Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology.

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperforms existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor (normal) lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heat maps. The network was further tested using endobronchial biopsies from two data cohorts, containing normal to carcinoma in situ histology, and it demonstrated a unique capability to differentiate carcinoma in situ lung squamous PMLs based on their progression status to invasive carcinoma. The network may have utility in stratifying PMLs for chemoprevention trials or more aggressive follow-up.

Graph attention-based fusion of pathology images and gene expression for prediction of cancer survival.

Multimodal machine learning models are being developed to analyze pathology images and other modalities, such as gene expression, to gain clinical and biological insights. However, most frameworks for multimodal data fusion do not fully account for the interactions between different modalities. Here, we present an attention-based fusion architecture that integrates a graph representation of pathology images with gene expression data and concomitantly learns from the fused information to predict patient-specific survival. In our approach, pathology images are represented as undirected graphs, and their embeddings are combined with embeddings of gene expression signatures using an attention mechanism to stratify tumors by patient survival. We show that our framework improves the survival prediction of human non-small cell lung cancers, outperforming existing state-of-the-art approaches that leverage multimodal data. Our framework can facilitate spatial molecular profiling to identify tumor heterogeneity using pathology images and gene expression data, complementing results obtained from more expensive spatial transcriptomic and proteomic technologies.

Epistaxis and Facial Swelling Due to Nasal Blastomycosis in a Cat.

A 5 yr old castrated male domestic longhair was examined because of left-sided facial swelling and epistaxis. Head computed tomography with contrast identified a mass within the left nasal cavity and multifocal regions of nasal bone osteolysis. Histopathology of nasal mass biopsies and cytology of the facial swelling revealed pyogranulomatous inflammation due to Blastomyces dermatitidis. The cat experienced resolution of clinical signs following 8 mo of treatment with itraconazole. Although rare, clinicians should include blastomycosis on the differential diagnoses list of infectious causes for feline nasal disease if within an endemic area.

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates.

Epidemiological data have indicated that invasive infections caused by the Gram-positive cocci Streptococcus pyogenes (group A streptococcus, GAS) have increased in many Australian states over the past two decades. In July 2022, invasive GAS (iGAS) infections became nationally notifiable in Australia via public-health agencies. Surveillance for S. pyogenes infections has been sporadic within the state of New South Wales (NSW). This has led to a lack of genetic data on GAS strains in circulation, particularly for non-invasive infections, which are the leading cause of GAS's burden on the Australian healthcare system. To address this gap, we used whole-genome sequencing to analyse the genomes of 318 S. pyogenes isolates collected within two geographical regions of NSW. Invasive isolates were collected in 2007-2017, whilst non-invasive isolates were collected in 2019-2021. We found that at least 66 different emm-types were associated with clinical disease within NSW. There was no evidence of any Australian-specific clones in circulation. The M1UK variant of the emm1 global pandemic clone (M1global) has been detected in our isolates from 2013 onwards. We detected antimicrobial-resistance genes (mainly tetM, ermA or ermB genes) in less than 10 % of our 318 isolates, which were more commonly associated with non-invasive infections. Superantigen virulence gene carriage was reasonably proportionate between non-invasive and invasive infection isolates. Our study adds rich data on the genetic makeup of historical S. pyogenes infections within Australia. Ongoing surveillance of invasive and non-invasive GAS infections within NSW by whole-genome sequencing is warranted to inform on outbreaks, antimicrobial resistance and vaccine coverage.

A population modification gene drive targeting both Saglin and Lipophorin impairs Plasmodium transmission in Anopheles mosquitoes.

Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this antimalarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.

Epidemiology of Group A Streptococcal bacteraemia in Hunter New England Local Health District, 2008 to 2019.

Invasive Group A Streptococcal infection (iGAS) is an uncommon but serious infection with Streptococcus pyogenes in a normally sterile body site. Manifestations include bacteraemia, necrotising fasciitis and toxic shock syndrome with attendant serious morbidity and mortality. An increasing incidence of iGAS has been observed in some regions of Australia. iGAS became a nationally notifiable condition from 1 July 2021. To determine if regional incidence has increased, and to identify priority populations, we undertook a retrospective data analysis of Group A Streptococcal (GAS) bacteraemia cases in Hunter New England Local Health District (HNELHD), New South Wales, Australia, from 1 January 2008 to 31 December 2019, as identified by NSW Health Pathology, John Hunter Hospital. A total of 486 cases were identified (age-standardised rate: 4.05 cases per 100,000 population per year). Incidence in HNELHD gradually increased over the study period (adjusted incidence rate ratio: 1.04; 95% confidence interval: 1.01-1.07) and was significantly higher in children under 5 years of age; in adults over 70 years of age; in males; and in First Nations peoples. A significant peak occurred in 2017 (9.00 cases per 100,000 population), the cause of which remains unclear. GAS bacteraemia is uncommon but severe, and incidence in HNELHD has slowly increased. Public health and clinical guidelines must address the needs of priority populations, which include young children, older adults and First Nations peoples. Routine surveillance and genomic analysis will help improve our understanding of iGAS and inform best public health management.

Bird clades with less complex appendicular skeletons tend to have higher species richness.

Species richness is strikingly uneven across taxonomic groups at all hierarchical levels, but the reasons for this heterogeneity are poorly understood. It is well established that morphological diversity (disparity) is decoupled from taxonomic diversity, both between clades and across geological time. Morphological complexity has been much less studied, but there is theory linking complexity with differential diversity across groups. Here we devise an index of complexity from the differentiation of the fore and hind limb pairs for a sample of 983 species of extant birds. We test the null hypothesis that this index of morphological complexity is uncorrelated with clade diversity, revealing a significant and negative correlation between the species richness of clades and the mean morphological complexity of those clades. Further, we find that more complex clades tend to occupy a smaller number of dietary and habitat niches, and that this proxy for greater ecological specialisation correlates with lower species richness. Greater morphological complexity in the appendicular skeleton therefore appears to hinder the generation and maintenance of species diversity. This may result from entrenchment into morphologies and ecologies that are less capable of yielding further diversity.

Cultivating an Active Living Plan Through a Social-Ecological Evaluation.

Physical activity (PA) social-ecological model (SEM) posits the importance of several levels of influence critical for PA promotion within communities. The purpose of this study was to examine an SEM evaluation informing a county-wide active living plan in McLennan County, Texas in the United States. Mixed-methods evaluation occurred in 4 stages: (1) county policies (n = 15) were evaluated for PA promoting strategies; (2) PA resource assessments (PARAs) were conducted via Google Maps (n = 171); (3) surveys (n = 244) included the International Physical Activity Questionnaire and interpersonal and intrapersonal factors related to PA; and (4) focus groups (n = 5) were conducted with residents (n = 30), discussing barriers and facilitators to being active. Logistic regression determined significant associations between SEM factors and meeting PA recommendations. Policy scans and PARAs identified strengths and areas of improvement (eg, equitable project selection and disparities in resource quality). Residents reporting fewer barriers (OR = 0.89, P =.01), more perceived behavioral control (odds ratio [OR] = 1.38, P = .01), more social co-participation in PA (OR = 1.20, P = .03), and living in zip codes with higher mean PARA score (OR = 1.22, P = .04) were significantly more likely to meet PA recommendations (Nagelkerke R2 = 0.32). Focus groups also discussed safety and disparities in access and quality. This study suggests the utility of the SEM when evaluating and promoting community PA.

Cecum axis (CecAx) preservation reveals physiological and pathological gradients in mouse gastrointestinal epithelium.

The mouse cecum has emerged as a model system for studying microbe-host interactions, immunoregulatory functions of the microbiome, and metabolic contributions of gut bacteria. Too often, the cecum is falsely considered as a uniform organ with an evenly distributed epithelium. We developed the cecum axis (CecAx) preservation method to show gradients in epithelial tissue architecture and cell types along the cecal ampulla-apex and mesentery-antimesentery axes. We used imaging mass spectrometry of metabolites and lipids to suggest functional differences along these axes. Using a model of Clostridioides difficile infection, we show how edema and inflammation are unequally concentrated along the mesenteric border. Finally, we show the similarly increased edema at the mesenteric border in two models of Salmonella enterica serovar Typhimurium infection as well as enrichment of goblet cells along the antimesenteric border. Our approach facilitates mouse cecum modeling with detailed attention to inherent structural and functional differences within this dynamic organ.

Divergent vertebral formulae shape the evolution of axial complexity in mammals.

Complexity, defined as the number of parts and their degree of differentiation, is a poorly explored aspect of macroevolutionary dynamics. The maximum anatomical complexity of organisms has undoubtedly increased through evolutionary time. However, it is unclear whether this increase is a purely diffusive process or whether it is at least partly driven, occurring in parallel in most or many lineages and with increases in the minima as well as the means. Highly differentiated and serially repeated structures, such as vertebrae, are useful systems with which to investigate these patterns. We focus on the serial differentiation of the vertebral column in 1,136 extant mammal species, using two indices that quantify complexity as the numerical richness and proportional distribution of vertebrae across presacral regions and a third expressing the ratio between thoracic and lumbar vertebrae. We address three questions. First, we ask whether the distribution of complexity values in major mammal groups is similar or whether clades have specific signatures associated with their ecology. Second, we ask whether changes in complexity throughout the phylogeny are biased towards increases and whether there is evidence of driven trends. Third, we ask whether evolutionary shifts in complexity depart from a uniform Brownian motion model. Vertebral counts, but not complexity indices, differ significantly between major groups and exhibit greater within-group variation than recognized hitherto. We find strong evidence of a trend towards increasing complexity, where higher values propagate further increases in descendant lineages. Several increases are inferred to have coincided with major ecological or environmental shifts. We find support for multiple-rate models of evolution for all complexity metrics, suggesting that increases in complexity occurred in stepwise shifts, with evidence for widespread episodes of recent rapid divergence. Different subclades evolve more complex vertebral columns in different configurations and probably under different selective pressures and constraints, with widespread convergence on the same formulae. Further work should therefore focus on the ecological relevance of differences in complexity and a more detailed understanding of historical patterns.

What is the effect of a brief intervention to promote physical activity when delivered in a health care setting? A systematic review.

ISSUE ADDRESSED: What are the effects of a brief intervention to promote physical activity (PA) delivered in a health care setting other than primary care? METHODS: MEDLINE, EMBASE, CINAHL and PsycINFO were used to identify randomised controlled trials which evaluated the effect of brief interventions to increase PA, delivered in a health care setting. Review outcomes included subjectively or objectively measured PA, adherence to prescribed interventions, adverse events, health-related quality of life, self-efficacy and stage of change in relation to PA. Where possible, clinically homogenous studies were combined in a meta-analysis. RESULTS: Twenty-five eligible papers were included. Brief counselling interventions were associated with increased PA compared to control, for both self-reported PA (mean difference 34 minutes/week, 95% confidence intervals [95% CI] 9-60 minutes), and pedometer (MD 1541 steps/day, 95% CI 433-2649) at medium term follow up. CONCLUSION: Our findings suggest that some brief interventions to increase PA, delivered in the health care setting, are effective at increasing PA in the medium term. There is limited evidence for the long-term efficacy of such interventions. The wide variation in types of interventions makes it difficult to determine which intervention features optimize outcomes. SO WHAT?: Brief counselling interventions delivered in a health care setting may support improved PA. Clinicians working in health care settings should consider the implementation of brief interventions to increase PA in vulnerable patient groups, including older adults and those with chronic illness.

Nanoparticulate air pollution disrupts proteostasis in Caenorhabditis elegans.

The proteostasis network comprises the biochemical pathways that together maintain and regulate proper protein synthesis, transport, folding, and degradation. Many progressive neurodegenerative diseases, such as Huntington's disease (HD) and Alzheimer's disease (AD), are characterized by an age-dependent failure of the proteostasis network to sustain the health of the proteome, resulting in protein misfolding, aggregation, and, often, neurotoxicity. Although important advances have been made in recent years to identify genetic risk factors for neurodegenerative diseases, we still know relatively little about environmental risk factors such as air pollution. Exposure to nano-sized particulate air pollution, referred to herein as nanoparticulate matter (nPM), has been shown to trigger the accumulation of misfolded and oligomerized amyloid beta (Aß) in mice. Likewise, air pollution is known to exacerbate symptoms of AD in people. We asked whether nPM contributes to the misfolded protein load, thereby overwhelming the proteostasis network and triggering proteostasis decline. To address this, we utilized C. elegans that express reporter proteins that are sensitive to changes in the protein folding environment and respond by misfolding and displaying readily scorable phenotypes, such as localized YFP fluorescence or paralysis. We found that nPM exacerbated protein aggregation in body wall muscle cells, increasing the number of large visible protein aggregates, the amount of high molecular weight protein species, and proteotoxicity. Taken together, the data point to nPM negatively impacting proteostasis. Therefore, it seems plausible that nPM exposure may exacerbate symptoms of AD and age-related dementia in a manner that is at least partially dependent on proteostasis decline.

Bottled water contaminant exposures and potential human effects.

BACKGROUND: Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW. METHODS: BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity. Health-benchmark-weighted cumulative hazard indices and ratios of organic-contaminant in vitro exposure-activity cutoffs were assessed for detected regulated and unregulated inorganic and organic contaminants. RESULTS: 48 inorganics and 45 organics were detected in sampled BW. No enforceable chemical quality standards were exceeded, but several inorganic and organic contaminants with maximum contaminant level goal(s) (MCLG) of zero (no known safe level of exposure to vulnerable sub-populations) were detected. Among these, arsenic, lead, and uranium were detected in 67 %, 17 %, and 57 % of BW, respectively, almost exclusively in spring-sourced samples not treated by advanced filtration. Organic MCLG exceedances included frequent detections of disinfection byproducts (DBP) in tapwater-sourced BW and sporadic detections of DBP and volatile organic chemicals in BW sourced from tapwater and springs. Precautionary health-based screening levels were exceeded frequently and attributed primarily to DBP in tapwater-sourced BW and co-occurring inorganic and organic contaminants in spring-sourced BW. CONCLUSION: The results indicate that simultaneous exposures to multiple drinking-water contaminants of potential human-health concern are common in BW. Improved understandings of human exposures based on more environmentally realistic and directly comparable point-of-use exposure characterizations, like this BW study, are essential to public health because drinking water is a biological necessity and, consequently, a high-vulnerability vector for human contaminant exposures.

Pandemic-Era Digital Education: Insights from an Undergraduate Medical Programme.

The undergraduate medical programme at Newcastle University (NU) includes a fundamental 'Essentials of Medical Practice' (EOMP) phase comprising the first 2 years of study. This period is designed to support entrants in their transition from further education into the advanced study and practice of clinical medicine. The anatomical sciences of gross anatomy, histology and embryology, and life sciences including physiology, pharmacology and genetics are key disciplines taught within the integrated case-based EOMP curriculum. Learners apply basic science knowledge to clinical scenarios during training in practical examination, communication and reasoning skills. Within the modern pedagogic landscape, the development and introduction of technology-enhanced learning strategies have enhanced the provision of remote learning resources in pre-clinical education. However, the emergence of COVID-19 has resulted in widespread technological challenges for educators and learners, and has raised pedagogic, logistical and ethical concerns. Nonetheless, the pandemic has produced favourable conditions for the creation of valuable digital visualisation strategies for learning and teaching, and for developing and modernising universal approaches to remote education. Here, we describe our technology-enhanced adaptations to COVID-19 across the domains of teaching, learning and academic support for pre-clinical learners studying basic life sciences and clinical skills. Moreover, we outline research-informed digital visualisation solutions to pandemic-era challenges and reflect upon experiences gained within our own educational context. In doing so, we provide insights into the impacts and successes of our interventions. While providing a record of unprecedented contemporary circumstances, we also aim to utilise our observations and experiences of COVID-19 pedagogy when developing ongoing strategies for delivering curricula and futureproofing educational practice.

Trachymyrmex septentrionalis Ant Microbiome Assembly Is Unique to Individual Colonies and Castes.

Within social insect colonies, microbiomes often differ between castes due to their different functional roles and between colony locations. Trachymyrmex septentrionalis fungus-growing ants form colonies throughout the eastern United States and northern Mexico that include workers, female and male alates (unmated reproductive castes), larvae, and pupae. How T. septentrionalis microbiomes vary across this geographic range and between castes is unknown. Our sampling of individual ants from colonies across the eastern United States revealed a conserved T. septentrionalis worker ant microbiome and revealed that worker ant microbiomes are more conserved within colonies than between them. A deeper sampling of individual ants from two colonies that included all available castes (pupae, larvae, workers, and female and male alates), from both before and after adaptation to controlled laboratory conditions, revealed that ant microbiomes from each colony, caste, and rearing condition were typically conserved within but not between each sampling category. Tenericute bacterial symbionts were especially abundant in these ant microbiomes and varied widely in abundance between sampling categories. This study demonstrates how individual insect colonies primarily drive the composition of their microbiomes and shows that these microbiomes are further modified by developmental differences between insect castes and the different environmental conditions experienced by each colony. IMPORTANCE This study investigates microbiome assembly in the fungus-growing ant Trachymyrmex septentrionalis, showing how colony, caste, and lab adaptation influence the microbiome and revealing unique patterns of mollicute symbiont abundance. We find that ant microbiomes differ strongly between colonies but less so within colonies. Microbiomes of different castes and following lab adaptation also differ in a colony-specific manner. This study advances our understanding of the nature of individuality in social insect microbiomes and cautions against the common practice of only sampling a limited number of populations to understand microbiome diversity and function.

A Graph-Transformer for Whole Slide Image Classification.

Deep learning is a powerful tool for whole slide image (WSI) analysis. Typically, when performing supervised deep learning, a WSI is divided into small patches, trained and the outcomes are aggregated to estimate disease grade. However, patch-based methods introduce label noise during training by assuming that each patch is independent with the same label as the WSI and neglect overall WSI-level information that is significant in disease grading. Here we present a Graph-Transformer (GT) that fuses a graph-based representation of an WSI and a vision transformer for processing pathology images, called GTP, to predict disease grade. We selected 4,818 WSIs from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), the National Lung Screening Trial (NLST), and The Cancer Genome Atlas (TCGA), and used GTP to distinguish adenocarcinoma (LUAD) and squamous cell carcinoma (LSCC) from adjacent non-cancerous tissue (normal). First, using NLST data, we developed a contrastive learning framework to generate a feature extractor. This allowed us to compute feature vectors of individual WSI patches, which were used to represent the nodes of the graph followed by construction of the GTP framework. Our model trained on the CPTAC data achieved consistently high performance on three-label classification (normal versus LUAD versus LSCC: mean accuracy = 91.2 ± 2.5%) based on five-fold cross-validation, and mean accuracy = 82.3 ± 1.0% on external test data (TCGA). We also introduced a graph-based saliency mapping technique, called GraphCAM, that can identify regions that are highly associated with the class label. Our findings demonstrate GTP as an interpretable and effective deep learning framework for WSI-level classification.

A Novel Cadaveric Embalming Technique for Enhancing Visualisation of Human Anatomy.

Within the discipline of anatomical education, the use of donated human cadavers in laboratory-based learning activities is often described as the 'gold standard' resource for supporting student understanding of anatomy. Due to both historical and educational factors, cadaveric dissection has traditionally been the approach against which other anatomy learning modalities and resources have been judged. To prepare human donors for teaching purposes, bodies must be embalmed with fixative agents to preserve the tissues. Embalmed cadavers can then be dissected by students or can be prosected or plastinated to produce teaching resources. Here, we describe the history of cadaveric preservation in anatomy education and review the practical strengths and limitations of current approaches for the embalming of human bodies. Furthermore, we investigate the pedagogic benefits of a range of established modern embalming techniques. We describe relevant cadaveric attributes and their impacts on learning, including the importance of colour, texture, smell, and joint mobility. We also explore the emotional and humanistic elements of the use of human donors in anatomy education, and the relative impact of these factors when alternative types of embalming process are performed. Based on these underpinnings, we provide a technical description of our modern Newcastle-WhitWell embalming process. In doing so, we aim to inform anatomy educators and technical staff seeking to embalm human donors rapidly and safely and at reduced costs, while enhancing visual and haptic tissue characteristics. We propose that our technique has logistical and pedagogic implications, both for the development of embalming techniques and for student visualisation and learning.

Beliefs about social norms and racial inequalities predict variation in the early development of racial bias.

Racism remains a pervasive force around the world with widespread and well documented harmful consequences for members of marginalized racial groups. The psychological biases that maintain structural and interpersonal racism begin to emerge in early childhood, but with considerable individual variation-some children develop more racial bias than others. The present study (N = 116; 4-year-old children) provides novel insights into the developmental mechanisms underlying the emergence of racial bias by longitudinally documenting how two psychological processes-normative beliefs about interracial friendships and explanatory beliefs about racial inequalities-developmentally predict the emergence of pro-White/anti-Black racial bias during early childhood. In a 6-month, three-wave, longitudinal study, we found that 4-year-old children's beliefs that their parents and peers do not value interracial friendships predicted increased racial bias in and across time and that children's endorsement of essentialist over extrinsic explanations for racial inequalities predicted the developmental trajectory of racial bias over time. These findings suggest that children's foundational beliefs about the social world developmentally predict the emergence of racial bias in early childhood and speak to the importance of early and persistent intervention efforts targeting children's normative beliefs about interracial friendships and explanatory beliefs about racial inequalities.

A Brief Intervention of Physical Activity Education and Counseling in Community Rehabilitation: A Feasibility Randomized Controlled Trial.

This study aimed to assess the feasibility of delivering a brief physical activity (PA) intervention to community rehabilitation clients. Participants were randomized to receive one session of stage-of-change-based PA education and counseling in addition to written educational material, or education material alone. Outcomes were measured at baseline and 3 months; the primary outcome was feasibility, measured by the percentage of those who were eligible, consented, randomized, and followed-up. A total of 123 individuals were both eligible and interested in participating, 32% of those screened on admission to the program. Forty participants consented, and 35 were randomized, with mean age 72 years (SD = 12.2). At baseline, 66% had recently commenced or intended to begin regular PA in the next 6 months. A total of 30 participants were followed-up. It is feasible to deliver education and counseling designed to support the long-term adoption of regular PA to community rehabilitation clients. Further refinement of the protocol is warranted (ACTRN12617000519358).

Sodium bicarbonate administration and subsequent potassium concentration in hyperkalemia treatment.

BACKGROUND: Hyperkalemia is an electrolyte disorder commonly encountered in the emergency department that can result in significant morbidity and mortality. While sodium bicarbonate is often used for acute lowering of serum potassium, its efficacy is not well established. The purpose of this study was to evaluate and quantify the amount of potassium reduction in emergency department patients who received intravenous sodium bicarbonate as part of treatment for hyperkalemia compared with those who did not. METHODS: A retrospective electronic chart review was conducted on adult patients who presented to the emergency department with initial potassium concentration greater than or equal to 5.4 mMol/L and received intravenous insulin as part of hyperkalemia treatment. Patients who received intravenous sodium bicarbonate in addition to intravenous insulin were included in the sodium bicarbonate group. The control group included patients who did not receive intravenous sodium bicarbonate. The primary objective of this study was to compare the absolute reduction in serum potassium between initial and second concentrations in patients from the sodium bicarbonate group and those in the control group. RESULTS: A total of 106 patients were included in this study with 38 patients in the sodium bicarbonate group and 68 patients in the control group. Median initial potassium concentration was 6.6 mMol/L in the sodium bicarbonate group and 6.1 mMol/L in the control group (P = 0.009). Absolute reduction of potassium at first repeat was 1 and 0.9 mMol/L in sodium bicarbonate group and control group respectively (P = 0.976). CONCLUSIONS: The addition of sodium bicarbonate therapy to intravenous insulin in the treatment of hyperkalemia did not offer statistically significant added efficacy in potassium lowering. Larger studies are needed to further validate the result findings.