Inheritance of paternal DNA damage by histone-mediated repair restriction.

How paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring has been a long-standing question in radiation biology. In humans, nearly 80% of transmitted mutations arise in the paternal germline1, but the transgenerational effects of ionizing radiation exposure has remained controversial and the mechanisms are unknown. Here we show that in sex-separated Caenorhabditis elegans strains, paternal, but not maternal, exposure to ionizing radiation leads to transgenerational embryonic lethality. The offspring of irradiated males displayed various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement and aneuploidy. Paternal DNA double strand breaks were repaired by maternally provided error-prone polymerase theta-mediated end joining. Mechanistically, we show that depletion of an orthologue of human histone H1.0, HIS-24, or the heterochromatin protein HPL-1, could significantly reverse the transgenerational embryonic lethality. Removal of HIS-24 or HPL-1 reduced histone 3 lysine 9 dimethylation and enabled error-free homologous recombination repair in the germline of the F1 generation from ionizing radiation-treated P0 males, consequently improving the viability of the F2 generation. This work establishes the mechanistic underpinnings of the heritable consequences of paternal radiation exposure on the health of offspring, which may lead to congenital disorders and cancer in humans.

Prospectively accelerated dynamic speech magnetic resonance imaging at 3 T using a self-navigated spiral-based manifold regularized scheme.

This work develops and evaluates a self-navigated variable density spiral (VDS)-based manifold regularization scheme to prospectively improve dynamic speech magnetic resonance imaging (MRI) at 3 T. Short readout duration spirals (1.3-ms long) were used to minimize sensitivity to off-resonance. A custom 16-channel speech coil was used for improved parallel imaging of vocal tract structures. The manifold model leveraged similarities between frames sharing similar vocal tract postures without explicit motion binning. The self-navigating capability of VDS was leveraged to learn the Laplacian structure of the manifold. Reconstruction was posed as a sensitivity-encoding-based nonlocal soft-weighted temporal regularization scheme. Our approach was compared with view-sharing, low-rank, temporal finite difference, extra dimension-based sparsity reconstruction constraints. Undersampling experiments were conducted on five volunteers performing repetitive and arbitrary speaking tasks at different speaking rates. Quantitative evaluation in terms of mean square error over moving edges was performed in a retrospective undersampling experiment on one volunteer. For prospective undersampling, blinded image quality evaluation in the categories of alias artifacts, spatial blurring, and temporal blurring was performed by three experts in voice research. Region of interest analysis at articulator boundaries was performed in both experiments to assess articulatory motion. Improved performance with manifold reconstruction constraints was observed over existing constraints. With prospective undersampling, a spatial resolution of 2.4 × 2.4 mm2 /pixel and a temporal resolution of 17.4 ms/frame for single-slice imaging, and 52.2 ms/frame for concurrent three-slice imaging, were achieved. We demonstrated implicit motion binning by analyzing the mechanics of the Laplacian matrix. Manifold regularization demonstrated superior image quality scores in reducing spatial and temporal blurring compared with all other reconstruction constraints. While it exhibited faint (nonsignificant) alias artifacts that were similar to temporal finite difference, it provided statistically significant improvements compared with the other constraints. In conclusion, the self-navigated manifold regularized scheme enabled robust high spatiotemporal resolution dynamic speech MRI at 3 T.

Patient-Reported Outcomes Following Severe Abdominal Trauma: A Secondary Analysis of the Damage Control Laparotomy Trial.

INTRODUCTION: Little is known about patient-reported outcomes (PROs) following abdominal trauma. We hypothesized that patients undergoing definitive laparotomy (DEF) would have better PROs compared to those treated with damage control laparotomy (DCL). METHODS: The DCL Trial randomized DEF versus DCL in abdominal trauma. PROs were measured using the European Quality of Life-5 Dimensions-5 Levels (EQ-5D) questionnaire at discharge and six months postdischarge (1 = perfect health, 0 = death, and <0 = worse than death) and Posttraumatic Stress Disorder (PTSD) Checklist-Civilian. Unadjusted Bayesian analysis with a neutral prior was used to assess the posterior probability of achieving minimal clinically important difference. RESULTS: Of 39 randomized patients (21 DEF versus 18 DCL), 8 patients died (7 DEF versus 1 DCL). Of those who survived, 28 completed the EQ-5D at discharge (12 DEF versus 16 DCL) and 25 at 6 mo (12 DEF versus 13 DCL). Most patients were male (79%) with a median age of 30 (interquartile range (IQR) 21-42), suffered blunt injury (56%), and were severely injured (median injury severity score 33, IQR 21 - 42). Median EQ-5D value at discharge was 0.20 (IQR 0.06 - 0.52) DEF versus 0.31 (IQR -0.03 - 0.43) DCL, and at six months 0.51 (IQR 0.30 - 0.74) DEF versus 0.50 (IQR 0.28 - 0.84) DCL. The posterior probability of minimal clinically important difference DEF versus DCL at discharge and six months was 16% and 23%, respectively. CONCLUSIONS: Functional deficits for trauma patients persist beyond the acute setting regardless of laparotomy status. These deficits warrant longitudinal studies to better inform patients on recovery expectations.

Material Flow Analysis and Occupational Exposure Assessment in Additive Manufacturing End-of-Life Material Management.

Additive manufacturing (AM) offers a variety of material manufacturing techniques for a wide range of applications across many industries. Most efforts at process optimization and exposure assessment for AM are centered around the manufacturing process. However, identifying the material allocation and potentially harmful exposures in end-of-life (EoL) management is equally crucial to mitigating environmental releases and occupational health impacts within the AM supply chain. This research tracks the allocation and potential releases of AM EoL materials within the US through a material flow analysis. Of the generated AM EoL materials, 58% are incinerated, 33% are landfilled, and 9% are recycled by weight. The generated data set was then used to examine the theoretical occupational hazards during AM EoL material management practices through generic exposure scenario assessment, highlighting the importance of ventilation and personal protective equipment at all stages of AM material management. This research identifies pollution sources, offering policymakers and stakeholders insights to shape pollution prevention and worker safety strategies within the US AM EoL management pathways.

GaN/NbN epitaxial semiconductor/superconductor heterostructures.

Epitaxy is a process by which a thin layer of one crystal is deposited in an ordered fashion onto a substrate crystal. The direct epitaxial growth of semiconductor heterostructures on top of crystalline superconductors has proved challenging. Here, however, we report the successful use of molecular beam epitaxy to grow and integrate niobium nitride (NbN)-based superconductors with the wide-bandgap family of semiconductors-silicon carbide, gallium nitride (GaN) and aluminium gallium nitride (AlGaN). We apply molecular beam epitaxy to grow an AlGaN/GaN quantum-well heterostructure directly on top of an ultrathin crystalline NbN superconductor. The resulting high-mobility, two-dimensional electron gas in the semiconductor exhibits quantum oscillations, and thus enables a semiconductor transistor-an electronic gain element-to be grown and fabricated directly on a crystalline superconductor. Using the epitaxial superconductor as the source load of the transistor, we observe in the transistor output characteristics a negative differential resistance-a feature often used in amplifiers and oscillators. Our demonstration of the direct epitaxial growth of high-quality semiconductor heterostructures and devices on crystalline nitride superconductors opens up the possibility of combining the macroscopic quantum effects of superconductors with the electronic, photonic and piezoelectric properties of the group III/nitride semiconductor family.

Prehospital Validation of the Assessment of Blood Consumption (ABC) Score.

INTRODUCTION: The Assessment of Blood Consumption (ABC) score is a previously validated scoring system designed to predict which severely injured trauma patients will require massive transfusion. When the ABC score is used in the prehospital setting to activate massive transfusion at the receiving hospital, a 23% decrease in mortality has been demonstrated. However, the ABC score was developed and validated using hospital data from the emergency department (ED). The sensitivity and specificity of the ABC score when calculated using data from the prehospital setting are unknown. We hypothesized that the sensitivity and specificity of the prehospital ABC score will be similar to the sensitivity and specificity of the ED ABC score. METHODS: A 5-year retrospective analysis (2015-2019) of highest-activation adult trauma patients arriving to a quaternary Level I trauma center by hospital-based helicopter air medical service (HEMS) was performed. Demographic, prehospital, ED triage, and blood product utilization data were collected. Prehospital ABC score was calculated using the highest heart rate, lowest systolic blood pressure, and focused assessment with sonography for trauma (FAST) exam results obtained prior to arrival at the trauma center. ED ABC score was calculated using ED triage vital signs and ED FAST results. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristics (AUROC) curve were calculated for each ABC score. RESULTS: 2,067 patients met inclusion criteria. Mean age 39 (±17) years, 76% male, 22% penetrating mechanism. Of these, 128 patients (6%) received massive transfusion using the definition from the original study. Prehospital ABC score at a cutoff of 2 was 51% sensitive and 85% specific for predicting massive transfusion, with 83% correctly classified and an AUROC = 0.73. ED ABC score at the same cutoff was 60% sensitive and 84% specific, with 83% correctly classified and an AUROC = 0.81. By logistic regression, the odds of massive transfusion increased by 2.76 for every 1-point increase in prehospital ABC score (95%CI 2.25-3.37, p < 0.001). CONCLUSIONS: The ABC score is a useful prehospital tool for identifying who will require massive transfusion. Future studies to evaluate the effect of the prehospital ABC score on clinical care and mortality are necessary.

Prospective Evaluation of a Tiered Opioid Prescribing Guideline for Inpatient Colorectal Operations.

OBJECTIVE: This study sought to prospectively validate an institutional prescribing guideline based on previously defined opioid consumption patterns following inpatient colorectal operations. BACKGROUND: In light of the opioid epidemic, reducing excess prescription quantities is key while still tailoring to patient needs. METHODS: This is a cohort study of elective colorectal operations (colectomies, proctectomies, and ostomy reversals) at a single tertiary care medical center. Opioid prescribing and consumption patterns [quantified as Equianalgesic 5 mg Oxycodone Pills (EOP)] were compared before and after adoption of a tiered opioid prescribing guideline. Tiers were divided based on opioid consumption in the 24 hours before discharge: Tier 1 (0 EOP), Tier 2 (0.1-3 EOP), and Tier 3 (>3 EOP). Our guideline recommended maximum prescriptions of 0 EOP for Tier 1, 12 EOP for Tier 2, and 30 EOP for Tier 3. Results: The study included 100 patients before and 101 after guideline adoption. Demographic and operative characteristics were similar between cohorts. Guideline adherence was 85%. Overall, there was a 41%reduction in mean prescription quantity and 53% reduction in excess pills per prescription. No change in opioid consumption or refill rates was observed. CONCLUSIONS: Adoption of a tiered opioid prescribing guideline significantly reduced opioid prescription quantity with no change in consumption or refill rates. Standardization of discharge prescriptions based on patient consumption in the 24 hours before discharge may be an important step toward minimizing excess prescribing.

Randomized Controlled Trial of Surgical Rib Fixation to Nonoperative Management in Severe Chest Wall Injury.

OBJECTIVE: To compare the effectiveness of surgical stabilization of rib fractures (SSRFs) to nonoperative management in severe chest wall injury. BACKGROUND: SSRF has been shown to improve outcomes in patients with clinical flail chest and respiratory failure. However, the effect of SSRF outcomes in severe chest wall injuries without clinical flail chest is unknown. METHODS: Randomized controlled trial comparing SSRF to nonoperative management in severe chest wall injury, defined as: (1) a radiographic flail segment without clinical flail or (2) ≥5 consecutive rib fractures or (3) any rib fracture with bicortical displacement. Randomization was stratified by the unit of admission as a proxy for injury severity. Primary outcome was hospital length of stay (LOS). Secondary outcomes included intensive care unit (ICU) LOS, ventilator days, opioid exposure, mortality, and incidences of pneumonia and tracheostomy. Quality of life at 1, 3, and 6 months was measured using the EQ-5D-5L survey. RESULTS: Eighty-four patients were randomized in an intention-to-treat analysis (usual care = 42, SSRF = 42). Baseline characteristics were similar between groups. The numbers of total fractures, displaced fractures, and segmental fractures per patient were also similar, as were the incidences of displaced fractures and radiographic flail segments. Hospital LOS was greater in the SSRF group. ICU LOS and ventilator days were similar. After adjusting for the stratification variable, hospital LOS remained greater in the SSRF group (RR: 1.48, 95% CI: 1.17-1.88). ICU LOS (RR: 1.65, 95% CI: 0.94-2.92) and ventilator days (RR: 1.49, 95% CI: 0.61--3.69) remained similar. Subgroup analysis showed that patients with displaced fractures were more likely to have LOS outcomes similar to their usual care counterparts. At 1 month, SSRF patients had greater impairment in mobility [3 (2-3) vs 2 (1-2), P = 0.012] and self-care [2 (1-2) vs 2 (2-3), P = 0.034] dimensions of the EQ-5D-5L. CONCLUSIONS: In severe chest wall injury, even in the absence of clinical flail chest, the majority of patients still reported moderate to extreme pain and impairment of usual physical activity at one month. SSRF increased hospital LOS and did not provide any quality of life benefit for up to 6 months.

A flexible 16-channel custom coil array for accelerated imaging of upper and infraglottic airway at 3 T.

PURPOSE: To develop a custom coil and evaluate its utility for accelerated upper and infraglottic airway MRI at 3 T. METHODS: A 16-channel flexible and anatomy-conforming coil was developed to provide localized sensitivity over upper and infraglottic airway regions of interest. Parallel-imaging capabilities were compared against existing head and head-neck coils. SENSE geometry factor losses were quantified for retrospectively accelerating 3D MRI. Blinded image-quality ratings from two experts were performed. Spiral GRAPPA reconstructions were evaluated for a speaking task at a time resolution of 40 ms. Contrast-to-noise ratios between air and tissue at key landmarks along the vocal tract were compared. SENSE imaging with the custom coil in the lateral recumbent posture was evaluated. Multislice imaging was performed to image swallowing at 17 ms/frame via constrained reconstruction. RESULTS: The custom coil showed improved SENSE imaging up to 3-fold acceleration when accelerated along either the anterior-posterior or the superior-inferior direction and a net 4-fold acceleration when accelerated along both directions. Spiral GRAPPA reconstructions with the custom coil showed higher contrast-to-noise ratio when compared with existing coils. In the lateral posture, robust SENSE imaging was achieved at up to 2-fold and 3-fold acceleration levels in the superior-inferior and anterior-posterior directions, respectively. Key events of swallowing in the multislice dynamic images were identified by an otolaryngologist. CONCLUSION: The coil provided improved parallel imaging of upper and infraglottic airway in both supine and lateral recumbent postures. It enabled efficient accelerated dynamic imaging of speaking and swallowing.

Association of distance traveled on receipt of surgery in patients with locally advanced rectal cancer.

PURPOSE: Studies have shown patients residing in rural settings have worse cancer-related outcomes than those in urban settings. Specifically, rural patients with colorectal cancer have lower rates of screening and longer time to treatment. However, physical distance traveled has not been as well studied. This study sought to determine disparities in receipt of surgery in patients by distance traveled for care. METHODS: A retrospective cohort study of patients with AJCC stage II/III rectal adenocarcinoma was identified within the National Cancer Database (2004-2017). Primary outcome was correlation of distance traveled to receipt of surgery. Multi-variable logistic regression was used to adjust for confounding factors. RESULTS: 65,234 patients were included in the analysis. 94.6% resided in urban-metro areas while 2.2% resided in rural areas. Patients were predominantly non-Hispanic White (NHW) (75.2%) with an overall median age at diagnosis of 61 (IQR 52-71). Overall, 82.6% of patients received surgery. NHW patients were more likely to receive surgery than non-Hispanic Black patients (OR 0.67; 95% CI 0.61-0.73, p < 0.001), as were patients who were privately insured (OR 1.90, 95% CI 1.67-2.15, p < 0.001) or had Medicare (OR 1.68, 95% CI 1.47-1.92, p < 0.001) compared to uninsured patients. Patients traveling distances in the 4th quartile (median 47.9 miles) were more likely to receive surgery than those traveling the shortest distances (1st quartile: median 2.5 miles) (OR 1.37, 95% CI 1.24-1.50, p < 0.001). CONCLUSION: Patients traveling farther distances were more likely to receive surgery than those traveling shorter distances. Shorter distance traveled does not appear to be associated with higher rates of surgical resection in patients with stage II/III rectal cancer.

Continuum of Care: A Multiagency Approach to Seamless Warmed Prehospital Whole Blood Resuscitation of a Patient with Noncompressible Truncal Hemorrhage.

BACKGROUND: Prehospital transfusion capabilities vary widely in the United States. Here we describe a case of prehospital resuscitation using warmed, whole blood in a patient with penetrating torso trauma and associated hemorrhagic shock. CASE REPORT: A 68-year-old man sustained a single gunshot wound to the left chest and was found to have a shock index of 1.5 at the time of emergency medical services (EMS) arrival. Rapid peripheral intravenous and central venous access enabled the infusion of warmed low-titer O-positive whole blood. The EMS crew intentionally resuscitated the patient before managing the airway by means of rapid sequence intubation. An air medical services helicopter crew assumed patient care from the ground EMS crew and continued the warmed, whole blood transfusion during the flight to a regional Level I trauma center. The patient went directly to the operating room from the helipad, underwent definitive operative management, and was ultimately discharged home on hospital day nine. CONCLUSION: Early recognition of hemorrhagic shock, implementation of prehospital transfusion protocols that emphasize transfusion of warmed blood without interruption, and an organized, regional approach to trauma care are critical for improving patient survival.

Perinatal Obesity Sensitizes for Premature Kidney Aging Signaling.

Chronic Kidney Disease (CKD), a global health burden, is strongly associated with age-related renal function decline, hypertension, and diabetes, which are all frequent consequences of obesity. Despite extensive studies, the mechanisms determining susceptibility to CKD remain insufficiently understood. Clinical evidence together with prior studies from our group showed that perinatal metabolic disorders after intrauterine growth restriction or maternal obesity adversely affect kidney structure and function throughout life. Since obesity and aging processes converge in similar pathways we tested if perinatal obesity caused by high-fat diet (HFD)-fed dams sensitizes aging-associated mechanisms in kidneys of newborn mice. The results showed a marked increase of γH2AX-positive cells with elevated 8-Oxo-dG (RNA/DNA damage), both indicative of DNA damage response and oxidative stress. Using unbiased comprehensive transcriptomics we identified compartment-specific differentially-regulated signaling pathways in kidneys after perinatal obesity. Comparison of these data to transcriptomic data of naturally aged kidneys and prematurely aged kidneys of genetic modified mice with a hypomorphic allele of Ercc1, revealed similar signatures, e.g., inflammatory signaling. In a biochemical approach we validated pathways of inflammaging in the kidneys after perinatal obesity. Collectively, our initial findings demonstrate premature aging-associated processes as a consequence of perinatal obesity that could determine the susceptibility for CKD early in life.

Review of generic scenario environmental release and occupational exposure models used in chemical risk assessment.

Under the Toxic Substances Control Act (TSCA), the United States Environmental Protection Agency (USEPA) is required to determine whether a new chemical substance poses an unreasonable risk to human health or the environment before the chemical is manufactured in or imported into the United States. This manuscript provides a review of the process used to evaluate the risk associated with a chemical based on the scenarios and models used in the evaluation. Specifically, the Generic Scenarios and Emission Scenario Documents developed by the USEPA were reviewed, along with background documentation prepared by USEPA to identify the core elements of the environmental release and occupational exposure scenarios used to assess the risk of the chemical being evaluated. Additionally, this contribution provides an overview of methods used to model occupational exposures and environmental releases as part of the chemical evaluation process used in other jurisdictions, along with work being performed to improve these models. Finally, the alternative methods to evaluate occupational exposures and environmental releases that may be used as part of the decision-making process regarding a chemical are identified. The contribution provides a path forward for reducing the time required and improving the chemical evaluation of the unreasonable risk determination regarding the manufacture or import of a chemical.

Understanding the trade-offs of national municipal solid waste estimation methods for circular economy policy.

Policies embracing circular economy concepts have taken hold in national legislation around the world. As the number of governments and organizations adopting circular economy policies increases, so does the need for accurate and timely measurement of material resource flows. Since many countries do not have access to centrally reported municipal solid waste (MSW) data, estimation and modeling are critical in evaluating circular economy policy effectiveness. The purpose of this paper is to examine three modeling approaches estimating national MSW data in the United States, including industry-based material flow analysis, waste-extended input-output modeling, and aggregated regional waste reporting. We establish five criteria to guide the analysis through the context of policy monitoring (data quality, flow totality, update frequency, sensitivity to disruption, and product granularity) and use these criteria to analyze and score each model. We then use a literature search to identify five, internationally-implemented options for circular economy policy and determine the data and modeling components that are most helpful in evaluating policy effectiveness. Finally, we provide a crosswalk of the model scores and policy needs to inform the suitability of model selection by policy type. We found that data quality and update frequency are identified as critical components for evaluating circular economy policies within the models evaluated, and can both be fulfilled by aggregated regional waste reporting. Flow totality, sensitivity to disruption, and product granularity requirements vary by both model and policy types. While none of the evaluated models satisfy the combination of requirements for any of the five policies, industry-based material flow analysis offers flow totality for extended producer responsibility, landfill bans, and recycling rate target policies that typically require it. The waste-extended input-output model can provide disruption sensitivity and product granularity as needed for policies like minimum recycled content and market restrictions. Policy developers in areas where strong centralized data collection is not an option should design policy action(s) with modeling tradeoffs in mind, including the potential hybridization of modeling approaches that may provide the most accurate national MSW estimates.

Prospective Observational Evaluation of the ER-REBOA Catheter at 6 U.S. Trauma Centers.

OBJECTIVE: To describe the current use of the ER-REBOA catheter and associated outcomes and complications. INTRODUCTION: Noncompressible truncal hemorrhage is the leading cause of potentially preventable death in trauma patients. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a novel strategy to obtain earlier temporary hemorrhage control, supporting cardiac, and cerebral perfusion before definitive hemostasis. METHODS: Prospective, observational study conducted at 6 Level 1 Trauma Centers over 12-months. Inclusion criteria were age >15 years of age with evidence of truncal hemorrhage below the diaphragm and decision for emergent hemorrhage control intervention within 60 minutes of arrival. REBOA details, demographics, mechanism of injury, complications, and outcomes were collected. RESULTS: A total of 8166 patients were screened for enrollment. In 75, REBOA was utilized for temporary hemorrhage control. Blunt injury occurred in 80% with a median injury severity score (ISS) 34 (21, 43). Forty-seven REBOAs were placed in Zone 1 and 28 in Zone 3. REBOA inflation increased systolic blood pressure from 67 (40, 83) mm Hg to 108 (90, 128) mm Hg 5 minutes after inflation (P = 0.02). Cardiopulmonary resuscitation was ongoing during REBOA insertion in 17 patients (26.6%) and 10 patients (58.8%) had return of spontaneous circulation after REBOA inflation. The procedural complication rate was 6.6%. Overall mortality was 52%. CONCLUSION: REBOA can be used in blunt and penetrating trauma patients, including those in arrest. Balloon inflation uniformly improved hemodynamics and was associated with a 59% rate of return of spontaneous circulation for patients in arrest. Use of the ER-REBOA catheter is technically safe with a low procedural complication rate.

Intra-cavity frequency-doubled VECSEL system for narrow linewidth Rydberg EIT spectroscopy.

High-power, narrow-linewidth light sources in the visible and UV spectra are in growing demand, particularly as quantum information and sensing research proliferates. Vertical external-cavity surface-emitting lasers (VECSELs) with intra-cavity frequency conversion are emerging as an attractive platform to fill these needs. Using such a device, we demonstrate 3.5 MHz full-width half-maximum Rydberg-state spectroscopy via electromagnetically induced transparency (EIT). The laser's 690 mW of output power at a wavelength of 475 nm enables large Rabi frequencies and strong signal-to-noise ratio in shorter measurement times. In addition, we characterize the frequency stability of the VECSEL using the delayed self-heterodyne technique and direct comparison with a commercial external-cavity diode laser (ECDL). We measure the pre-doubled light's Lorentzian linewidth to be 2π × 5.3(2) kHz, and the total linewidth to be 2π × 23(2) kHz. These measurements provide evidence that intra-cavity frequency-doubled VECSELs can perform precision spectroscopy at and below the MHz level, and are a promising tool for contemporary, and future, quantum technologies.

Oncologic Outcomes After Transanal Total Mesorectal Excision for Rectal Cancer.

BACKGROUND: Recent series have raised concerns about the oncologic outcomes of transanal total mesorectal excision for mid and low rectal cancer. There is a paucity of large data sets from the United States to contribute to the ongoing international discourse. OBJECTIVE: This study aimed to investigate the rate of local recurrence and other oncologic outcomes in patients undergoing transanal total mesorectal excision for rectal adenocarcinoma. DESIGN: This study is a retrospective review of patients undergoing transanal total mesorectal excision for primary rectal cancer from January 2014 to December 2019. SETTINGS: This study was conducted at a single academic tertiary care medical center in the United States. PATIENTS: Consecutive patients aged ≥18 years undergoing surgical resection for primary rectal cancer were selected. INTERVENTION: The transanal total mesorectal excision procedures were performed utilizing a 2-team approach. MAIN OUTCOME MEASURES: Primary outcomes were pathologic quality, local and distant recurrence, treatment-related complications, and overall- and cancer-specific survival. RESULTS: Seventy-nine consecutive patients were included. The median age was 58 years (interquartile range, 50-64), and median BMI was 28 kg/m2 (interquartile range, 24.6-32.4). The mesorectum was complete in 69 patients (87.3%), nearly complete in 9 (11.4%), and incomplete in 1 (1.3%). There was circumferential resection margin involvement (<1 mm) in 4 patients (5.1%), and no patients had a positive distal margin (<1 mm) or intraoperative rectal perforation. Composite optimal pathology was achieved in 94.9% of specimens. Median follow-up was 29 months (range, 6-68). There were no local recurrences. Distant metastases were found in 10 (13.5%) patients and diagnosed after a median of 14 months (range, 0.6-53). Disease-free survival was 91.2% at 2 years, and overall survival was 94.7% at 2 years. LIMITATIONS: Retrospective design, a single center, and relatively short follow-up period were limitations of this study. CONCLUSION: The oncologic outcomes of this cohort support the use of transanal total mesorectal excision in the surgical management of mid to low rectal cancer at centers with appropriate expertise. See Video Abstract at http://links.lww.com/DCR/B723. RESULTADOS ONCOLGICOS DESPUS DE LA EXCISIN TOTAL DEL MESORRECTO POR VA TRANSANAL EN CASOS DE CNCER RECTAL: ANTECEDENTES:Estudios recientes han suscitado preocupación sobre los resultados oncológicos de la excisión total del mesorecto por vía transanal en casos de cáncer de recto medio y bajo. Existe una gran escasez de conjuntos de datos en los Estados Unidos, para contribuir en el actual discurso internacional sobre el tema.OBJETIVO:Investigar la tasa de recurrencia local y otros resultados oncológicos en pacientes sometidos a una excisión total del mesorrecto por vía transanal por adenocarcinomas de recto.DISEÑO:Revisión retrospectiva de pacientes sometidos a excisión total del mesorecto por vía transanal en casos de cáncer de recto primario desde enero de 2014 hasta diciembre de 2019.AJUSTE:Centro médico Universitario de atención terciaria único en los Estados Unidos.PACIENTES:Aquellos pacientes consecutivos de ≥ 18 años de edad, sometidos a resección quirúrgica por cáncer de recto primario.INTERVENCIÓN:Los procedimientos de excisión total del mesorecto por vía transanal se realizaron utilizando un enfoque de dos equipos.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la calidad anatomo-patológica de las piezas, la recidiva local y a distancia, las complicaciones relacionadas con el tratamiento y la sobrevida global específica para el cáncer.RESULTADOS:Se incluyeron 79 pacientes consecutivos. La mediana de edades fue de 58 años (IQR, 50-64) y la mediana del índice de masa corporal fue de 28 kg / m (IQR, 24,6-32,4). El mesorrecto se encontraba completo en 69 pacientes (87,3%), casi completo en 9 (11,4%) e incompleto en 1 (1,3%). Hubo afectación de CRM (<1 mm) en 4 pacientes (5,1%) y ningún paciente tuvo un margen distal positivo (<1 mm) o perforación rectal intraoperatoria. La histopatología óptima compuesta se logró en el 94,9% de las muestras. La mediana de seguimiento fue de 29 meses (rango 6-68). No se presentaron recurrencias locales. Se encontraron metástasis a distancia en 10 (13,5%) pacientes y se diagnosticaron después de una mediana de 14 meses (rango 0,6-53). La sobrevida libre de enfermedad fue del 91,2% a los 2 años y la sobrevida global fue del 94,7% a los 2 años.LIMITACIONES:Diseño retrospectivo, unicéntrico y período de seguimiento relativamente corto.CONCLUSIÓN:Los resultados oncológicos de este estudio de cohortes, apoyan la realización de excisión total del mesorecto por vía transanal para el tratamiento quirúrgico del cáncer de recto medio y bajo, en centros con la experiencia adecuada. Consulte Video Resumen en http://links.lww.com/DCR/B723. (Traducción-Dr. Xavier Delgadillo).

Blood pressure variability during pediatric cardiac surgery is associated with acute kidney injury.

BACKGROUND: Blood pressure variability (BPV), defined as the degree of variation between discrete blood pressure readings, is associated with poor outcomes in acute care settings. Acute kidney injury (AKI) is a common and serious postoperative complication of cardiac surgery with cardiopulmonary bypass (CPB) in children. No studies have yet assessed the association between intraoperative BPV during cardiac surgery with CPB and the development of AKI in children. METHODS: A retrospective chart review of children undergoing cardiac surgery with CPB was performed. Intraoperative BPV was calculated using average real variability (ARV) and standard deviation (SD). Multiple regression models were used to examine the association between BPV and outcomes of AKI, hospital and intensive care unit (PICU) length of stay, and length of mechanical ventilation. RESULTS: Among 231 patients (58% males, median age 8.6 months) reviewed, 51.5% developed AKI (47.9% Stage I, 41.2% Stage II, 10.9% Stage III). In adjusted models, systolic and diastolic ARV were associated with development of any stage AKI (OR 1.40, 95% CI 1.08-1.8 and OR 1.4, 95% CI 1.05-1.8, respectively). Greater diastolic SD was associated with longer PICU length of stay (ß 0.94, 95% CI 0.62-1.2). When stratified by age, greater systolic ARV and SD were associated with AKI in infants ≤ 12 months, but there was no relationship in children > 12 months. CONCLUSIONS: Greater BPV during cardiac surgery with CPB was associated with development of postoperative AKI in infants, suggesting that BPV is a potentially modifiable risk factor for AKI in this high-risk population.

Expanding Our Reach: Development of a Civilian Helicopter Air Ambulance K9 Response Program.

This short communication highlights the development and implementation of the first civilian helicopter air ambulance canine response program in the United States.

Development of a Practice Guideline for Discharge Opioid Prescribing After Major Colorectal Surgery.

BACKGROUND: Better alignment of opioid prescription quantities with patient need could help reduce excessive prescribing. OBJECTIVE: The study sought to develop an institutional prescribing guideline based on defined opioid consumption patterns after inpatient colorectal operations. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: Patients who underwent elective major colorectal procedures between July 2018 and January 2019 were included. MAIN OUTCOME MEASURES: The study measured prescription and consumption quantities measured as equianalgesic oxycodone 5-mg pills. RESULTS: Patients were categorized into 3 groups based on consumption in the 24-hour period before discharge: tier 1 consumed 0 equianalgesic oxycodone 5-mg pills (n = 53), tier 2 consumed 0.1 to 3.0 equianalgesic oxycodone 5-mg pills (n = 25), and tier 3 consumed >3.0 equianalgesic oxycodone 5-mg pills (n = 22). Average prescription quantity was 17.5 ± 10.5 equianalgesic oxycodone 5-mg pills (range, 0-78). Patients consumed a mean of 6.7 ± 10.9 equianalgesic oxycodone 5-mg pills after discharge and had 10.8 ± 10.2 equianalgesic oxycodone 5-mg pill excess, whereas 51% of patients consumed no pills. Opioid consumption was significantly different between each tier (p < 0.001). A prescribing guideline was developed to satisfy the majority of patients: 0 equianalgesic oxycodone 5-mg pills if tier 1, 12 pills if tier 2, and 30 pills if tier 3. Tiered guideline adoption could reduce prescribed pills by 45% and excess pills per prescription by 73%. Patient history of IBD was independently associated with increased odds of exceeding the guideline (adjusted OR = 7.2 (95% CI, 1.6-32.6)). LIMITATIONS: The study was limited by its single-center, retrospective design and that outpatient opioid consumption was self-reported. CONCLUSIONS: Following hospital discharge after major colorectal surgery, more than half of patients consumed no opioid pills, and 62% of prescribed opioids were in excess. Outpatient opioid consumption was highly associated with inpatient opioid use in the 24 hours before discharge. Prospective validation of this prescribing guideline is needed, but adoption could reduce excessive prescribing. See Video Abstract at http://links.lww.com/DCR/B575. DESARROLLO DE UNA GUA PRCTICA PARA LA PRESCRIPCIN DE OPIOIDES AL EGRESO DESPUS DE UNA CIRUGA COLORRECTAL MAYOR: ANTECEDENTES:Una mejor alineación de las cantidades de prescripción de opioides con las necesidades del paciente podría ayudar a reducir la prescripción excesiva.OBJETIVO:El estudio buscó desarrollar una guía institucional de prescripción basada en patrones definidos de consumo de opioides luego de cirugías colorrectales hospitalarias.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLÍNICO:El estudio se llevó a cabo en un solo centro de atención terciaria.PACIENTES:Pacientes que se sometieron a procedimientos colorrectales mayores electivos entre julio de 2018 y enero de 2019.PRINCIPALES MEDIDAS DE RESULTADO:El estudio midió las cantidades de prescripción y consumo medidas como píldoras de 5 mg de oxicodona equianalgésica (EOP).RESULTADOS:Los pacientes se clasificaron en tres grupos según el consumo en el período de 24 horas antes del egreso: el nivel 1 consumió 0 EOP (n = 53), el nivel 2 consumió 0,1-3 EOP (n = 25) y el nivel 3 consumió más de 3 EOP (n = 22). La cantidad promedio de prescripción fue 17,5 (± 10,5) EOP (rango: 0-78). Los pacientes consumieron una media de 6,7 (± 10,9) EOP posterior al egreso y tuvieron un exceso de 10,8 (± 10,2) EOP, mientras que el 51% de los pacientes no consumieron píldoras. El consumo de opioides fue significativamente diferente entre cada nivel (p <0,001). Se desarrolló una guía de prescripción para satisfacer a la mayoría de los pacientes: 0 EOP del nivel 1, 12 EOP del nivel 2 y 30 EOP del nivel 3. La adquisición de una guía escalonada podría reducir las píldoras recetadas en un 45% y el exceso de píldoras por receta en un 73%. El historial del paciente de enfermedad inflamatoria intestinal se asoció de forma independiente con un aumento de las probabilidades de superar la guía (ORa 7,2; IC del 95%: 1,6-32,6).LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo de un solo centro y por el consumo de opioides del paciente ambulatorio el cual fue autoinformado.CONCLUSIONES:Tras el egreso hospitalario de una cirugía colorrectal mayor, más de la mitad de los pacientes no consumieron pastillas opioides y el 62% de los opioides prescritos estaban en exceso. El consumo de opioides como paciente ambulatorio estuvo altamente asociado con el uso de opioides como paciente hospitalizado en las 24 horas previas al egreso. Se necesita una validación prospectiva de esta guía de prescripción, pero la adopción podría reducir la prescripción excesiva. Consulte Video Resumen en http://links.lww.com/DCR/B575.