Preferential Use Research Articles

Impact of chronic opioid use on acute health care utilization in children with IBD and arthritis: a retrospective cohort study

BackgroundOpioid use is non-trivial in children with inflammatory bowel disease (IBD) and arthritis, and options are limited for pain management. We aimed to determine the impacts of chronic opioid use on acute care utilization in children with both IBD and arthritis in United States.MethodsParticipants less than 18 years of age with IBD and arthritis, with at least one year of continuous enrollment (no interruption of insurance for at least 1 year) and at least one pharmacy claim in the Truven Health MarketScan Claims and Encounter Database, were included in the study. The primary exposure was chronic opioid use. Chronic opioid users were matched to non-exposed controls. The primary outcome was acute healthcare utilization (total number of emergency department visits and hospitalizations within 12–24 months after the index date). The association between acute care utilization and chronic opioid use was assessed using a multivariable negative binomial regression model.Results480 children with IBD and arthritis met inclusion criteria, out of which 59 (12.3%) met the criteria for chronic opioid exposure, and 46 of them had at least one year of follow-up. IRR (incidence rate ratio) of acute healthcare use for patients exposed to chronic opioid use was 1.7 higher than controls. Additionally, public insurance and having a chronic pain condition were independently and significantly associated with greater acute healthcare use.ConclusionChronic opioid use was significantly associated with greater acute health care utilization in children with IBD and arthritis than matched unexposed controls. Future investigation is warranted to determine if preferential use of non-opioid therapy for pain control can reduce acute healthcare costs in this population.

Summary of the National Advisory Committee on Immunization (NACI) Supplemental Guidance on Influenza Vaccination in Adults 65 Years of Age and Older.

Adults 65 years of age and older are at higher risk of influenza complications, such as hospitalization and death. As a result, seasonal influenza immunization is particularly important for this group. This supplemental statement provides an evidence summary on the preferential use of one or more of the age-appropriate influenza vaccines for adults 65 years of age and older, over other age-appropriate influenza vaccines. The National Advisory Committee on Immunization (NACI)'s Influenza Working Group undertook an overview of existing systematic reviews on the efficacy, effectiveness, safety and cost effectiveness of influenza vaccination in adults 65 years of age and older. Additionally, NACI's evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings and apply an ethics, feasibility and acceptability lens to develop recommendations. The evidence suggests that high-dose inactivated influenza vaccine (IIV-HD), adjuvanted inactivated influenza vaccine (IIV-Adj) and recombinant influenza vaccine (RIV) offer increased benefits for adults 65 years of age and older when compared to standard dose influenza vaccines. The IIV-HD had the most supporting evidence, followed by IIV-Adj and then RIV. Evidence comparing these enhanced vaccines was limited. Following a thorough review of the complete body of evidence, NACI recommends that IIV-HD, IIV-Adj or RIV should be offered over other influenza vaccines for adults 65 years of age and older. NACI also continues to strongly recommend the inclusion of adults 65 years of age and older among those for whom it is particularly important to receive influenza vaccination.

The correlation between cardiac magnetic resonance imaging and echocardiography in patients with severe ischaemic cardiomyopathy

Abstract Background Left ventricular ejection fraction is the single metric that guides therapeutic decision-making, risk stratification and prognosis in patients with severely impaired systolic function. Although cardiac magnetic resonance imaging (CMR) is the current reference standard for quantification of ventricular volume and function, echocardiography is used more often as it is more widely available and less expensive.(1) Aims To evaluate the correlation between CMR and echocardiography in quantifying left ventricular (LV) volume and function and to determine whether these measurements are associated with clinical outcomes in patients with severe ischemic cardiomyopathy (ICM). Methods Participants recruited to the REVIVED-BCIS2 trial who had undergone baseline CMR or echocardiography were included in this analysis. All scans were analyzed in blinded core laboratories as previously reported.(2,3) All volumes were indexed to body surface area. Spearman correlation, Bland Altman analysis and coverage probability methods were performed to assess the correlation between the two modalities. A Cox proportional hazards model was used to assess the association between imaging metrics and the primary outcome, a composite of all-cause death and aborted sudden death. A sensitivity analysis was conducted a priori, restricted to patients undergoing both scans within 60 days of each other. Results A total of 373 participants with paired imaging data were included: mean age 69±9 years, 87% male, BMI 28±5. A moderate correlation was detected for volume measurements between the modalities (end diastolic volume index (EDVI) r=0.66 end systolic volume index (ESVI) r=0.68), with a weaker correlation for LV ejection fraction (EF) (r=0.41). Bland-Altman plots showed moderate agreement in LVEF measurements (Table 1). The sensitivity analysis included 199 patients, and showed similar results (EDVI r=0.72, ESVI r=0.73 LVEF r=0.43, all p<0.000). Only 7.5% of the paired LVEF measurements were within 5% of each other. 30% of participants were misclassified by echocardiography as having an LVEF>35%. (Figure 1) CMR ESVI was associated with the occurrence of the primary outcome (HR 1.05 per 10ml increment, 95% CI 1.00-1.10) however echo ESVI (HR 1.05 per 10ml increment 95% CI 0.99 – 1.10) and all other imaging metrics were not. Conclusion Left ventricular volumes and ejection fraction on CMR and echocardiography were only modestly correlated in this population with severe ICM. When using the binary EF threshold of 35% that is commonly used to select patients of implantable defibrillator therapy, almost a third of patients at risk would have been missed by echocardiography alone. The additional insights provided by CMR, including scar burden, further support preferential use of this modality in the assessment such patients.

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events. A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process. The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker. RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Rapid urease test according to the rules and without

The article discusses the problems of diagnosing Helicobacter pylori (H.pylori) using a rapid urease test (RUT). Features of H.pylori colonization and persistence are highlighted, which affect the results of RUT and determine the preferential use of biopsy specimens for the study, rather than gastric mucus aspirate, the localization of biopsy collection and their optimal number and the factors influencing the urease activity of H.pylori are indicated. Based on the described properties, the main causes of erroneous results and methods for preventing false negative and false positive results are given, the basic rules for working with RUT are formulated to obtain optimal results.

Streptokinase or Alteplase for Acute Limb Ischemia? A Meta-Analysis

Background: Acute limb ischemia (ALI) is a vascular emergency that necessitates prompt and effective treatment to restore blood flow and prevent limb loss. Thrombolytic therapy, particularly with agents like streptokinase and alteplase, plays a pivotal role in ALI management. This meta-analysis and systematic review aimed to compare the efficacy and safety of streptokinase and alteplase in treating ALI. Methods: A comprehensive search of PubMed, Embase, Science Direct, and the Cochrane Library databases was conducted up to August 13, 2024, to identify relevant studies. The inclusion criteria encompassed clinical trials involving patients diagnosed with ALI who received either streptokinase or alteplase as the initial thrombolytic treatment. The quality of the included studies was rigorously assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Methodological Index for Non-Randomized Studies (MINOR) criteria. A meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Results: The final analysis included 20 studies, encompassing both qualitative and quantitative assessments. A comparative analysis of streptokinase and alteplase for limb salvage at 30 days revealed a significant advantage in favor of alteplase, with a relative risk ratio (RR) of 0.78 (95% CI 0.69-0.88, I² = 0%). Furthermore, streptokinase was associated with a higher rate of primary amputation, with an RR of 2.54 (95% CI 1.50-4.32, I² = 0%) compared to alteplase. The use of streptokinase also correlated with a higher risk of complications, including major bleeding (RR 1.75, 95% CI 0.04-84.30, I² = 77%) and minor bleeding (RR 1.41, 95% CI 0.60-3.32, I² = 0%). Conclusion: The findings of this meta-analysis underscore the superior efficacy of alteplase in achieving limb salvage in ALI, coupled with a more favorable safety profile. The preferential use of alteplase in clinical practice is recommended, particularly in patients with severe ischemia. However, careful patient selection and close monitoring are crucial when streptokinase therapy is considered.

Analysis of prescriptive monitoring regarding the current therapeutic landscape of rheumatoid arthritis: the experience of an Italian local health authority

ABSTRACT Introduction Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs. Methods In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti – tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations. Results Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug. Conclusion The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs.

Preferential use of full glottal stops in vowel-initial glottalization in child speech: Evidence from novel words.

Vowel-initial glottalization constitutes a cue to prosodic prominence, realized on a strength continuum from creaky phonation to complete glottal stops. While there is considerable research on children's early utilization of acoustic cues for stress marking, less is understood about the specific implementation of vowel-initial glottalization in American English. Eight sequences of function + novel words were elicited from groups of 5-to-8-year-olds, 8-to-11-year-olds, and adults. Children exhibit a similar rate of prevocalic glottalization to adults but differ in its phonetic implementation, producing a higher rate of glottal stops compared to creaky phonation with respect to adults.

Abuse of Anabolic-Androgenic Steroids as a Social Phenomenon and Medical Problem—Its Potential Negative Impact on Reproductive Health Based on 50 Years of Case Report Analysis

Background/Objectives: Illegal anabolic-androgenic steroids are a significant lifestyle factor in infertility. The aim of our study was to analyze clinical cases resulting from their use for their frequency, geographical location, dynamics, substances used, the age and gender of the users, and the types of clinical complications. Methods: Publications were obtained by searching PubMed for the following terms: ‘anabolic-androgenic steroids’ and ‘clinical case’. Publications from 1973 to 2022 were qualified for the analysis. Results: An increasing trend in the number of clinical cases resulting from the use of steroids, as well as the number of substances used simultaneously, was observed. The substances changed over the decades, but in the last 20 years, testosterone, nandrolone, stanozolol, methandienone, trenbolone, and methenolone have predominated. Cardiological side effects predominated in each period, with a continuous increase in their occurrence. The most common among these were myocardial infarctions and hypertrophic cardiomyopathy. The next most numerous adverse events involved psychiatric, endocrinological, hepatic, and oncological problems. We demonstrated a possible relationship between the use of individual steroids and medical issues; the strongest associations were between testosterone and endocrine complications, and methylstenbolone and hepatic complications. Conclusions: There has been an increasing trend in case reports describing serious health problems associated with the use of anabolic-androgenic steroids, a tendency to use several substances simultaneously, and a preferential use of substances with a high potential of causing serious side effects. These phenomena mainly concern men, with an average age of 30, and the health problems that dominate in clinical case reports—including serious cardiological, psychiatric, endocrinological, hepatic, and oncological diseases—may potentially affect reproductive health and pose a challenge for reproductive medicine.

Comparative Analysis of the Codon Usage Pattern in the Chloroplast Genomes of Gnetales Species

Codon usage bias refers to the preferential use of synonymous codons, a widespread phenomenon found in bacteria, plants, and animals. Codon bias varies among species, families, and groups within kingdoms and between genes within an organism. Codon usage bias (CUB) analysis sheds light on the evolutionary dynamics of various species and optimizes targeted gene expression in heterologous host plants. As a significant order of gymnosperms, species within Gnetales possess extremely high ecological and pharmaceutical values. However, comprehensive analyses of CUB within the chloroplast genomes of Gnetales species remain unexplored. A systematic analysis was conducted to elucidate the codon usage patterns in 13 diverse Gnetales species based on the chloroplast genomes. Our results revealed that chloroplast coding sequences (cp CDSs) in 13 Gnetales species display a marked preference for AT bases and A/T-ending codons. A total of 20 predominantly high-frequency codons and between 2 and 7 optimal codons were identified across these species. The findings from the ENC-plot, PR2-plot, and neutrality analyses suggested that both mutation pressure and natural selection exert influence on the codon bias in these 13 Gnetales species, with natural selection emerging as the predominant influence. Correspondence analysis (COA) demonstrated variation in the codon usage patterns among the Gnetales species and indicated mutation pressure is another factor that could impact CUB. Additionally, our research identified a positive correlation between the measure of idiosyncratic codon usage level of conservatism (MILC) and synonymous codon usage order (SCUO) values, indicative of CUB’s potential influence on gene expression. The comparative analysis concerning codon usage frequencies among the 13 Gnetales species and 4 model organisms revealed that Saccharomyces cerevisiae and Nicotiana tabacum were the optimal exogenous expression hosts. Furthermore, the cluster and phylogenetic analyses illustrated distinct patterns of differentiation, implying that codons, even with weak or neutral preferences, could affect the evolutionary trajectories of these species. Our results reveal the characteristics of codon usage patterns and contribute to an enhanced comprehension of evolutionary mechanisms in Gnetales species.

Improved outcomes with leadless vs. single-chamber transvenous pacemaker in haemodialysis patients.

Cardiac conduction disorders are common in haemodialysis patients, with a relatively high rate of pacemaker implantations. Pacemaker-related complications, especially lead infections and central venous stenosis, pose significant challenges in this population. This study aims to compare single-chamber leadless pacemaker to single-chamber transvenous pacemakers in terms of survival and related complications in haemodialysis patients. This retrospective study included adult haemodialysis patients who received a first single-chamber transvenous or leadless pacemaker between January 2017 and December 2020. Data were obtained from the French national REIN registry matched to the national health databases (Système National des Données de Santé). Propensity score matching was used to balance baseline characteristics. Survival and complications were compared between groups by Cox regression and by competitive risk models, respectively. One hundred and seventy-eight patients were included after propensity score matching, with 89 patients in each group. The median follow-up time was 24 (range 7-37) months. Leadless pacemakers were associated with significantly lower all-cause mortality rates compared to transvenous pacemakers [hazard ratio (HR) = 0.68, 95% confidence interval (CI) (0.47-0.99)]. Device-related infections are significantly lower with leadless pacemakers throughout the follow-up period (HR 0.43, 95% CI 0.21-0.86). Leadless pacemaker recipients also required fewer vascular access interventions [odds ratio 0.53, 95% CI (0.33-0.68)] on arteriovenous fistula. With the limitations of its observational design, this study suggests that leadless pacemakers are associated with a lower rate of complications and better survival as compared with transvenous VVI pacemakers in haemodialysis patients, supporting to consider their preferential use in this population.

Lymphatic Fistula Treatment: Indocyanine Green Lymphography-guided Microsurgery

Background: Lymphatic fistulas are a common complication from surgery or interventional procedures resulting in persistent lymphatic leakage and delayed wound healing. The management of lymphatic fistula remains a subject of debate, ranging from conservative treatment to surgical lymphatic ligation. The implementation of a novel microsurgical approach involving lymphatic fistula ligation and/or lymphovenous anastomosis (LVA) using indocyanine green (ICG) lymphography is expected to decrease occurrence and complications. In this study, we share our experience in treating lymphatic fistula–guided microsurgical treatment. Methods: A total of 13 patients from our hospital with persistent lymphatic fistula were enrolled in this retrospective study. Lymphatic fistulas and their leakages were identified and ligated by using ICG lymphography and a surgical microscope. In two cases, additional LVA surgery was performed. Results: We were able to precisely identify lymphatic fistulas and treat them in all 13 patients. Lymph ligation was performed in all 13 cases, with additional distal LVA in two cases. In all patients, wound healing occurred following lymphatic ligation, except in one patient due to persistent infection. Patients with a lymphatic fistula were referred to our unit within 3 weeks to 1 year after onset, with an average consultation occurring after 5 months of persistent lymphatic fistula. Conclusions: Targeted lymphatic vessel ligation with or without LVA with ICG-guided surgical microscope represents a promising highly efficacious therapy for persistent lymphatic fistula. This technique may accelerate wound healing and reduce hospitalization duration, thus advocating for its preferential use in managing lymphatic fistulas.

Intestinal microbiota composition in broilers fed protein-free or casein-based diets

Growing broiler chickens of the Cobb500 strain were used to determine the effects on intestinal microbiota composition of a protein-free (PF) diet as compared to a diet based in casein (CAS) as the only protein source. CAS was formulated to contain the same amount of protein (190 g kg-1) as a commercial Maize-soy diet which was used as a practical reference. The ileal AA flow (g kg-1 dry matter intake) was significantly higher (P < 0.001) than PF in birds fed protein containing diets (CAS or Maize-soy). Taken as a whole (discriminant and ANOSIM analysis), the intestinal (ileal and caecal contents and ileal tissue) microbiota composition of PF and CAS were significantly (P < 0.001) different from Maize-soy and not different from each other in some cases. RT-qPCR and sequencing analysis of the ileal and caecal microbiota revealed significant (P < 0.05) differences in a number of bacterial groups between broilers fed PF, CAS or Maize-soy diets. The main result was that the lack of protein in the intestinal medium of PF birds resulted in a drop of Lactobacillus spp. counts (on average, 43 in PF vs 1,734 in the Maize-soy diet) and increased Enterobacteriaceae (on average, 419 in PF vs 172 in the Maize-soy diet) and other potentially pathogenic bacterial groups (in both intestinal contents and tissue). Thus, the lack of protein in the intestinal medium of PF birds resulted in a microbiota composition compatible with a pro-inflammatory state, and this effect was somewhat less marked in birds fed CAS. The results reported here suggest that the adverse effects on microbiota composition in broilers fed CAS were less marked than in those fed PF, which would be in line with a preferential use of a highly digestible protein containing diet to determine endogenous AA excretion instead of a PF diet.

Association of Technology Usage and Decreased Revision TKA Rates for Low-Volume Surgeons Using an Optimal Prosthesis Combination: An Analysis of 53,264 Primary TKAs.

Technology (navigation and robotics) usage during total knee arthroplasty (TKA) is often supported by literature involving high-volume surgeons and hospitals, but the value of technology for lower-volume surgeons is uncertain. This study aimed to determine if there was a relationship among surgeon volume, technology usage, and revision rate when using an optimal prosthesis combination (OPC). Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) data were obtained from January 1, 2008, to December 31, 2022, for all primary TKA procedures performed for osteoarthritis using an OPC by a known surgeon ≥5 years after their first recorded procedure. The interaction between surgeon volume and conventional-instrumentation (CV) versus technology-assisted (TA) TKA was assessed. The cumulative percent revision (CPR) was determined by Kaplan-Meier estimates. Cox proportional-hazards methods were used to compare rates of revision by surgeon volume and by the interaction of volume and technology. Subanalyses were undertaken to examine major and minor revisions separately, and to assess the influence of technology on revision rates relative to those of a surgeon undertaking 100 TKA/year. Of the 53,264 procedures that met the inclusion criteria, 31,536 were TA-TKA and 21,728 were CV-TKA. Use of technology reduced the all-cause revision rate for surgeons with a volume of <50 TKA/year and the rate of minor revisions for surgeons with a volume of <40 TKA/year. No interaction between surgeon volume and the rate of major revision surgery was found. With CV-TKA by a surgeon with a 100-TKA/year volume as the comparator, all-cause and major revision rates were significantly elevated for surgeons undertaking <50 and <100 TKA/year, respectively. In contrast, analysis of TA-TKA showed no difference in rates of all-cause or major revisions for surgeons undertaking <100 TKA/year compared with 100 TKA/year. TA-TKA was associated with a decrease in the revision rate for lower-volume surgeons but no significant alterations in revision rate for higher-volume surgeons. Preferential use of TA-TKA by lower-volume surgeons should be considered. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Improved Outcomes in Myelofibrosis after Allogeneic Stem-Cell Transplantation in the Era of Ruxolitinib Pretreatment and Intensified Conditioning Regimen—Single-Center Analysis

(1) Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the only treatment with the potential for cure in patients with myelofibrosis (MF). However, the risk of graft rejection, which is particularly high in MF, and the risk of significant non-relapse mortality must be considered. (2) Methods: In this retrospective, single-center study, we compared allo-HSCT outcomes in 36 adult patients with MF transplanted at two-time intervals (2001–2015 versus 2016–2021). (3) Results: The estimated median overall survival was 48.9 months (95%CI 0.00–98.2) in the cohort transplanted before 2016 and not reached in the more recent years (p = 0.04) due to markedly lower non-relapse mortality (p = 0.02). The 3-year relapse incidence was low in both cohorts (11.1% and 12.5%, p &gt; 0.99). When comparing only subgroups within the more recent cohort based on the presence or absence of total body irradiation (TBI) or the use of sequential regimens, OS and PFS were comparable. (4) Conclusion: Pretreatment with ruxolitinib, intensified conditioning, and the preferential use of haploidentical related instead of mismatched unrelated donors for patients lacking an HLA-identical donor are most likely responsible for the improved outcome after allo-HCT in MF in recent years.

Time-resolved multi-omics reveals diverse metabolic strategies of Salmonella during diet-induced inflammation.

With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. In this study, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation in high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity in samples based on Salmonella ribosomal activity, which is separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expressions descriptive of each phase. Surprisingly, we identified genes associated with host cell entry expressed throughout infection, suggesting subpopulations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.IMPORTANCEIdentifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts toward Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella. We observed differential gene expression across infection phases in mice over time on a high-fat diet. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, which explores the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.

Use of in vivo confocal microscopy in suspected Acanthamoeba keratitis: a 12-year real-world data study at a Swedish regional referral center

PurposeTo report real-world data (RWD) on the use of in vivo confocal microscopy (IVCM) in handling cases of suspected Acanthamoeba keratitis (AK) cases at a regional referral center during a 12-year period.MethodsRetrospective study of patients with suspected AK presenting at a regional referral center for IVCM in Sweden from 2010 to 2022. Demographics, symptoms, outcomes, and clinical management were analyzed, and IVCM images were interpreted.ResultsOf 74 included patients with suspected AK, 18 (24%) were IVCM-positive, 33 (44%) were IVCM-negative, 15 had inconclusive IVCM results (20.2%), and 8 (11%) were referred for a second opinion based on IVCM, 4 of which were IVCM-positive (5.5%), yielding an overall IVCM-positive rate of 29.5%. Cultures were taken in 38 cases (51%) with only 2 cases (2.7%) culture-positive for AK. Of IVCM-negative cases, cultures were taken in 22 (67%) of cases and 100% of these were AK-negative. IVCM-positive cases had more clinic visits (median 30, P = 0.018) and longer follow-up time (median 890 days, P = 0.009) than IVCM-negative patients, while visual acuity improvement did not differ (P > 0.05). Of IVCM-positive cases, 10 (56%) underwent surgery despite prior anti-amoebic treatment, and 14 (78%) had 3 or more IVCM examinations during follow-up, with cysts (100%), dendritic cells (89%) and inflammatory infiltrate (67%) as the most prevalent features. Longitudinal IVCM indicated improvement in cysts, dendritic cells and subbasal nerves with treatment, while clinical resolution was not always consistent with complete absence of cysts.ConclusionsIn a real-world setting, IVCM has a high reliability in classifying AK-negative cases, while IVCM detects AK-positive cases more frequently than the gold-standard culture method, leading to its preferential use over the culture method where time or resources are limited. Despite this, a subset of cases are IVCM-inconclusive, the clinical course of referred patients is long requiring many hospital visits, and visual acuity in most cases does not improve with medical treatment alone. Information sharing across centers and standardization of referral and diagnostic routines is needed to exploit the full potential of IVCM in AK patient management.

SP2.4 - Appendicetomy in pregnancy: a retrospective analysis of 39 cases between 2012-2022

Abstract Background Acute appendicitis is the commonest surgical emergency in pregnant women. Physiological changes during pregnancy can obscure symptoms. Prompt diagnosis and surgical intervention is essential to minimise risks such as sepsis and preterm labour. Objective This study aims to evaluate how gestational age, type of imaging, surgeons' expertise, and antibiotics management affect the surgical outcomes in pregnant patients with acute appendicitis. Methods A retrospective analysis of 39 obstetric cases between 2012 and 2022 in the Royal infirmary of Edinburgh. Statistical methods for analysis including ANOVA were used to compare different surgical techniques, and correlation assessments to investigate links between gestational age and aspects of post-operative care. Results The study found that the surgical method significantly impacted post-operative recovery, with laparoscopic procedures leading to shorter hospital stays and decreased antibiotic use compared to open surgeries (p=0.001169 for hospitalisation length and p=0.01049 for antibiotic course, respectively). Surgeon grade did not significantly alter these outcomes. There was a moderate correlation between gestational age and both post-operative antibiotic duration (r = 0.3293) and length of hospital stay (r = 0.3640. The varied use of imaging techniques across different stages of pregnancy suggests there is no consensus of best practice. Conclusion The study identifies a need for consistent guidelines on treating pregnant women with appendicitis, particularly regarding antibiotic use. The results support the preferential use of minimally invasive surgery and value MRI as a non-invasive diagnostic tool, both contributing to a comprehensive, multidisciplinary approach required for these complex clinical scenarios.

Dysregulation of muscle cholesterol transport in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, with a typical lifespan of 3-5 years. Altered metabolism is a key feature of ALS that strongly influences prognosis, with an increase in whole-body energy expenditure and changes in skeletal muscle metabolism, including greater reliance on fat oxidation. Dyslipidemia has been described in ALS as part of the metabolic dysregulation, but its role in the pathophysiology of the disease remains controversial. Among the lipids, cholesterol is of particular interest as a vital component of cell membranes, playing a key role in signal transduction and mitochondrial function in muscle. The aim of this study was to investigate whether motor dysfunction in ALS might be associated with dysregulation of muscle cholesterol metabolism. We determined cholesterol content and analyzed the expression of key determinants of the cholesterol metabolism pathway in muscle biopsies from thirteen ALS patients and ten asymptomatic ALS-mutation gene carriers compared to sixteen controls. Using human control primary myotubes, we further investigated the potential contribution of cholesterol dyshomeostasis to reliance on mitochondrial fatty acid. We found that cholesterol accumulates in the skeletal muscle of ALS patients and that cholesterol overload significantly correlates with disease severity evaluated by the Revised ALS Functional Rating Scale. These defects are associated with overexpression of the genes of the lysosomal cholesterol transporters Niemann-Pick type C1 (NPC1) and 2 (NPC2), which are required for cholesterol transfer from late endosomes/lysosomes to cellular membranes. Most notably, a significant increase in NPC2 mRNA levels could be detected in muscle samples from asymptomatic ALS-mutation carriers, long before disease onset. We found that filipin-stained unesterified cholesterol accumulated in the lysosomal compartment in ALS muscle samples, suggesting dysfunction of the NPC1/2 system. Accordingly, we report here that experimental NPC1 inhibition or lysosomal pH alteration in human primary myotubes was sufficient to induce the overexpression of NPC1 and NPC2 mRNA. Finally, acute NPC1 inhibition in human control myotubes induced a shift towards a preferential use of fatty acids, thus reproducing the metabolic defect characteristic of ALS muscle. We conclude that cholesterol homeostasis is dysregulated in ALS muscle from the presymptomatic stage. Targeting NPC1/2 dysfunction may be a new therapeutic strategy for ALS to restore muscle energy metabolism and slow motor symptom progression.

Risk of Incident Cardiovascular Events Following Roux en Y Gastric Bypass versus Sleeve Gastrectomy: A Claims-Based Retrospective Cohort Study.

To compare the risk of incident cardiovascular disease (CVD) events following sleeve gastrectomy (SG) and Roux en Y gastric bypass (RYGB). Bariatric surgery is associated with reduced CVD risk but the differential effect of contemporary bariatric procedures is unclear. We used insurance claims to conduct a retrospective cohort study of CVD outcomes for patients who underwent RYGB versus SG between 2010 and 2021. Patients were followed for up to 5 years for a primary composite major adverse cardiovascular event (MACE) outcome as well as individual outcomes including myocardial infarction, stroke, heart failure, and arrhythmia. We compared cumulative risks of CVD events using multivariable Cox proportional hazards modeling, in overall cohorts and in sub-cohorts of older adults and those with type 2 diabetes (T2D) or pre-existing CVD and elevated morbidity. Matched, weighted cohorts of 13,545 SG and RYGB patients were observed for an average of 2.5 years after surgery, with 26.2% not lost to follow-up by the end of 5 years. There was no difference in MACE risk between procedures (aHR 1.01 for RYGB vs. SG [95% CI 0.90, 1.12]) in the overall cohort or among the subgroup of older adults (aHR 0.97 for RYGB vs. SG [95% CI 0.85, 1.10]). Patients with T2D experienced lower risk of MACE following RYGB compared to SG (aHR 0.78 [95% CI 0.66, 0.92]), as did those with pre-existing CVD or elevated morbidity prior to surgery (aHR 0.81 [95% CI 0.70, 0.93]). These findings further support the preferential use of RYGB over SG for patients with T2D or who have pre-existing CVD. However, among other groups of patients, including older adults, we did not observe a relative benefit of RYGB during the time horizon in this study.