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INTRODUCTION: To report outcomes of a 3-year quality improvement pilot study to improve advance directive (AD) completion. METHODS: The pilot consisted of champions, education, electronic health record templates, and workflow changes. We assessed changes, predictors, and effects of AD completion. RESULTS: The pilot led to greater (8.3%-36%) and earlier AD completion, particularly among those divorced, with alcohol-associated liver disease, and with higher Model of End-Stage Liver Disease-Sodium score. Decedents whose AD specified nonaggressive goals experienced lower hospital lengths of stay. DISCUSSION: Advance care planning initiatives are feasible and may reduce health care utilization among decedents requesting less aggressive care.

BACKGROUND: Robotic assistance has been shown to increase instrumentation placement accuracy in open and minimally invasive spinal fusion. These gains have been achieved without increases in operative times, blood loss, or hospitalization duration. However, most work has been done in the degenerative population and little is known of the utility of robotic assistance when applied to spinal trauma. This is largely due to the uncertainty stemming from the disruption of normal anatomy by the traumatic injury. Since the robot depends upon registration for instrumentation guidance according to the fiducials it uses, trauma can introduce unique challenges. The present study sought to evaluate the safety and efficacy of robotic assistance in a consecutive cohort of spine trauma patients. METHODS: All patients with Thoracolumbar Injury Classification and Severity Scale (TLICS) >4 who underwent robot-assisted spinal fusion using the Globus ExcelsiusGPS at a single tertiary care center for trauma between 2020 and 2022 were identified. Demographic, clinical, and surgical data were collected and analyzed; the primary endpoints were operative time, fluoroscopy time, estimated blood loss, postoperative complications, admission time, and 90-day readmission rate. The paired t-test was used to compare differences between mean values when looking at the number of surgical levels. RESULTS: Forty-two patients undergoing robot-assisted spinal surgery were included (mean age 61.3±17.1 year; 47% female. Patients were stratified by the number of operative levels, 2 (n = 10), 3-4 (n = 11), 5 to 6 (n = 13), or >6 (n = 8). There appeared to be a positive correlation between number of levels instrumented and odds of postoperative complications, admission duration, fluoroscopy time, and estimated blood loss. There were no instances of screw malposition or breach. CONCLUSIONS: This initial experience suggests robotic assistance can be safely employed in the spine trauma population. Additional experiences in larger patient populations are necessary to delineate those traumatic pathologies most amenable to robotic assistance.

Embolization of the middle meningeal artery (MMA) is a safe and effective adjunct in the treatment of chronic subdural hematoma. While prior authors describe the use of coils to assist embolization by preventing reflux through eloquent collaterals, we de- scribe the use of coils to further open the MMA, allowing the administration of greater amounts of embolisate for a more robust embolization. The objective of this study was to demonstrate that helical coils can safely open the MMA following the administration of polyvinyl alcohol (PVA) particles. This allows for more embolisate to be administered into the MMA for more effective treatment. A retrospective review was conducted at our institution including intraoperative images and postoperative clinical and radiographic follow up. Failure rates using MMA embolization with PVA and helical coil augmentation were compared to failure rates in the literature of MMA embolization with PVA or ethylene vinyl-alcohol copolymer alone. A total of 8 cases were reviewed in which this technique was implemented. There were no immediate complications after treatment. All patients that underwent helical coil embolization following the administration of PVA had increased amount of embolisate delivered into the MMA. All patients at follow up had resolution of the subdural hematoma on outpatient imaging. Helical coil embolization allows for more embolisate administration into the MMA and provides a technical advantage for patients that fail traditional techniques of embolization. Case series are taking place to further test this hypothesis and identify the ideal patient population that may gain maximal yield from this novel technique.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

PurposePrimary spinal infections (PSIs) are a group of infectious diseases characterized by inflammation of the end plate-disk unit or its surroundings. PSI is considered more prevalent and aggressive among patients with chronic immunocompromised states. Association of PSIs, immunocompromising cancers, and hemoglobinopathies has not been systematically analyzed. We conducted a systematic review to study characteristics, clinical presentation, and mortality of patients with PSI in the setting of hematologic disease.MethodsA systematic literature search in PubMed, Web of Science, and Scopus was conducted in April 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included retrospective case series and individual case reports.ResultsOn careful review, 28 articles published between 1970 and 2022 were selected. These studies featured 29 patients who met inclusion criteria (mean age 29 years, age range 1.5 to 67 years; 63.3% male). Lumbar infection was the most common location (65.5%), with Salmonella (24.1%) as the main causative microorganism. Neurologic compromise was present in 41% of patients, and surgical intervention occurred in 48.3%. Average antibiotic duration was 13 weeks. The postoperative complication rate was 21.4%, with a mortality of 6.9%.ConclusionPSI in patients with hematologic disease, while having shorter periods to diagnosis, presents increased rates of neurologic deficit, surgical intervention, and complications.

Antimicrobials are widely used worldwide in food animal production for controlling and preventing disease and for improving feed conversion efficiency and growth promotion. Inappropriate use of antimicrobials in animal agriculture has the potential to promote antimicrobial resistance, which represents a threat to human, animal, and environmental health. State and municipal policies in the United States have recently been implemented to improve antimicrobial use and reporting in this sector. This study analyzed the implementation of two state-level policies (California (CA) and Maryland (MD)) and a city-level policy in San Francisco (SF), California that aimed to reduce the use of antimicrobials in food-animals and increase transparency of antimicrobial use. A qualitative analysis was based on in-depth interviews with key informants (KIs) (n = 19) who had direct experience implementing or working in the context of these sub-national policies. Interviews were recorded and transcriptions were analyzed independently by two researchers using a three-stage, grounded theory coding procedure. This study identified four major findings, including 1) vague language on antimicrobial use within policies reduces policy effectiveness; 2) the lack of reporting by producers challenges the ability to evaluate the impact of the policies on actual use; 3) diverse stakeholders need to be involved in order to develop a more effective policy; and 4) funding should be linked to the policy to provide for reporting and data analysis. This analysis provides insights on the successes and failures of existing policies and serves to inform future sub-national policies aiming to improve the judicious use of antimicrobials in food-animals.

BackgroundThe presence of active or inactive (i.e., postproduction) oil and gas wells in neighborhoods may contribute to ongoing pollution. Racially discriminatory neighborhood security maps developed by the Home-Owners Loan Corporation (HOLC) in the 1930s may contribute to environmental exposure disparities.ObjectiveTo determine whether receiving worse HOLC grades was associated with exposure to more oil and gas wells.MethodsWe assessed exposure to oil and gas wells among HOLC-graded neighborhoods in 33 cities from 13 states where urban oil and gas wells were drilled and operated. Among the 17 cities for which 1940 census data were available, we used propensity score restriction and matching to compare well exposure neighborhoods that were similar on observed 1940 sociodemographic characteristics but that received different grades.ResultsAcross all included cities, redlined D-graded neighborhoods had 12.2 ± 27.2 wells km-2, nearly twice the density in neighborhoods graded A (6.8 ± 8.9 wells km-2). In propensity score restricted and matched analyses, redlined neighborhoods had 2.0 (1.3, 2.7) more wells than comparable neighborhoods with a better grade.SignificanceOur study adds to the evidence that structural racism in federal policy is associated with the disproportionate siting of oil and gas wells in marginalized neighborhoods.

PremiseEvolution of separate sexes from hermaphroditism often proceeds through gynodioecy, but genetic constraints on this process are poorly understood. Genetic (co-)variances and between-sex genetic correlations were used to predict evolutionary responses of multiple reproductive traits in a sexually dimorphic gynodioecious species, and predictions were compared with observed responses to artificial selection.MethodsSchiedea (Caryophyllaceae) is an endemic Hawaiian lineage with hermaphroditic, gynodioecious, subdioecious, and dioecious species. We measured genetic parameters of Schiedea salicaria and used them to predict evolutionary responses of 18 traits in hermaphrodites and females in response to artificial selection for increased male (stamen) biomass in hermaphrodites or increased female (carpel, capsule) biomass in females. Observed responses over two generations were compared with predictions in replicate lines of treatments and controls.ResultsIn only two generations, both stamen biomass in hermaphrodites and female biomass in females responded markedly to direct selection, supporting a key assumption of models for evolution of dioecy. Other biomass traits, pollen and ovule numbers, and inflorescence characters important in wind pollination evolved indirectly in response to selection on sex allocation. Responses generally followed predictions from multivariate selection models, with some responses unexpectedly large due to increased genetic correlations as selection proceeded.ConclusionsResults illustrate the power of artificial selection and utility of multivariate selection models incorporating sex differences. They further indicate that pollen and ovule numbers and inflorescence architecture could evolve in response to selection on biomass allocation to male versus female function, producing complex changes in plant phenotype as separate sexes evolve.

BackgroundPrimary spinal infections (PSIs) are a group of uncommon but serious infectious diseases that are characterized by inflammation of the endplate-disc unit. Pediatric spinal infection is rare and challenging to diagnose due to vague presenting symptoms. Most cases are conservatively managed with surgery rarely indicated. The authors performed a systematic review to study the baseline characteristics, clinical presentation, and outcomes of pediatric patients with PSIs who underwent surgical treatment.ObservationsPSI in pediatric patients might behave differently in terms of epidemiology, clinical presentation, and outcomes when compared with nonpediatric patients. Overall, PSI ultimately managed surgically in pediatric patients is associated with a high rate of localized pain, neurological compromise, and treatment failure when compared with nonsurgically managed pediatric spinal infections.LessonsPSIs managed surgically in the pediatric population were found to be caused by Mycobacterium tuberculosis in 74.4% of cases and were associated with higher rates of localized pain, neurological compromise, and treatment failure than nonsurgically managed pediatric spinal infections. Thoracic involvement (71.8%) in the spinal infection was reported most commonly in our review. When omitting the cases involving M. tuberculosis infection, it was revealed that 50% of the pediatric cases involved infection in the cervical region, suggesting increased severity and disease course of cervical spinal infections in the pediatric population. Surgical treatment is indicated only in cases of severe neurological compromise and treatment failure.

This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the electrode material of choice and combines it with an electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the electrode measurements, neural activity was classified in two ways: (1) pre-to-post CPT, and (2) during a timed respiratory challenge. Unique to this work: (1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and (2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.

Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.

Wastewater-based surveillance has gained prominence and come to the forefront as a leading indicator of forecasting COVID-19 (coronavirus disease 2019) infection dynamics owing to its cost-effectiveness and its ability to inform early public health interventions. A university campus could especially benefit from wastewater surveillance, as universities are characterized by largely asymptomatic populations and are potential hot spots for transmission that necessitate frequent diagnostic testing. In this study, we employed a large-scale GIS (geographic information systems)-enabled building-level wastewater monitoring system associated with the on-campus residences of 7,614 individuals. Sixty-eight automated wastewater samplers were deployed to monitor 239 campus buildings with a focus on residential buildings. Time-weighted composite samples were collected on a daily basis and analyzed on the same day. Sample processing was streamlined significantly through automation, reducing the turnaround time by 20-fold and exceeding the scale of similar surveillance programs by 10- to 100-fold, thereby overcoming one of the biggest bottlenecks in wastewater surveillance. An automated wastewater notification system was developed to alert residents to a positive wastewater sample associated with their residence and to encourage uptake of campus-provided asymptomatic testing at no charge. This system, integrated with the rest of the "Return to Learn" program at the University of California (UC) San Diego-led to the early diagnosis of nearly 85% of all COVID-19 cases on campus. COVID-19 testing rates increased by 1.9 to 13× following wastewater notifications. Our study shows the potential for a robust, efficient wastewater surveillance system to greatly reduce infection risk as college campuses and other high-risk environments reopen. IMPORTANCE Wastewater-based epidemiology can be particularly valuable at university campuses where high-resolution spatial sampling in a well-controlled context could not only provide insight into what affects campus community as well as how those inferences can be extended to a broader city/county context. In the present study, a large-scale wastewater surveillance was successfully implemented on a large university campus enabling early detection of 85% of COVID-19 cases thereby averting potential outbreaks. The highly automated sample processing to reporting system enabled dramatic reduction in the turnaround time to 5 h (sample to result time) for 96 samples. Furthermore, miniaturization of the sample processing pipeline brought down the processing cost significantly ($13/sample). Taken together, these results show that such a system could greatly ameliorate long-term surveillance on such communities as they look to reopen.

BackgroundCholinesterase inhibitor pesticides, especially organophosphates, are endocrine disruptors and a few existing studies have linked self-reports of exposure with increased depression and anxiety. Some evidence suggests that associations may be stronger in women, but the mechanism of this gender difference is unclear. We assessed whether acetylcholinesterase (AChE) inhibition between 2 time points (reflecting greater cholinesterase inhibitor exposure) during different agricultural seasons in the year was associated with anxiety/depression symptoms.MethodsWe examined 300 adolescents (ages 11-17y, 51% female) living near agricultural settings in Ecuador (ESPINA study) twice in 2016: April and July-October. We assessed AChE activity (finger stick), estradiol, testosterone, dehydroepiandrosterone, cortisol (saliva) and anxiety and depression scales (CDI-2 and MASC-2).ResultsThe mean (SD) depression and anxiety scores were 52.8 (9.3) and 58.1 (9.6), respectively. The median (25th, 75th percentile) AChE change (July-October vs April) was -3.94% (-10.45%, 5.13%). For every 10% decrease in AChE activity, there was a 0.96 unit (95%CI: 0.01, 1.90) increase in depression symptoms and an OR of elevated depression score of 1.67 (1.04, 2.66). These associations were stronger in girls (OR=2.72 [1.23, 6.00]) than boys (1.18 [0.59, 2.37]). Adjustment for cortisol, testosterone and dehydroepiandrosterone reduced gender differences by 18-62%. No associations were observed with anxiety.DiscussionInhibition of AChE activity at 2 points in time during different pesticide spray periods was associated with greater depression symptoms, affecting girls more than boys. Gender differences may be partly explained by endocrine disruption. These findings suggest that AChE inhibition may transiently affect the mood of adolescents.