Stable Group Research Articles

Serum levels of soluble receptor activator for nuclear factor kB ligand play a crucial role in the association of osteoprotegerin with coronary artery disease.

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of nuclear factor kB ligand (RANKL), and is implicated in the pathogenesis of atherosclerosis. The aim of the present study was to examine the hypothesis that serum OPG concentrations are increased in patients with stable coronary artery disease (CAD) at different serum levels of soluble RANKL (sRANKL). The study used a case-control design in which consecutively hospitalized individuals were recruited. Fasting blood samples were taken upon admission for serum testing. Participants with previously diagnosed CAD that was asymptomatic or had controlled symptoms constituted the stable CAD group, whereas patients with negative coronary computed tomography angiography results constituted the control non-CAD group. Exclusion criteria included recent acute coronary syndrome, severe heart failure, CAD-complicating autoimmune, blood or thyroid diseases, cancer, elevated temperature with or without infection, severe liver or kidney dysfunction, abnormal calcium metabolism, recent surgery and trauma history. A total of 118 individuals were included in the study. Smoothed plots generated using the recursive method and multivariate models showed that the incidence of stable CAD increased with serum OPG level up to the turning point of 18 pg/ml. This trend was observed at both high [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.04-2.50; P=0.032) and low sRANKL concentrations (OR, 1.52; 95% CI, 1.06-2.17; P=0.022) after adjustment for cardiovascular risk factors. In conclusion, serum OPG levels ≤18 pg/ml are positively associated with stable CAD, regardless of sRANKL levels. In addition, at the same serum OPG level, higher sRANKL levels are associated with a greater incidence of stable CAD compared with lower sRANKL levels. This study identified the relationship between OPG, sRANKL, and stable CAD, and established the reference range for future clinical use.

Changes in pre-haemodialysis serum creatinine levels over 2years and long-term survival in maintenance haemodialysis.

Pre-haemodialysis (HD) serum creatinine levels are reliable and inexpensive markers of muscle mass and important predictors of survival in patients with stable chronic HD. We aimed to assess whether changes in pre-HD serum creatinine levels during a 2-year period are linked to long-term patient survival. We retrospectively analysed patients enrolled in a periodic HD quality assessment program. Of the 21846 participants in the fourth HD quality assessment program, 13765 were presented in the fifth, of which 10299 eligible patients were included in this study. We assessed the change in serum creatinine levels over 2years. The patients were categorized into the following three groups: stable group (patients with change in serum creatinine<1mg/dL during 2years of HD, n=5664), increasing group (patients with increase in serum creatinine≥1mg/dL, n=2419) and decreasing group (patients with decrease in serum creatinine≥1mg/dL, n=2216). The duration of HD at baseline was 62-83months, with diabetic kidney disease being the most common cause of kidney failure in 36.4% of patients. The 5-year patient survival rates in the stable, increasing and decreasing groups were 69.1%, 71.3% and 66.8%, respectively. The decreasing group had poorer patient survival than the other two groups (P=0.083 for stable vs. increasing group; P=0.011 for stable vs. decreasing group; P<0.001 for increasing vs. decreasing group). There was no significant difference in the cardiovascular event-free survival rate among the three groups. Multivariable Cox regression analyses revealed the highest hazard ratio (HR) for mortality in the decreasing group (HR 1.33, 95% confidence interval [CI] 1.21-1.45, P<0.001 vs. stable group; HR 1.50, 95% CI 1.34-1.69, P<0.001 vs. increasing group). The increasing group exhibited a lower risk of mortality than the stable group (HR 0.88, 95% CI 0.81-0.97, P=0.008). Subgroup analyses based on age, HD vintage, sex, Charlson comorbidity index score, presence of diabetes and baseline serum creatinine level tertiles revealed that the decreasing group exhibited the highest mortality among all subgroups. Our results demonstrate that changes in pre-HD serum creatinine levels over 2years of HD were associated with all-cause mortality in patients undergoing HD. This finding suggests a simple and promising approach for clinicians in the prognosis and management of patients undergoing HD.

Weight change and risk of incident type 2 diabetes: short, medium and long-term follow-up in tehran lipid and glucose study

BackgroundDespite the high burden of obesity and Type 2 diabetes (T2DM) in the Middle East/West Asia region, the effect of weight change on the development of T2DM is poorly addressed. Therefore, we aimed to assess the impact of 3-year body weight change on incident of T2DM over 3-, 6-, and 9-year periods among Iranian adults.MethodsA total of 6930 participants (men = 2567) aged ≥ 20 years free of T2DM or cancer at baseline were included. Weight measurements were taken at baseline (2002–2005) and approximately 3 years later. Participants were categorized based on their weight change ratio into ≥ 5% loss, stable (± 5%), and ≥ 5% gain. Generalized estimating equations (GEE), adjusted with age, sex, education levels, baseline measurements of fasting plasma glucose, weight, waist circumference, triglycerides to high-density lipoprotein cholesterol ratio, family history of diabetes, current smoker, hypertension, and prevalent cardiovascular disease were applied to estimate the Odds ratios (ORs) and 95% confidence intervals (CIs) of weight change categories for incident T2DM, considering stable weight as a reference.ResultsDuring median follow-ups of 3-, 6-, and 9-year, 295, 505, and 748 cases of T2DM occurred, respectively. Weight gain of ≥ 5%, as compared to stable weight group (± 5%), was associated with increased T2DM risk, with ORs of 1.58 (95% CI 1.16–2.14), 1.76 (1.41–2.20), and 1.70 (1.40–2.05) for the 3-, 6-, and 9-year follow-ups, respectively, in multivariable analysis; corresponding values for weight loss ≥ 5% were 0.48 (0.29–0.80), 0.57 (0.40–0.81), and 0.51 (0.38–0.68), respectively. This association persisted even after adjusting for attained weight. Subgroup analysis showed consistent associations across age, gender, and body mass index categories.ConclusionWeight gain and loss of ≥ 5% were associated with increased and decreased risks of incident T2DM, respectively, regardless of attained weight. This association was consistent over various follow-up durations among the Iranian population as recommended by guidelines.

The Development of New Scoring System to Define the Presence of Instability and the Need of Fusion in Degenerative Lumbar Spinal Stenosis - Jakarta Instability Score.

Systematic review, expert opinion and Delphi technique, and validity and reliability studies. We developed Jakarta Instability Score (JIS) to identify spinal instability and the need of fusion in degenerative lumbar spinal stenosis (LSS). This study consisted of systematic review to find predictors of spinal instability, expert opinion and modified Delphi technique to develop JIS, and validity and reliability studies of the newly developed JIS. A total of 54 studies were included in the systematic reviews to obtain predictors of spinal instability. Through expert opinion and modified Delphi technique, JIS was developed and consisted of the clinical component (back pain), dynamic radiograph component (dynamic translation and angulation), and MRI component (facet joint effusion), each of the component would be scored, and the total scoring would be from 0 to 14. The final scoring would classify patients into three groups: stable group (score of 0 to 4) in which the fusion is not needed, potentially unstable group (score of 5 to 8) in which the decision of fusion is based on surgeon's clinical judgment, and unstable group (score of 9 to 14) in which the fusion is needed. Final step of study concluded that this JIS had a high validity and reliability. The newly developed JIS was a valid and reliable scoring system that could help to identify the presence of instability in LSS and can be used as a guideline to decide whether spinal fusion will be needed.

Un progetto per promuovere la competenza digitale nella scuola: Patentino per cittadini digitali

This article presents the training course aimed at primary, first and second level secondary schools, carried out by teachers using a kit of materials prepared by experts and designed for each individual school level entitled: License for digital citizens. The initiative aims to attract younger people from the age group in which we know independent use of the internet is widespread (9-15 years). Promoted and coordinated by the USR for Umbria in collaboration with EFT Umbra and Corecom Umbria, it is implemented and managed by a stable working group. The logic of the project aims at prevention through the training and awareness of multiple social actors, rather than intervening in the face of emergencies.

The relationship between changes in peritoneal membrane solute transfer characteristics and cardiac remodeling in patients with peritoneal dialysis.

We aimed to determine the relationship between the dilatation of the heart chambers and the change in peritoneal membrane solute transfer characteristics (PMTC) in long-term peritoneal dialysis (PD) patients. This is a retrospective, single-center study including the follow-up of maintenance PD patients. According to the changes in PMTC from baseline to the last visit, patients were divided into three groups; stable (n = 11), increased (n = 41), and decreased transporters (n = 35). Left atrium (LA) and Right ventricle (RV) dilatation were more prominent in the PMTC-decreased group compared to PMTC-increased and stable groups (p < 0.001 and p = 0.07, respectively). The Cox regression analysis showed that only decreased PMTC was associated with LA dilatation (HR 2.89 [CI 95%1.54, 5.45] p < 0.01) and RV dilatation (HR 3.01 [CI 95%1.40, 6.21] p < 0.01). PD can be associated with unfavorable dynamic changes in cardiac structure and functions even at the subclinical level.

Increased serum IL‑41 associated with acute exacerbation of chronic obstructive pulmonary disease.

Interleukin (IL)-41 is a novel immunomodulatory cytokine involved in the pathogenesis of several inflammatory and metabolic illnesses. However, it remains unclear how IL-41 contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, the aim of the present study was to explore the correlation between the expression level of IL-41 and acute exacerbation of COPD (AECOPD). In total, 107 patients with COPD and 56 healthy controls were recruited from the First Affiliated Hospital of Ningbo University (Ningbo, China). Serum IL-41, IL-6, and matrix metalloproteinase-2 (MMP-2) levels were evaluated using enzyme-linked immunosorbent assay. Serum amyloid A (SAA) and C-reactive protein (CRP) levels were assessed in the hospital laboratory. The levels of IL-41 were higher in the AECOPD group than in the stable COPD (SCOPD) and control groups (P<0.0001). IL-6, SAA and CRP levels, the percentage of neutrophils, as well as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were higher in the AECOPD group than those in the SCOPD and control groups. The smoking index was positively correlated with serum IL-41, CRP and SAA levels. The expression level of IL-41 was correlated with the number of acute exacerbations, severity of the exacerbations, and COPD assessment test scores in the AECOPD group. Examination of the receiver operating characteristic (ROC) curves showed that IL-41, especially when combined with other inflammatory factors, had a specific diagnostic value for AECOPD. According to the ROC curve analysis, the area under the curve (AUC) for IL-41 was 0.742 (P=0.051), and the AUC for IL-41 combined with other inflammatory factors was 0.925 (P=0.030). Increased serum IL-41 levels were associated with AECOPD and may play a role in the monitoring and evaluation of COPD.

Lawn covers of Dnipropetrovsk region as a global phenomenon of urban green space in conditions of hostilities

In order to facilitate the creation of lawns and maintain the regime of caring for lawn covers in difficult wartime, in which Ukraine and Dnipropetrovsk region is located, suffering from shelling and man-made disturbances of habitats, it is important to conduct observations and studies of the behavior of lawn plants in comparison with natural conditions in order to be able to preserve existing and restore damaged herbaceous groups with the least cost. We hypothesize that these solutions can be found in suburban natural ecosystems and various plant communities that are rich in species, able to withstand harsh climatic and microclimatic living conditions, severe trampling and droughts. Realizing that stable artificial plant groupings can exist only when using the laws of their existence in natural conditions, trial areas of urban agglomerations and out-of-town influence were investigated. 75 lawn covers and grass stands of the lawn type of the Dnipropetrovsk region with a size of 100 m2 in Dnipro, Kamenskoye, Andreevka village were described using the method of route trial areas. The dominant families are defined in the creation of lawn grass stands by their occurrence, projective coating, phytocenotic activity, number of species. It is established that, among other families, the Fabaceae family was in third place with participation in the projective cover among phytocenoses of Dnipro and Andreevka, in fifth ‒ in Kamianske. Phytocenotic activity, used as a criterion for the effect of plants on herbal grouping, was high in Fabaceae plant family (up to k = 19,5), Asteraceae (up to k = 18,7), Plantaginaceae (up to k = 15,4) on lawn grass stands in Andreevka village, which indicates the future trend of their displacement of cereals. Among the grasses plant family Plantaginaceae has significant phytocenotic activity (k = 10.1), which competes even with the main sod-forming plants of the Poaceae plant family (k = 10.7) in Dnipro. This trend is also observed in Kamenskoye (here in Plantaginaceae k = 10.0). This city has a high rating of industrial influence among other territories of the region and those that we have studied so far. In all studied phytocenoses, mutual influence between plants families Poaceae and Fabaceae is established. So, with a larger percentage of projective coverage of the Poaceae plant family, the percentage of the Fabaceae plant family is reduced, and vice versa. In dynamics, these fluctuations can vary in favor of each other, taking into account the further saturation of the upper horizon of the soil with nitrogen by the Fabaceae plant family, or the use of this trace element by representatives of the Poaceae plant family and the displacement of legumes. Such fluctuations will be constant. At the same time, lawn covers will not lose their aesthetics as a green carpet, because the projective coating will be occupied by plants and will not have gaps of free soil. This interdependence of lawn covers should be taken into account when creating high-quality long-term green lawns of cities where the soils are depleted, and constant fertilization is not always possible. Due to environmental conditions, the botanical diversity of the studied herbivores is expanded by adventive plant species from plants families Brassicaceae (up to 5 species in Dnipro), Lamiaceae (up to 7 species in v. Andreevka), Rosaceae (up to 6 species in Dnipro), Scrophulariaceae (up to 4 species in v. Andreevka), which, under favorable conditions, will occupy free ecological niches with grass. The spectrum of the first largest percentage of the occurrence of families reproduces the composition of the regional flora, which corresponds to cereal-grass groups of the structure of meadow lawns and ordinary urban grass stands with the expansion of ruderal representatives. 29% of the trial areas in the Dnieper city indicate the presence in the species composition of seedlings of woody and shrub life forms, the seeds of which are stored in the soil of adjacent territories, and their entry into lawn groups is a consequence of anemochoria and ornithochoria. Currently, given the current state of the country, lawn care is reduced to a minimum or it is absent at all. As a result, seedlings freely begin to take possession of the territory of lawn grass stands along with ruderal representatives of the local flora. This trend is also evidenced by the ratio of monocotyledonous and dicotyledonous plants as a criterion for decorativeness and phytocenotic constancy of lawns. It was ‒ 1:4 in Kamenskoye; 1:6 ‒ in Dnipro and Andreevka village. These are the conclusions that for the existing military period can be used to maintain the stability and aesthetic condition of lawn covers and grass beds of the lawn type of the Dnipropetrovsk region.

RBM10 mutation as a potential negative prognostic/predictive biomarker to therapy in non-small-cell lung cancer.

e20544 Background: According to WHO, lung cancer is the leading cause of cancer-related death worldwide, but treatment has advanced in the last decade. The widespread use of Next Generation Sequencing has led to the discovery of several pathogenic mutations including RNA binding motif 10 [RBM10], a part of the spliceosome complex that regulates splicing of pre-mRNA [Pan Q, Nat Genet. 2008]. The knock down of RBM10 increases the growth of mouse tumor xenografts [Hernández J, RNA Biol. 2016]. Mutated RBM10increased spliceosome inhibition in EGFR mutated lung cancer cells thereby contributing to EGFR TKI resistance [Bao Y, Cancer Res. 2023]. Methods: Electronic medical records were utilized to create a database of patients [50 patients] seen from 2018-2023 with NSCLC and RBM10 mutations, with appropriate IRB approval. For sub-group analysis, we separated into groups by rapid progression vs stable disease defined as progression free survival earlier than respective clinical trials. Fisher’s exact tests were used to assess the association between mutation and clinical outcomes. Results: From analysis of treatment response, 71% [20 patients out of 28] of the patients with complete treatment data had rapid progression of disease. In our patient dataset, 20 out of the 50 RBM10 mutated patients had EGFR mutations while 18 had KRAS mutations. RBM10 mutations did not seem to correlate with alterations in MSI stability as all patients had MSI stable disease and there was no relationship between the tumor mutation burden and the clinical response in the RBM10 mutated patients (odds ratio (OR) = 1.33, 95% CI 0.24-7.35, p = 0.741). In comparing the mutated RBM10 population to wild type RBM10 population, controlled for driver mutations, median PFS was 6.7 (95% CI [4.5, 17.]) compared to 13.9 (95% CI [10.4, 24.2]). RBM10 mutations in EGFR mutated patients often developed later in the course of disease, commonly at progression leading to late EGFR TKI resistance. The most common non driver concurrent mutation with RBM10 was TP53, while the most common VUS were SPTA1 and ZFHX3. TP53 mutation had a higher representation in the RBM10 mutated rapid progression group, OR (odds ratio) 8.081, 95% CI [0.773, 431/717], P-value = 0. 00838). The ZFHX3 mutation had a higher representation in the RBM10 mutated stable disease group OR 0.0430, 95% CI [0.0007, 0.5506]. Conclusions: From this single institution investigation, RBM10 mutations were associated with aggressive disease with treatment progression faster than median durations of response. RBM10 mutations with concurrent ZFHX3 and EGFR mutations were associated with more stable disease, while concurrent KRAS and TP53 predicted even more aggressive disease. However, once the RBM10 mutation developed in the EGFR population, rapid progression was observed, indicating a mechanism of late resistance. More investigation is warranted into RBM10 to further certify its use as a biomarker.

Sex differences in optimal medical therapy following invasive angiography for coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): HARP Wellcome Trust PhD Fellowship Grant &amp; NIHR Biomedical Research Centre Introduction Coronary artery disease (CAD) remains the number one cause of death in women worldwide despite advances in treatment (1). Women who experience myocardial infarction (MI) and undergo invasive angiography experience higher morbidity and mortality compared to their male counterparts. Data suggests that this mortality difference may be predominantly in women &amp;gt;55 years (2). Treatment bias may be an important factor. Prognostic benefit of optimal medical therapy (OMT) following MI is well established, however studies and meta-analyses suggest women may be less likely to receive this compared to men e.g (3, 4). Purpose We aimed to establish whether there were sex differences in OMT received following invasive angiography for obstructive CAD at a large cardiac centre. Methods In this single centre retrospective study, we examined OMT received by females and males undergoing invasive angiography in 2019 with proven obstructive CAD, as defined by an angiographic lesion ≥50% of luminal diameter. Discharge medications were extracted from the electronic patient record and entered into a database. Pooled analysis of sex differences and sub-group analysis according to diagnosis (STEMI, NSTEMI, stable angina) and age (≤ 55 years or &amp;gt;55 years) was performed. Multivariate binomial logistic regression was used to adjust for confounders including BMI, diabetes, hypertension, hypercholesterolaemia, previous MI and previous percutaneous coronary intervention. Results 4,346 patients underwent invasive angiography during the study period. 2,358 with obstructive CAD and full medication details available at the present time were included (STEMI: 649 [mean age: 59.7, 20.6 % female], NSTEMI: 439 [mean age 63.4, 22.6% female], Stable angina: 1,270 [mean age 63.7, 22.2% female]). Pooled analysis showed females were less likely to receive aspirin and beta-blockers (OR=0.64, p=0.009, OR=0.66, p=0.001). They also received fewer angiotensin-converting enzyme inhibitors (ACE-I) but more angiotensin receptor blockers (ARB) (OR=0.58, p&amp;lt;0.001, OR=1.45, p=0.009). Subgroup analysis revealed females &amp;gt;55 with STEMI were less likely to receive beta-blockers and high potency antiplatelets compared to males (OR=0.49, p=0.009, OR=0.44, p=0.011). In the NSTEMI group females ≤55 received fewer beta-blockers and statins (OR=0.16, p=0.020, OR=0.004, p=0.045). In the stable angina group females ≤55 were less likely to receive aspirin (OR=0.07, p&amp;lt;0.001). Fewer ACE-I and more ARB in females was predominantly in the stable angina group (OR=0.56, p&amp;lt;0.001, OR= 1.50, p=0.021). Conclusion Women undergoing invasive angiography for obstructive CAD appeared to receive less OMT compared to men across several drug categories, diagnoses and age groups. Future work will be directed at understanding why these differences occurred and the mechanistic consequences of these differences in OMT pharmacology between females and males.

Elastic Stable Intramedullary Nailing in Length Stable Versus Unstable Pediatric Femoral Shaft Fractures: A Comparison of Clinical, Radiographic, and Pedobarographic Outcomes.

Pediatric diaphyseal femoral fracture (PDFF) is one of the most common injuries requiring hospitalization. Elastic stable intramedullary nailing (ESIN) is commonly used for PDFFs in ages 5 to 11. The optimal treatment method for length unstable PDFF is a subject of ongoing debate. This study aimed to compare clinical, radiographic, and pedobarographic outcomes of ESIN between length stable and unstable PDFF. We retrospectively reviewed patients undergoing ESIN treatment for isolated PDFF between 2016 and 2021. Exclusion criteria were (1) history of ipsilateral or contralateral lower extremity fractures, (2) highly comminuted or segmental fractures, (3) body weight >50kg, and (4) comorbidities affecting bone quality, range of motion, or neurologic status. The patients were divided into 2 groups according to length stability. Clinical, radiographic, and pedobarographic data were then assessed to compare groups. Twenty-five patients were included (17 length stable and 8 length unstable PDFF) with a mean age of 73.6±17.8 months. There was no significant difference between groups in age, side of injury, body weight, follow-up duration, and nail-canal diameter ratio. Mean deformity in the fracture site in the early postoperative x-rays was not significantly different between groups ( P =0.661). After a mean follow-up of 27.8±14.2 months (range, 12-67), there was no significant difference in mechanical axis deviation, distal femur joint orientation angle, or limb-length discrepancy in both groups. The pedobarographic assessment revealed that the length unstable group had a significantly higher external foot progression angle in the injured extremity (9.8°±6.9° vs. 1.3°±5.6°, P =0.031). However, the length stable group had no significant difference in the foot progression angle (4.9°±5° vs. 3°±4.3°, P =0.326). There was no significant difference in either group for other pedobarographic parameters. ESIN is a safe and effective option for length-unstable PDFF, yet attention should be paid to the rotational alignment. Although significant external rotation deformity occurs in length-unstable PDFF, it has no implications for the other pedobarographic parameters. Level IV.

Serendipity and surprise: A diachronic analysis of &lt;em&gt;International Baccalaureate&lt;/em&gt; in the global press 1977-2019

This study examines perceptions of the International Baccalaureate (IB) over five decades to better understand its growing influence on education systems around the world. As part of the global education industry, the IB plays an important role in shaping national public education discourse. Building on previous synchronic analyses that used a corpus-assisted discourse studies (CADS) approach, the present study conducts a diachronic exploration of the same 28 million word corpus of global press articles to see how perceptions of the IB may have changed over its 55-year history. Trends over time revealed five main shifts in IB discourse: (i) from education to brand; (ii) from concrete curriculum-related lexis to recurring value-laden terms; (iii) from comparison to competition with other national curricula; (iv) from academic qualification to institutional regulation; and (v) from students to IB coordinator. Findings also showed a stable group of collocates that occurred consistently across all time periods, pointing to an “invariant core” (Morley &amp; Partington, 2009) meaning of the IB that provides fresh insight into how the dominant view of the IB as a singular standardized brand may be entrenched and taken for granted.

Spatiotemporal stability of digital twin-guided atrial fibrillation dominant frequency sites and the clinical outcome of catheter ablation

Abstract Background Although the dominant frequency (DF) may localize the reentrant drivers of atrial fibrillation (AF), its meandering nature makes it difficult to localize as an extra-pulmonary vein (extra-PV) target. Purpose We explored and quantified the spatiotemporal stability of DF by sophisticated digital-twin maps and the association with the rhythm outcome of clinical AF catheter ablation (AFCA). Methods We retrospectively examined the DF sites in the digital twin integrated by high-density electroanatomical maps (EAM) of 170 patients previously included in the CUVIA-AF2 trial (male 70.6%, 59.2±11.3 years old, 100% persistent AF). We monitored 34 seconds of virtual AF and analyzed DF sites in 10 different left atrial (LA) regions at 3 consecutive periods (6 seconds each after 16sec induction and blanking periods). The spatiotemporal stability index (STSI) was calculated to quantify mean DF's spatial and temporal variability. During protocol-based rhythm follow-up, we assessed the atrial arrhythmia recurrence rate by dividing patients into two groups based on STSI 0.75. Results During the simulation, 108 out of 170 (63.5%) patients obtained mean DF values in all three consecutive periods. There were 26 (24.1%) patients in the stable DF group (STSI ≥0.75, Stable group) and 82 (75.9%) patients in the unstable DF group (STSI &amp;lt;0.75, Unstable group). Although the proportion of patients with hypertension (73.1 vs. 47.6%, p=0.041) was higher and left ventricular end-diastole diameter (51.3±3.9 vs. 49.0±4.4 mm, p=0.020) was larger in the stable DF group than in the unstable DF group, other parameters, including LA size, LA voltage, or AF ablation targets, did not differ between two groups. During the median 19 [15-22] months follow-up, the atrial arrhythmia recurrence rate of the Stable group is higher than that of the Unstable group (log-rank p=0.031, HR = 2.06, CI [1.06-4.01]) Conclusions We found that the temporally stable DF in EAM-integrated virtual AF, the potential extra-PV AF drivers, is a surrogate marker of the adverse rhythm outcome of AFCA. A prospective clinical trial targeting the spatiotemporally stable DF will be warranted.

#1779 Assessment of inflammation score in immune cells of atypical hemolytic uremic syndrome using single-cell sequencing analysis

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening form of thrombotic microangiopathy (TMA) characterized by a complex interplay of genetic and immunological factors. Historically, research into aHUS has primarily focused on genes associated with complement activation and coagulation pathways. Our previous studies, employing single cell sequencing analysis, have revealed a significant association between aHUS and various immune cell types [1]. The clinical manifestation of aHUS is often initiated by infections, autoimmune diseases, or pregnancy, with many instances not reverting to a stable state even after the elimination of these triggering factors. Additionally, a significant portion of patients, despite lacking identifiable anomalies in complement or coagulation genes, respond positively to anti-complement therapy. This observation suggests a potential role for inflammation-related genes in the pathogenesis of aHUS. Given the extensive array of genes linked to inflammation, our study is designed to quantitatively assess inflammation gene expression, converting these measures into an inflammation score for each immune cell type in aHUS patients, their nuclear families, and healthy controls. This approach allows for a detailed comparison of disease activity variations within aHUS cases, aiming to deepen our understanding of aHUS and explore new avenues for therapeutic intervention. Method This study enrolled 13 aHUS patients, 3 nuclear families without aHUS, and 4 healthy subjects from Taiwan. Peripheral blood samples were collected for single-cell RNA sequencing analysis. aHUS patients were categorized into stable and unstable groups. The definition of stable disease activity is characterized by consistent TMA-related organ involvement and normal markers of hemolysis. Single-cell RNA sequencing data was processed using CellRanger and analyzed using the Seurat package in R. We obtained inflammatory genes from the Molecular Signatures Database, and we used the AddModuleScore function in Seurat to calculate inflammation score (IS). Results Our analysis demonstrated that non-switch memory B cells, classical monocytes, intermediate monocytes, non-classical monocytes, low-density basophils, naïve CD8 T cells, central memory CD8 T cells, terminal effector CD4 T cells, Th1 cells, Th17 cells, Th1/Th17 cells, and follicular helper T cells had the highest IS in aHUS patients, followed by aHUS patients' nuclear family members without aHUS and healthy control subjects. Furthermore, we observed that the IS of classical monocytes, non-switch memory B cells (Fig. 1), intermediate monocytes, non-classical monocytes, naïve CD8 T cells, central memory CD8 T cells, non-vd2 gd T cells, terminal effector CD4 T cells, Th17 cells, and follicular helper T cells were highest in aHUS patients with unstable disease activity, followed by aHUS patients with stable disease activity, aHUS patients' nuclear family members without aHUS, and healthy control subjects. Conclusion Our study underscores a pivotal link between elevated inflammation scores and aHUS severity aHUS. This finding not only emphasizes the critical role of inflammation in disease progression but also opens new avenues for therapeutic intervention, particularly in cases of unstable aHUS. By highlighting inflammation as a key factor in aHUS pathophysiology, our research offers fresh insights for disease management and future investigations. Moreover, exploring anti-inflammatory pathways presents promising therapeutic possibilities, potentially leading to improved patient outcomes and enhanced management strategies for aHUS.

Association of clinical and imaging characteristics with pulmonary function testing in patients with Long-COVID

PurposeThe purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline. MethodsThis study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values <0.05 were considered statistically significant. ResultsThe Decline group had a higher proportion of neutrophils (79.47 ± 4.83 % vs. 65.45 ± 10.22 %; p = 0.003), a higher absolute neutrophil count (5.73 ± 2.68 × 109/L vs. 3.43 ± 1.74 × 109/L; p = 0.031), and a lower proportion of lymphocytes (9.90 ± 4.20 % vs. 21.21 ± 10.97 %; p = 0.018) compared to the Stable group. The Decline group also had significantly higher involvement of ground-glass opacities (GGO) on follow-up chest CT [8.50 (4.50, 14.50) vs. 3.0 (1.50, 9.50); p = 0.032] and significantly higher extent of reticulations on chest CT at time of COVID diagnosis [6.50 (4.00, 9.00) vs. 2.00 (0.00, 6.00); p = 0.039] and follow-up [5.00 (3.00, 13.00) vs. 2.00 (0.00, 5.00); p = 0.041]. ICU admission was higher in the Decline group than in the Stable group (71.4 % vs. 13.3 %; p = 0.014). ConclusionsThis study provides novel insight into factors influencing post-COVID lung function, irrespective of pre-existing pulmonary conditions. Our findings underscore the significance of neutrophil counts, reduced lymphocyte counts, pulmonary reticulation on chest CT at diagnosis, and extent of GGOs on follow-up chest CT as potential indicators of decreased post-COVID lung function. This knowledge may guide prediction and further understanding of long-term sequelae of COVID-19 infection.

H3K27me3 Expression Level and Its Epigenetic Regulation Mechanisms in Th17 Cell Differentiation in Patients With Ankylosing Spondylitis

To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS), to unveil their potential involvement in the pathogenesis of AS, and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors. A total of 84 AS patients (42 active AS patiens and 42 patients in the stable phase of AS) were enrolled for the study, while 84 healthy volunteers were enrolled as the controls. Blood samples were collected. Peripheral blood mononuclear cells were isolated. ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21, IL-22, and IL-17. The mRNA expressions of RORc, JAK2, and STAT3 were analyzed by RT-PCR, the protein expressions of RORc, JAK2/STAT3 pathway protein, H3K27me3 and the relevant protease (EZH2 and JMJD3) were determined by Western blot. Correlation between H3K27me3, EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis. The mRNA expressions of RORc, JAK2, and STAT3 were significantly higher in the active phase group than those in the stable phase group ( P<0.05). The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group, which were lower than those of the control group, with the differences being statistically significant ( P<0.05). The relative grayscale values of JMJD3, RORc, JAK2, pJAK2, STAT3, and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group, which were higher than those in the control group (all P<0.05). The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups (P<0.05). H3K27me3 was negatively correlated with RORc, JAK2, STAT3, and IL-17, JMJD3 was positvely correlated with JAK2, STAT3, and IL-17, and EZH2 was negatively correlated with JAK2, STAT3, and IL-17 (all P<0.05). The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2, which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.

The ISAKOS subclassification of Rockwood type III AC joint dislocations in a stable type A and an unstable type B is not clinically relevant.

The treatment of Rockwood type III AC joint dislocations has been debated for decades. In 2014, theInternational Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Upper Extremity Committee suggested a subclassification of the injury into type A, considered stable and best treated nonsurgically, and type B, considered unstable and best treated surgically. Type B is defined by the presence of scapular dyskinesis and overriding of the clavicle to the acromion on a modified lateral radiograph. The objective of the study was to investigate if this subclassification is clinically relevant. This was a prospective cohort study. Inclusion criteria were patients aged 18-60 years with acute AC joint dislocation and a baseline Zanca radiograph with an increase in the CC distance of >25% compared to the uninjured side. All patients were treated nonsurgically with 3 months of home-based training and with the option of delayed surgical intervention. Patients were assessed at baseline and at follow-ups 6 weeks, 3 months, 6 months and 1 year after the injury. At the 6-weekfollow-up, patients were graded as stable and unstable according to the ISAKOS criteria. Outcomes were the Western Ontario Shoulder Instability Index (WOSI) and referral for surgery. At 6 weeks of follow-up,20 patients were classified as stable type A and 69 were classified as unstable type B. The ISAKOS subclassification was not clinically relevant, but patients graded as stable had statistically significantly better WOSI scores at 6 months compared to the unstable group (p = 0.03)but not at 3 months or 1 year. Nine patients (9.5%), all from the unstable group, were referred for surgery. No patients from the stable group underwent surgery (n.s). The ISAKOS subclassification of Rockwood type III in a stable type A and an unstable type B is not clinically applicable. Level II.

Comparison of the sputum microbiome between patients with stable nontuberculous mycobacterial pulmonary disease and patients requiring treatment.

We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.

Knowledge mapping of paediatric fever-a visual analysis based on CiteSpace.

This study aimed to analyse the research hotspots and frontiers in the field of paediatric fever between 2013 and 2023. The included articles were visually analysed using CiteSpace 6.1.R6 software. A total of 2,662 Chinese-language articles and 1,456 English-language articles were included in the study. Based on the Chinese literature, research groups were identified represented by Xinmin Li, Jinling Hong and Hongshuang Luo. Based on the English literature, research groups were formed represented by Henriette Moll, Santiago Mintegi and Elizabeth Alpern. Tianjin University of Traditional Chinese Medicine was the institution with the largest number of publications in the Chinese literature, and the Centers For Disease Control And Prevention was the institution with the largest number of publications in the English literature. The research on paediatric fever mainly focused on mechanism exploration, green treatment and clinical management. Several relatively stable research groups have been formed. Future studies on the differential diagnosis, rational drug use, standardised management and clinical practice guidelines for paediatric fever are needed.

BE-WEL trial (breast: evaluation of weight and exercise for lymphoedema) testing weight control and exercise programmes for women with breast cancer related lymphoedema: a feasibility trial

PurposeA combined body weight loss and upper body/arm exercise programme is a potential strategy for managing Breast cancer related lymphoedema (BCRL), but there is limited data on the best method for delivery or its potential efficacy.MethodsFifty-seven women with overweight/obesity and BCRL were randomised to a 12 week supervised (n = 12) or home-based combined weight loss and upper body/arm exercise programme (n = 16), a home-based upper-body arm exercise only programme (n = 17) or standard care (n = 12). Primary outcomes were uptake, retention and changes in weight and change in Relative Arm Volume Increase (RAVI) using analysis of covariance (ANCOVA).ResultsSixteen percent of women invited joined the study and 49 completed the trial (85% retention). Reductions in weight occurred in the supervised and home-based weight control and exercise programmes; Mean (95% CI) change compared to standard care − 1.68 (− 4.36 to − 1.00), − 2.47(− 4.99 to − 0.04) Kg. Reductions in perometer assessed RAVI were seen in the supervised and home-based combined weight control and arm exercise groups and the weight stable home-based arm exercise only group: mean (95% CI) change compared to standard care − 2.4 (− 5.0 to + 0.4),− 1.8 (− 4.3 to + 0.7), − 2.5(− 4.9 to − 0.05)%.ConclusionWomen with BCRL and overweight and obesity engaged in diet and exercise weight loss programmes. Both weight loss/arm exercise programmes led to modest changes in weight and BCRL. Comparable reductions in BCRL were reported in the weight stable group undertaking arm exercise only. The independent and combined effects of weight loss and exercise on BCRL need further study.Trial registrationISRCTN86789850 https://doi.org/10.1186/ISRCTN86789850, registered 2011.