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Background: Firearm-related injury is the leading cause of death among children and adolescents. There is a need to clarify the association of neighborhood environment with gun violence affecting children. We evaluated the relative contribution of specific social determinants to observed rates of firearm-related injury in children of different ages. Methods: This was a population-based study of firearm injury in children (age <18 years) that occurred in Philadelphia census tracts (2015-2021). The exposure was neighborhood Social Deprivation Index (SDI) quintile. The outcome was the rate of pediatric firearm injury due to interpersonal violence stratified by age, sex, race, and year. Hierarchical negative binomial regression measured the risk-adjusted association between SDI quintile and pediatric firearm injury rate. The relative contribution of specific components of the SDI to neighborhood risk of pediatric firearm injury was estimated. Effect modification and the role of specific social determinants were evaluated in younger (<15 years old) versus older children. Results: 927 children were injured due to gun violence during the study period. Firearm-injured children were predominantly male (87%), of black race (89%), with a median age of 16 (IQR 15-17). Nearly one-half of all pediatric shootings (47%) occurred in the quintile of highest SDI (Q5). Younger children represented a larger proportion of children shot in neighborhoods within the highest (Q5), compared with the lowest (Q1), SDI quintile (25% vs 5%; p<0.007). After risk adjustment, pediatric firearm-related injury was strongly associated with increasing SDI (Q5 vs Q1; aRR 14; 95% CI 6 to 32). Specific measures of social deprivation (poverty, incomplete schooling, single-parent homes, and rented housing) were associated with significantly greater increases in firearm injury risk for younger, compared with older, children. Component measures of the SDI explained 58% of observed differences between neighborhoods. Conclusions: Neighborhood measures of social deprivation are strongly associated with firearm-related injury in children. Younger children appear to be disproportionately affected by specific adverse social determinants compared with older children. Root cause evaluation is required to clarify the interaction with other factors such as the availability of firearms and interpersonal conflict that place children at risk in neighborhoods where gun violence is common. Level of evidence: Level III - Observational Study.
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Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.
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BACKGROUND: The Woven EndoBridge (WEB) device is designed to treat wide-necked bifurcation aneurysms. The WEB 17 is the latest iteration and can be delivered through a 0.017â³ microcatheter. The CLEVER study demonstrated that WEB 17 is safe and effective for providing protection against bleeding or rebleeding at 1 month and 1 year. OBJECTIVE: To evaluate angiographic stability at 1 year. METHODS: The CLEVER study was a prospective multicenter study conducted in 17 European centers, involved 163 subjects, comprising 60 ruptured and 103 unruptured aneurysms. Independent assessment of 1-year follow-up imaging was incorporated into the study design. RESULTS: Aneurysm diameters ranged from 2.0 to 9.2 mm, with 95.7% being broad-based (dome-to-neck ratio <2). Follow-up imaging at 1 year was completed for 146 out of 163 subjects (89.6%) and evaluated by an independent core laboratory. The primary efficacy endpoint of adequate occlusion without re-treatment at 1 year was achieved for 120 (82.2%) of all subjects. At 1 year, the adequate occlusion rate was 86.5% for ruptured aneurysms (73.1% complete occlusion) and 82.4% for unruptured aneurysms (57.1% complete occlusion). The overall re-treatment rate at 1 year was 2.6% (4/152), with 3.1% (3/97) for unruptured aneurysms and 1.8% (1/55) for ruptured aneurysms CONCLUSION: Delivery of the WEB 17 via 0.017 inch catheters represents a significant evolution of the WEB design. The results of CLEVER presented here demonstrate that it maintains the same efficacy as previous generations of WEB.
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Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel.
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OBJECTIVE: Few large studies have investigated the factors and outcomes related to concomitant injuries occurring alongside mild traumatic brain injury (mTBI) after motor vehicle collisions (MVCs). Thus, the objective of this study was to assess whether MVC characteristics predict which patients with mTBI will have concomitant whiplash injury, and whether concomitant whiplash injury affects care utilization for these patients. METHODS: This retrospective cohort study included 22,213 patients with mTBI after MVC identified from the American College of Surgeons Trauma Quality Programs dataset. A hierarchical logistic regression model was constructed to investigate patient and MVC factors associated with concomitant whiplash injury. Propensity score matching on whiplash status, in conjunction with a multivariable logistic regression model, assessed if concomitant whiplash affected odds of hospitalization. In the subgroup of patients who were hospitalized, associations with hospital length of stay (LOS) and discharge disposition were investigated. RESULTS: The median (IQR) age was 34 (24-51) years, with a median Glasgow Coma Scale score at presentation of 15 (15-15). Patients with concomitant whiplash were older (median 36 years vs 34 years, p = 0.03) and had higher rates of hospitalization (75% vs 64%, p < 0.001). In the hierarchical model for associations with concomitant whiplash injury, patients with blood alcohol content (BAC) greater than the federal driving limit had lower odds of concomitant whiplash (OR 0.63, 95% CI 0.49-0.81) along with those who had airbag deployment (OR 0.80, 95% CI 0.68-0.95), but seatbelt use was associated with greater odds (OR 1.41, 95% CI 1.16-1.71). After matching, concomitant whiplash was independently associated with increased odds of hospitalization (OR 1.67, 95% CI 1.40-1.99) while seatbelt use was associated with decreased odds (OR 0.88, 95% CI 0.81-0.95). Among hospitalized patients, concomitant whiplash was not associated with hospital LOS or discharge disposition. CONCLUSIONS: MVC characteristics such as alcohol consumption and airbag deployment were protective toward development of concomitant whiplash for mTBI patients, while seatbelt use was associated with higher risk. Concomitant whiplash increases the odds of hospitalization for mTBI patients but does not affect hospital LOS or discharge disposition, while seatbelt use is associated with lower rates of hospitalization and a more favorable hospital course. These findings provide context to injury patterns and care provision after a common mechanism of injury.
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Acidentes de Trânsito , Hospitalização , Traumatismos em Chicotada , Humanos , Acidentes de Trânsito/estatística & dados numéricos , Masculino , Feminino , Adulto , Traumatismos em Chicotada/epidemiologia , Traumatismos em Chicotada/complicações , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , Concussão Encefálica/epidemiologia , Concussão Encefálica/complicações , Estudos de Coortes , Tempo de Internação/estatística & dados numéricos , Escala de Coma de GlasgowRESUMO
There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.
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Firearm injuries are a common and major public health problem in Baltimore, Maryland. The city is also one of the first U.S. cities in which the 1930s discriminatory practice of redlining first emerged. This study examines the association between current day firearm injuries and residence in these historically redlined areas at a neighborhood level using zip codes. Firearm injury outcomes in patients who presented to a hospital in Maryland from 2015 to 2020 were measured from the Health Services Cost Review Commission (HSCRC) in conjunction with both geospatial data from Richmond's Digital Scholarship Lab's Mapping Inequality project and population data from the U.S. Census. A redlining score was calculated to represent the extent of redlining in each zip code. Negative binomial regression models were utilized to measure the association between neighborhood zip codes and rate of firearm injuries. Our adjusted regression model shows that for every one-unit increase of the Home Owners' Loan Corporation (HOLC) redlining score, there is a 2.24-fold increase in the rate of firearm injuries (RR 2.24; 95% CI: 0.31, 1.31, p < 0.001). These findings suggest a strongassociation between historically redlined areas and population risk of firearm injury today. Further research is needed to investigate the underlying mechanisms that may contribute to this relationship, such as access to firearms or social and economic factors. Overall, our study highlights the potential impact of historical redlining policies on contemporary health outcomes in Baltimore.
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Diabetic wound healing is uniquely challenging to manage due to chronic inflammation and heightened microbial growth from elevated interstitial glucose. Carbon monoxide (CO), widely acknowledged as a toxic gas, is also known to provide unique therapeutic immune modulating effects. To facilitate delivery of CO, we have designed hyaluronic acid-based CO-gas-entrapping materials (CO-GEMs) for topical and prolonged gas delivery to the wound bed. We demonstrate that CO-GEMs promote the healing response in murine diabetic wound models (full-thickness wounds and pressure ulcers) compared to N2-GEMs and untreated controls.
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Background and Objective Timely palliative care involvement offers demonstrable benefits for traumatic brain injury (TBI) patients; however, palliative care consultations (PCCs) are used inconsistently during TBI management. This study aimed to employ advanced machine learning techniques to elucidate the primary drivers of PCC timing variability for TBI patients. Methods Data on admission, hospital course, and outcomes were collected for a cohort of 232 TBI patients who received both PCCs and neurosurgical consultations during the same hospitalization. Principal Component Analysis (PCA) and K-means clustering were used to identify patient phenotypes, which were then compared using Kaplan-Meier analysis. An extreme gradient boosting model (XGBoost) was employed to determine drivers of PCC timing, with model interpretation performed using SHapley Additive exPlanations (SHAP). Results Cluster A (n = 86) consisted mainly of older (median [IQR] = 87 [78, 94] years), White females with mild TBIs and demonstrated the shortest time-to-PCC (2.5 [1.0, 7.0] days). Cluster B (n = 108) also sustained mild TBIs but comprised moderately younger (81 [75, 86] years) married White males with later PCC (5.0 [3.0, 10.8] days). Cluster C (n = 38) represented much younger (46.5 [29.5, 59.8] years), more severely injured, non-White patients with the latest PCC initiation (9.0 [4.2, 17.0] days). The clusters did not differ by discharge disposition (p = 0.4) or frequency inpatient mortality (p > 0.9); however, Kaplan-Meier analysis revealed a significant difference in the time from admission to PCC (p < 0.001), despite no differences in time from admission to mortality (p = 0.18). SHAP analysis of the XGBoost model identified age, sex, and race as the most influential drivers of PCC timing. Conclusions This study highlights crucial disparities in PCC timing for TBI patients and underscores the need for targeted strategies to ensure timely and equitable palliative care integration for this vulnerable population.
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OBJECTIVE: The Glasgow Coma Scale-Pupils (GCS-P) score has been suggested to better predict patient outcomes compared with GCS alone, while avoiding the need for more complex clinical models. This study aimed to compare the prognostic ability of GCS-P versus GCS in a national cohort of traumatic subdural hematoma (SDH) patients. METHODS: Patient data were obtained from the National Trauma Data Bank (2017-2019). Inclusion criteria were traumatic SDH diagnosis with available data on presenting GCS score, pupillary reactivity, and discharge disposition. Patients with severe polytrauma or nonsurvivable head injury at presentation were excluded. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of GCS-P versus GCS scores for inpatient mortality prediction were evaluated across the entire cohort, as well as in subgroups based on age and traumatic brain injury (TBI) type (blunt vs penetrating). Calibration curves were plotted based on predicted probabilities and actual outcomes. RESULTS: A total of 196,747 traumatic SDH patients met the study inclusion criteria. Sensitivity (0.707 vs 0.702), specificity (0.821 vs 0.823), and AUC (0.825 vs 0.814, p < 0.001) of GCS-P versus GCS scores for prediction of inpatient mortality were similar. Calibration curve analysis revealed that GCS scores slightly underestimated inpatient mortality risk, whereas GCS-P scores did not. In patients > 65 years of age with blunt TBI (51.9%, n = 102,148), both GCS-P and GCS scores underestimated inpatient mortality risk. In patients with penetrating TBI (2.4%, n = 4,710), the AUC of the GCS-P score was significantly higher (0.902 vs 0.851, p < 0.001). In this subgroup, both GCS-P and GCS scores underestimated inpatient mortality risk among patients with lower rates of observed mortality and overestimated risk among patients with higher rates of observed mortality. This effect was more pronounced in the GCS-P calibration curve. CONCLUSIONS: The GCS-P score provides better short-term prognostication compared with the GCS score alone among traumatic SDH patients with penetrating TBI. The GCS-P score overestimates inpatient mortality risk among penetrating TBI patients with higher rates of observed mortality. For penetrating TBI patients, which comprised 2.4% of our SDH cohort, a low GCS-P score should not justify clinical nihilism or forgoing aggressive treatment.
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Sleeve gastrectomy (SG) is the most frequently performed bariatric procedure worldwide. The incidence and consequences of sleeve migration (SM) are not clearly understood. There is no clear consensus on appropriate measures to reduce the risk of SM. This study systematically reviewed the literature and identified 405 cases of SM from 21 studies. Age ranged from 18 to 68 years. Thirty-two percent and 11% of patients were females and males respectively, while sex was not reported in 57%. Time to diagnosis ranged from 1 day to 5 years postoperatively. A total of 9.6% and 58.8% of patients had or had no previous hiatal hernia respectively. SM incidence, risk factors, proposed mechanisms, clinical presentation, diagnosis, management, and potential preventive strategies are described in this review.
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Gastrectomia , Obesidade Mórbida , Humanos , Gastrectomia/efeitos adversos , Obesidade Mórbida/cirurgia , Feminino , Masculino , Adulto , Fatores de Risco , Pessoa de Meia-Idade , Incidência , Migração de Corpo Estranho/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cirurgia Bariátrica/efeitos adversos , Idoso , Hérnia Hiatal/cirurgia , AdolescenteRESUMO
Purpose: An effective didactic curriculum is a cornerstone for a successful residency program, as it is the basis upon which residents acquire the necessary knowledge and perspective to provide high-quality, evidence-based care. Here we describe our success in creating a standardized curriculum in clinical radiation oncology - one that was well-received and led to significantly improved performance on the national in-service examination. Methods and Materials: One-hundred and fifty topics were outlined in accordance with the American Board of Radiology; to accommodate this breadth of material, didactic frequency was increased from biweekly to daily. As a clinical correlate to these sessions, a teaching library of over 100 real-world cases was compiled for individual learning. Finally, comprehensive dosimetric constraints were compiled to aid residents in radiation therapy plan evaluation. To evaluate these curricular changes, anonymous questionnaires were provided to all residents and faculty, and de-identified resident clinical performance from the annual in-service examination was analyzed. Results: Before the introduction of the standardized curriculum, the mean clinical percentage on the in-service examination was 46%, equivalent to the 17th percentile. Within 2 years of implementation of the new curriculum, both the mean percentage and percentile were significantly improved, with the mean percentage correct at 69.3% and the mean percentile at the 59th percentile (P < .001 and P = .034, respectively). Feedback showed the curriculum to be well-received and used frequently outside of standard didactic hours. Conclusions: This is the first report of the creation of a standardized curriculum and outcomes in radiation oncology. Although there are certainly developmental challenges, addressing these barriers creates an education model that effectively imparts knowledge, fosters multidisciplinary thinking, and prepares residents for the diverse challenges of clinical practice. We present our institutional experience with the intent of publishing this curriculum on a national platform in the coming years.
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BACKGROUND AND OBJECTIVES: Recent evidence suggests earlier tracheostomy is associated with fewer complications in patients with complete cervical spinal cord injury (SCI). This study aims to evaluate the influence of spine surgical approach on the association between tracheostomy timing and in-hospital adverse events treating patients with complete cervical SCI. METHODS: This retrospective cohort study was performed using Trauma Quality Improvement Program data from 2017 to 2020. All patients with acute complete (American Spinal Injury Association-A) cervical SCI who underwent tracheostomy and spine surgery were included. Tracheostomy timing was dichotomized to early (within 1 week after surgery) and delayed (more than 1 week after surgery). Primary outcome was the occurrence of major in-hospital complications. Secondary outcomes included occurrences of immobility-related complications, surgical-site infection, hospital and intensive care unit length of stay, and time on mechanical ventilation. RESULTS: The study included 1592 patients across 358 trauma centers. Mean time to tracheostomy from surgery was 8.6 days. A total of 495 patients underwent anterior approach, 670 underwent posterior approach, and 427 underwent combined anterior and posterior approach. Patients who underwent anterior approach were significantly more likely to have delayed tracheostomy compared with posterior approach (53% vs 40%, P < .001). Early tracheotomy significantly reduced major in-hospital complications (odds ratio 0.67, 95% CI 0.53-0.84) and immobility complications (odds ratio = 0.78, 95% CI 0.6-1.0). Those undergoing early tracheostomy spent 6.0 (95% CI -8.47 to -3.43) fewer days in hospital, 5.7 (95% CI -7.8 to -3.7) fewer days in the intensive care unit, and 5.9 (95% CI -8.2 to -3.7) fewer days ventilated. Surgical approach had no significant negative effect on the association between tracheostomy timing and the outcomes of interest. CONCLUSION: Earlier tracheostomy for patients with cervical SCI is associated with reduced complications, length of stay, and ventilation time. This relationship appears independent of the surgical approach. These findings emphasize that tracheostomy need not be delayed because of the SCI treatment approach.
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Vértebras Cervicais , Traumatismos da Medula Espinal , Traqueostomia , Humanos , Traumatismos da Medula Espinal/cirurgia , Traqueostomia/métodos , Traqueostomia/efeitos adversos , Traqueostomia/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Fatores de Tempo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação/estatística & dados numéricos , Idoso , Medula Cervical/lesões , Medula Cervical/cirurgia , Estudos de Coortes , Respiração Artificial/estatística & dados numéricos , Respiração Artificial/métodos , Tempo para o Tratamento/estatística & dados numéricosRESUMO
Importance: Although robotic surgery has become an established approach for a wide range of elective operations, data on its utility and outcomes are limited in the setting of emergency general surgery. Objectives: To describe temporal trends in the use of laparoscopic and robotic approaches and compare outcomes between robotic and laparoscopic surgery for 4 common emergent surgical procedures. Design, Setting, and Participants: A retrospective cohort study of an all-payer discharge database of 829 US facilities was conducted from calendar years 2013 to 2021. Data analysis was performed from July 2022 to November 2023. A total of 1â¯067â¯263 emergent or urgent cholecystectomies (n = 793â¯800), colectomies (n = 89â¯098), inguinal hernia repairs (n = 65â¯039), and ventral hernia repairs (n = 119â¯326) in patients aged 18 years or older were included. Exposure: Surgical approach (robotic, laparoscopic, or open) to emergent or urgent cholecystectomy, colectomy, inguinal hernia repair, or ventral hernia repair. Main Outcomes and Measures: The primary outcome was the temporal trend in use of each operative approach (laparoscopic, robotic, or open). Secondary outcomes included conversion to open surgery and length of stay (both total and postoperative). Temporal trends were measured using linear regression. Propensity score matching was used to compare secondary outcomes between robotic and laparoscopic surgery groups. Results: During the study period, the use of robotic surgery increased significantly year-over-year for all procedures: 0.7% for cholecystectomy, 0.9% for colectomy, 1.9% for inguinal hernia repair, and 1.1% for ventral hernia repair. There was a corresponding decrease in the open surgical approach for all cases. Compared with laparoscopy, robotic surgery was associated with a significantly lower risk of conversion to open surgery: cholecystectomy, 1.7% vs 3.0% (odds ratio [OR], 0.55 [95% CI, 0.49-0.62]); colectomy, 11.2% vs 25.5% (OR, 0.37 [95% CI, 0.32-0.42]); inguinal hernia repair, 2.4% vs 10.7% (OR, 0.21 [95% CI, 0.16-0.26]); and ventral hernia repair, 3.5% vs 10.9% (OR, 0.30 [95% CI, 0.25-0.36]). Robotic surgery was associated with shorter postoperative lengths of stay for colectomy (-0.48 [95% CI, -0.60 to -0.35] days), inguinal hernia repair (-0.20 [95% CI, -0.30 to -0.10] days), and ventral hernia repair (-0.16 [95% CI, -0.26 to -0.06] days). Conclusions and Relevance: While robotic surgery is still not broadly used for emergency general surgery, the findings of this study suggest it is becoming more prevalent and may be associated with better outcomes as measured by reduced conversion to open surgery and decreased length of stay.
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Herniorrafia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Herniorrafia/métodos , Adulto , Emergências , Idoso , Colectomia/métodos , Hérnia Inguinal/cirurgia , Tempo de Internação/estatística & dados numéricos , Colecistectomia/métodos , Colecistectomia/estatística & dados numéricos , Hérnia Ventral/cirurgia , Estados Unidos , Conversão para Cirurgia Aberta/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos , Cirurgia de Cuidados CríticosRESUMO
Rhodopseudomonas palustris TIE-1 grows photoautotrophically with Fe(II) as an electron donor and photoheterotrophically with a variety of organic substrates. However, it is unclear whether R. palustris TIE-1 conducts Fe(II) oxidation in conditions where organic substrates and Fe(II) are available simultaneously. In addition, the effect of organic co-substrates on Fe(II) oxidation rates or the identity of Fe(III) minerals formed is unknown. We incubated R. palustris TIE-1 with 2 mM Fe(II), amended with 0.6 mM organic co-substrate, and in the presence/absence of CO2 . We found that in the absence of CO2 , only the organic co-substrates acetate, lactate and pyruvate, but not Fe(II), were consumed. When CO2 was present, Fe(II) and all organic substrates were consumed. Acetate, butyrate and pyruvate were consumed before Fe(II) oxidation commenced, whereas lactate and glucose were consumed at the same time as Fe(II) oxidation proceeded. Lactate, pyruvate and glucose increased the Fe(II) oxidation rate significantly (by up to threefold in the case of lactate). 57 Fe Mössbauer spectroscopy revealed that short-range ordered Fe(III) oxyhydroxides were formed under all conditions. This study demonstrates phototrophic Fe(II) oxidation proceeds even in the presence of organic compounds, and that the simultaneous oxidation of organic substrates can stimulate Fe(II) oxidation.
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Dióxido de Carbono , Compostos Férricos , Rodopseudomonas , Oxirredução , Ácido Láctico , Compostos Ferrosos , Piruvatos , Acetatos , GlucoseRESUMO
Despite their rapid spread over the last 15 years, little research has explored the perceptions of Veterans Treatment Courts (VTCs) team members regarding the viability and longevity of VTCs. The present qualitative study explores the perceptions of 145 VTC team members from 20 VTCs around the United States regarding the future of their own VTC and VTCs in general. Our analysis revealed four overarching themes about team members' expectations and hopes for VTCs in the future: the need for continued funding and increased resources; desires to expand participation in VTCs; hope and uncertainty about the future of VTCs; and depending on specific people to ensure the future of VTCs. While interviewees in general felt quite hopeful and optimistic that VTCs would continue to exist and may even expand, there was unease about exactly how this would occur. These concerns included securing stable funding sources, maintaining 'buy in' from key individuals, and resource needs for expanding the participation and eligibility criteria of VTCs. Given the important role that VTCs can play in effectively supporting justice-involved veterans, and offering more benefits compared to a traditional justice-system response, it seems vital to ensure that VTCs are able to continue operating in the future.
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In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug-transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model's predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety.