Inactive Patients Research Articles

Influence of Sociodemographic Determinants on the Hodgkin Lymphoma Baseline Characteristics in Long Survivors Patients Enrolled in the Prospective Phase 3 Trial AHL2011.

Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10-15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events-SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data-marital status, living area, level of education, socio-professional category, and professional situation-were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0-2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area's inhabitants and TMTV (R Pearson = -0.29, p = 0.0004) was observed. This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

Fully automatic software for detecting radiographic joint space narrowing progression in rheumatoid arthritis: phantom study and comparison with visual assessment.

We have developed an in-house software equipped with partial image phase-only correlation (PIPOC) which can automatically quantify radiographic joint space narrowing (JSN) progression. The purpose of this study was to evaluate the software in phantom and clinical assessments. In the phantom assessment, the software's performance on radiographic images was compared to the joint space width (JSW) difference using a micrometer as ground truth. A phantom simulating a finger joint was scanned underwater. In the clinical assessment, 15 RA patients were included. The software measured the radiological progression of the finger joints between baseline and the 52nd week. The cases were also evaluated with the Genant-modified Sharp score (GSS), a conventional visual scoring method. We also quantitatively assessed these joints' synovial vascularity (SV) on power Doppler ultrasonography (0, 8, 20 and 52weeks). In the phantom assessment, the PIPOC software could detect changes in JSN with a smallest detectable difference of 0.044mm at 0.1mm intervals. In the clinical assessment, the JSW change of the joints with GSS progression detected by the software was significantly greater than those without GSS progression (p = 0.004). The JSW change of joints with positive SV at baseline was significantly higher than those with negative SV (p = 0.024). Our in-house software equipped with PIPOC can automatically and quantitatively detect slight radiographic changes of JSW in clinically inactive RA patients.

Association of physical activity with the risk of major adverse cardiac and cerebrovascular events and mortality in patients with concomitant atrial fibrillation and coronary artery disease

BackgroundAlthough regular physical activity benefits cardiovascular health, there is a concern that intense exercise is linked to the promotion of atrial fibrillation (AF) and coronary plaque rupture. However, the impact of physical activity on the outcomes of patients with concomitant AF and coronary artery disease (CAD) remains unclear. This study aimed to evaluate the association with clinical outcomes according to the level of physical activity in patients with concomitant AF and CAD. MethodsWe assessed 551 patients with AF and CAD (mean age, 67.1 ± 9.8 years) who completed a self-reported questionnaire for physical activity from 2015 to 2020 in a single tertiary-care hospital. Physical activity levels were converted into metabolic equivalent of task (MET) per week and categorized to correspond with multiple public health recommendations. We examined the association between physical activity, all-cause mortality, and major adverse cardiac and cerebrovascular events (MACCE).ResultsThe risks of all-cause mortality (P for linear trend = 0.017) and MACCE (P for linear trend = 0.05) appeared inverse trend with a greater level of physical activity. Compared with inactive patients, patients who met the recommended target range of physical activity (500–1,000 MET-min/week: unadjusted hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.36–0.99) and highly active patients who exceeded the minimum recommended level (≥ 1,000 MET-min/week: unadjusted HR = 0.47, 95% CI = 0.25–0.88) had a lower risk of all-cause mortality in the unadjusted model; however, these associations did not remain significant after adjusting for the model. There was no evidence of increased risk of all-cause mortality and MACCE at levels of physical activity above the recommended target range, even with vigorous-intensity physical activity exceeding the recommended target range.ConclusionsThere appears to be an inverse trend between physical activity levels and all-cause mortality and MACCE in patients with concomitant AF and CAD. No excess risk of mortality or MACCE was found at exercise levels above the recommended target range. Further large-scale studies are warranted to create an improved evidence base concerning the effects of physical activity in patients with AF and CAD.

Exercise capacity and physical activity in COPD patients treated with a LAMA/LABA combination: a systematic review and meta-analysis

BackgroundPersistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes.MethodsA systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted.ResultsSeventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0–1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities.ConclusionsLAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study)

BackgroundPhysical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. MethodsChemotherapy-exposed breast cancer patients (stage I-III, 2–4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale ‘fatigue’ of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. ResultsMultiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 – 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = −52.3 mm3, 95 % CI = −100.3 – −4.4)), which was related to improved memory functioning (HVLT-R total recall: B = −0.022, 95 % CI = −0.039 – −0.005; ACS Wordlist Learning: B = −0.039, 95 % CI = −0.062 – −0.015). ConclusionsNo exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.

Physical Activity and Health-related Quality of Life from Diagnosis to One Year After Radical Cystectomy in Patients with Bladder Cancer: A Longitudinal Cohort Study.

Emerging evidence shows a positive impact of physical activity (PA) on health-related quality of life (HRQoL) in cancer patients. However, longitudinal evidence on PA and HRQoL in patients with bladder cancer (BC) undergoing radical cystectomy (RC) is lacking. To investigate PA levels, HRQoL outcomes and their relationship from diagnosis to one year after RC in BC patients. A longitudinal cohort study in 90 BC patients was conducted at Ghent and Leuven University Hospitals between April 2017 and December 2020. The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the EORTC QLQ-C30 and BLM30 were used to measure PA and HRQoL, respectively, before RC, one, three, six and twelve months after RC. Linear mixed models were used for statistical analyses. The majority was physically inactive before RC (58%), at month one (79%), three (53%), six (61%) and twelve (64%). Among (moderately) active patients, light-intensity activities (mainly walking) were important contributors to the total amount of PA. Clinically important and low HRQoL outcomes in different domains were identified with lowest scores at diagnosis and one month after RC. Active patients before RC have better physical functioning (mean difference (MD) -22.7, standard error (SE) 8.7, p = 0.011), global health status (MD -15.9, SE 6.9, p = 0.023) and fatigue (MD 19.9, SE 9.5, p = 0.038) one month after RC, compared to inactive patients. Active patients at month have better physical functioning (MD -16.2, SE 6.9, p = 0.023) and sexual functioning (MD -16.8, SE 5.4, p = 0.003; MD -13.5, SE 5.5, p = 0.017) at month six and twelve, respectively, compared to inactive patients. Higher PA levels are associated with better HRQoL outcomes for BC patients undergoing RC. The data suggests that PA interventions could be an asset to improve BC patients' HRQoL, but should be tested in future trials.

Urine Galectin-3 binding protein reflects nephritis activity in systemic lupus erythematosus.

Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.

Multi-stakeholder perspectives on co-production: Five key recommendations following the Liverpool Co-PARS project

ABSTRACT Discerning the perspectives and working practices of those who deliver and receive a health service makes for a sensible step towards improving it. The Liverpool Co-PARS project was a four-year iterative process in which a physical activity referral scheme for inactive patients with health conditions was developed, refined, and evaluated. The aim of the present study was to explore multidisciplinary stakeholder perspectives of those involved in the co-production of Co-PARS and inform recommendations for future co-production research. We invited 5 stakeholders (service user, exercise referral practitioner, fitness centre manager, general practitioner/public health commissioner, and an academic) to co-author the present paper and provide their reflections of co-production. Four non-academic stakeholders completed a ~ 30-minute phone discussion of their personal reflections of the co-production process, transcribed in real-time by the first author and edited and checked for accuracy by the stakeholder. The fifth, academic author completed their reflections in writing. The multi-stakeholder reflections presented in this paper highlight identified strengths (multidisciplinary perspectives that were listened to and acted upon, co-production that permeated throughout the research project, real-time intervention adaptation) and challenges (homogeneous sample of service users, power imbalances, and a modestly adapted intervention) of co-production. We propose that co-production could be seen as a pro-active tool for the development of health service interventions, by mitigating potential issues encountered during latter implementation phases. We conclude with five key recommendations to facilitate future co-production research.

Selected Articles from This Issue

Physical activity and body mass index (BMI) are well established risk factors of colorectal cancer. Whether physical activity can counteract adverse obesity-induced metabolic profiles, including inflammation, remains unclear. Using data from the ColoCare Study, Himbert and colleagues tested associations of individual and combined physical activity and BMI groups with pro-inflammatory biomarkers in the largest cohort of colorectal cancer patients to date. The authors identified BMI as the key driver of inflammation, yet, biomarker levels were higher among inactive colorectal cancer patients across BMI groups. Results suggest that physical activity may reduce obesity-induced inflammation among colorectal cancer patients.Hodgkin lymphoma (HL) survivors (HLS) treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer (CRC). Ykema, Gini, and colleagues investigated the cost-effectiveness of CRC surveillance in Dutch HLS to determine the optimal surveillance strategy for different HL subgroups. The authors adjusted well-established MISCANColon model to reflect the HL survivor population. Subsequently the model was used to evaluate benefits, harms and costs of a range of potential surveillance strategies. CRC surveillance in HL survivors at increased risk for CRC (treated with IRT and/or procarbazine-containing chemotherapy) is cost-effective and should commence earlier than in the general population. For all examined HL subgroups, FIT surveillance was the most cost-effective strategy.Multiple myeloma disproportionately affects individuals of African descent, occurring more often in Black populations compared to White. Cicero and colleagues investigated the prevalence of monoclonal gammopathy of undetermined significance (MGUS), the precursor to myeloma, in 386 Black South African men. They found MGUS in 8.03% of their cohort, nearly 1.6-fold higher than the historic White Olmsted County males. Moreover, they explored the association between MGUS and various clinical factors, notably determining a correlation between MGUS and HIV status, as well as cigarette use. Their study demonstrates that racial disparities in MGUS exist and may be associated with potentially modifiable risk factors.This study by Chien and colleagues proposed methods for adapting risk models, with or without polygenic score, for another population without prospective cohorts to help alleviate the health disparities caused by advances in absolute risk models. The authors adapted the lung cancer risk model PLCOM2012 for Taiwan, by forming an age-matched case-control study of ever-smokers, synthesizing a dataset resembling the population of cancer-free ever-smokers in 2010, and estimating the number of ever-smoking lung cancer patients in 2011–2016. The adapted PLCOT models had high performance in calibration, discrimination, and clinical usefulness, and could be used to counsel individuals and design screening programs in Taiwan. The methods could be applicable to other cancer models.

Prognostic implications of inactive status in highest urgency categories among heart transplantation recipients in the new donor heart allocation system.

Patients on the waiting list for heart transplantation (HT) can become inactive or made status seven because of medical reasons, such adverse events, complications, or psychosocial circumstances. If the condition that caused the inactivation is resolved, patients are re- activated. Information about the prognostic implications of Status 7 in the new donor heart allocation system has not been described. To bridge this knowledge gap, we performed an analysis of the United Network of Organ Sharing (UNOS) registry. Data on adult patients who underwent HT between October 18th, 2018 and October 2021, were queried from the UNOS registry. The main outcomes were post- transplant all-cause mortality, 1-year all-cause mortality and treated acute rejection. Since re-transplantation is a competing event for all-cause mortality, we performed competing risk survival analysis and reported sub distribution hazard ratios (SHR) from the Fine and Gray model to examine the relationship between inactive status and all-cause mortality. A total of 5267 adult patients underwent HT and were previously listed as Status 1 or Status 2 in the new allocation system. We identified 946 HT recipients temporarily inactivated while on HT list (18%). The number of temporarily inactive patients remained stable since the implementation of the new donor allocation system (p=.37). Approximately, two-thirds of temporarily inactive patients (65.9%) were inactivated for being too sick, whereas other frequent justifications for inactivity included left ventricular assist device implantation (7.8%) and insurance related issues (4.8%). Temporarily inactive HT recipients were more likely to be African Americans, males, have a higher body mass index (BMI) and significantly longer waiting time (391.6±600vs. 72.3±223 days, p<.001) compared with never inactivated patients. In the unadjusted analyses 30-day mortality did not differ between groups, but both 1-year and overall all-cause mortality was significantly higher in temporarily inactive patients (1-year: SHR: 1.3; 95% confidence intervals [CI]: 1.03, 1.64; p=.028, overall mortality SHR: 1.31; 95% CI: 1.06, 1.64; p=.014). After adjustment for donor and recipient characteristics, a trend towards higher 1-year and overall mortality remained (1-year: SHR 1.32; 95% CI .99, 1.76, p=.006, overall mortality SHR: 1.29; 95% CI: .98-1.68, p=.065). No differences in treated acute allograft rejection at 1 year were found between groups. Temporary inactive status while waiting for HT occurs in approximately one in five HT recipients listed in higher urgency categories after the implementation of the new allocation system. A signal of adverse long-term outcomes was found, and this could be explained by differences in recipient characteristics. Further research is required to elucidate pathways involved and possible implications for clinical practice.

Native-tissue pelvic organ prolapse (POP) repair with perineorrhaphy for level III support results in reduced genital hiatus size and improved quality of life in sexually active and inactive patients

Introduction and hypothesisRecent findings address the importance of Level III defects with increased genital hiatus being associated with pelvic organ prolapse (POP), correlated with Level I defects and strongly related to POP recurrence. We hypothesised that concomitant perineorrhaphy in POP repair reduces genital hiatus (gh) and increases perineal body (pb), that gh would be larger with number of vaginal deliveries and that patients’ QOL was not different comparing sexually active vs inactive patients with overall judgement of cure comparable to the literature at evaluation. MethodsRetrospective observational study including consecutive patients with indications for posterior repair and Level III support between 2016 and 2018. Concomitant perineorrhaphy was indicated due to complaints of wide introitus or genital hiatus of ≥ 3.5 cm. Primary objective was to compare pre- and postoperative gh and pb according to POP-Q. Secondary objectives were preoperative gh and pb values by parity, POMs obtained with P-QOL/D comparing sexually active vs inactive patients, and subjective judgement of cure according to EGGS system. ResultsIn n = 121 patients, mean gh value was reduced postoperatively by 29.5 % (31 ± 6 vs 44 ± 10 mm, p < 0.001), mean pb value increased by 25.5 % (47 ± 8 vs 35 ± 8 mm, p < 0.001). Influence of parity on preoperative gh (p = 0.020), but not pb values (p = 0.119) was observed. All P-QOL/D domain scores improved significantly postoperatively without differences seen in sexually active vs inactive patients. EGGS responses indicated partial/full goal achievement in 90 % and cure in 87 %. ConclusionsIn the study cohort, perineorrhaphy as concomitant in POP repair led to Level III support reflected by decreased genital hiatus size. Functional QOL was improved regardless of sexual activity status and the majority of patients reported partial or full cure.

Fibulin-1: a novel biomarker for predicting disease activity of the thyroid-associated ophthalmopathy.

This study was designed to investigate the association between fibulin-1(FBLN1) and thyroid-associated ophthalmopathy (TAO). The plasma FBLN1 levels were measured in 80 participants, including 30 active TAO patients, 25 inactive TAO patients, and 25 Graves disease (GD) patients without TAO using enzyme-linked immunosorbent assay (ELISA). TAO patients had significantly higher TRAb level than GD patients (p < 0.05). The active TAO patients consumed more tobacco and had higher CAS than inactive TAO patients (all p < 0.05). No significant differences were found in age, sex, and the level of FT3, FT4, and TSH between TAO and GD patients, and between the active and inactive TAO patients (all p > 0.05). The plasma FBLN1 level in TAO patients was higher than that in GD patients, and that in active patients was higher than that in inactive patients (all p < 0.05). Furthermore, the plasma FBLN1 level showed strong association with clinical activity score (CAS) of TAO (r = 0.67, p < 0.01). By receiver operator characteristic (ROC) curve analysis, FBLN1 demonstrated good efficiency for predicting disease activity at the cut-off value > 625.33 pg/ml with a sensitivity of 93.3% and a specificity of 88.0% (AUC:0.92, p < 0.01). The plasma FBLN1 levels correlated with TAO activity and a value >625.33 pg/ml was associated with active disease. Our results suggest that the plasma FBLN1 level could be a novel biomarker for predicting disease activity of TAO.

Supervised Exercise in Water: Is It a Viable Alternative in Overweight/Obese People with or without Type 2 Diabetes? A Pilot Study.

The study of the effects of a water-based exercise program in overweight/obese people with or without type 2 diabetes is a topic of relatively recent interest. This type of exercise presents some advantages in reducing the risk of injury or trauma, and it can be a valuable therapeutic card to play for sedentary or physically inactive patients who have chronic metabolic diseases. This work aims to make a contribution showing the effects of a water-based exercise intervention, supervised by graduates in sports sciences, in a group of overweight/obese people with or without type 2 diabetes. In total, 93 adults (age 60.59 ± 10.44 years), including 72 women (age 60.19 ± 10.97 years) and 21 men (age 61.95 ± 8.48 years), were recruited to follow a water-based exercise program (2 sessions/week, for 12 weeks) at the C.U.R.I.A.Mo. Healthy Lifestyle Institute of Perugia University. Results showed an improvement in body mass index (−0.90 ± 1.56, p = 0.001), waist circumference (−4.32 ± 6.03, p < 0.001), and systolic (−7.78 ± 13.37, p = 0.001) and diastolic (−6.30 ± 10.91, p = 0.001) blood pressure. The supervised water-based intervention was useful in managing patients with metabolic diseases who often present with other health impairments, such as musculoskeletal problems or cardiovascular or rheumatic disease that could contraindicate gym-based exercise.

Abstract 15427: Reduction of Epicardial Fat, Clinical Risk Factors &amp; Symptomatology in Paroxysmal AF Patient With Severe Aortic Stenosis and Metabolic Syndrome via Mobile Cardiometabolic Health &amp; Weight Loss Program

Atrial fibrillation (AF) is dependent on epicardial fat (EpF) accumulation and infiltration. Complementary therapeutic strategies specifically targeting EpF present an opportunity for slowing progression and reversing the course of AF. A 73-year-old man with a history paroxysmal AF (managed by rate control/anticoagulation), severe aortic valve stenosis (AVS, area 1cm 2 , EF 55%), controlled hypertension, diabetes, and obesity (BMI 37.9) completed a 2-month cardiometabolic health program (CHP). The ‘tech plus touch’ CHP, delivered via a smartphone, utilized a comprehensive approach with physiological, nutritional, and behavioral components. Along with patented dietary regimens and nutritional supplementation implemented with personalized treatment algorithms, the CHP included direct daily engagement (messaging &amp; telehealth) with a staff clinician via the HIPAA compliant mobile app. Patient data visible to both the patient and staff clinician was synced automatically via Bluetooth-linked devices. EpF dropped by 25.5% over 9w (transthoracic echo, Fig1). BMI, visceral adiposity, and body fat were significant reduced, while lean body mass (LBM), muscle mass (MM) and intracellular fluid (ICF, a validated surrogate of chronic inflammation) improved (Fig1). Encouragingly, LBM, MM, and ICF improvements were unusual and particularly large in this older, physically inactive patient. Other clinical risk factors improved including diabetes, kidney function and inflammation. The patient reported resolution of chest pain and dyspnea, improved cardiorespiratory fitness, and began aerobic exercise. Our data demonstrate a nonpharmacologic complementary approach produces significant reductions of EpF and modifiable risk factors linked to hypertension, diabetes, and chronic inflammation in an AF patient with AVS and metabolic syndrome. Whether this will lead to a reduction in AF burden or conversion to persistent AF, remains to be determined.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI&nbsp;VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

Relationship between histopathological features of non-infectious aortitis and the results of pre-operative 18F-FDG-PET/CT: a retrospective study of 16 patients.

To describe the characteristics of 18F-fluorodeoxyglucose positron-emission tomography/computed-tomography (18FDG-PET/CT) findings before surgery in patients with active, histologically confirmed aortitis, and to correlate the degree of arterial wall inflammation with PETVAS score. This was a multiple-centre retrospective study including cases with histologically proven active, non-infectious aortitis who had a 18FDG-PET/CT performed within one year before surgery for aneurysm repair. PETVAS score was determined by radiologists blinded to the pathology findings. Cardiovascular pathologists reviewed aortic tissue samples and graded the degree of inflammation in the vessel wall. Sixteen patients were included (8 giant cell arteritis, 4 clinically isolated aortitis, 2 Takayasu's arteritis, 1 relapsing polychondritis, and 1 rheumatoid arthritis). In 5/16 (31%) patients, 18FDG-PET/CT did not detect the presence of aortic inflammation; two of whom were being treated with glucocorticoids at the time of procedure. Ascending thoracic and abdominal aorta had the highest FDG uptake among the affected territories. Patients without active aortitis on 18FDG-PET/CT were significantly older (p=0.027), had a lower PETVAS score (p=0.007), and had a lower degree of adventitial inflammation (p=0.035). In contrast, there was no difference between 18FDG-PET/CT active and inactive aortitis patients as regards the timing between PET/CT and surgery, serum CRP level (during 18FDG-PET/CT) and, FDG uptake per study site. In histologically proved aortitis, 18FDG-PET/CT before surgery did not detect vascular inflammation in 31% patients, and PETVAS score correlated with the degree of adventitial histopathologic inflammation.

Müllerotomy with anterior graded Müller muscle disinsertion for Graves upper eyelid retraction: validation of surgical outcomes using Bézier curves.

To assess with Bézier curves the outcomes of Müllerotomy with anterior graded Müller muscle disinsertion for the treatment of Graves upper eyelid retraction (UER). Eighty-six eyelids of 52 inactive GO patients operated from November 2018 to June 2021 were included in this study. All measurements were performed on Bézier curves adjusted to the upper lid contour with a previously validated algorithm. Lid contour was classified regarding grade of superposition (GS) as excellent (GS > 90%), good (GS 85-90%) or poor (< 85%). Surgical success was defined as complete or partial if postoperative grade of asymmetry was < 10% with an excellent or good lid contour, respectively. The mean age was 51 ± 10.4years with a range from 31 to 78years and a mean follow-up of 14.4 ± 7.4months. There was a significant improvement of median GS (p < 0.0001) from preoperative (74.3%; 10.7 IQR) to postoperative values (91.7%; 6.3 IQR). A normalization of postoperative contour peak (- 0.69; 1.27 SD) and MPLD90 (4.2mm; 0.8 SD) was noticed (p < 0.0001). Postoperative lid contour was excellent in 62 (72%), good in 16 (19%) and poor in 8 eyelids (9%). Surgical success was achieved in 42 patients (81%), from which 34 (81%) were complete. Reintervention was required in 14 eyelids (16%). Measuring surgical outcomes with Bézier curves allows an automated, complete and objective assessment, giving more consistency to our data compared to previous reports. Müllerotomy with graded Müller muscle disinsertion is a safe and effective procedure for Graves UER, offering predictable results.

Myostatin in idiopathic inflammatory myopathies: Serum assessment and disease activity.

In idiopathic inflammatory myopathies (IIM), disease activity is difficult to assess, and IIM may induce severe muscle damage, especially in immune-mediated necrotising myopathies (IMNM) and inclusion body myositis (IBM). We hypothesise that myostatin, a negative regulator of muscle mass, could be a new biomarker of disease activity and/or muscle damage. Prospective assessment of myostatin protein level in 447 IIM serum samples (dermatomyositis [DM], n= 157; IBM, n= 72; IMNM, n= 125; and antisynthetase syndrome [ASyS], n= 93) and 59 healthy donors (HD) was performed by ELISA. A gene transcript analysis was also carried out on 18 IIM muscle biopsies and six controls to analyse myostatin and myostatin pathway-related gene expression. IIM patients had lower myostatin circulating protein levels and gene expression compared to HD (2379 [1490; 3678] pg/ml vs 4281 [3169; 5787] pg/ml; p< 0.0001 and log2FC = -1.83; p= 0.0005, respectively). Myostatin-related gene expression varied accordingly. Based on the Physician Global Assessment, inactive IIM patients showed higher myostatin levels than active ones. This was the case for all IIM subgroups, except IMNM where low myostatin levels were maintained (2186 [1235; 3815] vs 2349 [1518; 3922] pg/ml; p= 0.4). Myostatin protein and RNA levels are decreased in all IIM patients, and protein levels correlate with disease activity. Inactive ASyS and DM patients have higher myostatin levels than active patients. Myostatin could be a marker of disease activity in these subgroups. However, IMNM patients do not have significant increase in myostatin levels after disease remission. This may highlight a new pathological disease mechanism in IMNM patients.