Ancillary Analysis Research Articles

Association between volume of lung damage and endoplasmic reticulum stress expression among severe COVID-19 ICU patients.

Links have been established between SARS-CoV-2 and endoplasmic reticulum stress (ERS). However, the relationships between inflammation, ERS, and the volume of organ damage are not well known in humans. The aim of this study was to explore whether ERS explains lung damage volume (LDV) among COVID-19 patients admitted to the intensive care unit (ICU). We conducted a single-center retrospective study (ancillary analysis of a prospective cohort) including severe COVID-19 ICU patients who had a chest computed tomography (CT) scan 24 h before/after admission to assess LDV. We performed two multivariate linear regression models to identify factors associated with plasma levels of 78 kDa-Glucose-Regulated Protein (GRP78; ERS marker) and Interleukin-6 (IL-6; inflammation marker) at admission. Among 63 patients analyzed, GRP78 plasma level was associated with LDV in both multivariate models (β = 22.23 [4.08;40.38]; p = 0.0179, β = 20.47 [0.74;40.20]; p = 0.0423) but not with organ failure (Sequential Organ Failure Assessment (SOFA) score) at admission (r = 0.03 [-0.22;0.28]; p = 0.2559). GRP78 plasma level was lower among ICU survivors (1539.4 [1139.2;1941.1] vs. 1714.2 [1555.2;2579.1] pg./mL. respectively; p = 0.0297). IL-6 plasma level was associated with SOFA score at admission in both multivariate models (β = 136.60 [65.50;207.70]; p = 0.0003, β = 193.70 [116.60;270.90]; p < 0.0001) but not with LDV (r = 0.13 [-0.14;0.39]; p = 0.3219). IL-6 plasma level was not different between ICU survivors and non-survivors (12.2 [6.0;43.7] vs. 30.4 [12.9;69.7] pg./mL. respectively; p = 0.1857). There was no correlation between GRP78 and IL-6 plasma levels (r = 0.13 [-0.13;0.37]; p = 0.3106). Among severe COVID-19 patients, ERS was associated with LDV but not with systemic inflammation, while systemic inflammation was associated with organ failure but not with LDV.

Effect of early initiation of noninvasive ventilation in patients transported by emergency medical service for acute heart failure

Background While the indication for noninvasive ventilation (NIV) in severely hypoxemic patients with acute heart failure (AHF) is often indicated and may improve clinical course, the benefit of early initiation before patient arrival to the emergency department (ED) remains unknown. Objective This study aimed to assess the impact of early initiation of NIV during emergency medical service (EMS) transportation on outcomes in patients with AHF. Design A secondary retrospective analysis of the EAHFE (Epidemiology of AHF in EDs) registry. Setting Fifty-three Spanish EDs. Participants Patients with AHF transported by EMS physician-staffed ambulances who were treated with NIV at any time during of their emergency care were included and categorized into two groups based on the place of NIV initiation: prehospital (EMS group) or ED (ED group). Outcome measures Primary outcome was the composite of in-hospital mortality and 30-day postdischarge death, readmission to hospital or return visit to the ED due to AHF. Secondary outcomes included 30-day all-cause mortality after the index event (ED admission) and the different component of the composite primary endpoint considered individually. Multivariate logistic regressions were employed for analysis. Results Out of 2406 patients transported by EMS, 487 received NIV (EMS group: 31%; EMS group: 69%). Mean age was 79 years, 48% were women. The EMS group, characterized by younger age, more coronary artery disease, and less atrial fibrillation, received more prehospital treatments. The adjusted odds ratio (aOR) for composite endpoint was 0.66 (95% CI: 0.42–1.05). The aOR for secondary endpoints were 0.74 (95% CI: 0.38–1.45) for in-hospital mortality, 0.74 (95% CI: 0.40–1.37) for 30-day mortality, 0.70 (95% CI: 0.41–1.21) for 30-day postdischarge ED reconsultation, 0.80 (95% CI: 0.44–1.44) for 30-day postdischarge rehospitalization, and 0.72 (95% CI: 0.25–2.04) for 30-day postdischarge death. Conclusion In this ancillary analysis, prehospital initiation of NIV in patients with AHF was not associated with a significant reduction in short-term outcomes. The large confidence intervals, however, may preclude significant conclusion, and all point estimates consistently pointed toward a potential benefit from early NIV initiation.

Reciprocal Relationship Between Learning Interest and Learning Persistence: Roles of Strategies for Self-Regulated Learning Behaviors and Academic Performance.

Learning interest (internal driving motivation) and learning persistence (explicit behaviors) are important factors affecting students' academic development, yet whether they operate reciprocally and how to bolster them are still issues requiring attention. This study aimed to examine the reciprocal relationship between learning interest and persistence as well as the potential mechanisms behind the relationship from the perspectives of internal self-regulation and external feedback (i.e., academic performance). 510 students (Mage = 13.71, SD = 1.77, 44.1% girls) were tracked for one year using questionnaires. Results showed that higher learning interest was linked to greater subsequent learning persistence and vice versa; and both predicted each other over time indirectly through academic performance and the multiple mediating paths from strategies for self-regulated learning behaviors to academic performance. Ancillary analysis verifies the robustness of these results. The findings not only provide evidence of a dynamic relationship between learning motivation and behaviors, highlighting the important role of positive performance feedback in leading to a benign cycle, but also contribute to understanding the potential avenue (i.e., teaching strategies for self-regulation) for optimizing student learning.

Population-based study of eclampsia: Lessons learnt to improve maternity care.

Among hypertensive disorders of pregnancy (HDP), eclampsia is a rare but serious event, often considered avoidable. Detailed assessment of the adequacy of care for the women who have eclampsia can help identify opportunities for improvement and for prevention of the associated adverse maternal and neonatal outcomes. 1/ To estimate the incidence and describe the characteristics of women with eclampsia and to compare them with those of women with non-eclamptic hypertensive disorders of pregnancy (HDP)-related severe maternal morbidity (SMM) and of control women without SMM 2/ To analyse the quality of management in women who had eclampsia, at various stages of their care pathway. It was a planned ancillary analysis of the EPIMOMS population-based study, conducted in six French regions in 2012-2013. Among the 182,309 maternities of the source population, all women with eclampsia (n = 51), with non-eclamptic HDP-related SMM (n = 351) and a 2% representative sample of women without SMM (n = 3,651) were included. Main outcome was the quality of care for eclampsia assessed by an independent expert panel at three different stages of management: antenatal care, care for pre-eclampsia and care for eclampsia. The eclampsia incidence was 2.8 per 10,000 (95%CI 2.0-4.0). Antenatal care was considered completely inadequate or substandard in 39% of women, as was pre-eclampsia care in 76%. Care for eclampsia was judged completely inadequate or substandard in 50% (21/42), mainly due to inadequate use of magnesium sulphate. The high proportion of inadequate quality of care underlines the need for an evidence-based standardisation of care for HDP.

Abstract PO4-05-07: Differential dynamics of fragmentomic and epigenetic circulating tumor DNA (ctDNA) features in first-line Palbociclib and Ribociclib treatment for Hormone Receptor (HR) positive, HER2 negative metastatic breast cancer (MBC)

Abstract Background: Cyclin-dependent kinase inhibitors (CDK4/6i) in combination with endocrine therapy (ET) represent the cornerstone for the management of HR positive, HER2 negative MBC. However, the lack of prospective cohorts comparing the distinctions among palbociclib (PAL), ribociclib (RIB) and abemaciclib (ABE) poses a significant clinical knowledge gap. The aim of this ancillary analysis was to explore the differential clinical impact of CDK4/6i by leveraging new ctDNA biomarkers in a prospective clinical study. Methods: A total of 114 patients (pts) with HR positive, HER2 negative MBC were prospectively enrolled in the multicenter MAGNETIC.1 study (CRO-2018-56) from January 2018 to January 2023. At baseline (BL) and every 3 months (mos.), ctDNA samples were collected concurrently with radiological restaging. The samples were then analyzed through methylation-specific (MS) droplet digital PCR (ddPCR), ddPCR fragmentomics, and next generation sequencing. Matched pairs of variations were tested through Wilcoxon signed rank test, and survival was analyzed by log-rank test. Results: Out of the 114 pts enrolled, 59 received PAL, 48 RIB, and 16 ABE. In the de novo subgroup, 51.4 % of pts were treated with PAL, 42.9% with RIB, and 5.7% with ABE. Among the pts who received PAL, 7 harbored an ESR1 mutation at BL (D538G: 2, H377R: 1, Y537N: 1, Y537S: 3). Additionally,12 pts had PIK3CA mutations, and 2 pts had AKT1 mutations. In the RIB group, 5 and 2 pts, respectively, had a PIK3CA- and AKT-mutated MBC, while no ESR1 mutations were detected. When comparing matched pairs of variations, it was found that at BL, at first radiological restaging (T1), and at 6 mos. after initiation of CDK4/6i (T2), only PAL showed significantly higher levels of promoter A and B methylation (promA and promB) at T1 (P = 0.0005 and P = 0.0056, respectively for promA and promB), A significant decrease in promA and promB levels was detected at T2 for PAL (P = 0.0005 and P &amp;lt; 0.0001 respectively for promA and promB) but not for RIB. Both PAL and RIB demonstrated a significant decrease in ctDNA short fragments at T1 (P = 0.0263 for PAL and P = 0.0001 for RIB), However, PAL showed a significant rebound at T2, with an increase in 80% of samples (P = 0.0014). The same was not seen with RIB. After a median follow-up of 34.8 mos., there were no significant differences between PAL and RIB in terms of PFS (P= 0.2573) and OS (P= 0.3783). The PFS rates at 12 and 24 mos. were 69% and 48% for PAL, and 76% and 64% for RIB. The OS rates at 12 and 24 mos. were 94% and 84% for PAL, compared to 97% and 82% of RIB, respectively. Conclusions This analysis of MAGNETIC.1 highlighted significant differences in ctDNA biomarkers between palbociclib and ribociclib, suggesting their potential impact on the development of endocrine resistance. Further biomarker-driven clinical trials leveraging this concept are needed to refine the sequencing algorithms for CDK4/6i. Citation Format: Claudia Noto, Linda Cucciniello, Elisabetta Molteni, Silvia Bolzonello, Alessandra Franzoni, Lucia Da Ros, Silvia Buriolla, Arianna Dri, Lorenzo Foffano, Simon Spazzapan, Stefania Russo, Brenno Pastò, Giulia Cudia, Giada Targato, Serena Della Rossa, Marta Bonotto, Alessandro Marco Minisini, Giuseppe Damante, Barbara Belletti, Lorenzo Gerratana, Fabio Puglisi. Differential dynamics of fragmentomic and epigenetic circulating tumor DNA (ctDNA) features in first-line Palbociclib and Ribociclib treatment for Hormone Receptor (HR) positive, HER2 negative metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-07.

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland

ObjectivesIn trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of...

The Association between Circulating Cytokines and Body Composition in Frail Patients with Cardiovascular Disease.

The burden of cardiovascular disease and the percentage of frail patients in the aging population will increase. This study aims to assess the circulating levels of several cytokines in frail patients. This is an ancillary analysis of the FRAPICA trial. The ratio of men/women changed from robust through frail groups from 3:1 to 1:2. The groups are comparable in terms of age and body measurements analysis (weight, height, and BMI), yet the frail patients have significantly reduced fat-free mass, and more often have been diagnosed with diabetes. Frail patients have higher fibroblast growth factor basic (FGF basic) and follistatin levels (borderline significance). In multiple linear regression modeling of fat-free mass, we identified FGF basic, osteopontin, stem cell factor, soluble suppression of tumorigenicity 2, soluble epidermal growth factor receptor, soluble human epidermal growth factor receptor 2, follistatin, prolactin, soluble interleukin 6 receptor alfa, platelet endothelial cell adhesion molecule 1, soluble vascular endothelial cell growth factor receptor 1, leptin, soluble angiopoietin/tyrosine kinase 2, and granulocyte colony-stimulating factor. We have identified a few cytokines that correlate with fat-free mass, a hallmark of frailty. They comprise the kinins implicated in bone and muscle metabolism, fibrosis, vascular wall function, inflammation, endocrine function, or regulation of bone marrow integrity.

Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis

BackgroundPatients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP.Patients and methodsWe performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included.ResultsWe included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07–2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02–1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994–0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15–12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP.ConclusionESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Diet Intake After Diet Modification Intervention in Women With Fecal Incontinence.

Older women with fecal incontinence (FI) who underwent diet modification intervention (DMI) showed significant improvement in FI symptoms. It is unclear whether improvement in symptoms was associated with objective changes in dietary intake quality. The primary aim was to determine if improvement in overall dietary intake quality was associated with improvement in FI symptoms. Our secondary aim was to evaluate whether individual food group consumption changes were associated with changes in FI symptoms. This was an ancillary analysis of a prospective cohort study of women aged 65 years and older with FI who underwent DMI. Seven-day diet-and-bowel diaries at baseline and 6 weeks after DMI were examined for how frequently participants consumed food categories and FI triggers. Adherence to recommended dietary guidelines was assessed between 2 and 4 weeks using a 24-hour diet recall. Baseline and postintervention consumption were compared using the Wilcoxon signed rank test. Spearman correlation was used to compare dietary intake changes with FI symptom changes. Twenty-four women completed the 24-hour diet recalls, and 17 women completed the 7-day diet-and-bowel diaries at baseline and 6 weeks. More participants who were adherent had clinically significant improvement in symptoms compared with those who were not adherent (70% vs 30%, P =0.57). Decreased consumption of saturated fats ( P =0.01) and fried foods ( P <0.001) was associated with improvement in FI symptoms. In this small population, overall dietary intake quality was not associated with change in FI symptom improvement. Decreased intake of saturated fat and fried food was associated with FI symptom improvement.

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 μg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 μg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

The Drug Burden Index Is Associated With Measures of Cognitive Function Among Older Adults in the Health, Aging, and Body Composition Study.

Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70-79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models. After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death. Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure.

High Circulating Dipeptidyl Peptidase 3 Predicts Mortality and Need for Organ Support in Cardiogenic Shock: An Ancillary Analysis of the ACCOST-HH Trial

BackgroundCardiogenic shock (CS) is burdened with high mortality. Efforts to improve outcome are hampered by the difficulty of individual risk stratification and the lack of targetable pathways. Previous studies demonstrated that elevated circulating dipeptidyl peptidase 3 (cDPP3) is an early predictor of short-term outcome in CS, mostly of ischemic origin. Our objective was to investigate the association between cDPP3 and short-term outcomes in a diverse population of patients with CS. Methods and ResultscDPP3 was measured at baseline and after 72 hours in the AdreCizumab against plaCebO in SubjecTs witH cardiogenic sHock (ACCOST-HH) trial. The association of cDPP3 with 30-day mortality and need for organ support was assessed. Median cDPP3 concentration at baseline was 43.2 ng/mL (95% confidence interval [CI], 21.2–74.0 ng/mL) and 77 of the 150 patients (52%) had high cDPP3 over the predefined cutoff of 40 ng/mL. Elevated cDPP3 was associated with higher 30-day mortality (adjusted hazard ratio [aHR] = 1.7; 95% CI, 1.0–2.9), fewer days alive without cardiovascular support (aHR, 3 days [95% CI, 0–24 days] vs aHR, 21 days [95% CI, 5–26 days]; P < .0001) and a greater need for renal replacement therapy (56% vs 22%; P < .0001) and mechanical ventilation (90 vs 74%; P = .04). Patients with a sustained high cDPP3 had a poor prognosis (reference group). In contrast, patients with an initially high but decreasing cDPP3 at 72 hours had markedly lower 30-day mortality (aHR, 0.17; 95% CI, 0.084–0.34), comparable with patients with a sustained low cDPP3 (aHR, 0.23; 95% CI, 0.12–0.41). The need for organ support was markedly decreased in subpopulations with sustained low or decreasing cDPP3. ConclusionsThe present study confirms the prognostic value of cDPP3 in a contemporary population of patients with CS.

Prevalence of fatigue and cognitive impairment after traumatic brain injury.

Following traumatic brain injury (TBI) some patients develop lingering comorbid symptoms of fatigue and cognitive impairment. The mild cognitive impairment self-reported by patients is often not detected with neurocognitive tests making it difficult to determine how common and severe these symptoms are in individuals with a history of TBI. This study was conducted to determine the relative prevalence of fatigue and cognitive impairment in individuals with a history of TBI. The Fatigue and Altered Cognition Scale (FACs) digital questionnaire was used to assess self-reported fatigue and cognitive impairment. Adults aged 18-70 were digitally recruited for the online anonymous study. Eligible participants provided online consent, demographic data, information about lifetime TBI history, and completed the 20 item FACs questionnaire. A total of 519 qualifying participants completed the online digital study which included 204 participants with a history of TBI of varied cause and severity and 315 with no history of TBI. FACs Total Score was significantly higher in the TBI group (57.7 ± 22.2) compared to non-TBI (39.5 ± 23.9; p<0.0001) indicating more fatigue and cognitive impairment. When stratified by TBI severity, FACs score was significantly higher for all severity including mild (53.9 ± 21.9, p<0.0001), moderate (54.8 ± 24.4, p<0.0001), and severe (59.7 ± 20.9, p<0.0001) TBI. Correlation analysis indicated that more severe TBI was associated with greater symptom severity (p<0.0001, r = 0.3165). Ancillary analysis also suggested that FACs scores may be elevated in participants with prior COVID-19 infection but no history of TBI. Adults with a history of even mild TBI report significantly greater fatigue and cognitive impairment than those with no history of TBI, and symptoms are more profound with greater TBI severity.

The reporting quality of randomized controlled trials in pharmacotherapy for pituitary adenomas.

Medical therapy has become an increasingly important intervention owing to improvements in the multidisciplinary care for pituitary adenomas (PAs). This study aimed to assess the reporting quality of randomized controlled trials (RCTs) on PAs pharmacotherapy. RCTs evaluating the efficacy of pharmacotherapy in PAs published in English between January 1, 1974, and December 31, 2022, were searched for and collected from PubMed and MEDLINE. The 2010 Consolidated Standards for Test Reports (CONSORT) statement-based 28 items overall quality score (OQS) was used to evaluate the overall quality of each report. Twenty-seven related RCTs including 1816 patients were retrieved. The median OQS score was 12 (range, 6-19) on a scale of 0 to 28. Important items, such as background, objectives, participants, interventions, and outcomes, were sufficiently reported in 100% (27/27) of the articles. Statistical methods were adequately described in 93% (25/27) of patients. However, RCTs underreported identification as randomized trials in the title (3/27, 11%), sample size, allocation concealment, implementation, ancillary analysis method, and Diagram and Ancillary analyses (1/27, 4%). The OQS of published RCTs has significantly increased since 2010 (P = .012). The multivariate final model showed significant associations between higher OQS and publication since 2010 and enrollment of more than 100 patients. The overall reporting quality of RCTs on pharmacotherapy in PAs was poor, based on the 2010 CONSORT statement. However, we noticed an improvement in the OQS over the years and identified the factors associated with a better report. Increased effort is necessary to raise awareness of these issues among writers, readers, reviewers, and editors.

Determination of differences in ultrasound parameters for patellar tendons in males with unilateral patellar tendinopathy-An ancillary analysis of data from two randomized controlled trials.

To investigate power Doppler (PD) activity and tendon structure (between the injured and contralateral limb) in patients with unilateral patellar tendinopathy (PT) using ultrasonography (US). Secondly, the aim was to determine the intra-rater reliability of the PD activity and tendon structure. This study analyzed US baseline data from 57 male participants with symptomatic unilateral PT who had been enrolled in one of two randomized clinical trials. Data were analyzed to examine if systematic differences existed between injured and contralateral limbs using Fiji ImageJ. The PD activity of the symptomatic tendon was larger 25.6 (Q1 = 14.9; Q3 = 41.6) mm2 than the asymptomatic 0 (Q1 = 0.0; Q3 = 0.0) mm2 (p < 0.001). There was a significantly greater tendon thickness at the proximal (2.5 mm 95% CI [2.0; 3.0]), mid (0.8 mm 95% CI [0.5; 1.1]), and distal (0.2 mm 95% CI [0.1; 0.4]) part of the tendon for the symptomatic compared to the asymptomatic tendon. Intra-rater reliability for PD activity and tendon structure ranged from moderate-to-excellent (0.74; 0.99). These results provide mean estimates for tendon thickness of symptomatic and asymptomatic tendons, that can be used for clinicians to reliably estimate pathological tendon thickness.

Effects of Prune (Dried Plum) Supplementation on Cardiometabolic Health in Postmenopausal Women: An Ancillary Analysis of a 12-Month Randomized Controlled Trial, The Prune Study

BackgroundEstrogen withdrawal during menopause is associated with an unfavorable cardiometabolic profile. Prunes (dried plums) represent an emerging functional food and have been previously demonstrated to improve bone health. However, our understanding of the effects of daily prune intake on cardiometabolic risk factors in postmenopausal women is limited. ObjectivesWe conducted an ancillary investigation of a randomized controlled trial (RCT), The Prune Study, to evaluate the effect of 12-mo prune supplementation on cardiometabolic health markers in postmenopausal women. MethodsThe Prune Study was a single-center, parallel-design, 12-mo RCT in which postmenopausal women were allocated to no-prune control, 50 g/d prune, or 100 g/d prune groups. Blood was collected at baseline, 6 mo, and 12 mo/post to measure markers of glycemic control and blood lipids. Body composition was assessed at baseline, 6 mo, and 12 mo/post using dual-energy X-ray absorptiometry. Linear mixed-effects models were used to evaluate the effect of time, treatment, and their interaction on cardiometabolic health markers, all quantified as exploratory outcomes. ResultsA total of 183 postmenopausal women (mean age, 62.1 ± 4.9 y) completed the entire 12-mo RCT: control (n = 70), 50 g/d prune (n = 67), and 100 g/d prune (n = 46). Prune supplementation at 50 g/d or 100 g/d did not alter markers of glycemic control and blood lipids after 12 mo compared with the control group (all P > 0.05). Furthermore, gynoid percent fat and visceral adipose tissue (VAT) indices did not significantly differ in women consuming 50 g/d or 100 g/d prunes compared with the control group after 12 mo of intervention. However, android total mass increased by 3.19% ± 5.5% from baseline in the control group, whereas the 100 g/d prune group experienced 0.02% ± 5.6% decrease in android total mass from baseline (P < 0.01). ConclusionsPrune supplementation at 50 g/d or 100 g/d for 12 mo does not improve glycemic control and may prevent adverse changes in central adiposity in postmenopausal women.This trial was registered at clinicaltrials.gov as NCT02822378.

Alterations in the fecal microbiota in patients with advanced cystic fibrosis liver disease after 6 months of elexacaftor/tezacaftor/ivacaftor

BackgroundCystic fibrosis associated liver disease (CFLD) carries a significant disease burden with no effective preventive therapies. According to the gut-liver axis hypothesis for CFLD pathogenesis, dysbiosis and increased intestinal inflammation and permeability permit pathogenic bacterial translocation into the portal circulation, leading to hepatic inflammation and fibrosis. Evaluating the effect of CFTR (cystic fibrosis transmembrane conductance regulator) modulation with elexacaftor/tezacaftor/ivacaftor (ETI) may help determine the role of CFTR in CFLD and increase understanding of CFLD pathogenesis, which is critical for developing therapies. We aimed to characterize the fecal microbiota in participants with CF with and without advanced CFLD (aCFLD) before and after ETI. MethodsThis is an ancillary analysis of stool samples from participants ages ≥12 y/o enrolled in PROMISE (NCT04038047). Included participants had aCFLD (cirrhosis with or without portal hypertension, or non-cirrhotic portal hypertension) or CF without liver disease (CFnoLD). Fecal microbiota were defined by shotgun metagenomic sequencing at baseline and 1 and 6 months post-ETI. ResultsWe analyzed 93 samples from 34 participants (11 aCFLD and 23 CFnoLD). Compared to CFnoLD, aCFLD had significantly higher baseline relative abundances of potential pathogens Streptococcus salivarius and Veillonella parvula. Four of 11 aCFLD participants had an initially abnormal fecal calprotectin that normalized 6 months post-ETI, correlating with a significant decrease in S. salivarius and a trend towards decreasing V. parvula. ConclusionsThese results support an association between dysbiosis and intestinal inflammation in CFLD with improvements in both post-ETI, lending further support to the gut-liver axis in aCFLD.

Infective Endocarditis in Belgium: Prospective Data in Adults from the ESC EORP European Endocarditis Registry.

(1) Background: infective endocarditis (IE) is a significant health concern associated with important morbidity and mortality. Only limited, often monocentric, retrospective data on IE in Belgium are available. This prospective study sought to assess the clinical characteristics and outcomes of Belgian IE patients in the ESC EORP European endocarditis (EURO-ENDO) registry; (2) Methods: 132 IE patients were identified based on the ESC 2015 criteria and included in six tertiary hospitals in Belgium; (3) Results: The average Belgian IE patient was male and 62.8 ± 14.9 years old. The native valve was most affected (56.8%), but prosthetic/repaired valves (34.1%) and intracardiac device-related (5.3%) IE are increasing. The most frequently identified microorganisms were S. aureus (37.2%), enterococci (15.5%), and S. viridans (15.5%). The most frequent complications were acute renal failure (36.2%) and embolic events (23.6%). Cardiac surgery was effectively performed when indicated in 71.7% of the cases. In-hospital mortality occurred in 15.7% of patients. Predictors of mortality in the multivariate analysis were S. aureus (HR = 2.99 [1.07-8.33], p = 0.036) and unperformed cardiac surgery when indicated (HR = 19.54 [1.91-200.17], p = 0.012). (4) Conclusion: This prospective EURO-ENDO ancillary analysis provides valuable contemporary insights into the profile, treatment, and clinical outcomes of IE patients in Belgium.

The plasma metabolome is associated with preservation of physiological function following lifelong aerobic exercise in mice.

Declines in physiological function with aging are strongly linked to age-related diseases. Lifelong voluntary aerobic exercise (LVAE) preserves physiological function with aging, possibly by increasing cellular quality control processes, but the circulating molecular transducers mediating these processes are incompletely understood. The plasma metabolome may predict biological aging and is impacted by a single bout of aerobic exercise. Here, we conducted an ancillary analysis using plasma samples, and physiological function data, from previously reported studies of LVAE in male C57BL/6N mice randomized to LVAE (wheel running) or sedentary (SED) (n = 8-9/group) to determine if LVAE alters the plasma metabolome and whether these changes correlated with preservation of physiological function with LVAE. Physical function (grip strength, coordination, and endurance) was assessed at 3 and 18months of age; vascular endothelial function and the plasma metabolome were assessed at 19months. Physical function was preserved (%decline; mean ± SEM) with LVAE vs SED (all p < 0.05)-grip strength, 0.4 ± 1.7% vs 12 ± 4.0%; coordination, 10 ± 4% vs 73 ± 10%; endurance, 1 ± 15% vs 61 ± 5%. Vascular endothelial function with LVAE (88.2 ± 2.0%) was higher than SED (79.1 ± 2.5%; p = 0.03) and similar to the young controls (91.4 ± 2.9%). Fifteen metabolites were different with LVAE compared to SED (FDR < 0.05) and correlated with the preservation of physiological function. Plasma spermidine, a polyamine that increases cellular quality control (e.g., autophagy), correlated with all assessed physiological indices. Autophagy (LC3A/B abundance) was higher in LVAE skeletal muscle compared to SED (p < 0.01) and inversely correlated with plasma spermidine (r = - 0.5297; p = 0.054). These findings provide novel insight into the circulating molecular transducers by which LVAE may preserve physiological function with aging.

Comparison of Joint Mobilization and Movement Pattern Training for Hip-Related Groin Pain: Ancillary Analysis to Assess 12-Month Outcomes of a Pilot Randomized Clinical Trial

Comparison of Joint Mobilization and Movement Pattern Training for Hip-Related Groin Pain: Ancillary Analysis to Assess 12-Month Outcomes of a Pilot Randomized Clinical Trial