subsequently, 3963 (21%) required spinal surgery. Eight thousand twenty-nine (42%) cases were seen among construction workers, which had the highest proportion of Hispanic patients (36%). Smoking was prevalent in labor-intensive occupations with high rates of spine injury such as building and grounds maintenance. The most common mechanism of injury was a fall from a roof. The most common injury diagnoses were L1, L2, and L3 fractures, and the most common procedures were T12-L1 fusion, multilevel thoracic fusion, and multilevel lumbar fusion. CONCLUSION: Spine injuries represent a significant portion of work-related injuries in the USA and a considerable portion require neurosurgical intervention. Initial efforts should focus on the prevention and management of lumbar spine injuries in the construction industry.

Capillary-Scale Hydrogel Microchannel Networks by Wire Templating.

Microvascular networks are essential for the efficient transport of nutrients, waste products, and drugs throughout the body. Wire-templating is an accessible method for generating laboratory models of these blood vessel networks, but it has difficulty fabricating microchannels with diameters of ten microns and narrower, a requirement for modeling human capillaries. This study describes a suite of surface modification techniques to  selectively control the interactions amongst wires, hydrogels, and world-to-chip interfaces. This wire templating method enables the fabrication of perfusable hydrogel-based rounded cross-section capillary-scale networks whose diameters controllably narrow at bifurcations down to 6.1 ± 0.3 microns in diameter. Due to its low cost, accessibility, and compatibility with a wide range of common hydrogels of tunable stiffnesses such as collagen, this technique may increase the fidelity of experimental models of capillary networks for the study of human health and disease.