Characteristics of Intracranial Injuries in Pediatric Patients Following Blunt Head Trauma.

OBJECTIVES: Pediatric head trauma is a frequent reason for presentation to the emergency department. Despite this, there are few reports on specific characteristics and injury patterns in head injured children. The goal of this study was to evaluate head injury patterns in children with blunt head injury and their prevalence by age group. METHODS: This is a planned secondary analysis of the NEXUS II Head CT validation study. Consecutive patients with blunt head trauma were enrolled between 2006 and 2015. Demographics and criteria from 2 clinical decision instruments (NEXUS and Canadian Head CT rules) were gathered at the time of enrollment. We abstracted and cataloged injuries for pediatric patients based on radiologist report. Frequencies of injuries and severity were analyzed by developmental age group. RESULTS: A total of 1018 pediatric patients were enrolled, 128 (12.6%) of whom had an injury on computed tomography scan. Median age was 11.9 (Interquartile range 4.5-15.5) for all patients and 12 (4.8-15.5) for injured patients. Of injured patients, 49 (38.3%) had a significant injury, and 27 (21.1%) received an intervention. Teenagers had the highest rate of significant injury (50%) and intervention (30%). Injuries were most frequently noted in the temporal (46.1%), frontal (45.3%), and parietal (45.3%) regions. Subarachnoid hemorrhage (29.7%) and subdural hematoma (28.9%) were the most common injuries observed.Intraparenchymal hemorrhage and cerebral edema were more prevalent in older age groups. The most common injury mechanism overall was fall from height (24.7%). Motor vehicle accidents and nonmotorized wheeled vehicle accidents were more common in older patients. CONCLUSIONS: Serious injuries requiring intervention were rarely encountered in pediatric patients experiencing blunt head trauma. Mechanisms of injury, type of injury, and rates of intervention varied between developmental age groups.

Blunt Head Injury in the Elderly: Analysis of the NEXUS II Injury Cohort.

BACKGROUND: Changes with aging make older patients vulnerable to blunt head trauma and alter the potential for injury and the injury patterns seen among this expanding cohort. High-quality care requires a clear understanding of the factors associated with blunt head injuries in the elderly. Our objective was to develop a detailed assessment of the injury mechanisms, presentations, injury patterns, and outcomes among older blunt head trauma patients. METHODS: We conducted a planned secondary analysis of patients aged 65 or greater who were enrolled in the National Emergency X-Radiography Utilization Study (NEXUS) Head Computed Tomography validation study. We performed a detailed assessment of the demographics, mechanisms, presentations, injuries, interventions, and outcomes among older patients. RESULTS: We identified 3,659 patients aged 65 years or greater, among the 11,770 patients enrolled in the NEXUS validation study. Of these older patients, 325 (8.9%) sustained significant injuries, as compared with significant injuries in 442 (5.4%) of the 8,111 younger patients. Older females (1,900; 51.9%) outnumbered older males (1,753; 47.9%), and occult presentations (exhibiting no high-risk clinical criteria beyond age) occurred in 48 (14.8%; 95% confidence interval (CI) 11.1 to 19.1) patients with significant injuries. Subdural hematomas (377 discreet lesions in 299 patients) and subarachnoid hemorrhages (333 discreet instances in 256 patients) were the most frequent types of injuries occurring in our elderly population. A ground-level fall was the most frequent mechanism of injury among all patients (2,211; 69.6%), those sustaining significant injuries (180; 55.7%), and those who died of their injuries (37; 46.3%), but mortality rates were highest among patients experiencing a fall from a ladder (11.8%; 4 deaths among 34 cases [95% CI 3.3% to 27.5%]) and automobile versus pedestrian events (10.7%; 16 deaths among 149 cases [95% CI 6.3% to 16.9%]). Among older patients who required neurosurgical intervention for their injuries, only 16.4% (95% CI 11.1% to 22.9%) were able to return home, 32.1% (95% CI 25.1% to 39.8%) required extended facility care, and 41.8% (95% CI 34.2% to 49.7%) died from their injuries. CONCLUSIONS: Older blunt head injury patients are at high risk of sustaining serious intracranial injuries even with low-risk mechanisms of injury, such as ground-level falls. Clinical evaluation is unreliable and frequently fails to identify patients with significant injuries. Outcomes, particularly after intervention, can be poor, with high rates of long-term disability and mortality.

Transition-Metal-Catalyzed Silylation and Borylation of C-H Bonds for the Synthesis and Functionalization of Complex Molecules.

The functionalization of C-H bonds in organic molecules containing functional groups has been one of the holy grails of catalysis. One synthetically important approach to the diverse functionalization of C-H bonds is the catalytic silylation or borylation of C-H bonds, which enables a broad array of downstream transformations to afford diverse structures. Advances in both undirected and directed methods for the transition-metal-catalyzed silylation and borylation of C-H bonds have led to their rapid adoption in early-, mid-, and late-stage of the synthesis of complex molecules. In this Review, we review the application of the transition-metal-catalyzed silylation and borylation of C-H bonds to the synthesis of bioactive molecules, organic materials, and ligands. Overall, we aim to provide a picture of the state of art of the silylation and borylation of C-H bonds as applied to the synthesis and modification of diverse architectures that will spur further application and development of these reactions.

Iridium-Catalyzed, Site-Selective Silylation of Secondary C(sp3)-H Bonds in Secondary Alcohols and Ketones.

We report the iridium-catalyzed, stereoselective conversion of secondary alcohols or ketones to anti-1,3-diols by the silylation of secondary C-H bonds γ to oxygen and oxidation of the resulting oxasilolane. The silylation of secondary C-H bonds in secondary silyl ethers derived from alcohols or ketones is enabled by a catalyst formed from a simple bisamidine ligand. The silylation occurs with high selectivity at a secondary C-H bond γ to oxygen over distal primary or proximal secondary C-H bonds. Initial mechanistic investigations suggest that the source of the newly achieved reactivity is a long catalyst lifetime resulting from the high binding constant of the strongly electron-donating bisamidine ligand.

Discovery of Antimicrobial Phosphonopeptide Natural Products from Bacillus velezensis by Genome Mining.

Phosphonate natural products are renowned for inhibitory activities which underly their development as antibiotics and pesticides. Although most phosphonate natural products have been isolated from Streptomyces, bioinformatic surveys suggest that many other bacterial genera are replete with similar biosynthetic potential. While mining actinobacterial genomes, we encountered a contaminated Mycobacteroides data set which included a biosynthetic gene cluster predicted to produce novel phosphonate compounds. Sequence deconvolution revealed that the contig containing this cluster, as well as many others, belonged to a contaminating Bacillus and is broadly conserved among multiple species, including the epiphyte Bacillus velezensis. Isolation and structure elucidation revealed a new di- and tripeptide composed of l-alanine and a C-terminal l-phosphonoalanine which we name phosphonoalamides E and F. These compounds exhibit broad-spectrum antibacterial activity, including strong inhibition against the agricultural pests responsible for vegetable soft rot (Erwinia rhapontici), onion rot (Pantoea ananatis), and American foulbrood (Paenibacillus larvae). This work expands our knowledge of phosphonate metabolism and underscores the importance of including underexplored microbial taxa in natural product discovery. IMPORTANCE Phosphonate natural products produced by bacteria have been a rich source of clinical antibiotics and commercial pesticides. Here, we describe the discovery of two new phosphonopeptides produced by B. velezensis with antibacterial activity against human and plant pathogens, including those responsible for widespread soft rot in crops and American foulbrood. Our results provide new insight on the natural chemical diversity of phosphonates and suggest that these compounds could be developed as effective antibiotics for use in medicine or agriculture.

Adherence to guideline-directed hepatocellular carcinoma screening: A single-center US experience.

BACKGROUND: The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma (HCC) using imaging with or without alpha-fetoprotein every six months. Unfortunately, screening rates remain inadequate. AIM: To assess root causes of screening failure in a subspecialty hepatology clinic. METHODS: The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening, defined as two cross-sectional images between five and seven months apart. The authors characterized the primary driver of screening failure. Finally, other hepatologists were surveyed to determine provider perceptions of screening failure causes. RESULTS: 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1 ± 3.8. Hepatitis C virus was the most common cirrhosis etiology. 489 (47%) underwent appropriate screening. No demographic or clinical differences were detected between those who underwent appropriate screening and those who did not. The most common etiologies of screening failure, in descending order, were: radiology unable to schedule timely imaging, provider did not order imaging, patient canceled follow up appointment, appointments scheduled too far apart, lost to follow up, no-show to radiology appointment, and provider canceled appointment. Hepatologists surveyed believed the most common cause of screening failure was no-show to radiology. CONCLUSION: Rates of screening were poor even in a subspecialty hepatology clinic. Screening failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.

Physical Examination Sensitivity for Skull Fracture in Pediatric Patients With Blunt Head Trauma: A Secondary Analysis of the National Emergency X-Radiography Utilization Study II Head Computed Tomography Validation Study.

STUDY OBJECTIVE: We evaluated the emergency department (ED) providers' ability to detect skull fractures in pediatric patients presenting with blunt head trauma. METHODS: This was a secondary analysis of the National Emergency X-Radiography Utilization Study (NEXUS) Head computed tomography (CT) validation study. Demographics and clinical characteristics were analyzed for pediatric patients. Radiologist interpretations of head CT imaging were abstracted and cataloged. Detection of skull fractures was evaluated through provider response to specific clinical decision instrument criteria (NEXUS or Canadian head CT rules) at the time of initial patient evaluation. The presence of skull fracture was determined by formal radiologist interpretation of CT imaging. RESULTS: Between April 2006, and December 2015, 1,018 pediatric patients were enrolled. One hundred twenty-eight (12.5%) children had a notable injury reported on CT head. Skull fracture was present in most (66.4%) children with intracranial injuries. The sensitivity and specificity of provider physical examination to detect skull fractures was 18.5% (95% confidence interval 10.5% to 28.7%) and 96.6% (95.3% to 97.7%), respectively. The most common injuries associated with skull fractures were subarachnoid hemorrhage (27%) and subdural hematoma (22.3%). CONCLUSION: Skull fracture is common in children with intracranial injury after blunt head trauma. Despite this, providers were found to have poor sensitivity for skull fractures in this population, and these injuries may be missed on initial emergency department assessment.

Impact of ß-blockers on survival outcomes in patients with unresectable hepatocellular carcinoma.

Background: ß-blockers (BBs) have shown promise in improving overall survival (OS) in patients with breast, ovarian, pancreatic and lung cancer. However, few studies have evaluated the impact of BBs on unresectable hepatocellular carcinoma (HCC). Methods: The authors compared clinical data and outcomes between unresectable HCC patients based on whether they were prescribed BBs. Results: There was significantly decreased disease progression in the BB group compared with the non-BB group (22.8 vs 28.0%; p < 0.05). No difference was seen in OS or progression-free survival between groups. Those specifically on selective BBs had improved OS (hazard ratio: 0.75; 95% CI: 0.61-0.94; p = 0.01) and progression-free survival (hazard ratio: 0.66; 95% CI: 0.45-0.96; p = 0.03) compared with non-BB patients. Conclusion: Although the authors' study did not demonstrate that BBs improve OS in HCC, it did show decreased disease progression among patients with HCC who were taking BBs compared with those who were not.

Valinophos Reveals a New Route in Microbial Phosphonate Biosynthesis That Is Broadly Conserved in Nature.

Phosphonate natural products are potent inhibitors of cellular metabolism with an established record of commercialization in medicine and biotechnology. Although genome mining has emerged as an accelerated method for the discovery of new phosphonates, a robust framework of their metabolism is needed to identify the pathways most likely to yield compounds with desired activities. Here we expand our understanding of these natural products by reporting the complete biosynthetic pathway for valinophos, a phosphonopeptide natural product containing the unusual (R)-2,3-dihydroxypropylphosphonate (DHPPA) scaffold. The pathway was defined by several enzymatic transformations and intermediates previously unknown to phosphonate natural products. A dedicated dehydrogenase served as a new phosphoenolpyruvate mutase coupling enzyme. Notably, its reduction of phosphonopyruvate to phosphonolactate defined a new early branchpoint in phosphonate biosynthesis. Functionally interconnected kinase and reductase enzymes catalyzed reactions reminiscent of glycolysis and arginine biosynthesis to produce a transient, but essential, phosphonolactaldehyde intermediate. We demonstrate esterification of l-valine onto DHPPA as a new biochemical activity for ATP-Grasp ligase enzymes. Unexpectedly, a second amino acid ligase then adjoined additional amino acids at the valinyl moiety to produce a suite of DHPPA-dipeptides. The genes for DHPPA biosynthesis were discovered among genomes of bacteria from wide-ranging habitats, suggesting a wealth of unknown compounds that may originate from this core pathway. Our findings establish new biosynthetic principles for natural products and provide definition to unexplored avenues for bioactive phosphonate genome mining.

Margin marking before colorectal endoscopic mucosal resection and its impact on neoplasia recurrence (with video).

BACKGROUND AND AIMS: Ablation of resection margins after EMR of large nonpedunculated colorectal polyps decreases recurrence. Margin marking before EMR (EMR-MM) may represent an alternative method to achieve a healthy resection margin. We aimed to determine the efficacy of EMR-MM in reducing neoplasia recurrence. METHODS: We conducted a single-center historical control study of EMR cases (EMR-MM vs conventional EMR) for nonpedunculated polyps ≥20 mm between 2016 and 2021. For EMR-MM, cautery marks were placed along the lateral margins of the polyp with the snare tip. EMR was then performed to include resection of the healthy mucosa containing the marks. We compared recurrence at surveillance colonoscopy after EMR-MM versus historical control subjects. Multivariable logistic regression was performed to identify factors associated with recurrence. RESULTS: Two hundred ten patients with 210 polyps (median size, 30 mm; interquartile range: 25-40) underwent EMR-MM (n = 74) or conventional EMR (n = 136). Patient and lesion characteristics were similar between the groups. At a median follow-up of 6 months, the recurrence rate was lower with EMR-MM (6/74; 8%) compared with historical control subjects (39/136; 29%) (P < .001). EMR-MM was not associated with an increased rate of adverse events. On multivariable analysis, EMR-MM remained the strongest predictor of recurrence (odds ratio, .20; 95% confidence interval, .13-.64; P = .003) aside from polyp size (odds ratio, 2.81; 95% confidence interval, 1.35-6.01; P = .008). CONCLUSIONS: In this single-center historical control study, EMR-MM of large nonpedunculated colorectal polyps reduced the recurrence risk by 80% when compared with conventional EMR. This simple technique may provide an alternative to margin ablation.

Hydroxyl Radical Production by Air Pollutants in Epithelial Lining Fluid Governed by Interconversion and Scavenging of Reactive Oxygen Species.

Air pollution is a major risk factor for human health. Chemical reactions in the epithelial lining fluid (ELF) of the human respiratory tract result in the formation of reactive oxygen species (ROS), which can lead to oxidative stress and adverse health effects. We use kinetic modeling to quantify the effects of fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) on ROS formation, interconversion, and reactivity, and discuss different chemical metrics for oxidative stress, such as cumulative production of ROS and hydrogen peroxide (H2O2) to hydroxyl radical (OH) conversion. All three air pollutants produce ROS that accumulate in the ELF as H2O2, which serves as reservoir for radical species. At low PM2.5 concentrations (<10 µg m-3), we find that less than 4% of all produced H2O2 is converted into highly reactive OH, while the rest is intercepted by antioxidants and enzymes that serve as ROS buffering agents. At elevated PM2.5 concentrations (>10 µg m-3), however, Fenton chemistry overwhelms the ROS buffering effect and leads to a tipping point in H2O2 fate, causing a strong nonlinear increase in OH production. This shift in ROS chemistry and the enhanced OH production provide a tentative mechanistic explanation for how the inhalation of PM2.5 induces oxidative stress and adverse health effects.

Modeling the Formation, Degradation, and Spatiotemporal Distribution of 2-Nitrofluoranthene and 2-Nitropyrene in the Global Atmosphere.

Polycyclic aromatic hydrocarbons (PAHs) are common atmospheric pollutants and known to cause adverse health effects. Nitrated PAHs (NPAHs) are formed in combustion activities and by nitration of PAHs in the atmosphere and may be equally or more toxic, but their spatial and temporal distribution in the atmosphere is not well characterized. Using the global EMAC model with atmospheric chemistry and surface compartments coupled, we investigate the formation, abundance, and fate of two secondarily formed NPAHs, 2-nitrofluoranthene (2-NFLT) and 2-nitropyrene (2-NPYR). The default reactivity scenario, the model with the simplest interpretation of parameters from the literature, tends to overestimate both absolute concentrations and NPAH/PAH ratios at observational sites. Sensitivity scenarios indicate that NO2-dependent NPAH formation leads to better agreement between measured and predicted NPAH concentrations and that photodegradation is the most important loss process of 2-NFLT and 2-NPYR. The highest concentrations of 2-NFLT and 2-NPYR are found in regions with strong PAH emissions, but because of continued secondary formation from the PAH precursors, these two NPAHs are predicted to be spread across the globe.

Effect of referral pattern and histopathology grade on surgery for nonmalignant colorectal polyps.

BACKGROUND AND AIMS: The incidence of surgery for nonmalignant colorectal polyps is rising. The aims of this study were to evaluate referral patterns to surgery for nonmalignant polyps, to compare outcomes between surgery and endoscopic resection (ER), and to identify factors associated with surgery in a university-based, tertiary care center. METHODS: Patients referred to colorectal surgery (CRS) for nonmalignant colorectal polyps between 2014 and 2019 were selected from the institution's integrated data repository. Clinical characteristics were obtained through chart review. Multivariate analysis was performed to identify factors associated with surgery for nonmalignant polyps. RESULTS: Six hundred sixty-four patients with colorectal lesions were referred to CRS, of which 315 were for nonmalignant polyps. Most referrals (69%) came from gastroenterologists. Of the 315 cases, 136 underwent surgery and 117 were referred for attempt at ER. Complete ER was achieved in 87.2% (n = 102), with polyp recurrence in 27.2% at a median of 14 months (range, 0-72). When compared with surgery, ER was associated with a lower hospitalization rate (22.2% vs 95.6%; P < .0001), shorter hospital stay (mean, .5 ± .9 vs 2.23 ± 1 days; P < .0001), and fewer adverse events (5.9% vs 22.8%; P = .0002). Intramucosal adenocarcinoma on baseline pathology (odds ratio, 5.7; 95% confidence interval, 1.2-28.2) and referrals by academic gastroenterologists (odds ratio, 2.5; 95% confidence interval, 1.11-5.72) were associated with a higher likelihood of surgery on multivariate analysis. CONCLUSIONS: Gastroenterologists commonly refer nonmalignant colorectal polyps to surgery, even though ER is effective and associated with lower morbidity. Both referrals from academic gastroenterologists and baseline pathology of intramucosal adenocarcinoma were factors associated with surgery. All colorectal polyps should be evaluated in a multidisciplinary approach to identify lesions suitable for ER before embarking in surgery.

Impact of Prolonged Skeletal Traction in Patients With Acetabular Fractures.

OBJECTIVES: To explore the association between increased time in traction and in-hospital pulmonary complications in patients with acetabular fractures. DESIGN: Retrospective. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: One hundred ninety consecutive patients. INTERVENTION: Application of skeletal traction before fixation of acetabular fracture. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was pulmonary complication as defined by pulmonary embolism, pneumonia, and acute respiratory distress syndrome. Secondary outcome measures included length of intensive care unit stay (in days), total length of hospital stay (in days), deep hardware-associated infection, subsequent conversion to total hip arthroplasty, urinary tract infection, and lower-extremity deep venous thrombosis. RESULTS: The mean time in traction for patients who developed a pulmonary complication was 210 hours compared with 62 hours for those who did not (P < 0.001). After controlling for Injury Severity Score, chest injury, and concomitant long bone injury requiring intramedullary nailing, the odds of developing a pulmonary complication for patients who spent longer than 120 hours in traction were over 40 times higher than those treated within 5 days (P < 0.001). The mean intensive care unit stay for patients who spent at least 120 hours in traction was 17 days compared with 5 days for those treated in less than 120 hours (P < 0.001). CONCLUSION: Early definitive fixation and decreased time in skeletal traction is associated with a lower rate of complications in patients with acetabular fractures. Our results would suggest that fixation of acetabular fractures before 120 hours (5 days) confers a significant risk-reduction benefit. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Fast Formation of Nitro-PAHs in the Marine Atmosphere Constrained in a Regional-Scale Lagrangian Field Experiment.

Polycyclic aromatic hydrocarbons (PAHs) and some of their nitrated derivatives, NPAHs, are seemingly ubiquitous in the atmospheric environment. Atmospheric lifetimes may nevertheless vary within a wide range, and be as short as a few hours. The sources and sinks of NPAH in the atmosphere are not well understood. With a Lagrangian field experiment and modeling, we studied the conversion of the semivolatile PAHs fluoranthene and pyrene into the 2-nitro derivatives 2-nitrofluoranthene and 2-nitropyrene in a cloud-free marine atmosphere on the time scale of hours to 1 day between a coastal and an island site. Chemistry and transport during several episodes was simulated by a Lagrangian box model i.e., a box model coupled to a Lagrangian particle dispersion model, FLEXPART-WRF. It is found that the chemical kinetic data do capture photochemical degradation of the 4-ring PAHs under ambient conditions on the time scale of hours to 1 day, while the production of the corresponding NPAH, which sustained 2-nitrofluoranthene/fluoranthene and 2-nitropyrene/pyrene yields of (3.7 ± 0.2) and (1.5 ± 0.1)%, respectively, is by far underestimated. Predicted levels of NPAH come close to observed ones, when kinetic data describing the reactivity of the OH-adduct were explored by means of theoretically based estimates. Predictions are also underestimated by 1-2 orders of magnitude, when NPAH/PAH yields reported from laboratory experiments conducted under high NOx conditions are adopted for the simulations. It is concluded that NPAH sources effective under low NOx conditions, are largely underestimated.

Antioxidant activity of cerium dioxide nanoparticles and nanorods in scavenging hydroxyl radicals.

Cerium oxide nanoparticles (CeNPs) have been shown to exhibit antioxidant capabilities, but their efficiency in scavenging reactive oxygen species (ROS) and the underlying mechanisms are not yet well understood. In this study, cerium dioxide nanoparticles (CeNPs) and nanorods (CeNRs) were found to exhibit much stronger scavenging activity than ·OH generation in phosphate buffered saline (PBS) and surrogate lung fluid (SLF). The larger surface area and higher defect density of CeNRs may lead to higher ·OH scavenging activity than for CeNPs. These insights are important to understand the redox activity of cerium nanomaterials and provide clues to the role of CeNPs in biological and environmental processes.

Modeling the Interaction of Carbon Monoxide with Flexible Graphene: From Coupled Cluster Calculations to Molecular-Dynamics Simulations.

The interaction of CO with graphene was studied at different theoretical levels. Quantum-mechanical calculations on finite graphene models with the use of coronene for coupled cluster calculations and circumcoronene for B97D calculations showed that there was no preferential site for adsorption and that the most important factor was the orientation of CO relative to graphene. The parallel orientation was preferred, with binding energies around 9 kJ mol-1 at the CCSD(T) and B97D levels, which was in good agreement with experimental findings. From a large number of CO-circumcoronene and CO-CO interactions, computed at different distances and randomly generated orientations, parameters were fit to the improved Lennard-Jones potential. Such potentials, together with others describing the intramolecular dynamics of graphene, were subsequently employed in classical molecular-dynamics simulations of the adsorption of CO on graphene by using the canonical ensemble. The obtained results showed that the introduction of flexibility in graphene, which simulated the effects associated to curvature of the surface, diminished the adsorption level and that, as expected, adsorption also diminished with temperature.