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1.
Can J Surg ; 67(4): E307-E312, 2024.
Article in English | MEDLINE | ID: mdl-39089819

ABSTRACT

BACKGROUND: Patients who require emergency general surgery (EGS) are at a substantially higher risk for perioperative morbidity and mortality than patients undergoing elective general surgery. The acute care surgery (ACS) model has been shown to improve EGS patient outcomes and cost-effectiveness. A recent systematic review has shown extensive heterogeneity in the structure of ACS models worldwide. The objective of this study was to describe the current landscape of ACS models in academic centres across Canada. METHODS: We sent an online questionnaire to the 18 academic centres in Canada. The lead ACS physicians from each institution completed the questionnaire, describing the structure of their ACS models. RESULTS: In total, 16 institutions responded, all of which reported having ACS models, with a total of 29 ACS services described. All services had resident coverage. Of the 29, 18 (62%) had dedicated allied health care staff. The staff surgeon was free from elective duties while covering ACS in 17/29 (59%) services. More than half (15/29; 52%) of the services described protected ACS operating room time, but only 7/15 (47%) had a dedicated ACS room all 5 weekdays. Four of 29 services (14%) had no protected ACS operating room time. Only 1/16 (6%) institutions reported a mandate to conduct ACS research, while 12/16 (75%) found ACS research difficult, owing to lack of resources. CONCLUSION: We saw large variations in the structure of ACS models in academic centres in Canada. The components of ACS models that are most important to patient outcomes remain poorly defined. Future research will focus on defining the necessary cornerstones of ACS models.


Subject(s)
Academic Medical Centers , Acute Care Surgery , Humans , Academic Medical Centers/organization & administration , Academic Medical Centers/statistics & numerical data , Acute Care Surgery/organization & administration , Acute Care Surgery/statistics & numerical data , Canada , Critical Care/statistics & numerical data , Critical Care/organization & administration , General Surgery/statistics & numerical data , Models, Organizational , Surveys and Questionnaires
2.
Sleep Med Clin ; 19(3): 405-417, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39095139

ABSTRACT

This review provides an up-to-date summary of the prevalence, pathophysiology, diagnosis, and treatment of the chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS). The presence of OVS is high in patients with COPD and in patients with OSA and is associated with profound nocturnal oxygen desaturation and systemic inflammation. There is a high prevalence of cardiovascular disease among patients with OVS and this likely contributes to increased mortality. Observational studies suggest that positive airway pressure therapy improves survival and reduces COPD exacerbations; however, randomized controlled trials will be required to confirm these findings.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/complications , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology
3.
Epigenetics Chromatin ; 17(1): 22, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033118

ABSTRACT

Regenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains only partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of changes in chromatin modifications during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios. We deliver high-resolution enrichment maps for H3K4me3 of uninjured and regenerating fin tissues. During regeneration, we find that H3K4me3 levels increase over gene promoters which become transcriptionally active and genes which lose H3K4me3 become silenced. Interestingly, these reprogramming events recapitulate the H3K4me3 patterns observed in developing fin folds of 24-h old zebrafish embryos. Our results indicate that changes in genomic H3K4me3 patterns during fin regeneration occur in a manner consistent with reactivation of developmental programs, demonstrating CUT&Tag to be an effective tool for profiling chromatin landscapes in regenerating tissues.


Subject(s)
Animal Fins , Histones , Regeneration , Zebrafish , Animals , Histones/metabolism , Histones/genetics , Animal Fins/metabolism , Animal Fins/physiology , Chromatin/metabolism
5.
Risk Anal ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38932600

ABSTRACT

Distributed clean, reliable energy resources like solar plus battery storage (solar + storage) can reduce harmful emissions while supporting resilience. Solar + storage-powered resilience hubs provide energy for critical services during disasters while increasing human adaptive capacity year round. We studied where utility rates, local climate, and historical injustice make solar + storage resilience hubs more valuable and more challenging. We modeled the economic and climate impacts of outfitting candidate hub sites across California with solar + storage for everyday operations and identified designs and costs required to withstand a range of outages considering weather impacts on energy needs and availability. We integrated sociodemographic data to prioritize the siting of resilience hubs, to focus potential policy and funding priorities on regions where solar + storage for resilience hubs is hard or expensive, and where populations are most in need. We identified almost 20,000 candidate buildings with more than 8 GW of total rooftop solar potential capable of reducing CO2 emissions by 5 million tons per year while providing energy for community resilience. Hub capacity for one of the most challenging missions-providing emergency shelter during a power outage and smoke event-could have a statewide average lifetime cost of less than $2000 per seat. We identified regional challenges including insufficient rooftop solar capacity in cities, low sunlight in northern coastal California, and high costs driven by utility rate structures in Sacramento and the Imperial Valley. Results show that rates and net metering rules that incentivize solar + storage during everyday operations decrease resilience costs.

6.
Sci Robot ; 9(91): eadi2377, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38865477

ABSTRACT

Repetitive overhead tasks during factory work can cause shoulder injuries resulting in impaired health and productivity loss. Soft wearable upper extremity robots have the potential to be effective injury prevention tools with minimal restrictions using soft materials and active controls. We present the design and evaluation of a portable inflatable shoulder wearable robot for assisting industrial workers during shoulder-elevated tasks. The robot is worn like a shirt with integrated textile pneumatic actuators, inertial measurement units, and a portable actuation unit. It can provide up to 6.6 newton-meters of torque to support the shoulder and cycle assistance on and off at six times per minute. From human participant evaluations during simulated industrial tasks, the robot reduced agonist muscle activities (anterior, middle, and posterior deltoids and biceps brachii) by up to 40% with slight changes in joint angles of less than 7% range of motion while not increasing antagonistic muscle activity (latissimus dorsi) in current sample size. Comparison of controller parameters further highlighted that higher assistance magnitude and earlier assistance timing resulted in statistically significant muscle activity reductions. During a task circuit with dynamic transitions among the tasks, the kinematics-based controller of the robot showed robustness to misinflations (96% true negative rate and 91% true positive rate), indicating minimal disturbances to the user when assistance was not required. A preliminary evaluation of a pressure modulation profile also highlighted a trade-off between user perception and hardware demands. Finally, five automotive factory workers used the robot in a pilot manufacturing area and provided feedback.


Subject(s)
Equipment Design , Range of Motion, Articular , Robotics , Shoulder , Torque , Wearable Electronic Devices , Humans , Robotics/instrumentation , Biomechanical Phenomena , Male , Shoulder/physiology , Adult , Range of Motion, Articular/physiology , Muscle, Skeletal/physiology , Electromyography/instrumentation , Industry/instrumentation , Shoulder Injuries/prevention & control , Female , Young Adult , Task Performance and Analysis , Shoulder Joint/physiology , Exoskeleton Device
7.
Chaos ; 34(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38787314

ABSTRACT

Pair-annihilation events are ubiquitous in a variety of spatially extended systems and are often studied using computationally expensive simulations. Here, we develop an approach in which we simulate the pair-annihilation of spiral wave tips in cardiac models using a computationally efficient particle model. Spiral wave tips are represented as particles with dynamics governed by diffusive behavior and short-ranged attraction. The parameters for diffusion and attraction are obtained by comparing particle motion to the trajectories of spiral wave tips in cardiac models during spiral defect chaos. The particle model reproduces the annihilation rates of the cardiac models and can determine the statistics of spiral wave dynamics, including its mean termination time. We show that increasing the attraction coefficient sharply decreases the mean termination time, making it a possible target for pharmaceutical intervention.

8.
Chemistry ; 30(35): e202401218, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38644346

ABSTRACT

High-valent Fe(IV)=O intermediates of metalloenzymes have inspired numerous efforts to generate synthetic analogs to mimic and understand their substrate oxidation reactivities. However, high-valent M(IV) complexes of late transition metals are rare. We have recently reported a novel Co(IV)-dinitrate complex (1-NO3) that activates sp3 C-H bonds up to 87 kcal/mol. In this work, we have shown that the nitrate ligands in 1-NO3 can be replaced by azide, a more basic coordinating base, resulting in the formation of a more potent Co(IV)-diazide species (1-N3) that reacts with substrates (hydrocarbons and phenols) at faster rate constants and activates stronger C-H bonds than the parent complex 1-NO3. We have characterized 1-N3 employing a combination of spectroscopic and computational approaches. Our results clearly show that the coordination of azide leads to the modulation of the Co(IV) electronic structure and the Co(IV/III) redox potential. Together with the higher basicity of azide, these thermodynamic parameters contribute to the higher driving forces of 1-N3 than 1-NO3 for C-H bond activation. Our discoveries are thus insightful for designing more reactive bio-inspired high-valent late transition metal complexes for activating inert aliphatic hydrocarbons.

9.
Res Sq ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38645155

ABSTRACT

Regenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of epigenetic changes during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios. We deliver high-resolution enrichment maps for H3K4me3 of uninjured and regenerating fin tissues. During regeneration, we find that H3K4me3 levels increase over gene promoters which become transcriptionally active and genes which lose H3K4me3 become silenced. Interestingly, these epigenetic reprogramming events recapitulate the H3K4me3 patterns observed in developing fin folds of 24-hour old zebrafish embryos. Our results indicate that changes in genomic H3K4me3 patterns during fin regeneration occur in a manner consistent with reactivation of developmental programs, demonstrating CUT&Tag to be an effective tool for profiling chromatin landscapes in regenerating tissues.

10.
Trauma Surg Acute Care Open ; 9(1): e001420, 2024.
Article in English | MEDLINE | ID: mdl-38686174

ABSTRACT

Introduction: Venous thromboembolism (VTE) prophylaxis implementation strategies are well-studied in some hospitalized medical and surgical patients. Although VTE is associated with substantial mortality and morbidity in trauma patients, implementation strategies for the prevention of VTE in trauma appear to be based on limited evidence. Therefore, we conducted a systematic review and meta-analysis of published literature on active implementation strategies for VTE prophylaxis administration in hospitalized trauma patients and the impact on VTE events. Methods: A systematic review and meta-analysis was performed in adult hospitalized trauma patients to assess if active VTE prevention implementation strategies change the proportion of patients who received VTE prophylaxis, VTE events, and adverse effects such as bleeding or heparin-induced thrombocytopenia as well as hospital length of stay and the cost of care. An academic medical librarian searched Medline, Scopus, and Web of Science until December 2022. Results: Four studies with a total of 1723 patients in the active implementation strategy group (strategies included education, reminders, human and computer alerts, audit and feedback, preprinted orders, and/or root cause analysis) and 1324 in the no active implementation strategy group (guideline creation and dissemination) were included in the analysis. A higher proportion of patients received VTE prophylaxis with an active implementation strategy (OR=2.94, 95% CI (1.68 to 5.15), p<0.01). No significant difference was found in VTE events. Quality was deemed to be low due to bias and inconsistency of studies. Conclusions: Active implementation strategies appeared to improve the proportion of major trauma patients who received VTE prophylaxis. Further implementation studies are needed in trauma to determine effective, sustainable strategies for VTE prevention and to assess secondary outcomes such as bleeding and costs. Level of evidence: Systematic review/meta-analysis, level III. PROSPERO registration number: CRD42023390538.

11.
Nat Commun ; 15(1): 2863, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627362

ABSTRACT

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable.


Subject(s)
Melanoma , Skin Neoplasms , Uveal Neoplasms , Humans , Melanoma/genetics , Melanoma/therapy , Uveal Neoplasms/genetics , Uveal Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating , Immunotherapy , Tumor Microenvironment/genetics
13.
J Trauma Acute Care Surg ; 97(1): 119-124, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38437527

ABSTRACT

BACKGROUND: Delays in initiating venous thromboembolism (VTE) prophylaxis in patients suffering from traumatic brain injury (TBI) persist despite guidelines recommending early initiation. We hypothesized that the expansion of a Trauma Program Performance Improvement (PI) team will improve compliance of early (24-48 hours) initiation of VTE prophylaxis and will decrease VTE events in TBI patients. METHODS: We performed a single-center retrospective review of all TBI patients admitted to a Level I trauma center before (2015-2016,) and after (2019-2020,) the expansion of the Trauma Performance Improvement and Patient Safety (PIPS) team and the creation of trauma process and outcome dashboards. Exclusion criteria included discharge or death within 48 hours of admission, expanding intracranial hemorrhage on CT scan, and a neurosurgical intervention (craniotomy, pressure monitor, or drains) prior to chemoprophylaxis initiation. RESULTS: A total of 1,112 patients met the inclusion criteria, of which 54% (n = 604) were admitted after Trauma PIPS expansion. Following the addition of a dedicated PIPS nurse in the trauma program and creation of process dashboards, the time from stable CT to VTE prophylaxis initiation decreased (52 hours to 35 hours; p < 0.001) and more patients received chemoprophylaxis at 24 hours to 48 hours (59% from 36%, p < 0.001) after stable head CT. There was no significant difference in time from first head CT to stable CT (9 vs. 9 hours; p = 0.15). The Contemporary group had a lower rate of VTE events (1% vs. 4%; p < 0.001) with no increase in bleeding events (2% vs. 2%; p = 0.97). On multivariable analysis, being in the Early cohort was an independent predictor of VTE events (adjusted odds ratio, 3.74; 95% confidence interval, 1.45-6.16). CONCLUSION: A collaborative multidisciplinary Trauma PIPS team improves guideline compliance. Initiation of VTE chemoprophylaxis within 24 hours to 48 hours of stable head CT is safe and effective. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.


Subject(s)
Brain Injuries, Traumatic , Guideline Adherence , Quality Improvement , Trauma Centers , Venous Thromboembolism , Humans , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Retrospective Studies , Guideline Adherence/statistics & numerical data , Female , Male , Middle Aged , Brain Injuries, Traumatic/complications , Adult , Patient Care Team/organization & administration , Anticoagulants/therapeutic use , Practice Guidelines as Topic
14.
J Trauma Acute Care Surg ; 97(1): 90-95, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38523131

ABSTRACT

INTRODUCTION: Retained hemothorax (HTX) is a common complication following thoracic trauma. Small studies demonstrate the benefit of thoracic cavity irrigation at the time of tube thoracostomy (TT) for the prevention of retained HTX. We sought to assess the effectiveness of chest irrigation in preventing retained HTX leading to a secondary surgical intervention. METHODS: We performed a single-center retrospective study from 2017 to 2021 at a Level I trauma center, comparing bedside thoracic cavity irrigation via TT versus no irrigation. Using the trauma registry, patients with traumatic HTX were identified. Exclusion criteria were TT placement at an outside hospital, no TT within 24 hours of admission, thoracotomy or video-assisted thoracoscopic surgery (VATS) prior to or within 6 hours after TT placement, VATS as part of rib fixation or diaphragmatic repair, and death within 96 hours of admission. Bivariate and multivariable analyses were conducted. RESULTS: A total of 370 patients met the inclusion criteria, of whom 225 (61%) were irrigated. Patients who were irrigated were more likely to suffer a penetrating injury (41% vs. 30%, p = 0.03) and less likely to have a flail chest (10% vs. 21%, p = 0.01). On bivariate analysis, irrigation was associated with lower rates of VATS (6% vs. 19%, p < 0.001) and retained HTX (10% vs. 21%, p < 0.001). The irrigated cohort had a shorter TT duration (4 vs. 6 days, p < 0.001) and hospital length of stay (7 vs. 9 days, p = 0.04). On multivariable analysis, thoracic cavity irrigation had lower odds of VATS (adjusted odds ratio, 0.37; 95% confidence interval [CI], 0.30-0.54), retained HTX (adjusted odds ratio, 0.42; 95% CI, 0.25-0.74), and a shorter TT duration ( ß = -1.58; 95% CI, -2.52 to -0.75). CONCLUSION: Our 5-year experience with thoracic irrigation confirms findings from smaller studies that irrigation prevents retained HTX and decreases the need for surgical intervention. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.


Subject(s)
Hemothorax , Therapeutic Irrigation , Thoracic Injuries , Thoracostomy , Humans , Hemothorax/etiology , Hemothorax/prevention & control , Hemothorax/surgery , Male , Retrospective Studies , Female , Thoracic Injuries/surgery , Thoracic Injuries/complications , Therapeutic Irrigation/methods , Thoracostomy/methods , Adult , Middle Aged , Thoracic Cavity/surgery , Trauma Centers , Chest Tubes , Thoracic Surgery, Video-Assisted/methods , Thoracic Surgery, Video-Assisted/adverse effects
15.
Injury ; 55(5): 111490, 2024 May.
Article in English | MEDLINE | ID: mdl-38523031

ABSTRACT

BACKGROUND: Damage control surgery aims to control hemorrhage and contamination in the operating room (OR) with definitive management of injuries delayed until normal physiology is restored in the intensive care unit (ICU). There are limited studies evaluating the use of damage control thoracotomy (DCT) in trauma, and the best method of temporary closure is unclear. METHODS: A retrospective review of trauma patients at two level I trauma centers who underwent a thoracotomy operation was performed. Subjects who underwent a thoracotomy after 24 h, age less than 16, expired in the trauma bay, or in the OR prior to ICU admission were excluded. One-way ANOVA and Kruskal-Wallis test were used to compare continuous and categorical variables between DCT and definitive thoracotomy (DT) patients. RESULTS: 207 trauma patients underwent thoracotomy, 76 met our inclusion criteria. DCT was performed in 30 patients (39%), 46 (61 %) underwent DT operation. Techniques for temporizing the chest varied from skin closure with suture (8), adhesive dressing (5), towel clamps (2), or negative pressure devices (12). Compared to definitive closure, DCT had more derangements in HR, pH, (110 vs. 95, p = 0.04; 7.05 vs 7.24, p < 0.001), and injury severity score (41 vs 25, p < 0.001), and required more blood transfusions (40 vs 6, p < 0.001). Eleven (36.7 %) DCT patients survived to discharge compared to 38 patients (95.0 %) in the DT group. DCT showed significantly higher differences in cardiac arrest and unplanned returns to the OR rates. No differences were observed in ventilator days, or ICU length of stay. CONCLUSIONS: DCT is a viable option for management of patients in extremis following thoracic trauma. DCT was associated with higher mortality rates, likely due to differences in injury and physiologic derangement. Despite this, DCT was associated with similar rates of complications, ICU stay, and ventilator days.


Subject(s)
Thoracic Injuries , Humans , Thoracic Injuries/surgery , Thoracotomy/methods , Hospitalization , Injury Severity Score , Retrospective Studies , Bandages
16.
J Trauma Acute Care Surg ; 96(6): 986-991, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38439149

ABSTRACT

ABSTRACT: Acute care surgery (ACS) patients are frequently faced with significant long-term recovery and financial implications that extend far beyond their hospitalization. While major injury and emergency general surgery (EGS) emergencies are often viewed solely as acute moments of crisis, the impact on patients can be lifelong. Financial outcomes after major injury or emergency surgery have only begun to be understood. The Healthcare Economics Committee from the American Association for the Surgery of Trauma previously published a conceptual overview of financial toxicity in ACS, highlighting the association between financial outcomes and long-term physical recovery. The aims of second-phase financial toxicity review by the Healthcare Economics Committee of the American Association for the Surgery of Trauma are to (1) understand the unique impact of financial toxicity on ACS patients; (2) delineate the current limitations surrounding measurement domains of financial toxicity in ACS; (3) explore the "when, what and how" of optimally capturing financial outcomes in ACS; and (4) delineate next steps for integration of these financial metrics in our long-term patient outcomes. As acute care surgeons, our patients' recovery is often contingent on equal parts physical, emotional, and financial recovery. The ACS community has an opportunity to impact long-term patient outcomes and well-being far beyond clinical recovery.


Subject(s)
Wounds and Injuries , Humans , United States , Wounds and Injuries/surgery , Wounds and Injuries/economics , Surgical Procedures, Operative/economics , Critical Care/economics , Acute Care Surgery
17.
ArXiv ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38410644

ABSTRACT

Pair-annihilation events are ubiquitous in a variety of spatially extended systems and are often studied using computationally expensive simulations. Here we develop an approach in which we simulate the pair-annihilation of spiral wave tips in cardiac models using a computationally efficient particle model. Spiral wave tips are represented as particles with dynamics governed by diffusive behavior and short-ranged attraction. The parameters for diffusion and attraction are obtained by comparing particle motion to the trajectories of spiral wave tips in cardiac models during spiral defect chaos. The particle model reproduces the annihilation rates of the cardiac models and can determine the statistics of spiral wave dynamics, including its mean termination time. We show that increasing the attraction coefficient sharply decreases the mean termination time, making it a possible target for pharmaceutical intervention. Many physical systems exhibit annihilation events during which pairs of objects collide and are removed from the system. These events occur in a number of soft-matter and active-matter systems that exhibit spatiotemporal patterning. For example, topological defects in nematic liquid crystals can develop motile topological defects that annihilate when they meet 1,2. Pair-wise annihilation of defects or singularities also plays a role in a number of biological systems. In bacterial biofilms, for instance, imperfect cell alignment results in point-like defects that carry half-integer topological charge and can annihilate in pairs. These topological defects explain the formation of layers and have been proposed as a model for the buckling of biofilms in colonies of nematically ordered cells3,4.

18.
Injury ; 55(3): 111368, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38309083

ABSTRACT

BACKGROUND: Non-aortic arterial injuries are common and are associated with high morbidity and mortality. Historically, open surgical repair (OSR) was the conventional method of repair. With recent advancements in minimally invasive techniques, endovascular repair (ER) has gained popularity. We sought to compare outcomes in patients undergoing endovascular and open repairs of traumatic non-aortic penetrating arterial injuries. METHODS: A systematic review and meta-analysis was conducted using MEDLINE (OVID), Web of Science, Cochrane Library, and Scopus Database from January 1st, 1990, to March 20th, 2023. Titles and abstracts were screened, followed by full text review. Articles assessing clinically important outcomes between OSR and ER in penetrating arterial injuries were included. Exclusion criteria included blunt injuries, aortic injuries, pediatric populations, review articles, and non-English articles. Odds ratios (OR) and Cohen's d ratios were used to quantify differences in morbidity and mortality. RESULTS: A total of 3770 articles were identified, of which 8 met inclusion criteria and were included in the review. The articles comprised a total of 8369 patients of whom 90 % were male with a median age of 28 years. 85 % of patients were treated with OSR while 15 % underwent ER. With regards to injury characteristics, those who underwent ER were less likely to present with concurrent venous injuries (OR: 0.41; 95 %CI: 0.18, 0.94; p = 0.03). Regarding hospital outcomes, patients who underwent ER had a lower likelihood of in-hospital or 30-day mortality (OR: 0.72; 95 %CI: 0.55, 0.95; p = 0.02) and compartment syndrome (OR: 0.29, 95 %CI: 0.12, 0.71; p = 0.007). The overall risk of bias was moderate. CONCLUSION: Endovascular repair of non-aortic penetrating arterial injuries is increasingly common, however open repair remains the most common approach. Compared to ER, OSR was associated with higher odds of compartment syndrome and mortality. Further prospective research is warranted to determine the patient populations and injury patterns that most significantly benefit from an endovascular approach. LEVEL OF EVIDENCE: Level III, Systematic Reviews & Meta-Analyses.

19.
Neuropsychopharmacology ; 49(8): 1285-1295, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38366138

ABSTRACT

Creating long-lasting memories requires learning-induced changes in gene expression, which are impacted by epigenetic modifications of DNA and associated histone proteins. Post-translational modifications (PTMs) of histones are key regulators of transcription, with different PTMs producing unique effects on gene activity and behavior. Although recent studies implicate histone variants as novel regulators of memory, effects of PTMs on the function of histone variants are rarely considered. We previously showed that the histone variant H2A.Z suppresses memory, but it is unclear if this role is impacted by H2A.Z acetylation, a PTM that is typically associated with positive effects on transcription and memory. To answer this question, we used a mutation approach to manipulate acetylation on H2A.Z without impacting acetylation of other histone types. Specifically, we used adeno-associated virus (AAV) constructs to overexpress mutated H2A.Z.1 isoforms that either mimic acetylation (acetyl-mimic) by replacing lysines 4, 7 and 11 with glutamine (KQ), or H2A.Z.1 with impaired acetylation (acetyl-defective) by replacing the same lysines with alanine (KA). Expressing the H2A.Z.1 acetyl-mimic (H2A.Z.1KQ) improved memory under weak learning conditions, whereas expressing the acetyl-defective H2A.Z.1KA generally impaired memory, indicating that the effect of H2A.Z.1 on memory depends on its acetylation status. RNA sequencing showed that H2A.Z.1KQ and H2A.Z.1KA uniquely impact the expression of different classes of genes in both females and males. Specifically, H2A.Z.1KA preferentially impacts genes involved in synaptic function, suggesting that acetyl-defective H2A.Z.1 impairs memory by altering synaptic regulation. Finally, we describe, for the first time, that H2A.Z is also involved in alternative splicing of neuronal genes, whereby H2A.Z depletion, as well as expression of H2A.Z.1 lysine mutants influence transcription and splicing of different gene targets, suggesting that H2A.Z.1 can impact behavior through effects on both splicing and gene expression. This is the first study to demonstrate that direct manipulation of H2A.Z post-translational modifications regulates memory, whereby acetylation adds another regulatory layer by which histone variants can fine tune higher brain functions through effects on gene expression and splicing.


Subject(s)
Alternative Splicing , Histones , Lysine , Memory , Protein Processing, Post-Translational , Transcription, Genetic , Histones/metabolism , Animals , Acetylation , Lysine/metabolism , Memory/physiology , Transcription, Genetic/physiology , Male , Mice , Protein Isoforms/genetics , Protein Isoforms/metabolism , Mice, Inbred C57BL , Female
20.
Surgery ; 175(5): 1439-1444, 2024 May.
Article in English | MEDLINE | ID: mdl-38388229

ABSTRACT

BACKGROUND: Traumatic brain injury patients who require neurosurgical intervention are at the highest risk of worsening intracranial hemorrhage. This subgroup of patients has frequently been excluded from prior research regarding the timing of venous thromboembolism chemoprophylaxis. This study aims to assess the efficacy and safety of early venous thromboembolism chemoprophylaxis in patients with traumatic brain injuries requiring neurosurgical interventions. METHODS: This is a single-center retrospective review (2016-2020) of traumatic brain injury patients requiring neurosurgical intervention admitted to a level I trauma center. Interventions included intracranial pressure monitoring, subdural drain, external ventricular drain, craniotomy, and craniectomy. Exclusion criteria included neurosurgical intervention after chemoprophylaxis initiation, death within 5 days of admission, and absence of chemoprophylaxis. The total population was stratified into Early (≤72 hours of intervention) versus Late (>72 hours after intervention) chemoprophylaxis initiation. RESULTS: A total of 351 patients met the inclusion criteria, of whom 204 (58%) had early chemoprophylaxis initiation. Overall, there were no significant differences in baseline and admission characteristics between cohorts. The Early chemoprophylaxis cohort had a statistically significant lower venous thromboembolism rate (5% vs 13%, P < .001) with no increased risk of worsening intracranial hemorrhage (10% vs 13%, P = .44) or neurosurgical reintervention (8% vs 10%, P = .7). On subgroup analysis, a total of 169 patients required either a craniotomy or a craniectomy before chemoprophylaxis. The Early chemoprophylaxis cohort had statistically significant lower venous thromboembolism rates (2% vs 11%, P < .001) with no increase in intracranial hemorrhage (8% vs 11%, P = .6) or repeat neurosurgical intervention (8% vs 10%, P = .77). CONCLUSION: Venous thromboembolism prophylaxis initiation within 72 hours of neurosurgical intervention is safe and effective. Further prospective research is warranted to validate the results of this study.


Subject(s)
Brain Injuries, Traumatic , Venous Thromboembolism , Humans , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Venous Thromboembolism/epidemiology , Anticoagulants/adverse effects , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/surgery , Intracranial Hemorrhages/etiology , Retrospective Studies , Chemoprevention/adverse effects
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