Clinical Indications Research Articles

A scoring model for the expression of genes related to programmed cell death predicts immunotherapy response and prognosis in lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) continues to be the leading cause of cancer death worldwide, driven by environmental factors like smoking and genetic predispositions. LUAD has a high mortality rate, and new biomarkers are urgently needed to improve treatment strategies and patient management. Programmed cell death (PCD) is involved in tumor progression and response to treatment. Therefore, there is a need for an extensive study of the role and functions of PCD-related genes (PCDRGs) in lung adenocarcinoma so as to understand the pathophysiologic features of lung adenocarcinoma.MethodsBased on TCGA and GEO databases, this research is aimed at screening differentially expressed PCD-related genes in lung adenocarcinoma. We conducted GO, and KEGG analysis to establish the link between these genes and biological processes. By applying various machine learning algorithms such as CoxBoost analysis, we developed PCD-related indices (PCDI) that were used to verify their ability to predict prognosis with the use of other datasets. This was done in addition to exploring the biological functions of PCD genes associated with lung adenocarcinoma by assessing the relationship between immune cell components of tumor microenvironment and PCD genes together with examining how they affect drug sensitivity.ResultsThe research presented in this article offers significant insights into LUAD. The authors identified 113 PCDRGs that were differentially expressed in LUAD. These genes are implicated in various biological functions, including High risk ing apoptosis, ferroptosis, and pathways specific to non-small cell lung cancer. Notably, the PCDI proved effective in distinguishing between High risk and Low risk LUAD patients, demonstrating a higher accuracy in prognosis prediction compared to traditional clinical indicators such as age and gender. This high prediction accuracy was validated in both test and validation cohorts. Additionally, these genes showed significant correlations with immune cell infiltration and drug sensitivity in LUAD patients.ConclusionWe analysed the expression and function of PCDRGs in LUAD and revealed their correlation with patient survival, the immune microenvironment and drug sensitivity. The constructed PCDI model provides a scientific basis for the personalised treatment of lung adenocarcinoma, and future optimisation of treatment strategies based on these genes may improve patient clinical outcomes.

Efficacy of ozonated autohemotherapy for improvement of myocardial injury following traumatic brain injury

BackgroundTraumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI).MethodsForty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded.Results(1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively).ConclusionPerioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress.Trial registrationThis study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020.

Clinical and laboratory features between anti-TIF1γ dermatomyositis with and without malignancy: 37 case series and a review.

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4or8weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with ahigher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects

BackgroundPatients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging. MethodsHere we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups. ResultsAs expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis. ConclusionOur study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.

Clinical and biochemical factors for bacteria in bile among patients with acute cholangitis.

Acute cholangitis is a clinical syndrome caused by a bacterial infection in the biliary system. The bacteria could exist in the bile before bile drainage despite empirical antibiotic treatment. Patients with acute cholangitis admitted to a tertiary hospital in Southeastern China from August 2011 to September 2021 were involved when bile cultures were performed. Patient information before bile cultures and during hospitalization was extracted from the clinical record database. The risk factors related to bacteria in bile were assessed by univariable and multivairable logistic regression analysis, respectively. A total of 533 patients (66.05%) had bacterial growth in bile. Alanine aminotransferase concentration [odds ratio (OR) = 0.998, P < 0.001], absolute monocyte count (OR = 0.335, P = 0.001), and duration of antibiotic use (OR = 0.933, P = 0.026) were negatively correlated with bacteria in bile. In contrast, C-reactive protein (OR = 1.006, P = 0.003), thrombin time (OR = 1.213, P = 0.033), prothrombin time (OR = 1.210, P = 0.011), and age (OR = 1.025, P < 0.001) were positively correlated with bacteria in bile. Based on an area under the receiver operating characteristic curve of 0.737 (95% CI, 0.697-0.776, P < 0.001), combining these seven variables could efficiently predict the presence of bacteria in bile among patients with acute cholangitis. The combination of clinical indicators before bile drainage could predict the risk of bacteria in bile for patients with acute cholangitis.

Optimizing outcomes with maintenance IV UST in highly bio-exposed patients with IBD. Efficacy and adjusted regimen in real world

Background and aimsUstekinumab is an effective treatment for inflammatory bowel diseases. However, some patients do not respond to conventional doses. The aim of the study was to evaluate the effectiveness of intravenous maintenance ustekinumab in patients with secondary failure. MethodsSingle-center, retrospective study in adult patients with intravenous maintenance ustekinumab. The reduction of biochemical activity markers, ustekinumab trough levels and clinical indices of activity were evaluated. Biological remission was defined as the percentage decrease fecal calprotectin ≥80% and/or final fecal calprotectin ≤250 and C reactive protein <5mg/L. ResultsThirty-one patients were included: Crohn's disease 77.4%. All included patients were bio-exposed and 61.3% had carried ≥2 biologics.Pre-intravenous maintenance mean Harvey–Bradshaw Index was 6.5±4.38 vs 5±3.1 at week 8 (p=0.024) vs 4.1±3.1 at week 24 (p=0.019). The median ustekinumab trough level pre-intravenous maintenance was 1.40μg/ml [IQR 2.3] vs 5.35μg/ml [IQR 4.1] at week 8 (p<0.001) vs 4.8μg/ml [IQR 3.9] at week 24 (p<0.001). The pre-intravenous maintenance median fecal calprotectin was 809μg/g [IQR: 2256] vs 423μg/g [IQR: 999] at week 8 (p=0.025) vs 333μg/g [508] (p=0.001) at week 24.At the end of follow-up 48% went into biological remission. The presence of perianal disease was associated with lower biological remission (70.6% vs 27.3%, p=0.025). Median intravenous ustekinumab maintenance time was 8.55 [IQR 23.9] months. In 83.9% of patients no serious infections or malignancy were documented. ConclusionsThe use of maintenance intravenous ustekinumab appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bio-exposed patients.

Screening, identification and targeted intervention of necroptotic biomarkers of asthma

BackgroundAs a pivotal pathway of programmed cell death, necroptosis significantly contributes to the pathogenesis of respiratory disorders. However, its role in asthma is not yet fully elucidated. Therefore, this study aimed to identify markers associated with necroptosis, evaluate their functions in asthma, and explore potential therapeutic agents targeting necroptosis for the management of asthma. MethodsFirstly, machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were utilized to identify necroptosis-related differentially expressed genes (NRDEGs) in asthma patients compared to healthy controls. Concurrently, the expression of NRDEGs was validated using external datasets, Western blot, and quantitative real-time polymerase chain reaction (qPCR). Secondly, the clinical relevance of NRDEGs was assessed through Receiver Operating Characteristic (ROC) curve analysis and correlation with clinical indicators. Thirdly, the relationship between NRDEGs and pulmonary immune cell infiltration, as well as the signaling interactions between different cells types, were analyzed through immune infiltration and single-cell analysis. Fourthly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were conducted to elucidate the functional roles of NRDEGs. Finally, compounds targeting NRDEGs were screened, and their binding affinities were evaluated using molecular docking studies. ResultsIn asthma, necroptosis is activated, leading to the identification of four NRDEGs: NLRP3, PYCARD, ALOX15, and VDAC3. Among these, NLRP3, PYCARD, and ALOX15 are upregulated, whereas VDAC3 is downregulated in asthma. Comprehensive clinical evaluations indicated that NRDEGs hold diagnostic value for asthma. Specifically, NLRP3 was inversely correlated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), while VDAC3 showed an inverse correlation with sputum neutrophils. Conversely, ALOX15 expression was positively correlated with fractional exhaled nitric oxide (FeNO) levels, as well as sputum eosinophils, blood eosinophils, and blood IgE levels. Subsequent immune infiltration analysis revealed associations between NRDEGs and activated dendritic cells, mast cells, and eosinophils. Single-cell RNA sequencing (scRNA-seq) further confirmed the communication signals between myeloid dendritic cells, fibroblasts, neutrophils, and helper T cells, predominantly related to fibrosis and immune-inflammatory responses. Pathway enrichment analysis demonstrated that NRDEGs are involved in ribosomal function, oxidative phosphorylation, and fatty acid metabolism. Finally, resveratrol and triptonide were identified as potential therapeutic agents targeting the proteins encoded by NRDEGs for asthma treatment. ConclusionsThe necroptosis pathway is activated in asthma, with NRDEGs—namely PYCARD, NLRP3, ALOX15, and VDAC3—correlated with declines in lung function and airway inflammation. These genes serve as reliable predictors of asthma risk and are involved in the regulation of the immune-inflammatory microenvironment. Resveratrol and triptolide have been identified as promising therapeutic candidates due to their potential to target the proteins encoded by these genes.

Visualizing Neighborhood COVID-19 Levels, Trends, and Inequities in Wastewater: An Equity-Centered Approach and Comparison to CDC Methods.

Monitoring neighborhood-level SARS-CoV-2 wastewater concentrations can help guide public health interventions and provide early warning ahead of lagging COVID-19 clinical indicators. To date, however, U.S. Centers for Disease Control and Prevention's (CDC) National Wastewater Surveillance System (NWSS) has provided methodology solely for communicating national and state-level "wastewater viral activity levels." In October 2022, the Boston Public Health Commission (BPHC) began routinely sampling wastewater at 11 neighborhood sites to better understand COVID-19 epidemiology and inequities across neighborhoods, which vary widely in sociodemographic and socioeconomic characteristics. We developed equity-centered methods to routinely report interpretable and actionable descriptions of COVID-19 wastewater levels, trends, and neighborhood-level inequities. To produce these data visualizations, spanning October 2022 to December 2023, we followed four general steps: (1) smoothing raw values; (2) classifying current COVID-19 wastewater levels; (3) classifying current trends; and (4) reporting and visualizing results. COVID-19 wastewater levels corresponded well with lagged COVID-19 hospitalizations and deaths over time, with "Very High" wastewater levels coinciding with winter surges. When citywide COVID-19 levels were at the highest and lowest points, levels and trends tended to be consistent across sites. In contrast, when citywide levels were moderate, neighborhood levels and trends were more variable, revealing inequities across neighborhoods, emphasizing the importance of neighborhood-level results. Applying CDC/NWSS state-level methodology to neighborhood sites resulted in vastly different neighborhood-specific wastewater cut points for "High" or "Low," obscured inequities between neighborhoods, and systematically underestimated COVID-19 levels during surge periods in neighborhoods with the highest COVID-19 morbidity and mortality. Our methods offer an approach that other local jurisdictions can use for routinely monitoring, comparing, and communicating neighborhood-level wastewater levels, trends, and inequities. Applying CDC/NWSS methodology at the neighborhood-level can obscure and perpetuate COVID-19 inequities. We recommend jurisdictions adopt equity-focused approaches in neighborhood-level wastewater surveillance for valid community comparisons.

Pathogenesis of Post-Covid Syndrome. The Key Role of the Immune System

When considering the pathogenesis of COVID-19 and post-Covid syndrome, disorders associated with the immune system come to the fore. Complexes of immune dysregulation, dissonant reactions of the patient’s innate and adaptive immune systems, should be considered the main causes of the complex pattern of lesions. These processes include cellular inflammation, disorder of hemovascular homeostasis, and organ damages. Consistent analysis of these processes serves as the basis for choosing therapeutic strategy schemes, taking into account clinical indicators and personal characteristics of patients.

A protocol for enhancing the diagnostic accuracy and predictive validity of neonatal opioid withdrawal syndrome: The utility of non-invasive clinical markers.

Every 15 minutes in the US, an infant exposed to opioids is born. Approximately 50% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS) within 5 days of birth. It is not known which infants will develop NOWS, therefore, the current hospital standard-of-care dictates a 96-hour observational hold. Understanding which infants will develop NOWS soon after birth could reduce hospital stays for infants who do not develop NOWS and decrease burdens on hospitals and clinicians. We propose noninvasive clinical indicators of NOWS, including newborn neurobehavior, autonomic biomarkers, prenatal substance exposures, and socioeconomic environments. The goals of this protocol are to use these indicators shortly after birth to differentiate newborns who will be diagnosed with NOWS from those who will have mild/no withdrawal, to determine if the indicators predict development at 6 and 18 months of age, and to increase NOWS diagnostic sensitivity for earlier, more accurate diagnoses.

Pericardium decellularization in a one-day, two-step protocol.

Scaffolds used in tissue engineering can be obtained from synthetic or natural materials, always focusing the effort on mimicking the extracellular matrix of human native tissue. In this study, a decellularization process is used to obtain an acellular, biocompatible non-cytotoxic human pericardium graft as a bio-substitute. An enzymatic and hypertonic method was used to decellularize the pericardium. Histological analyses were performed to determine the absence of cells and ensure the integrity of the extracellular matrix (ECM). In order to measure the effect of the decellularization process on the tissue's biological and mechanical properties, residual genetic content and ECM biomolecules (collagen, elastin, and glycosaminoglycan) were quantified and the tissue's tensile strength was tested. Preservation of the biomolecules, a residual genetic content below 50ng/mg dry tissue, and maintenance of the histological structure provided evidence for the efficacy of the decellularization process, while preserving the ECM. Moreover, the acellular tissue retains its mechanical properties, as shown by the biomechanical tests. Our group has shown that the acellular pericardial matrix obtained through the super-fast decellularization protocol developed recently retains the desired biomechanical and structural properties, suggesting that it is suitable for a broad range of clinical indications.

Integrative metagenomic and lipidomic analyses reveal alterations in children with obesity and after lifestyle intervention

BackgroundDespite emerging evidence linking alterations in gut microbiota to childhood obesity, the metabolic mechanisms linking gut microbiota to the lipid profile during childhood obesity and weight loss remain poorly understood.MethodologyIn this study, children with obesity were treated with lifestyle weight loss therapy. Metagenomics association studies and serum untargeted lipidomics analyses were performed in children with obesity and healthy controls before and after weight loss.Main findingsWe identified alterations in gut microbiota associated with childhood obesity, as well as variations in circulating metabolite concentrations. Children with obesity showed significant decreases in the levels of s-Rothia_kristinae and s-Enterobacter_roggenkampii, alongsige elevated levels of s-Clostridiales_bacterium_Marseille-P5551. Following weight loss, the levels of s-Streptococcus_infantarius and s-Leuconostoc_citreum increased by factors of 3.354 and 1.505, respectively, in comparison to their pre-weight loss levels. Correlation analyses indicated a significant positive relationship between ChE(2:0) levels and both with s-Lachnospiraceae_bacterium_TF09-5 and fasting glucose levels. CoQ8 levels were significantly negatively correlated with s-Rothia_kristinae and HOMA-IR.ConclusionWe linked altered gut microbiota and serum lipid levels in children with obesity to clinical indicators, indicating a potential impact on glucose metabolism via lipids. This study contributes to understanding the mechanistic relationship between altered gut microbiota and childhood obesity and weight loss, suggesting gut microbiome as a promising target for intervention.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178971, ChiCTR2300072179.

The value-laden nature of decision-making with the never-capacitated patient

The values of individuals who have never had the capacity to express their preferences are often overlooked or even ignored in the decision-making process. The case of “Michael,” a non-verbal young adult with a genetic condition and intellectual disability, is presented to challenge the traditional approach of relying solely on clinical indicators and the “best interest” standard narrowly construed in healthcare decision-making. Michael's interaction with his environment, gleaned through his family's input, illustrates that values and quality of life can be discerned through observed behaviors and preferences, even in the absence of communicative ability. We argue for a broader definition of “values” that encompasses any aspect of life that brings meaning or enjoyment to the individual. This model not only personalizes care for never-capacitated individuals but may also be applied to other incapacitated populations, such as those with dementia, suggesting that past directives may not always align with their evolving values and interests. Underlying this expanded understanding of values in healthcare is a patient-centered approach that accounts for personal elements that contribute to an individual's sense of purpose and satisfaction.

Positive events in psychotherapy: What do adolescents and young adults say is helpful?

Background The significant challenge in adolescent and young adult therapy lies in the fact that research in this field does not provide many clinical indications. This study addresses domains contributing to the establishment and sustenance of engagement, satisfaction, and progress among adolescents and young adults in their treatment by delving into the impact of events that, from the perspective of clients, have positively influenced their therapeutic process. Methods Employing a qualitative research approach, we conducted semi-structured interviews with 13 adolescents and young adults undergoing therapy, recounting positive and constructive events during their treatment. Results A structured thematic analysis revealed six primary domains of positive events: events linked to the management of the setting, events shaping the definition of therapy goals, occurrences tied to the therapist’s active role, collaborative events between therapists and clients, and events associated with both clients’ external and internal worlds. Conclusions The findings suggest that working with adolescents shares similarities with psychotherapy involving adult clients but demands specific attention to adolescents and young adults’ families, surrounding environment, and rapidly changing needs.

WP5.2 - Acute Pancreatitis: challenging the relevance of the modified Glasgow score and bridging the gap to optimise management

Abstract Aims Acute pancreatitis is a frequently encountered emergency surgical presentation, with an incidence of 56 cases per 100,000 per year. 10%- 20% of patients develop a rapidly progressive inflammatory response with an overall mortality rate of 5%. Deciding the need for intervention during pancreatitis is variable. Predicting severity is challenging and multifactorial. Scoring systems aid in standardisation of treatment, however they do not factor in the evolving knowledge on factors that predict mortality in severe acute pancreatitis. The aim of this audit was to identify any gaps in optimising the management of acute pancreatitis. Methods Prospective data was collected between January 2023 – May 2023 and analysed against current NICE and UK working Party on Acute Pancreatitis guidelines. Results 41 patients were identified with a median age of 60 (53.7% male, 46.3% female). No cases required admission to intensive care. Gallstones (56.2%) and alcohol (19.6%) were identified as leading causes. Key gaps in management were identified: 12.2% of patients were scored via the modified Glasgow score, 24.4% received antibiotics without a clinical indication, 34% received aggressive fluid therapy and 19.5% received education on disease diagnosis and management. Conclusion Supportive management can be optimised, with a significant need to address patient education to minimise recurrence. Our data supports the use of targeted scoring systems in patients who are already critically ill. As the majority of cases were mild, we propose that the Modified Glasgow score is a useful aide but should not replace clinical judgment and careful monitoring of patients. Potential ambulatory pathways could be considered for mild acute pancreatitis.

Patency and factors related to patency after percutaneous transluminal angioplasty for inflow arterial stenosis in native arteriovenous fistula dysfunction: a single-center retrospective study

Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P < 0.05), but the groups had similar secondary patency. Cox proportional hazard analysis indicated that none of the analyzed clinical and biochemical indexes had clinically meaningful effects on primary patency, assisted primary patency, or secondary patency in either group. The patency and safety after PTA for inflow arterial stenosis were satisfactory, and none of the examined risk factors had a major clinical impact on patency. We recommend PTA as treatment for inflow stenosis of an AVF.

Perspective: on the future of fecal microbiota transplantation

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.

SP5.2 - Reducing Elective Colorectal Surgical Site Infections with Change of Gloves and Instruments Prior to Abdominal Closure; A Multicycle Audit

Abstract Aims Surgical site infections (SSI) carry a significant impact on patient morbidity, length of stay and antibiotic resistance. Our local colorectal unit has made several interventions over many years with no significant nor sustained improvement in the rate of SSI. The ChEETAh trial (Lancet, 2022) demonstrated a reduction in the rate of 30-day SSI by 13% with routine change of gloves and instruments (COGI) prior to abdominal closure. We aim to reduce our rate of SSI through implementation of COGI prior to abdominal closure; involving whole scrub team change of gloves and use of sterile instruments. Methods Adults undergoing elective colorectal surgery with an abdominal wound greater than 5cm were eligible for this study. Diagnosis of SSI was made based on at least one clinical indicator of infection or at least one symptom of SSI with data collection over 3 cycles spanning 11 months using clinical notes, imaging and microbiology results. The primary outcome was the diagnosis of a SSI involving the skin, subcutaneous, muscle or fascial layer up to 30 days post-operatively. Results The baseline SSI rate prior to intervention was audited at 29%. After implementation of COGI the rate fell to 23%. Further reinforcement of COGI and team education has demonstrated a further decrease in SSI to 15%. This has been sustained across a 6-month period post intervention. Conclusions Change of gloves and instruments is an effective, reliable and sustainable method to reduce the rate of surgical site infection in elective colorectal abdominal surgery.

Effects of Loading Forces, Loading Positions, and Splinting of Two, Three, or Four Ti-Zr (Roxolid®) Mini-Implants Supporting the Mandibular Overdentures on Peri-Implant and Posterior Edentulous Area Strains

Clinical indications for the Ti-Zr alloy (Roxolid®) mini-implants (MDIs) in subjects with narrow ridges are still under review. The aim was to analyze peri-implant and posterior edentulous area strains dependent on the MDI number, splinting status, loading force, and loading position. Six models were digitally designed and printed. Two, three, or four Ti-Zr MDIs, splinted with a bar or unsplinted (single units), supported mandibular overdentures (ODs), loaded with 50–300 N forces unilaterally, bilaterally, and anteriorly. The artificial mucosa thickness was 2 mm. Strain gauges were bonded on the vestibular and oral peri-implant sides of each MDI, and on the posterior edentulous area under the ODs. Loadings were performed through the metal plate placed on ODs’ artificial teeth (15 times repeated). Arithmetic means with standard deviations and the significance of the differences (MANOVA, Sheffe post hoc) were calculated. Different MDI numbers, loading positions, forces, and splinting elicited different peri-implant microstrains. In the two-MDI models, 300 N force during unilateral loading elicited the highest microstrains (almost 3000 εμ on the loaded side), which can jeopardize bone reparation. On the opposite side, &gt;2500 εμ was registered, which represents high strains. During bilateral loadings, microstrains hardly exceeded 2000 εμ, indicating that bilateral chewers or subjects having lower forces can benefit from the two Ti-Zr MDIs, irrespective of splinting. However, in subjects chewing unilaterally, and inducing higher forces (natural teeth antagonists), or bruxers, only two MDIs may not be sufficient to support the OD. By increasing implant numbers, peri-implant strains decrease in both splinted and single-unit MDI models, far beyond values that can interfere with bone reparation, indicating that splinting is not necessary. When the positions of the loading forces are closer to the implant, higher peri-implant strains are induced. Regarding the distal edentulous area, microstrains reached 2000 εμ only during unilateral loadings in the two-MDI models, and all other strains were lower, below 1500 εμ, confirming that implant-supported overdentures do not lead to edentulous ridge atrophy.