Collaborative Implementation of Robotic Surgery Into an Academic Pediatric Surgery Practice.

INTRODUCTION: Robotic surgery continues to drive evolution in minimally invasive surgery. Due to the confined operative fields encountered, pediatric surgeons may uniquely benefit from the precise control offered by robotic technologies compared to open and laparoscopic techniques. We describe a unique collaborative implementation of robotic surgery into an academic pediatric surgery practice through adult robotic surgeon partnership. We compare robotic cholecystectomy (RC) and laparoscopic cholecystectomy (LC) outcomes, hypothesizing that RC will be equivalent to LC in key quality outcomes. METHODS: We evaluate 14 mo of systems development and training, and 24 mo of collaborative operative experience evoking a purposeful tiered case progression, establishing core robotic competencies, prior to advancing operative complexity. Univariate analyses compared LC versus RC. RESULTS: 36 robotic operations were performed in children aged 8-18 y, in a tiered progression from 24 cholecystectomies to 2 ileocecectomies, 2 paraesophageal hernia repairs, 1 anterior rectopexy, 1 spleen-preserving distal pancreatectomy, 1 Heller myotomy, 1 choledochal cyst resection with roux-en-y hepaticojejunostomy, 1 median arcuate ligament release, and 1 thoracic esophageal duplication cyst resection. For LC and RC, there were no significant differences in procedure duration, discharge opioids, hospital readmission, or rates of surgical site infection or bile duct injury. CONCLUSIONS: Robotic surgery has potential to significantly enhance pediatric surgery. RC appears equivalent to LC but presents multiple additional theoretical benefits in pediatric patients. Our pilot program experience supports the feasibility and safety of pediatric robotic surgery. We emphasize the importance of a stepwise progression in operative difficulty and collaboration with adult robotic surgery experts.

Cleaning Indoor Air- What Works for Respiratory Health: An Updated Literature Review and Recommendations.

Indoor air pollution is a growing public health concern globally and is associated with increased respiratory symptoms and morbidity. Individuals spend most of their time indoors, and pollutant-related health effects are often driven by the indoor environment. Understanding effective interventions to improve indoor air quality (IAQ) and their impact on respiratory outcomes is key to decreasing the burden of air pollution for high-risk populations across the lifespan. This review applies a hierarchy of interventions framework specific to respiratory health effects and focuses on recent studies of interventions to improve IAQ among high-risk populations with chronic respiratory disease published in the past three years. While policy and source control interventions are likely the most effective and equitable approaches to improve IAQ and benefit population health, these were less extensively investigated. Engineering interventions, such as air cleaner interventions, were the most widely studied. Several studies, including those focused on asthma and COPD, demonstrated improvement in symptoms and medication use with interventions in both home and school-based settings. Combined multilevel interventions with engineering and behavioral interventions led to improved respiratory outcomes in some, but not all, studies. Placing the recent work in the context of the broader literature, we identify gaps in research. Further research is needed to understand intervention effectiveness over time and an increased focus on policy and source control interventions that can mitigate risk in vulnerable populations.

Assessing Survival, Distribution, and Optimal Loading Technique of Schwann Cell-Derived Exosomes Into Second-generation Axon Guidance Channels.

INTRODUCTION: Peripheral nerve injury (PNI) occurs in approximately 3% of all trauma patients and can be challenging to treat, particularly when injury is severe such as with a long-segmental gap. Although peripheral nerves can regenerate after injury, functional recovery is often insufficient, leading to deficits in the quality of life of patients with PNI. Although nerve autografts are the gold standard of care, there are several disadvantages to their use, namely a lack of autologous nerve material for repair. This has led to the pursuit of alternative treatment methods such as axon guidance channels (AGCs). Second-generation AGCs have been shown to be able to deliver growth-enhancing substrates for nerve repair directly to the injury site. Although our laboratory has had success with second-generation AGCs filled with Schwann cells (SCs), SCs have their own set of issues clinically. Because of this, we have begun to utilize SC-derived exosomes as an alternative, as they have the appropriate protein markers, associate to axons in high concentrations, and are able to improve nerve regeneration. However, it is unknown how SC-derived exosomes may react within second-generation AGCs; thus, the aim of the present study was to assess the ability of SC-derived exosomes to be loaded into a second-generation AGC and how they would distribute within it. MATERIALS AND METHODS: A total of 4 dry second-generation AGCs were loaded with SC-derived exosomes that were derived from green fluorescent protein (GFP)-labeled SCs. They were subsequently frozen and sliced before imaging. RESULTS: Here, we present findings that SC-derived exosomes can be loaded into second-generation AGCs through our established loading method utilizing negative pressure and are able to survive and equally distribute along the length of the AGC. CONCLUSIONS: Although only 4 second-generation AGCs were utilized, these findings indicate a potential use for SC-derived exosomes within second-generation AGCs to treat severe PNI. Future research should focus on exploring this in greater detail and in different contexts to assess the ability of SC-derived exosomes to survive at the site of injury and treat PNI.

Indoor allergen exposure and its association to upper respiratory infections and pulmonary outcomes among children with asthma.

BACKGROUND: Certain environmental allergen exposures are more common in disadvantaged communities and may contribute to differences in susceptibility to upper respiratory infections (URIs). OBJECTIVES: We examined associations between indoor allergens and: (1) URI; (2) URI + cold symptoms; (3) URI + cold symptoms + pulmonary eosinophilic inflammation (fraction of exhaled nitric oxide ≥20 ppb); and (4) URI + cold symptoms + reduced lung function (percent predicted forced expiratory volume in 1 second of <80%). METHODS: We used data from the Environmental Control as Add-on Therapy for Childhood Asthma (ECATCh) study. Allergen concentrations were measured in air (mouse) and settled dust (mouse, cockroach, dog, and cat). URI was determined by testing nasal mucus for upper respiratory viruses. We evaluated associations between allergen concentrations and URI-associated outcomes accounting for age, sex, study month, season, health insurance, and household size. RESULTS: Ninety participants (92% Black, 92% public insurance) with 192 observations were included; 52 (27%) of observations were positive for URI. A doubling in cockroach allergen concentration increased the odds of a URI with cold symptoms by 18% (odds ratio [OR] = 1.18, 95% confidence interval [CI], 0.99-1.40), the odds of a URI + cold symptoms + pulmonary eosinophilic inflammation by 31% (OR = 1.31, 95% CI, 1.10-1.57), and the odds of a URI + cold symptoms + reduced lung function by 45% (OR = 1.45, 95% CI, 1.13-1.85). Mouse allergen concentrations were positively associated with all outcomes. Associations were suggestively stronger among children sensitized to pest allergens. CONCLUSIONS: Cockroach and mouse, but not dog or cat, allergen exposure may predispose children with asthma to URIs with colds and lower respiratory outcomes.

Situations and roles of cannabis versus cigarette use: Integrating ecological momentary assessment with qualitative mapping interviews.

Use of both cannabis and tobacco has surpassed use of tobacco alone among young adults in California. To better understand why, we collected data with 32 young adults ages 18-30 in Northern California who regularly used cigarettes and cannabis and had diverse sexual, gender, racial, and ethnic identities. Geographically-explicit ecological momentary assessment (EMA; 30 days) was integrated with qualitative mapping interviews. We found contrasting situations of use for cannabis (e.g., around other people) versus cigarettes (e.g., recent discrimination) and different reasons for why participants chose one substance over the other (e.g., enhancing experiences vs. stepping away). Understanding when and why diverse young adults choose cannabis versus cigarettes as they navigate everyday environments helps explain how cannabis and tobacco retail markets shape substance use disparities over time.

Evening regular activity breaks extend subsequent free-living sleep time in healthy adults: a randomised crossover trial.

Objective: To determine if performing regular 3-min bouts of resistance exercise spread over 4 hours in an evening will impact subsequent sleep quantity and quality, sedentary time and physical activity compared with prolonged uninterrupted sitting. Methods: In this randomised crossover trial, participants each completed two 4-hour interventions commencing at approximately 17:00 hours: (1) prolonged sitting and (2) sitting interrupted with 3 min of bodyweight resistance exercise activity breaks every 30 min. On completion, participants returned to a free-living setting. This paper reports secondary outcomes relating to sleep quality and quantity, physical activity and sedentary time which were assessed using wrist-worn ActiGraph GT3+ accelerometers paired with a sleep and wear time diary. Results: A total of 28 participants (women, n=20), age 25.6±5.6 years, body mass index 29.5±6.7 kg/m2 (mean±SD) provided data for this analysis. Compared with prolonged sitting, regular activity breaks increased mean sleep period time and time spent asleep by 29.3 min (95% CI: 1.3 to 57.2, p=0.040) and 27.7 min (95% CI: 2.3 to 52.4, p=0.033), respectively, on the night of the intervention. There was no significant effect on mean sleep efficiency (mean: 0.2%, 95% CI: -2.0 to 2.4, p=0.857), wake after sleep onset (1.0 min, 95% CI: -9.6 to 11.7, p=0.849) and number of awakenings (0.8, 95% CI: -1.8 to 3.3, p=0.550). Subsequent 24-hour and 48-hour physical activity patterns were not significantly different. Conclusions: Performing bodyweight resistance exercise activity breaks in the evening has the potential to improve sleep period and total sleep time and does not disrupt other aspects of sleep quality or subsequent 24-hour physical activity. Future research should explore the longer-term impact of evening activity breaks on sleep. Trial registration number: Australian New Zealand Clinical Trials Registry (ACTRN12621000250831).

Optimizing outpatient neurosurgery: evaluating ambulatory surgery and same-day discharge following intracranial tumor surgery and endoscopic third ventriculostomy.

OBJECTIVE: Outpatient surgery and same-day discharge are developing fields that align with the evolving needs of modern healthcare, presenting a notable advantage by reducing patient susceptibility to nosocomial infections, thromboembolic complications, and medical errors. When paired with enhanced recovery after surgery protocols, they hold promise in safely transitioning certain patients undergoing cranial surgery to outpatient care. This study aimed to evaluate discharge on the same day of surgery after intracranial tumor resection and endoscopic third ventriculostomy (ETV) and to investigate potential associations with anesthesia methods, complications, and readmission rates. METHODS: A retrospective analysis of patients scheduled for planned discharge on the same day of surgery between August 2020 and October 2023 was conducted. Data included patient demographic characteristics, preoperative clinical deficits, diagnosis, findings on preoperative and postoperative MRI, lesion characteristics, complications, and readmission rates. RESULTS: A total of 202 patients were included in the study. The mean age was 56.8 years and 117 (57.9%) patients were female. Patients were admitted the evening before surgery to obtain preoperative clearance and undergo MRI. The most common diagnoses were metastasis (23.3%), meningioma (20.8%), glioblastoma (12.4%), and low-grade glioma (10.4%). Craniotomy (46.5%), stereotactic needle biopsy (35.1), and ETV (6.9%) were the most common procedures performed. Thirteen (6.4%) patients underwent awake craniotomy, and 189 (93.6%) surgical procedures were conducted under general anesthesia. Complications occurred in 1.5% of patients, with no permanent complications observed during a mean follow-up of 9.3 months. In total, 179 (88.6%) patients were successfully discharged on the same day of surgery. The median length of hospitalization was 26.8 hours, with the median length of postoperative stay being 7 hours. Twenty-three (11.4%) patients were deemed ineligible for discharge on postoperative day 0 and instead discharged on postoperative day 1. The reasons for these delays included further clinical monitoring (n = 12), social factors (n = 4), and patient preference (n = 7). Age was positively correlated with length of hospitalization (p = 0.006). In total, 6.4% of patients were readmitted within 1-30 days after discharge, with 2.5% readmitted to the department of neurosurgery. CONCLUSIONS: This study demonstrates the safety and feasibility of discharge on the same day of surgery, with a high success rate and low complication rates. Early discharge did not increase morbidity or readmission rates. Implementation of clear discharge protocols and thorough patient education are crucial for successful same-day discharge programs in neurosurgery.

Anthropometric traits and risk of multiple myeloma: differences by race, sex and diagnostic clinical features.

BACKGROUND: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. METHODS: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. RESULTS: We observed an 18% increase in MM risk for every 5 kg/m2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m2) had the highest risk compared to those with a normal usual adult BMI (18.5-24.9 kg/m2; OR = 1.87, 95% CI 1.25-2.80), particularly among Black men (OR = 3.94, 95% CI 0.90-17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m2) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09-2.40), deletion 13q (OR = 1.73, 95% CI 1.08-2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82-7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31-0.81). CONCLUSIONS: Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.

Pulmonary sarcoidosis: differences in lung function change over time.

INTRODUCTION: Given the heterogeneity of sarcoidosis, predicting disease course of patients remains a challenge. Our aim was to determine whether the 3-year change in pulmonary function differed between pulmonary function phenotypes and whether there were differential longitudinal changes by race and sex. METHODS: We identified individuals seen between 2005 and 2015 with a confirmed diagnosis of sarcoidosis who had at least two pulmonary function test measurements within 3 years of entry into the cohort. For each individual, spirometry, diffusion capacity, Charlson Comorbidity Index, sarcoidosis organ involvement, diagnosis duration, tobacco use, race, sex, age and medications were recorded. We compared changes in pulmonary function by type of pulmonary function phenotype and for demographic groups. RESULTS: Of 291 individuals, 59% (173) were female and 54% (156) were black. Individuals with restrictive pulmonary function phenotype had significantly greater 3-year rate of decline of FVC% (forced vital capacity) predicted and FEV1% (forced expiratory volume in 1 s) predicted course when compared with normal phenotype. We identified a subset of individuals in the cohort, highest decliners, who had a median 3-year FVC decline of 156 mL. Black individuals had worse pulmonary function at entry into the cohort measured by FVC% predicted, FEV1% predicted and diffusing capacity for carbon monoxide % predicted compared with white individuals. Black individuals' pulmonary function remained stable or declined over time, whereas white individuals' pulmonary function improved over time. There were no sex differences in rate of change in any pulmonary function parameters. SUMMARY: We found significant differences in 3-year change in pulmonary function among pulmonary function phenotypes and races, but no difference between sexes.

The Reddit cannabis subjective highness rating scale: Applying computational social science to explore psychological and environmental correlates of naturalistic cannabis use.

Social media data provide unprecedented access to discussions of active, naturalistic, and often real-time cannabis use in an era of cannabis policy liberalization. The aim of this study was to explore psychological and environmental correlates of cannabis effects by applying computational social science approaches to a large dataset of unprompted reports of naturalistic cannabis use with corresponding self-reported numerical ratings of subjective highness. Post title text was extracted via the Pushshift dataset from N = 328,865 posts to the r/trees Reddit community, where posters self-assess and disclose how high they feel on a scale from 1 to 10 (M = 6.9, SD = 1.8). Structural topic modelling and Linguistic Inquiry and Word Count (LIWC) dictionary-based approaches were applied to identify (1) frequently discussed topics and (2) text indicative of 5 psychological processes (affective, social, cognitive, perceptual, biological), respectively, as well as to examine relationships between subjective highness and (1) topic prevalence and (2) psychological process word counts. A 40-topic model was selected for interpretation based on semantic coherence and exclusivity. The most discussed topics in a 40-topic model were characterized by references to smoking places, social contexts, positive affect, cognitive states, as well as food and media consumed. In LIWC dictionary analyses, words mentioning affective, social, and cognitive processes were referenced more often than perceptual or body processes. Posters reported greater subjective highness when using language that referred to in-person social environments and lower subjective highness when using language that referred to online social environments and positive affect psychological states. This examination of unprompted online reports of naturalistic cannabis use identified textual content referring to affect and to other people as being associated with perceived effects of cannabis. These affective and social aspects of the cannabis use experience were salient to active posters in this online community and should be integrated into experience sampling methods and behavioral pharmacology research, as well as public health messaging.

Covering the bases: Population genomic structure of Lemna minor and the cryptic species L. japonica in Switzerland.

Duckweeds, including the common duckweed Lemna minor, are increasingly used to test eco-evolutionary theories. Yet, despite its popularity and near-global distribution, the understanding of its population structure (and genetic variation therein) is still limited. It is essential that this is resolved, because of the impact genetic diversity has on experimental responses and scientific understanding. Through whole-genome sequencing, we assessed the genetic diversity and population genomic structure of 23 natural Lemna spp. populations from their natural range in Switzerland. We used two distinct analytical approaches, a reference-free kmer approach and the classical reference-based one. Two genetic clusters were identified across the described species distribution of L. minor, surprisingly corresponding to species-level divisions. The first cluster contained the targeted L. minor individuals and the second contained individuals from a cryptic species: Lemna japonica. Within the L. minor cluster, we identified a well-defined population structure with little intra-population genetic diversity (i.e., within ponds) but high inter-population diversity (i.e., between ponds). In L. japonica, the population structure was significantly weaker and genetic variation between a subset of populations was as low as within populations. This study revealed that L. japonica is more widespread than previously thought. Our findings signify that thorough genotype-to-phenotype analyses are needed in duckweed experimental ecology and evolution.

Factors associated with family decision-making after pediatric out-of-hospital cardiac arrest.

AIM: This study aims to identify demographic factors, area-based social determinants of health (SDOH), and clinical features associated with medical decision-making after pediatric out-of-hospital cardiac arrest (OHCA). METHODS: This is a retrospective, exploratory, descriptive analysis of patients < 18 years old admitted to the pediatric intensive care unit (ICU) after OHCA from 2011 to 2022 (n = 217) at an urban tertiary care, free-standing children's hospital. Outcomes of interest included: (1) whether a new advance care plan (ACP) (defined as a written advance directive including do not resuscitate and/or do not intubate) was ordered during hospitalization, and (2) whether the patient was discharged with new medical technology (defined as tracheostomy and/or feeding tube). Logistic regression models identified features associated with these outcomes. RESULTS: Of the 217 patients, 78 patients (36%) had a new ACP placed during their admission. Of the survivors, 26% (27/102) were discharged home with new medical technology. Factors associated with ACP were greater change in Pediatric Cerebral Performance Category (PCPC) score (aOR = 1.49, 95% CI [1.28-1.73], p-value < 0.001) and palliative care consultation (aOR = 2.39, 95% CI [1.16-4.89], p-value 0.018). Factors associated with new medical technology were lower change in PCPC score (aOR = 0.76, 95% C.I. [0.61-0.95], p-value = 0.015) and palliative care consultation (aOR = 7.07, 95% CI [3.01-16.60], p-value < 0.001). There were no associations between area-based SDOH and outcomes. CONCLUSIONS: Understanding factors associated with decision-making related to ACP after OHCA is critical to optimize counseling for families. Multi-institutional studies are warranted to identify whether these findings are generalizable.

Merging Flow Synthesis and Enzymatic Maturation to Expand the Chemical Space of Lasso Peptides.

Many peptidic natural products, such as lasso peptides, cyclic peptides, and cyclotides, are conformationally constrained and show biological stability, making them attractive scaffolds for drug development. Although many peptides can be synthesized and modified through chemical methods, knot-like lasso peptides such as microcin J25 (MccJ25) and their analogues remain elusive. As the chemical space of MccJ25 analogues accessible through purely biological methods is also limited, we proposed a hybrid approach: flow-based chemical synthesis of non-natural precursor peptides, followed by in vitro transformation with recombinant maturation enzymes, to yield a more diverse array of lasso peptides. Herein, we established the rapid, flow-based synthesis of chemically modified MccJ25 precursor peptides (57 amino acids). Heterologous expression of enzymes McjB and McjC was extensively optimized to improve yields and facilitate the synthesis of multiple analogues of MccJ25, including the incorporation of non-canonical tyrosine and histidine derivatives into the lasso scaffold. Finally, using our chemoenzymatic strategy, we produced a biologically active analogue containing three d-amino acids in the loop region and incorporated backbone N-methylations. Our method provides rapid access to chemically modified lasso peptides that could be used to investigate structure-activity relationships, epitope grafting, and the improvement of therapeutic properties.

Structure-sparing resection for the management of cervical chordomas: a retrospective institutional series.

OBJECTIVE: Chordomas are a rare and relatively slow-growing malignancy of notochordal origin with a nearly 50% recurrence rate. Chordomas of the cervical spine are particularly challenging tumors given surrounding vital anatomical structures. Although standard in other areas of the spine, en bloc resection of cervical chordomas is exceedingly difficult and carries the risk of significant postoperative morbidity. Here, the authors present their institutional experience with 13 patients treated with a structure-sparing radical resection and adjuvant radiation for cervical chordomas. METHODS: Records of the standing senior author and institutional database of spinal surgeries were retrospectively reviewed for surgically managed cervical and high thoracic chordomas between 1997 and 2022. Chordomas whose epicenter was cervical but touched the clivus or had extension to the thoracic spine were included in this series. Clinical and operative data were gathered and analyzed for the index surgery and any revisions needed. Outcome metrics such as recurrence rates, complication rates, functional status, progression-free interval (PFI) and overall survival (OS) were evaluated. RESULTS: The median patient age at diagnosis was 57 (range 32-80) years. The median modified Rankin Scale (mRS) score at the time of presentation was 1 (range 0-4). Approximately 40% of tumors were located in the upper cervical spine (occiput-C2). The median time from diagnosis to surgery was 74.5 (range 10-483) days. Gross-total resection was achieved in just under 40% of patients. All patients received adjuvant radiotherapy. The mean duration of follow-up was 4.09 years, with a mean PFI of 3.80 (range 1.16-13.1) years. Five patients experienced recurrence (38.5%). The mean OS was 3.44 years. Three patients died during the follow-up period; 2 due to disease progression and 1 died in the immediate postoperative period. One patient was lost to follow-up. A significant positive relationship was identified between high cervical tumor location and disease recurrence (p = 0.021). CONCLUSIONS: While en bloc resection is appropriate and feasible for tumors in the sacral spine, the cervical region poses a significant technical challenge and is associated with increased postoperative morbidity. Radical resection may allow for achievement of negative operative margins and, along with sparing postoperative morbidity following resection of cervical chordomas, maintaining a similar rate of recurrence when compared with en bloc resection while preserving quality of life.