Pediatric ACEs Screening and Referral: Facilitators, Barriers, and Opportunities for Improvement.

Despite well-documented associations between adverse childhood experiences (ACEs) and lifelong impairments in health and well-being, few studies have examined how to facilitate implementation of ACEs screening and referral programs in pediatric settings. We sought to identify facilitators and barriers related to screening for and addressing ACEs in a large integrated healthcare delivery system in Southern California. Using a developmental evaluation approach, we conducted twenty semi-structured interviews with pediatricians, nurses, social workers, and community referral organization staff. Interviews took place across six pediatric clinic pilot sites in Kaiser Permanente Southern California, where more than 7,000 pediatric patients were screened for ACEs between July 2018 and December 2019. Thematic analysis was conducted to identify themes. Key facilitators for screening and referrals for pediatric ACEs screening included providing clinician education to normalize conversations about ACEs, using screening data to provide more holistic and compassionate care, and collaborating across different types of clinicians. Key barriers included screening tool challenges related to patient confusion and cultural differences, capacity limitations, training issues, and care team silos. When used in the context of a trauma- and resilience-informed workforce, ACEs screening may be a powerful tool to support more collaborative and impactful care decisions that move away from symptom management to address root causes and promote prevention.

Use of ICD-10-CM Codes for Adverse Social Determinants of Health Across Health Systems.

OBJECTIVE: This study investigated ICD-10-CM codes for adverse social determinants of health (SDoH) across 12 U.S. health systems by using data from multiple health care encounter types for diverse patients covered by multiple payers. METHODS: The authors described documentation of 11 SDoH ICD-10-CM code categories (e.g., educational problems or social environmental problems) between 2016 and 2021; assessed changes over time by using chi-square tests for trend in proportions; compared documentation in 2021 by gender, age, race-ethnicity, and site with chi-square tests; and compared all patients' mental health outcomes in 2021 with those of patients with documented SDoH ICD-10-CM codes by using exact binomial tests and one-proportion z tests. RESULTS: Documentation of any SDoH ICD-10-CM code significantly increased, from 1.7% of patients in 2016 to 2.7% in 2021, as did that for all SDoH categories except educational problems. Documentation was often more prevalent among female patients and those of other or unknown gender than among male patients and among American Indian or Alaska Native, Black or African American, and Hispanic individuals than among those belonging to other race-ethnicity categories. More educational problems were documented for younger patients, and more social environmental problems were documented for older patients. Psychiatric diagnoses and emergency department visits and hospitalizations related to mental health were more common among patients with documented SDoH codes. CONCLUSIONS: SDoH ICD-10-CM code documentation was infrequent and differed by population subgroup. Differences may reflect documentation practices or true SDoH prevalence variation. Standardized SDoH documentation methods are needed in health care settings.

Rethinking Prehospital Response to Mass Casualty Events: Move, Treat, and Transport.

Herein, we present a simplified approach to prehospital mass casualty event (MASCAL) management called "Move, Treat, and Transport." Prior publications demonstrate a disconnect between MASCAL response training and actions taken during real-world incidents. Overly complex algorithms, infrequent training on their use, and chaotic events all contribute to the low utilization of formal triage systems in the real world. A review of published studies on prehospital MASCAL management and a recent series of military prehospital MASCAL responses highlight the need for an intuitive MASCAL management system that accounts for expected resource limitations and tactical constraints. "Move, Treat, and Transport" is a simple and pragmatic approach that emphasizes speed and efficiency of response; considers time, tactics, and scale of the event; and focuses on interventions and evacuation to definitive care if needed.

Expanding the repertoire of GalNAc analogues for cell-specific bioorthogonal tagging of glycoproteins.

Glycosylation is a ubiquitous modification of proteins, necessitating approaches for its visualization and characterization. Bioorthogonally tagged monosaccharides have been instrumental to this end, offering a chemical view into the cell biology of glycans. Understanding the use of such monosaccharides by cellular biosynthetic pathways has expanded their applicability in cell biology, for instance through the strategy named Bio-Orthogonal Cell-specific TAgging of Glycoproteins (BOCTAG). Here, we show that the cellular use of two azide-tagged analogues of the monosaccharide N-acetylgalactosamine (GalNAzMe and GalNPrAz) can be promoted through expression of two biosynthetic enzymes. More precisely, cellular expression of the bacterial kinase NahK and the engineered human pyrophosphorylase AGX1F383A led to biosynthesis of the corresponding activated nucleotide-sugars and subsequent bioorthogonal tagging of the cellular glycoproteome. We explore the use of both sugars for BOCTAG, demonstrating the visualization of cell surface glycosylation tagged with GalNPrAz in a specific cell line in a co-culture system. Our work adds to the toolbox of glycoprotein analysis in biomedicine.

Limitations of Triage in Military Mass Casualty Response: A Case Series.

INTRODUCTION: Mass casualty events (MASCALs) in the combat environment, which involve large numbers of casualties that overwhelm immediately available resources, are fundamentally chaotic and dynamic and inherently dangerous. Formal triage systems use diagnostic algorithms, colored markers, and four or more named categories. We hypothesized that formal triage systems are inadequately trained and practiced and too complex to successfully implement in true MASCAL events. This retrospective analysis evaluates the real-world application of triage systems in prehospital military MASCALs and other aspects of MASCAL management. METHODS: We surveyed Special Operations Forces (SOF) medics known to us who have participated in military prehospital MASCALs and analyzed them. Aggregated data describing the scope of the incidents, the use of formal triage algorithms and colored markers, the number of categories, and the interventions on scene were analyzed using descriptive statistics, and lessons learned were consolidated. RESULTS: From 1996 to 2022 we identified 29 MASCALs that were managed by military medics in the prehospital setting. There was a median of three providers (range 1-85) and 15 casualties (range 6-519) per event. Four or more formal triage categories were used in only one event. Colored markers and formal algorithms were not used. Life-saving interventions were performed in 27 of 29 (93%) missions and blood transfusions were performed in four (17%) MASCALs. The top lessons learned were: 1) security and accountability are cornerstones of MASCAL management; 2) casualty movement is a priority; 3) intuitive triage categories are the default; 4)life-saving interventions are performed as time and tacticspermit. CONCLUSION: Formal triage systems requiring the use ofdiagnostic algorithms, colored tags, and four or five categories are seldom implemented in real-world military prehospitalMASCAL management. The training of field triage should besimplified and pragmatic, as exemplified by these instances.

Prevalence and trends of suspected cannabinoid hyperemesis syndrome over an 11-year period in Northern California: An electronic health record study.

BACKGROUND: As access to cannabis has increased, there has been a rise in a condition called cannabinoid hyperemesis syndrome (CHS). This study estimates annual prevalence of suspected CHS at emergency department visits (ED) over an 11-year period in Northern California. METHODS: This retrospective observational cohort study used electronic health records from Kaiser Permanente Northern California. Two CHS case definitions were used to construct two cohorts of adults (18+) with ≥1 CHS visits from 2009 to 2019. The primary definition used a narrow definition based on past studies (CHS group 1) and an exploratory definition allowed for a broader range of codes (CHS group 2); both definitions required a primary diagnosis of vomiting. Annual prevalence of CHS and annual rates of counts of CHS visits estimated using a log-link Poisson model are reported per group. FINDINGS: There were 57,227 patients with ≥1 CHS visits included in CHS group 1 and 65,645 patients included in CHS group 2. Over eleven years, CHS increased across groups with the fastest rise in CHS group 1 (prevalence ratio = 2.75, 95 % confidence interval [CI] 2.65-2.85, p<.0001 from 2009 to 2019 vs. prevalence ratio = 2.34, 95 % CI 2.27-2.43). CHS group 1 also exhibited the largest increase in ED visits (rate ratio = 2.35, 95 % CI 2.27-2.43, p<.0001). CONCLUSION: In a large California population, suspected CHS increased over time across definitions. Annual prevalence increased by 134-175 %, depending on CHS definition. CHS group 2's definition may have been too broad and changes in ICD-10-CM coding may have impacted estimates.

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease.

Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.

Climate-driven succession in marine microbiome biodiversity and biogeochemical function.

Seasonal and El Niño-Southern Oscillation (ENSO) warming result in similar ocean changes as predicted with climate change. Climate-driven environmental cycles have strong impacts on microbiome diversity, but impacts on microbiome function are poorly understood. We quantified changes in microbial genomic diversity and functioning over 11 years covering seasonal and ENSO cycles at a coastal site in the southern California Current. We observed seasonal oscillations between large genome lineages during cold, nutrient rich conditions in winter and spring versus small genome lineages, including Prochlorococcus and Pelagibacter , in summer and fall. Parallel interannual changes separated communities depending on ENSO condition. Biodiversity shifts translated into clear oscillations in microbiome functional potential. Ocean warming induced an ecosystem with less iron but more macronutrient stress genes, depressed organic carbon degradation potential and biomass, and elevated carbon-to-nutrient biomass ratios. The consistent microbial response observed across time-scales points towards large climate-driven changes in marine ecosystems and biogeochemical cycles.

Obesity and Weight Loss Strategies for Patients With Heart Failure.

Obesity is a common comorbidity among patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), with the strongest pathophysiologic link of obesity being seen for HFpEF. Lifestyle measures are the cornerstone of weight loss management, but sustainability is a challenge, and there are limited efficacy data in the heart failure (HF) population. Bariatric surgery has moderate efficacy and safety data for patients with preoperative HF or left ventricular dysfunction and has been associated with reductions in HF hospitalizations and medium-term mortality. Antiobesity medications historically carried concerns for cardiovascular adverse effects, but the safety and weight loss efficacy seen in general population trials of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 agonists are highly encouraging. Although there are safety concerns regarding GLP-1 agonists in advanced HFrEF, trials of the GLP-1 agonist semaglutide for treatment of obesity have confirmed safety and efficacy in patients with HFpEF.

PRC1.6 localizes on chromatin with the human silencing hub (HUSH) complex for promoter-specific silencing.

An obligate step in the life cycle of HIV-1 and other retroviruses is the establishment of the provirus in target cell chromosomes. Transcriptional regulation of proviruses is complex, and understanding the mechanisms underlying this regulation has ramifications for fundamental biology, human health, and gene therapy implementation. The three core components of the Human Silencing Hub (HUSH) complex, TASOR, MPHOSPH8 (MPP8), and PPHLN1 (Periphilin 1), were identified in forward genetic screens for host genes that repress provirus expression. Subsequent loss-of-function screens revealed accessory proteins that collaborate with the HUSH complex to silence proviruses in particular contexts. To identify proteins associated with a HUSH complex-repressed provirus in human cells, we developed a technique, Provirus Proximal Proteomics, based on proximity labeling with C-BERST (dCas9-APEX2 biotinylation at genomic elements by restricted spatial tagging). Our screen exploited a lentiviral reporter that is silenced by the HUSH complex in a manner that is independent of the integration site in chromatin. Our data reveal that proviruses silenced by the HUSH complex are associated with DNA repair, mRNA processing, and transcriptional silencing proteins, including L3MBTL2, a member of the non-canonical polycomb repressive complex 1.6 (PRC1.6). A forward genetic screen confirmed that PRC1.6 components L3MBTL2 and MGA contribute to HUSH complex-mediated silencing. PRC1.6 was then shown to silence HUSH-sensitive proviruses in a promoter-specific manner. Genome wide profiling showed striking colocalization of the PRC1.6 and HUSH complexes on chromatin, primarily at sites of active promoters. Finally, PRC1.6 binding at a subset of genes that are silenced by the HUSH complex was dependent on the core HUSH complex component MPP8. These studies offer new tools with great potential for studying the transcriptional regulation of proviruses and reveal crosstalk between the HUSH complex and PRC1.6.

The thin red line: Blood planning factors and the enduring need for a robust military blood system to support combat operations.

ABSTRACT: Battlefield lessons learned are forgotten; the current name for this is the Walker Dip. Blood transfusion and the need for a Department of Defense Blood Program are lessons that have cycled through being learned during wartime, forgotten, and then relearned during the next war. The military will always need a blood program to support combat and contingency operations. Also, blood supply to the battlefield has planning factors that have been consistent over a century. In 2024, it is imperative that we codify these lessons learned. The linchpins of modern combat casualty care are optimal prehospital care, early whole blood transfusion, and forward surgical care. This current opinion comprised of authors from all three military Services, the Joint Trauma System, the Armed Services Blood Program, blood SMEs and the CCC Research Program discuss two vital necessities for a successful military trauma system: (1) the need for an Armed Services Blood Program and (2) Planning factors for current and future deployed military ere is no effective care for wounded soldiers, and by extension there is no effective military medicine.

Quantification and site-specific analysis of co-occupied N- and O-glycopeptides.

Protein glycosylation is a complex post-translational modification that is generally classified as N- or O-linked. Site-specific analysis of glycopeptides is accomplished with a variety of fragmentation methods, depending on the type of glycosylation being investigated and the instrumentation available. For instance, collisional dissociation methods are frequently used for N-glycoproteomic analysis with the assumption that one N-sequon exists per tryptic peptide. Alternatively, electron-based methods are indispensable for O-glycosite localization. However, the presence of simultaneously N- and O-glycosylated peptides could suggest the necessity of electron-based fragmentation methods for N-glycoproteomics, which is not commonly performed. Thus, we quantified the prevalence of N- and O-glycopeptides in mucins and other glycoproteins. A much higher frequency of co-occupancy within mucins was detected whereas only a negligible occurrence occurred within non-mucin glycoproteins. This was demonstrated from analyses of recombinant and/or purified proteins, as well as more complex samples. Where co-occupancy occurred, O-glycosites were frequently localized to the Ser/Thr within the N-sequon. Additionally, we found that O-glycans in close proximity to the occupied Asn were predominantly unelaborated core 1 structures, while those further away were more extended. Overall, we demonstrate electron-based methods are required for robust site-specific analysis of mucins, wherein co-occupancy is more prevalent. Conversely, collisional methods are generally sufficient for analyses of other types of glycoproteins.

Analysis of Mucin-Domain Glycoproteins Using Mass Spectrometry.

Mucin-domain glycoproteins are characterized by their high density of glycosylated serine and threonine residues, which complicates their analysis by mass spectrometry. The dense glycosylation renders the protein backbone inaccessible to workhorse proteases like trypsin, the vast heterogeneity of glycosylation often results in ion suppression from unmodified peptides, and search algorithms struggle to confidently analyze and site-localize O-glycosites. We have made a number of advances to address these challenges, rendering mucinomics possible for the first time. Here, we summarize these contributions and provide a detailed protocol for mass spectrometric analysis of mucin-domain glycoproteins. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Enrichment of mucin-domain glycoproteins Basic Protocol 2: Enzymatic digestion of mucin-domain glycoprotein(s) Basic Protocol 3: Mass spectrometry data collection for O-glycopeptides Basic Protocol 4: Mass spectrometry data analysis of O-glycopeptides.

Xylosyltransferase Bump-and-hole Engineering to Chemically Manipulate Proteoglycans in Mammalian Cells.

Mammalian cells orchestrate signalling through interaction events on their surfaces. Proteoglycans are an intricate part of these interactions, carrying large glycosaminoglycan polysaccharides that recruit signalling molecules. Despite their importance in development, cancer and neurobiology, a relatively small number of proteoglycans have been identified. In addition to the complexity of glycan extension, biosynthetic redundancy in the first protein glycosylation step by two xylosyltransferase isoenzymes XT1 and XT2 complicates annotation of proteoglycans. Here, we develop a chemical genetic strategy that manipulates the glycan attachment site of cellular proteoglycans. By employing a tactic termed bump- and-hole engineering, we engineer the two isoenzymes XT1 and XT2 to specifically transfer a chemically modified xylose analogue to target proteins. The chemical modification contains a bioorthogonal tag, allowing the ability to visualise and profile target proteins modified by both transferases in mammalian cells. The versatility of our approach allows pinpointing glycosylation sites by tandem mass spectrometry, and exploiting the chemical handle to manufacture proteoglycans with defined GAG chains for cellular applications. Engineered XT enzymes permit a view into proteoglycan biology that is orthogonal to conventional techniques in biochemistry.

A safety and feasibility analysis on the use of cold-stored platelets in combat trauma.

BACKGROUND: Damage-control resuscitation has come full circle, with the use of whole blood and balanced components. Lack of platelet availability may limit effective damage-control resuscitation. Platelets are typically stored and transfused at room temperature and have a short shelf-life, while cold-stored platelets (CSPs) have the advantage of a longer shelf-life. The US military introduced CSPs into the battlefield surgical environment in 2016. This study is a safety analysis for the use of CSPs in battlefield trauma. METHODS: The Department of Defense Trauma Registry and Armed Services Blood Program databases were queried to identify casualties who received room-temperature-stored platelets (RSPs) or both RSPs and CSPs between January 1, 2016, and February 29, 2020. Characteristics of recipients of RSPs and RSPs-CSPs were compared and analyzed. RESULTS: A total of 274 patients were identified; 131 (47.8%) received RSPs and 143 (52.2%) received RSPs-CSPs. The casualties were mostly male (97.1%), similar in age (31.7 years), with a median Injury Severity Score of 22. There was no difference in survival for recipients of RSPs (88.5%) versus RSPs-CSPs (86.7%; p = 0.645). Adverse events were similar between the two cohorts. Blood products received were higher in the RSPs-CSPs cohort compared with the RSPs cohort. The RSPs-CSPs cohort had more massive transfusion (53.5% vs. 33.5%, p = 0.001). A logistic regression model demonstrated that use of RSPs-CSPs was not associated with mortality, with an adjusted odds ratio of 0.96 (p > 0.9; 95% confidence interval, 0.41-2.25). CONCLUSION: In this safety analysis of RSPs-CSPs compared with RSPs in a combat setting, survival was similar between the two groups. Given the safety and logistical feasibility, the results support continued use of CSPs in military environments and further research into how to optimize resuscitation strategies. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Clinical Outcomes of Orthopedic Surgery Co-Management by Internal Medicine Advanced Practice Clinicians: A Cohort Study.

BACKGROUND: Comanagement of orthopedic surgery patients by internal medicine hospitalists is associated with improvements in clinical outcomes including complications, length of stay, and cost. Clinical outcomes of orthopedic comanagement performed solely by internal medicine advanced practice clinicians have not been reported. Our objecyive was to compare clinical outcomes between advanced practice clinician-based comanagement and usual orthopedic care. METHODS: This is a retrospective cohort study in patients 18 years or older, hospitalized for orthopedic joint or spine surgery between May 1, 2014 and January 1, 2022. Outcomes assessed were length of stay, intensive care unit (ICU) transfer, return to operating room, in-hospital and 30-day mortality, 30-day readmission, and total direct cost, excluding surgical implants. Generalized boosted regression and propensity score weighting was used to compare clinical outcomes and health care cost between usual care and advanced practice clinician comanagement. RESULTS: Advanced practice clinician comanagement was associated with a 5% reduction in mean length of stay (rate ratio = 0.95, P = .009), decreased odds of returning to the operating room (odds ratio [OR] 0.51, P = .002), and a significant reduction in 30-day mortality (OR 0.32, P = .037) compared with usual orthopedic care in a weighted analysis. Need for ICU transfer was higher with advanced practice clinician comanagement (OR 1.54, P = .009), without significant differences in 30-day readmission or in-hospital mortality. CONCLUSIONS: We observed reductions in length of stay, health care costs, return to the operating room, and 30-day mortality with advanced practice clinician comanagement compared with usual orthopedic care. Our findings suggest that advanced practice clinician-based comanagement may represent a safe and cost-effective model for orthopedic comanagement.

Nursing science at Mayo Clinic: An alternative model to traditional hospital-based nurse scientist positions.

The role of the Nurse Scientist in clinical settings represents a relatively new career path that has garnered attention in recent literature. Although there is considerable variability in how this role is operationalized across institutions, Mayo Clinic stands out as one of the few health systems in the United States employing nurse scientists who are fully and exclusively engaged in their own programs of research. Given the need for practical information to guide development and implementation of a research-focused nurse scientist role, the purpose of this paper is to describe the infrastructure and resources supporting Mayo Clinic nurse scientists, share role expectations and metrics for success, discuss both the facilitators of success and ongoing challenges, and compare our current practices to those found in the literature.

Obesity, Challenges, and Weight-Loss Strategies for Patients With Ventricular Assist Devices.

For adults with advanced heart failure, class II/III obesity (body mass index ≥35 kg/m2) represents major challenges, and it is even considered a contraindication for heart transplantation (HT) at many centers. This has led to growing interest in preventing and treating obesity to help patients with advanced heart failure become HT candidates. Among all weight-loss strategies, bariatric surgery (BSx) has the greatest weight loss efficacy and has shown value in enabling select patients with left ventricular assist devices (LVADs) and obesity to lose sufficient weight to access HT. Nevertheless, both BSx and antiobesity medications warrant caution in the LVAD population. In this review, the authors describe and interpret the available published reports on the impact of obesity and weight-loss strategies for patients with LVADs from general and HT candidacy standpoints. The authors also provide an overview of the journey of LVAD recipients who undergo BSx and review major aspects of perioperative protocols.