Polyamines regulate cell fate by altering the activity of histone-modifying enzymes.

Polyamines are polycationic alkyl-amines abundant in proliferating stem and cancer cells. How these metabolites influence numerous cellular functions remains unclear. Here we show that polyamine levels decrease during differentiation and that inhibiting polyamine synthesis leads to a differentiated-like cell state. Polyamines concentrate in the nucleus and are further enriched in the nucleoli of cells in culture and in vivo . Loss of polyamines drives changes in chromatin accessibility that correlate with altered histone post-translational modifications. Polyamines interact electrostatically with DNA on the nucleosome core, stabilizing histone tails in conformations accessible to modifying enzymes. These data reveal a mechanism by which an abundant metabolite influences chromatin structure and function in a non-sequence specific manner, facilitating chromatin remodeling during reprogramming and limiting it during fate commitment.

Ovarian Carcinosarcoma Mimicking Symptoms of Recurrent Diverticulitis: A Case Report.

Ovarian carcinosarcoma, also known as malignant mixed müllerian tumor, is a rare and highly aggressive form of ovarian cancer. This report discusses a case where initial misdiagnosis underscored the complexity of diagnosing this condition. The findings highlight the critical nature of considering ovarian malignancies in the differential diagnosis for postmenopausal women presenting with abdominal pain and altered bowel habits. The significance of utilizing advanced imaging techniques and tumor markers in the early detection of ovarian carcinosarcoma is emphasized, demonstrating how such strategies can substantially affect patient management and outcomes. This case also illustrates the effectiveness of a multidisciplinary approach in treating this challenging malignancy, contributing to our understanding and management of ovarian carcinosarcoma.

Social Risk Determinants for Successful Same Calendar Day Discharge in Total Joint Arthroplasty.

Background: While many studies have examined the impact of comorbidities on the success of same calendar day discharge (SCDD) in total joint arthroplasty (TJA), literature surrounding the impact of social determinants is lacking. Purpose: We sought to investigate the relationship between various social determinants and success of SCDD after primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods: We conducted a retrospective review of 1160 THA and 1813 TKA performed at a single academic institution between November 2020 and August 2022. Social factors including substance use, occupation, marital status, income, and participation in physical exercise were included. In addition, aspects of discharge planning were reviewed such as living situation and transportation details. Results: Overall, 952 (32%) patients had successful SCDD, whereas 2021 (68%) patients were discharged on postoperative day 1 (POD1) or greater. Successful SCDD patients were more likely to have health care (4.8% vs 2.5%) and active (5.4% vs 4.6%) rather than sedentary occupations, be married (79.6% vs 67.4%), have access to transportation (95.6% vs 92.9%), live in a higher median income area ($64,044 [16,183] vs $61,572 [14,594]), and exercise weekly (62.6% vs 23.9%). Interestingly, the successful patients had more stories in their homes (1.62 [0.56] vs 1.43 [0.53]), more stairs to enter their homes (5.19 [5.22] vs 4.60 [5.24]), lived farther from the hospital (43.3 [138.0] vs 32.0 [75.9] miles), and a higher prevalence of alcohol use (60.7% vs 44.7%) and tobacco use (19.3% vs 17.3%). Conclusion: These findings may help arthroplasty surgeons to better understand the social factors that contribute to successful SCDD in TJA patients, ultimately aiding in patient selection and preoperative counseling.

Nucleosome conformation dictates the histone code.

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' that are read by specialized regions (reader domains) in chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP: histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies. However, this has largely been done using the reductive approach of isolated reader domains and histone peptides, which cannot account for any higher-order factors. Here, we show that the [BPTF PHD finger and bromodomain: histone PTM] interaction is dependent on nucleosome context. The tandem reader selectively associates with nucleosomal H3K4me3 and H3K14ac or H3K18ac, a combinatorial engagement that despite being in cis is not predicted by peptides. This in vitro specificity of the BPTF tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. We propose that regulatable histone tail accessibility and its impact on the binding potential of reader domains necessitates we refine the 'histone code' concept and interrogate it at the nucleosome level.

Single-cell RNA sequencing comparison of the human metastatic prostate spine tumor microenvironment.

Spinal column tumors can be difficult to process for single-cell omic studies, given the heterogeneity in tissue. Here, we present a protocol for operating room-to-benchtop single-cell processing of clinical specimens from a prostate cancer patient. We describe steps for sample homogenization, red blood cell lysis, cryopreservation, and single-cell sequencing analysis. This protocol can be used to identify prognostic markers and therapeutic targets for patients with osseous spine metastases and better inform eligibility for clinical trials.

A Novel Achilles Tendon Repair Technique Utilizing a Bio-Composite Scaffold for a Sub-Acute Tear.

Achilles tendon ruptures are prevalent musculoskeletal injuries accounting for 20% of all large tendon ruptures with a re-rupture rate of 2.1-8.8%. Ineffectual management of these injuries can lead to a significant loss in push-off strength and overall ankle function. The field of orthopedic surgery has shown an increasing interest in biologic augmentation. Encouraged by its success in various other applications, this approach holds promise for potentially enhancing outcomes in Achilles tendon repairs, especially in poor tendon tissue. The BioBrace® (ConMed, New Haven, Connecticut) is a biocomposite scaffold made of highly porous type I collagen and bioresorbable poly (L-Lactide) (PLLA) microfilaments. It can be applied in conjunction with Achilles tendon repair or reconstruction. It provides immediate strength to the augmented repair upon implantation and simultaneously promotes new, organized tissue growth throughout its resorptive phase. Here, we outline a technique to effectively augment an acute Achilles tendon repair utilizing the BioBrace® reinforced bio-inductive implant.

The effectiveness of disinfection protocols in osteopathic family medicine offices.

CONTEXT: Healthcare-associated infections (HAIs) pose a substantial public health threat. Despite significant strides to curb HAIs in hospital environments, outpatient settings have not received the same degree of attention. Given their emphasis on holistic, patient-centered care, osteopathic family medicine offices are pivotal in both disease prevention and comprehensive patient treatment. The importance of simple yet effective disinfection protocols, such as thorough cleaning between patient appointments, cannot be overstated in these settings because they are integral to minimizing disease transmission. OBJECTIVES: This study aims to assess the effectiveness of the current disinfection protocols in osteopathic family medicine offices. METHODS: A cross-sectional study evaluating disinfection practices on 18 examination tables in an osteopathic family medicine office was conducted. Two high-touch surfaces (midtorso region and table edge) were examined. Initial swab samples were collected after morning disinfection by Environmental Services, and terminal swab samples were gathered after day's-end disinfection by the medical staff. Adenosine triphosphate (ATP) bioluminescence assays were performed utilizing AccuPoint Advanced HC Reader, which quantified ATP, indicating contamination levels in the samples. The higher the ATP levels found in a sample, the greater the amount of biological contamination. All samplers were handled and tested as per manufacturer's instructions. A preliminary trial was conducted to confirm the internal validity of ATP bioluminescence measurements. The statistical analysis involved Shapiro-Wilk and Wilcoxon signed-rank tests, with significance set at p<0.05. Cohen's d test was utilized to calculate the effect size, identifying meaningful differences in initial and terminal swab sample relative light units (RLUs). RESULTS: The midtorso region demonstrated an 11.1 % increase in failure rate after terminal disinfection when compared to initial disinfection. A Wilcoxon signed-rank test revealed a median estimated pathogen level for the midtorso region that was higher after terminal disinfection (median, 193 RLUs; range, 1-690 RLUs; n=18) compared to initial disinfection (median, 134 RLUs; range, 4-946 RLUs; n=18). However, this increase was not statistically significant, p=0.9124, with a small effect size, d=0.04. The edge showed no change in failure rate after terminal disinfection, maintaining a 100 % failure rate both before and after disinfection. However, the Wilcoxon signed-rank test revealed a slight reduction in the median estimated pathogen levels after terminal disinfection (median, 2095 RLUs; range, 891-5,540 RLUs; n=18) compared to before disinfection (median, 2,257 RLUs; range, 932-5,825 RLUs; n=18). However, this reduction was not statistically significant, p=0.61, with a small effect size, d=0.12. CONCLUSIONS: The findings from this study reveal a substantial disparity in outcomes between the two sample locations, midtorso and edge. The midtorso demonstrated a relatively low failure rate in both initial and terminal swab samples, indicating successful outcomes. In contrast, the edge consistently displayed a 100 % failure rate, emphasizing the need for more care and attention when cleaning the edge of the examination to ensure better outcomes. By prioritizing adequate disinfection protocols, including thorough cleaning between patients, osteopathic family medicine offices can more effectively prevent disease transmission and promote patient safety.

The effectiveness of disinfection protocols in medical school osteopathic manipulative medicine labs.

CONTEXT: In light of the COVID-19 pandemic, healthcare-associated infections have taken center stage. Healthcare has adjusted workflows to accommodate for more robust disinfecting regiments to help protect the community. This has resulted in the need for medical institutions to reevaluate the current disinfection protocols down to the student level. The osteopathic manipulative medicine (OMM) laboratory provides an optimal avenue for assessing the effectiveness of medical students' ability to clean examination tables. With OMM laboratories having a high level of interaction, adequate disinfection is important for the health and safety of students and teaching faculties. OBJECTIVES: This study will evaluate the effectiveness of the current disinfection protocols in the medical school OMM labs. METHODS: A cross-sectional, nonrandomized study was performed on 20 OMM examination tables utilized for osteopathic training. Tables were chosen based on their close proximity to the podium. Close proximity was utilized as a criteria to increase the probability of utilization by students. The sampled tables were observed to ensure their use by students during class. Initial samples were collected in the morning after disinfection by Environmental Services. Terminal samples were collected after Osteopathic medical students utilized and disinfected the OMM examination tables. Samples were collected from the face-cradle and midtorso regions and analyzed utilizing adenosine triphosphate (ATP) bioluminescence assays with an AccuPoint Advanced HC Reader. This reader provides a digital readout of the quantity of light measured in relative light units (RLUs), which is directly correlated to the amount of ATP present in the sample, providing an estimated pathogen count. For statistical analysis, a Wilcoxon signed-rank test was utilized to find statistical differences in RLUs in samples after initial and terminal disinfection. RESULTS: The face cradle showed a 40 % increase in failure rate in samples after terminal disinfection when samples were compared after initial disinfection. A Wilcoxon signed-rank test revealed an estimated pathogen level for face cradle that was significantly higher after terminal disinfection (median, 4,295 RLUs; range, 2,269-12919 RLUs; n=20) compared to initial disinfection (median, 769 RLUs; range, 29-2,422 RLUs; n=20), z=-3.8, p=0.00008, with a large effect size, d=2.2. The midtorso region showed a 75 % increase in samples after terminal disinfection when samples were compared after initial disinfection. A Wilcoxon signed-rank test revealed that the estimated pathogen levels for midtorso were significantly higher after terminal disinfecting (median, 656 RLUs; range, 112-1,922 RLUs; n=20) compared to initial disinfecting (median, 128 RLUs; range, 1-335 RLUs; n=20), z=-3.9, p=0.00012, with a large effect size, d=1.8. CONCLUSIONS: This study suggests that medical students frequently failed to disinfect high-touch regions on examination tables, such as the midtorso and the face cradle. It is recommended that the current OMM lab disinfection protocol be modified to include the disinfection of high-touch regions in order to reduce the possibility of pathogen transmission. Further research should explore the effectiveness of disinfection protocols in clinical settings such as outpatient offices.

Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.

Celiac disease (CeD) is an autoimmune disorder in which gluten-derived antigens trigger inflammation. Antigenic peptides must undergo site-specific deamidation to be presentable to CD4+ T cells in an HLA-DQ2 or -DQ8 restricted manner. While the biochemical basis for this post-translational modification is understood, its localization in the patient's intestine remains unknown. Here, we describe a mechanism by which gluten peptides undergo deamidation and concentration in the lysosomes of antigen-presenting cells, explaining how the concentration of gluten peptides necessary to elicit an inflammatory response in CeD patients is achieved. A ternary complex forms between a gluten peptide, transglutaminase-2 (TG2), and ubiquitous plasma protein α2-macroglobulin, and is endocytosed by LRP-1. The covalent TG2-peptide adduct undergoes endolysosomal decoupling, yielding the expected deamidated epitope. Our findings invoke a pathogenic role for dendritic cells and/or macrophages in CeD and implicate TG2 in the lysosomal clearance of unwanted self and foreign extracellular proteins.

Targeting the Microbiome to Improve Gut Health and Breathing Function After Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition characterized by impaired motor and sensory function, as well as internal organ pathology and dysfunction. This internal organ dysfunction, particularly gastrointestinal (GI) complications, and neurogenic bowel, can reduce the quality of life of individuals with an SCI and potentially hinder their recovery. The gut microbiome impacts various central nervous system functions and has been linked to a number of health and disease states. An imbalance of the gut microbiome, i.e., gut dysbiosis, contributes to neurological disease and may influence recovery and repair processes after SCI. Here we examine the impact of high cervical SCI on the gut microbiome and find that transient gut dysbiosis with persistent gut pathology develops after SCI. Importantly, probiotic treatment improves gut health and respiratory motor function measured through whole-body plethysmography. Concurrent with these improvements was a systemic decrease in the cytokine tumor necrosis factor-alpha and an increase in neurite sprouting and regenerative potential of neurons. Collectively, these data reveal the gut microbiome as an important therapeutic target to improve visceral organ health and respiratory motor recovery after SCI. Research Highlights: Cervical spinal cord injury (SCI) causes transient gut dysbiosis and persistent gastrointestinal (GI) pathology.Treatment with probiotics after SCI leads to a healthier GI tract and improved respiratory motor recovery.Probiotic treatment decreases systemic tumor necrosis factor-alpha and increases the potential for sprouting and regeneration of neurons after SCI.The gut microbiome is a valid target to improve motor function and secondary visceral health after SCI.

Do racial disparities exist in a spine surgery practice that serves a predominately minority population? Outcomes of transforaminal lumbar interbody fusion: A retrospective review.

Background: Racial minority status is associated with inferior peri-operative outcomes following spinal fusion. Findings have largely been reported within institutions serving few minority patients. This study aimed to identify if racial disparities exist for transforaminal lumbar interbody fusion (TLIF) procedures within an urban academic medical center which serves a majority non-White population. Methods: This is a retrospective review of patients who underwent a TLIF procedure at our institution between 06/2016-10/2019. Primary outcome measures included length of stay (LOS), discharge disposition, 30-day return to the emergency department (ED), 30-day readmission rate, and 30-day complication rates. One-hundred-fifty-six patients (female: male, 99: 57) met inclusion criteria. Demographic and clinical data (body mass index (BMI), comorbidities, preoperative lab values) were compared. Results: The mean LOS was 6.2, 5.9, and 6 days in the White, Hispanic, and Black cohorts, respectively (p = 0.92). There were no differences in discharge disposition between groups (p = 0.52). Thirty-day post-operative complication rates did not differ between groups (p > 0.07). Readmission rates did not differ between groups (p > 0.05). ED visits were more prevalent in the Hispanic group with 16 visits as compared to 8 and 4 in the White and Black groups respectively (p = 0.01). Conclusions: We found no racial disparities in terms of LOS, discharge disposition, or 30-day readmission rates. Hispanic patients demonstrated an increased utilization of the ED in the early post-operative period. Efforts to overcome language barriers, communicate instructions clearly, and outline post-operative expectations and plans may prevent the need for post-operative ED visits.

In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues.

Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.

High-dimensionality reduction clustering of complex carbohydrates to study lung cancer metabolic heterogeneity.

The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment.

Anatomic Distribution of Cherry Angiomas in the General Population.

BACKGROUND: Cherry angiomas are common benign vascular skin lesions of unknown aetiology, found largely on the trunk. However, their exact anatomic distribution besides their truncal predisposition, and how they manifest in the general population, has not been characterised. METHODS: Three-dimensional (3D) total body imaging was obtained from 163 adult participants of a general population cohort study in Brisbane, Australia. Demographic, phenotypic, and sun behaviour characteristics were collected using a standard questionnaire along with history of melanoma and keratinocyte cancers. Cherry angiomas were identified using an automated classification algorithm with a sensitivity of 87% and a specificity of 99%, developed specifically for this study population. RESULTS: The 3D total body images of 163 participants were analysed. Participants had a median age of 57 years and 61% were male. On average, males had more angiomas than females (median of 16 vs. 12) and the number and size of cherry angiomas increased with age. In addition to male sex and age, an increase in angiomas was associated with Caucasian ancestry other than British/Irish only, fair skin colour opposed to medium/olive, having green/hazel eyes compared to blue/grey, and personal history of melanoma. The most common site for cherry angiomas was the front trunk, followed by the back. Interestingly, although males had more angiomas overall, females had more angiomas on the legs. CONCLUSION: Describing the distribution of cherry angiomas by body site is an important step towards further understanding of the aetiology of angiomas. While personal history of melanoma is associated with an increased number of cherry angiomas, whether this association is prognostic, co-occurs with development of melanoma, or is merely fortuitous requires further investigation.

Heavy Metals and Health Risks Associated with Consumption of Herbal Plants Sold in a Major Urban Market in Southwest, Nigeria.

BACKGROUND: Although herbal medicines play an important role as a source of medicine, concerns have been raised about the risks posed by consumption of these plants, especially if consumed above permissible levels. OBJECTIVES: This study was undertaken to assess the level of exposure, toxicity and health risk associated with the consumption of herbal plants in Ado Ekiti urban market, Nigeria. METHODS: Ten commonly consumed herbal plants sold in Ado Ekiti urban market were subjected to heavy metal analysis. Health risk assessment was carried out to determine the estimated daily intake (EDI) of heavy metals, health risk index (HRI), target hazard quotient for non-carcinogenic risk and estimation of cancer risk (ECR). RESULTS: The EDIs for lead (Pb), nickel (Ni), chromium (Cr), copper (Cu) and magnesium (Mn) were above the upper tolerable daily intake reference for all studied plant species in both children and adults, an indication that herbal use poses a short-term to long-term health risk to consumers of these herbal products. The EDI for children was significantly lower compared to that of adults, indicating higher risks for adult consumers of these herbal products. The HRI in children for Pb (Alstonia congensis, Terminalia avicennioides, Aframomum melegueta, Cymbopogon citratus and Napoleona vogelii) were greater than 1; HRI in Cu and Mn also showed an unusually high concentration, an indication that long term exposure to the consumption of these herbal plants poses a serious health risk. The HRI in children and adults follows the order Mn > Cu > Ni > Pb > Cr; cadmium (Cd) was not detected in any of the herbal plants. The ECR for Pb, Ni and Cr present in the herbal plants for children ranged between 10-6 (low) to 10-3 (high), while the ECR for Pb, Ni and Cr for herbal plants for adults ranged between 10-5 (acceptable) to 10-2 (unacceptable). For both children and adults, there is a call for concern due to ECRs above the acceptable range; the consumption of these herbal plants poses a long-term cancer risk. CONCLUSIONS: In both children and adults, ECRs for some of the herbal plants in the present study above the acceptable range present a risk to human health. The consumption of such herbal plants poses a long-term cancer risk. COMPETING INTERESTS: The authors declare no competing financial interests.

An Australian tertiary hospital analysis of outpatient dermatology clinical and demographic characteristics.

OBJECTIVES: Literature on dermatology outpatient demographic and clinical data is limited, and the few studies on this topic are mainly conducted overseas, with medical systems and case mix different to Australia. This study presents demographic data relating to dermatology public outpatient referrals to a tertiary hospital in Brisbane, Australia, and determines what additional structured data should be collected to formulate and evaluate initiatives to address service issues such as referral quality, triage process and wait times. METHODS: A four-year retrospective audit was undertaken, summarising all referrals (n = 7140) and clinical dermatology encounters (n = 53 844) between January 2016 and December 2019 at Princess Alexandra Hospital (PAH), the largest hospital in Metro South Health (MSH), serving a population of one million. PAH has one of the two largest public dermatology clinics in Queensland and is the only dermatology service within MSH. RESULTS: Patient demographic data, wait time by triage category, referral rates over time and encounter durations were collected. Structured diagnostic data (e.g. ICD-10 coding) of the provisional diagnosis, comorbidities, medications and the final diagnosis are not collected in a structured format and would be a valuable addition. CONCLUSIONS: The clinical burden of public dermatology is increasing. Both collection and analysis of structured data pertaining to the referrals and encounters are important to help formulate, implement and evaluate initiatives that aim to improve health service provision in this area.

In Situ Analysis of N-Linked Glycans as Potential Biomarkers of Clinical Course in Human Prostate Cancer.

Prostate cancer is the most common cancer in men worldwide. Despite its prevalence, there is a critical knowledge gap in understanding factors driving disparities in survival among different cohorts of patients with prostate cancer. Identifying molecular features separating disparate populations is an important first step in prostate cancer research that could lead to fundamental hypotheses in prostate biology, predictive biomarker discovery, and personalized therapy. N-linked glycosylation is a cotranslational event during protein folding that modulates a myriad of cellular processes. Recently, aberrant N-linked glycosylation has been reported in prostate cancers. However, the full clinical implications of dysregulated glycosylation in prostate cancer has yet to be explored. Herein, we performed direct on-tissue analysis of N-linked glycans using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) from tissue microarrays of over 100 patient tumors with over 10 years of follow-up metadata. We successfully identified a panel of N-glycans that are unique between benign and prostate tumor tissue. Specifically, high-mannose as well as tri-and tetra-antennary N-glycans were more abundant in tumor tissue and increase proportionally with tumor grade. Further, we expanded our analyses to examine the N-glycan profiles of Black and Appalachian patients and have identified unique glycan signatures that correlate with recurrence in each population. Our study highlights the potential applications of MALDI-MSI for digital pathology and biomarker discovery for prostate cancer. IMPLICATIONS: MALDI-MSI identifies N-glycan perturbations in prostate tumors compared with benign tissue. This method can be utilized to predict prostate cancer recurrence and study prostate cancer disparities.

Multiple interventions following an acute coronary syndrome event increase uptake into cardiac rehabilitation.

AIMS: Cardiac rehabilitation (CR) improves morbidity and mortality. Uptake varies for patients following acute coronary syndrome (ACS). Entry into CR is often dependent on the management strategy received, lower following percutaneous coronary intervention (PCI), higher following coronary artery bypass grafting (CABG). This study sought to investigate differences in CR uptake following an ACS event for those patients receiving multiple treatments. METHODS: Data was from the National Audit of CR between 2016 and 2019. Patients with ACS were categorised as: no intervention; one treatment (such as any PCI, CABG, any valve surgery and any device therapy); two treatments; or three or more treatments. Baseline demographics and logistic regression were used to analyse the effect of multiple treatment intervention on uptake into CR. RESULTS: A total of 6833 ACS patients were included in the analysis (0 treatments 2014, 1 treatment 3104, ≥2 treatments 2799). Patients who received ≥2 therapeutic interventions were more likely to be male, partnered and >2 comorbidities. Logistic regression showed a positive relationship between uptake total intervention. Similar associations were seen: being younger, male, partnered and having any comorbidity. The hospital stay, history of angina, diabetes and stroke was negatively correlated with an uptake. CONCLUSION: This study showed for the first time that multiple interventions following ACS is a significant predictor of uptake into CR. The findings align with recent trends with medically managed myocardial infarction uptake. Our findings identify factors associated with poor uptake to CR which should be considered as part of strategy to increase participation.

Estimating the health loss due to poor engagement with cardiac rehabilitation in Australia.

BACKGROUND: Cardiac rehabilitation (CR) programs are effective in reducing cardiovascular mortality and readmissions. However, most patients are denied the benefits of CR due to low referral rates. Of those patients referred, commencement rates vary from 28.4% to 60%. This paper quantifies the scale of health loss in Australia due to poor engagement with the program, and estimates how much public funding can be justifiably reallocated to address the problem. METHODS: Economic decision modelling was undertaken to estimate the expected lifetime health loss and costs to Medicare. Key parameters were derived from Australian databases, CR registries and meta-analyses. Population health gains associated with uptake rates of 60%, and 85% were calculated. RESULTS: CR was associated with a 99.9% probability of being cost-effective, even at a cost-effectiveness threshold lower than conventionally applied. Importantly, an average of 0.52 years of life expectancy are lost due to national uptake being below 60% achieved in some best performing programs in Australia, equivalent to 0.28 quality adjusted life years. The analysis indicates that $12.9 million/year could be justifiably reallocated from public funds to achieve a national uptake rate of 60%, while maintaining cost-effectiveness of CR due to the large health gains that would be expected. CONCLUSION: CR is a cost-effective service for patients with coronary heart disease. In Australia, less than a third of patients commence CR, potentially resulting in avoidable patient harm. Additional investment in CR is vital and should be a national priority as the health gains for patients far outweigh the costs.