Multicenter Longitudinal Study Research Articles

5-years patency results of Zilver PTX on the femoro-popliteal arterial segment: A Northern Sydney experience.

The burden of peripheral arterial disease is increasing. Treatment of femoro-popliteal lesions remains challenging despite novel endovascular devices. Drug-eluting stents suppress post-treatment inflammation and reducing neo-intimal hyperplasia to reduce in-stent restenosis. A multi-centre retrospective 5-years longitudinal study was undertaken to evaluate freedom from clinically driven target limb revascularisation (FF CD-TLR) and patency of Zilver PTX stents in treating symptomatic femoro-popliteal stenotic lesions. Kaplan-Meier survival curves were used to demonstrate FF CD-TLR, primary, primary assisted and secondary patency. There were 148 patients and 183 lesions treated with a mean age of 80.3years and 52% males. The all-cause 5-years mortality was 25%. FF CD-TLR yearly patencies to 5years were 81%, 67%, 62%, 57% and 52%, respectively, with significantly poorer outcomes for in-stent restenosis, longer stent lengths and lesions at the femoro-popliteal junction. Primary patencies were 63%, 47%, 40%, 34% and 24%, assisted primary patencies were 90%, 75%, 68%, 59% and 48% and secondary patencies were 96%, 94%, 94%, 92% and 92%. Major adverse limb events were 5% at 1-year and cumulative at 5-years was 16%. The clinical outcomes in this study population are comparable to recent publications with smaller cohorts. Our study confirms Zilver PTX has very good primary patency over 5years with no discernible effect on all-cause mortality in an elderly cohort with particularly long treated lesions. Our results are similar to those seen in younger patients with shorter lesions. Nonetheless, longer lesions required more reinterventions to maintain patency. Zilver PTX is a safe and durable drug-eluting stent when utilised in the management of femoro-popliteal stenotic lesions with good long-term patency and limited need for re-intervention.

SARS-CoV-2 seroprevalence among people living with HIV in the German HIV-1 Seroconverter Cohort, 2020–2022

ObjectivesPeople living with HIV (PLWH) are a risk group for severe symptoms and higher mortality during COVID-19. We analyzed the dynamic rise of SARS-CoV-2 seroprevalence induced by coinfections and vaccinations in PLWH in the first three years of the pandemic in Germany and compared it with corresponding data available for the general population.MethodsEach month on average 93 blood samples from the German HIV-1 Seroconverter Cohort, a prospective longitudinal multicenter study that includes PLWH whose date of seroconversion is well defined, were received. The samples from 1569 PLWH were tested for the presence of anti-S1 and if positive, also for anti-N antibodies.ResultsIn 2020 the number of anti-S1 positive cases/month was between 0.0 and 6.9% (average 1.6%). Since then the anti-S1 prevalence increased reaching already 35% (33/94) in May 2021. At that time 3.2% of the cases were also anti-N positive. In 2022 the average anti-S1 seroprevalence reached 97.5%. In the vaccination era a positive anti-N response was associated with a younger age and females were overrepresented among anti-S1/anti-N negative samples (assuming no vaccination or infection).ConclusionsThe average 1.6% anti-S1 seroprevalence in the cohort in 2020 was comparable to that in the general population (1.3%). The increase in anti-S1 seroprevalence in the first half of 2021 occurred slightly earlier. This increase was likely caused by the prioritization of PLWH at the early stage of the vaccination campaign and by infections during the third wave of the pandemic.

Characterizing Non-Articular Pain at Early Rheumatoid Arthritis Diagnosis, Evolution over the First year of Treatment and Impact on Remission in a Prospective Real-World Early Rheumatoid Arthritis Cohort.

To characterize non-articular pain (NAP) at early RA diagnosis, the evolution over the first year of treatment, associations with active RA inflammation and impact on remission. This real-world, longitudinal multi-center cohort study followed participants with active early RA (symptoms<1 year, CDAI>2.8,) enrolled between 1/2017 and 1/2022, and who completed a body pain diagram (BPD) over 1-year. Participants were grouped by prespecified definitions of NAP: 1) none 2) regional or 3) widespread. Rheumatologists performed joint counts. Descriptive statistics summarized the frequency and evolution of NAP patterns over 1-year. Chi-square tests compared the proportions of tender and/or swollen joints by presence of pain in each NAP section. Multi-adjusted GEE regression models estimated associations of NAP patterns with remission outcomes. Participants (N=392) were 70% female, mean(Sd) age of 56(14) years and mean symptoms duration of 5.1(2.7) months. Over half reported NAP at baseline with most (73%) presenting with regional NAP. Common patterns of regional NAP were axial (40%) and pain in upper quadrants (17%). 43% of those with regional NAP persisted or worsened over 1-year, whereas 73% of those with widespread NAP resolved or improved. Joint inflammation was more frequently reported in areas with NAP vs areas without NAP. Regional and widespread NAP were associated with lower odds of reaching CDAI remission (adjusted OR [95%CI]):0.42[0.26 to 0.70] and 0.30[0.12 to 0.74], respectively. Regional NAP is common and persistent in early RA and impacts remission. RA activity may contribute to NAP. More attention to NAP in RA care is warranted.

Perivascular space enlargement accelerates in ageing and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study

BackgroundPerivascular space (PVS) enlargement in ageing and Alzheimer’s disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD.MethodsWe studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; meanage = 70.78 ± 5.78) of the ongoing observational multicentre “DZNE Longitudinal Cognitive Impairment and Dementia Study” (DELCODE) cohort. We analysed data from subjects who were cognitively unimpaired (n = 401), had amnestic mild cognitive impairment (n = 71), or had AD (n = 31). We used linear mixed-effects modelling to test for changes of PVS volumes in relation to cross-sectional and longitudinal age, as well as sex, years of education, hypertension, white matter hyperintensities, AD diagnosis, and cerebrospinal-fluid-derived amyloid (A) and tau (T) status (available for 46.71%; A-T-/A + T-/A + T + n = 143/48/39).ResultsPVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p < 0.001; BG: B = 0.05 [0.03, 0.07], p < 0.001). PVS enlargement rates varied substantially across subjects and depended on the participant’s age, white matter hyperintensities volumes, and amyloid and tau status. PVS volumes were higher across elderly participants, regardless of region of interest (CSO: B = 0.12 [0.02, 0.21], p = 0.017; BG: B = 0.19 [0.09, 0.28], p < 0.001). Faster BG-PVS enlargement related to lower baseline white matter hyperintensities volumes (ρspearman = -0.17, pFDR = 0.001) and was more pronounced in individuals who presented with combined amyloid and tau positivity versus negativity (A + T + > A-T-, pFDR = 0.004) or who were amyloid positive but tau negative (A + T + > A + T-, pFDR = 0.07). CSO-PVS volumes increased at a faster rate with amyloid positivity as compared to amyloid negativity (A + T-/A + T + > A-T-, pFDR = 0.021).ConclusionOur longitudinal evidence supports the relevance of PVS enlargement in presumably healthy ageing as well as in AD pathology. We further discuss the region-specific involvement of white matter hyperintensities and neurotoxic waste accumulation in PVS enlargement and the possibility of additional factors contributing to PVS progression. A comprehensive understanding of PVS dynamics could facilitate the understanding of pathological cascades and might inform targeted treatment strategies.Trial registrationGerman Clinical Trials Register DRKS00007966. Registered 04.05.2015 – retrospectively registered, https://drks.de/search/en/trial/DRKS00007966.

ABLE-SCORE: a simplified risk score for major adverse cardiovascular outcomes in patients with left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with life-threatening complications and variable prognosis [1,2]. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVNC is comparatively complex for clinical practice [3,4]. Purpose To develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVNC. Methods This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVNC patients between January 2009 and December 2020 at a single national-level medical center (derivation cohort n=300; internal validation cohort n=129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort n=95). The derivation/internal validation cohorts and the multicenter external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors for MACE in the multivariable Cox regression predictive model, and underwent both internal and external validation to confirm its discrimination (Harrell’s C-index), calibration (calibration plots), and clinical applicability (decision curve analysis). Results A total of 524 LVNC patients (43.5 ± 16.6 years, 65.8% male) were included in the study. At the end of the follow-up, 97 (32.3%), 38 (29.5%), and 20 (21.1%) individuals in the derivation, internal validation, and external validation cohort experienced at least one endpoint of MACE. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement and left ventricular ejection fraction≤40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell’s C-index of 0.821 (95%CI 0.772-0.869), 0.786 (95%CI 0.703-0.869), and 0.750 (95%CI 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVNC. According to decision curve analysis, the ABLE-SCORE displayed greater net benefit than the currently existing risk score for MACE in LVNC [3], indicating its strength in clinical applicability. Conclusions Derived from readily available laboratory and echocardiographic variables, a simplified and efficient risk score for MACE was developed and validated using a large LVNC cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVNC.Development of the ABLE-SCOREValidation of the ABLE-SCORE

Association between the cumulative excessive systolic blood pressure and left ventricular mass index

Abstract Background Ambulatory blood pressure (ABP) has been increasingly adopted in day-to-day clinical practices. Although clinicians can access an enormous amount of information regarding an individual’s blood pressures (BPs) through the ABP monitoring (ABPM), to date, only the mean BP is utilized as the diagnostic threshold of hypertension and the therapeutic target for BP control and no other indices were widely used to assess the burdens of high BP in the ABPM. Because elevated systolic BPs (SBPs) cumulatively damage the myocardium and induce hypertrophy and fibrosis, we hypothesized that the summated value of BP readings beyond a target level may be the better indicator of the overall BP loads than the mean BP value. Methods The Korean ABP registry is a multicenter prospective longitudinal cohort study performed in outpatients with hypertension. Among 5,965 patients enrolled in the registry, 951 patients with valid ABPM records and appropriate echocardiography measurements included in the study. The left ventricular mass (LVM) was normalized using the height2.7(m) (LVM index [LVMIH2.7] = LVM/Height2.7). The cumulative excessive SBP CE-SBP) was defined as the summation of the products of excessive SBPs (≥135 mmHg during wake, ≥10 mmHg during sleep) and the durations of the excessive SBP (Figure 1). Results The CE-SBP was non-linearly associated with both the office SBP and the mean SBP, but the association strength was much greater with the mean SBP than with the office SBP (R2=0.902 vs. R2=0.430). In linear regression models, the association of the CE-SBP with the LVMIH2.7 (R2=0.112 [0.074-0.149]) was greater than that of the office SBP (R2=0.072 [0.040-0.103]), the mean SBP (R2=0.082 [0.049-0.116]) or the mean SBP during sleep (R2=0.99 [0.063-0.134]). Non-linear regression models using restrictive cubic spline fits also showed that the association strength was greater with the CE-SBP (R2=0.117 [0.078-0.155]) than with the office SBP, mean SBP or mean SBP during sleep (Figure 2). Left ventricular hypertrophy (LVH) defined as the LVMIH27 ≥54 g/m2.7 was better predicted with the CE-SBP than with the other SBPs. The association between the CE-SBP and LVMIH27 was stronger in the patients not taking antihypertensive medications (R2=0.121) and strongest in those with the non-dipper pattern (R2=0.125). Combination with the variability indices (successive variation and average real variability) during sleep or the maximum SBP during sleep significantly improved the association strength of CE-SBP with LMMIH27, whereas the combination with the mean SBP or the variability indices during the entire period did not, in the linear models. Conclusion The CE-SBP was more strongly associated with the LVMIH27 than the office SBP and the mean SBP in the ABPM. This result suggests that the CE-SBP may be the better indicator of overall BP loads than the office SBP or the mean SBP in the ABPM, in patients with hypertension.Figure 1Figure 2

Differential impact of clinic BP target on the prevalence and predictors of the masked uncontrolled hypertension and white-coat uncontrolled hypertension

Abstract Background Although intensive blood pressure (BP) control have been advocated, major clinical practices guidelines still recommend clinic BP (cBP) &amp;lt; 149/90 mmHg as the target for antihypertensive therapy. But, cBP targets could influence the prevalence and predictors of any hypertension phenotype. We investigated how different cBP targets impacted on the prevalence and predictors of masked uncontrolled hypertension (MUCH) and white-coat uncontrolled hypertension (WUCH) using the Korean Ambulatory Blood Pressure (KorABP) registry. Methods A multicenter prospective longitudinal cohort study was performed in outpatients with hypertension. Among 5,965 patients enrolled in the KorABP registry, 1,601 patients on antihypertensive medications with a valid ambulatory BP monitoring record were included in this study. Two different cBP targets, &amp;lt;130/80mmHg (intensive) and &amp;lt;140/90 mmHg (conventional) were investigated. Results Controlled ambulatory BP (aBP; &amp;lt;130/80 mmHg) was observed in 472 patients (29.5%). Controlled cBP was shown in 348 patients (21.7%) with the intensive cBP target and in 697 patients (43.5%) with the conventional cBP target. Controlled hypertension, WUCH, MUCH and uncontrolled hypertension were found in 294, 174, 54, and 1,075 patients with the intensive target and in 378, 94, 319 and 810 patients with the conventional target, respectively. Among the patients with controlled cBP, the prevalence of MUCH markedly decreased with the intensive target (15.5%), compared to the conventional target (45.8%). In contrast, among the patients with uncontrolled cBP, the prevalence of WUCH had only 3.8% increase with the intensive target (10.4%), compared to the conventional target (14.2%) (Figure 1). With the conventional target, 75.9% of patients with MUCH had cBP between 130/80 mmHg and 139/89 mmHg. The concordance between the controlled aBP and controlled cBP was higher with the intensive target than with the conventional target (Cohen’s κ 0.62 [0.58-0.67] vs. 0.46 [0.41-0.50]). The logistic models for MUCH included the left ventricular mass index and underuse of antihypertensive drugs (&amp;lt;2 types of drugs) as the common predictors of the both targets. With the conventional target, clinic systolic BP and diastolic BP were the strongest predictors of MUCH, but the cBP was not a predictor of MUCH with the intensive target. The logistic models for WUCH included beta-blocker use, increased heart rate and lower waist circumference and clinic systolic BP as the common predictors of WUCH with the both target. The logistic model for MUCH performed better with the conventional target, whereas the logistic model for WUCH performed better with the intensive target (Figure 2). Conclusion The use of the intensive cBP target (&amp;lt;130/80 mmHg) could reduce the prevalence of MUCH with minimal increase in the prevalence of WUCH and would provide the better assessment for the BP control status than the use of the conventional cBP target (&amp;lt;140/90 mmHg).Figure 1Figure 2

Prospective longitudinal evaluation of AI-ECG in newly diagnosed heart failure (PLANE-HF)

Abstract Background * In the United Kingdom, there are one million people suffering from heart failure (HF), with more than 60,000 new cases annually (1). * Monitoring for declining left ventricular ejection fraction (LVEF) could optimise treatment approaches and avert healthcare episodes. * Easy home-based tracking of cardiac function would be transformative. * Previous studies have validated the capability of artificial intelligence-enabled electrocardiogram (AI-ECG) to correlated with changes in LVEF (2). * We hypothesize that longitudinal changes in AI-ECG probability score is associated with changes in the left ventricular (LV) function. Method * A prospective multicentre longitudinal study recruiting newly diagnosed HF with reduced ejection fraction (HFrEF) cases to investigate application of AI-ECG using longitudinal single-lead ECG recordings via patient-administered smart ECG-stethoscope examination – Figure 1. * A total of 36 patients were included in the analysis, with invitation to return for repeat echocardiography at 6-8 weeks. * Adjusted logistic regression was performed to analyze changes in LVEF by 10% as the outcome variable, investigating the relationship with the trajectory of AI-ECG probability scores. This study was approved by the UK Health Research Authority (reference 22/LO/0701). Result * Out of 36 patients, 19 patients had ischaemic and 17 had a non-ischaemic HF. * The mean age was 56.3 years, 97.2% patients were male and 46.6% were White. * 328 longitudinal single-lead ECGs were captured and used in the analysis. * 12 (33.3%) patients had an increase of their LVEF by 10%; preceding AI-ECGs was predictive of this recovery (OR 1.36; 95% CI, 1.05 – 1.65, p value = 0.016 – Table 1) Clinical Importance: * Individualised predictions of deterioration and improvement * Proactive medication adjustment * Enhanced triage for echocardiography Conclusion * AI-ECG designed to identify left ventricular systolic dysfunction (LVSD) can predict changes in LVEF% among newly diagnosed HFrEF patients. * Such results can place AI-ECG as a remote monitoring tool to track improvement or deterioration in patients’ LVEF%, which facilitate a proactive management and prevention strategies.

Imaging predictors of adverse prognosis in fabry disease cardiomyopathy: a systematic review and meta-analysis

Abstract Background Cardiac involvement represents the main cause of death in patients with Fabry disease (FD). Echocardiography and Cardiac Magnetic Resonance (CMR) have an established diagnostic role, but their prognostic value remains unresolved. This systematic review and meta-analysis sought to assess the prognostic implications of imaging parameters in FD. Methods PubMed, ClinicalTrials.gov, Embase and Cochrane Library databases were searched for studies published from inception through to October 1, 2023. Full-length original papers including FD patients undergoing baseline imaging assessment and clinical follow-up were selected. Pre-defined study outcomes were a cardiovascular endpoint and a composite clinical endpoint. A meta-analysis of the studies investigating the effect of single imaging parameters on a pre-specified cardiovascular endpoint and a separate analysis on a pre-specified composite clinical endpoint were performed to obtain the pooled estimates for the association between the imaging parameters and the study outcome. The study protocol was registered in PROSPERO. Results Thirteen studies including 1,399 FD patients (44.8% males) were selected. At pooled analysis, late gadolinium enhancement (HR 4.39; 95% CI 2.5-7.71), left atrium volume indexed (HR 1.02 per ml/m2; 95% CI 1.01-1.04), E/e’ (HR 1.14 per unit increase; 95% CI 1.08-1.21), left ventricular (LV) mass indexed (HR 1.014 per mg/m2; 95% CI 1.006-1.023), maximum LV wall thickness (HR 1.19 per mm, 95% CI 1.04-1.36), LV-global longitudinal strain (HR 1.2 per unit increase; 95% CI 1.2-1.27), were significantly associated with the cardiovascular endpoint, whereas T1-mapping (p=0.115) and LV-ejection fraction (p=0.305) were not. T1-mapping was associated with the composite endpoint (HR 0.986 per msec increase; 95% CI 0.976-0.997). Meta-regression analysis did not show any significant interaction between each of the potential effect modifiers. Conclusion This meta-analysis demonstrates a robust prognostic value regarding several imaging parameters in FD, specifically indexes of LV mass and wall thickness, diastolic dysfunction, LV-GLS, and LGE presence. These findings support multimodality cardiovascular imaging, including CMR, in FD disease patients to predict long-term prognosis and call for longitudinal multicentre studies to develop multi-modality-imaging derived risk-score algorithms.

Associations Between Physical, Cognitive, and Mental Health Domains of Post-Intensive Care Syndrome and Quality of Life: A Longitudinal Multicenter Cohort Study.

To explore associations between the physical, cognitive, and mental post-intensive care syndrome (PICS) health domains with changes in health-related quality of life (HRQoL) following ICU admission. A longitudinal prospective multicenter cohort study. Patients (n = 4092) from seven Dutch ICUs. None. At ICU admission, 3 and 12 months post-ICU, patients completed validated questionnaires regarding physical health problems, cognitive health problems, mental health problems, and HRQoL. Composite scores were created for the physical health domain (physical problems and fatigue) and mental health domain (anxiety, depression, and post-traumatic stress disorder). Adjusted multivariable linear regression analyses were performed, including covariables (e.g., patient characteristics, disease severity, pre-ICU HRQoL, etc.) to explore associations between the physical, cognitive, and mental health domains of PICS and changes in HRQoL at 3 and 12 months post-ICU. At 3 months (n = 3368), physical health problems (β = -0.04 [95% CI, -0.06 to 0.02]; p < 0.001), cognitive health problems (β = -0.05 [95% CI, -0.09 to -0.02]; p < 0.001), and mental health problems (β = -0.08 [95% CI, -0.10 to -0.05]; p < 0.001) were negatively associated with changes in HRQoL. Also, at 12 months (n = 2950), physical health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001), cognitive health problems (β = -0.04 [95% CI, -0.08 to -0.01]; p < 0.015), and mental health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001) were negatively associated with changes in HRQoL. PICS symptoms in the physical, cognitive, and mental domains are all negatively associated with changes in HRQoL at 3 and 12 months post-ICU. At 3 months, PICS symptoms in the mental domain seem to have the largest negative associations. At 12 months, the associations of PICS in the mental and physical domains are the same. This implies that daily ICU care and follow-up care should focus on preventing and mitigating health problems across all three PICS domains to prevent a decrease in HRQoL.

Impact of a Case-Based Sleep Apnoea Education on the Knowledge, Attitudes and Confidence of Dental Hygiene Students-A Multicentre Intervention Study.

This pilot study aimed to explore knowledge, attitudes and confidence levels of Obstructive Sleep Apnoea (OSA) before and after case-based education among dental hygiene students. Moreover, to give an international perspective, this study included students from the US and Scandinavia. A longitudinal multicentre study assessed dental hygiene students' OSA knowledge, attitudes and confidence through a case-based education model. Students from six dental hygiene programmes in the US, Norway and Sweden participated from 2021 to 2022. The intervention group (N = 89) received preview material, live synchronous OSA lecture, case-based screening of fictitious patients and clinical practice using the STOP-Bang screening tool. Controls (N = 70) followed the standard curriculum. The Obstructive Sleep Apnoea Knowledge and Attitudes (OSAKA) questionnaire, comprising 18 knowledge and five attitude/confidence questions, was used. Reliability was assessed and nonparametric tests determined OSAKA knowledge score differences among the baseline, 6 months and 12 months intervals. The intervention increased OSA knowledge with the largest increase in proportions of correct responses occurring between the baseline and 6 months and all single items showing a higher proportion of correct answers at 12 months compared to the baseline. Students' attitudes regarding the importance of OSAKA and confidence in managing patients increased from the baseline to both 6 months and 12 months. The case based educational intervention increased OSA knowledge and improved attitudes and confidence among dental hygiene students. The results also determined that the OSAKA questionnaire can be used in a setting with dental hygiene students to provide an overview of their knowledge, attitudes and confidence toward OSA. Current sleep medicine education in dental hygiene programmes is limited, suggesting the need for enhanced and sustained educational interventions to address this knowledge gap.

Impact of smoking habits on cardiovascular and neoplastic events and all-cause death in people living with HIVfrom the STOPSHIV cohort.

The study aimed to assess the impact of smoking exposure on major clinical events (MCE) in a real-life setting of people living with HIV (PWH). Observational longitudinal multicentre cohort study from Italy. Consecutive 983 PWH were enrolled in "STOP Smoking in HIV people" (STOPSHIV) projects and followed from July 2014 until September 2023. The observed MCE defined as cardiovascular (CV) events, neoplastic diseases or death for any reason was assessed according smoking status and related variables (number of cigarettes smoked daily, pack-years, Fagerström test) in participants. The association between exposure variables and the event was evaluated using the Cox proportional hazard model (hazard ratios, HR, and 95% CI). Over 6997.6 person-years of follow-up (PYFU), we found a total of 49 CV events, 61 neoplastic events, and 47 deaths. The overall incidence rate of MCE was 17.6 /1000 PYFU (95% confidence interval 14.7-21.0). All-cause death rate was 6.7 (95% CI 5.0-8.9)/1000 PYFU. In a multivariate analysis, older age (HR 1.07, CI 1.05-1.09), high Fagerström Test for Nicotine Dependence (HR 1.09, CI 1.03-1.15), a low nadir CD4 <200 cells/mm3 (HR 1.63, CI 1.10-1.41), history of previous neoplasm (HR 2.41; CI 1.34-4.43) and intravenous drug use as risk factor for HIV infection (HR 2.36; CI 1.52-3.68) were independent predictors of any MCE. Non-AIDS clinical conditions are the most observed clinical events in PWH from Italy. Smoking exposure significantly increases the risk of MCE in PWH and a high Fagerström Test for Nicotine Dependence is a predictor of MCE.

The impact of tau-PET in a selected memory clinic cohort: rationale and design of the TAP-TAU study

BackgroundTau-PET is a diagnostic tool with high sensitivity and specificity for discriminating Alzheimer’s disease (AD) dementia from other neurodegenerative disorders in well-controlled research environments. The role of tau-PET in real-world clinical practice, however, remains to be established. The aim of the TAP-TAU study is therefore to investigate the impact of tau-PET in clinical practice.MethodsTAP-TAU is a prospective, longitudinal multi-center study in 300 patients (≥ 50 years old) with mild cognitive impairment or mild dementia across five Dutch memory clinics. Patients are eligible if diagnostic certainty is < 85% after routine dementia screening and if the differential diagnosis includes AD. More specifically, we will include patients who (i) are suspected of having mixed pathology (e.g., AD and vascular pathology), (ii) have an atypical clinical presentation, and/or (iii) show conflicting or inconclusive outcomes on other tests (e.g., magnetic resonance imaging or cerebrospinal fluid). Participants will undergo a [18F]flortaucipir tau-PET scan, blood-based biomarker sampling, and fill out questionnaires on patient reported outcomes and experiences. The primary outcomes are change (pre- versus post- tau-PET) in diagnosis, diagnostic certainty, patient management and patient anxiety and uncertainty. Secondary outcome measures are head-to-head comparisons between tau-PET and less invasive and lower cost diagnostic tools such as novel blood-based biomarkers and artificial intelligence-based classifiers.ResultsTAP-TAU has been approved by the Medical Ethics Committee of the Amsterdam UMC. The first participant is expected to be included in October 2024.ConclusionsIn TAP-TAU, we will investigate the added clinical value of tau-PET in a real-world clinical setting, including memory clinic patients with diagnostic uncertainty after routine work-up. Findings of our study may contribute to recommendations regarding which patients would benefit most from assessment with tau-PET. This study is timely in the dawning era of disease modifying treatments as an accurate etiological diagnosis becomes increasingly important.Trial registrationThis trial is registered and authorized on December 21st, 2023 in EU Clinical Trials with registration number 2023-505430-10-00.

Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal Multicentre Study.

Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia. The aim of this study was to evaluate the potential of faecal VOCs-separately and with FIT-to guide optimal colonoscopy intervals in Lynch syndrome. Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 μg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance. Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide. In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies. NL8749.

Cerebral vasculitis as clinical manifestation of neuroborreliosis: Pattern of vascular pathology and prognostic factors of outcome.

Neuroborreliosis is a tick-borne condition that affects the central and/or peripheral nervous system. Cerebral infarction associated with neuroborreliosis-related vasculitis has been reported in only a handful of cases. Therefore, specific patterns of vascular pathology and prognostic outcome factors are still incompletely understood. To determine the pattern of vascular pathology and prognostic outcome factors in patients with neuroborreliosis-related vasculitis. We performed a longitudinal multicenter study between 1997 and 2022 in five academic study sites in Germany with a cumulative reference area of 1,620,000 inhabitants. All patients diagnosed with neuroborreliosis-associated cerebral vasculitis were included. The evaluation of clinical parameters, including NIH Stroke Scale (NIHSS), disability ranking (modified Rankin Scale, mRS), and neuroimaging, was performed at admission as well as after 3 and 12 months. Linear regression analysis was used to identify the independent predictors of recurrent strokes, involvement of posterior circulation, or multiple vessels. Patients with neuroborreliosis-related vasculitis (n = 51) were relatively young (mean age: 62 years) and displayed a predominance of vascular events within the posterior circulation (60.8%). A history of smoking was linked to recurrent strokes/TIA (64.7% vs. 23.5%; p = 0.006), strokes in multiple territories (100% vs. 35.9%; p < 0.0001), and posterior circulation events (64.5% vs. 30.0%, p = 0.017), whereas other cardiovascular risk factors showed no significant differences. Linear regression analysis corroborated smoking's association with recurrent strokes/ transient ischemic attacks (B: 0.412; p = 0.002), multiple territory strokes/TIA (B: 0.467; p = 0.033), and posterior circulation events (B: 0.317; p = 0.033). A thorough CSF examination for neuroborreliosis is crucial, especially in younger stroke patients, particularly those experiencing posterior circulation ischemic events. Smoking cessation should be prompted in patients with neuroborreliosis-associated cerebral vasculitis.

Spontaneous eye blinking as a diagnostic and prognostic marker in disorders of consciousness: Protocol of an international multicentre longitudinal study.

Diagnostic and prognostic decision-making in patients with Disorders of Consciousness (DoC) is challenging. It has been suggested that spontaneous eye blink rate is an index of patients' level of consciousness easy to detect in clinical practice. Further blinking features (i.e., amplitude, duration, variability in intervals between blinks) may change as a function of cognitive load, but have not been investigated in patients with DoC. This multicentre, longitudinal study aims at exploring the diagnostic and prognostic value of spontaneous eye blinking features in DoC. Eight European medical institutions will enrol consecutively admitted adult patients with DoC. Within two weeks from study entry demographic, anamnestic and clinical data will be collected. Moreover, patients will undergo two 20-minute EEG-EOG recordings at rest, to collect blinking features and EEG activity. A clinical follow-up will be performed after 6 months. A group of healthy individuals will be enrolled for reference. Possible differences in blink features between patients and the reference group, differences across diagnostic sub-groups, and correlations between blinking features and clinical outcome will be investigated. The results of this study might help clinicians to reduce misdiagnosis rate in DoC and provide useful information for prognostication and care pathway plan.

Diving deep into lupus: Gastrointestinal involvement insights from the Oman lupus study.

This multicenter longitudinal study investigated the prevalence of gastrointestinal (GI) manifestations in lupus patients and determined the risk factors associated with mortality. This study is part of the Oman Lupus Study, which included 1160 patients who met the classification criteria for systemic lupus erythematosus (SLE) from January 2006 to February 2020. All patients were screened for GI symptoms and involvement. We identified 91 patients with GI manifestations, with a prevalence rate of 8.53% in the pediatric group and 7.75% in the adult group, and this difference was not statistically significant (p = .755). Ischemic colitis was significantly associated with longer disease duration (p < .001) and positivity for B2-glycoprotein I (B2GPI) autoantibodies (p < .0001). Moreover, a significant correlation was found between ischemic colitis and hematologic manifestations (p = .001), lupus nephritis (p = .007), pulmonary complications (p = .000-.039), and some cardiac complications (p = .012-.269). Mortality rates were greater in patients with GI involvement (24.37%), including those with ischemic colitis (p = .005), chronic peritonitis (p < .001), and spleen/liver infarction (p = .001). Sepsis, thrombocytopenia, and different internal organ involvement rates were significantly associated with increased mortality. This research provides significant insights into GI manifestations in lupus patients. A higher mortality rate was found to be associated with organ involvement, disease duration, autoantibody profile, and specific complications. Considering this fact, it is vital to prioritize management strategies to improve clinical outcomes in this group of patients.

ABLE-SCORE, a simplified risk score for major adverse cardiovascular outcomes in left ventricular hypertrabeculation: a multicenter longitudinal cohort study.

Left ventricular hypertrabeculation (LVHT) is a heterogeneous entity with life-threatening complications and variable prognosis. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVHT is comparatively complex for clinical practice. This study aimed to develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVHT. This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2009 and December 2020 at Fuwai Hospital (derivation cohort, n = 300; internal validation cohort, n = 129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort, n = 95). The derivation/internal validation cohorts and the external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors in the multivariable Cox regression predictive model for MACE, and underwent both internal and external validations to confirm its discrimination, calibration, and clinical applicability. A total of 524 LVHT patients (43.5 ± 16.6years, 65.8% male) were included in the study. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement, and left ventricular ejection fraction ≤ 40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell's C-index of 0.821 [95% confidence interval (CI), 0.772-0.869], 0.786 (95%CI, 0.703-0.869), and 0.750 (95%CI, 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVHT. According to decision curve analysis, the ABLE-SCORE displayed greater net benefits than the existing risk score for LVHT, indicating its strength in clinical applicability. A simplified and efficient risk score for MACE was developed and validated using a large LVHT cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVHT.

Exploring the Prognostic Impact of Non-Obstructive Coronary Artery Lesions through Machine Learning

The prognostic impact of non-obstructive coronary artery disease (CAD) remains controversial. Therefore, the objective of this study is to assess the long-term prognostic significance of non-obstructive CAD using machine learning models. We designed a multicenter retrospective, longitudinal, and observational study that included 3265 patients classified into three groups: 1426 patients with lesions &lt; 20%, 643 patients with non-obstructive CAD (lesions 20–50%), and 1196 patients with obstructive CAD (lesions &gt; 70%). A composite cardiovascular event (acute myocardial infarction, stroke, hospitalization due to heart failure, or cardiovascular-related death) was assessed after a mean follow-up of 43 months. To achieve this, various machine learning models were constructed. The model with the highest accuracy was selected to perform a Shapley Additive Explanations (SHAP) analysis, revealing the contribution of different variables in predicting an event. The SHAP analysis suggested that the percentage of coronary lesion was the most significant predictor of cardiovascular events. None of the models demonstrated adequate capability in predicting the event, showing only a good predictive ability for the absence of an endpoint. In conclusions, this study demonstrates how machine learning techniques may facilitate the development of high-performing models for predicting long-term cardiovascular events in patients undergoing coronary angiography.

Alcohol consumption and smoking history at time of diagnosis, and risk of colorectal cancer recurrence and mortality: Results from the ColoCare Study.

Findings from studies investigating the impacts of alcohol use and smoking on colorectal cancer (CRC) outcomes are inconclusive. This study aimed to investigate associations between alcohol use and smoking status at the time of diagnosis on recurrence and overall mortality among patients with CRC. The present study included 2,216 stage I-IV patients with CRC from the longitudinal multi-center ColoCare study, with available data on recurrence and CRC-specific mortality. Cox proportional hazards models adjusted for age, sex, race, ethnicity, stage, tumor site, treatment, comorbidities, body mass index, and study site were fit, with imputations for missing data. We observed 235 recurrences and 308 CRC-specific deaths over an average of 3 years of follow-up. After adjusting for confounders, current alcohol consumption and ever smoking, relative to not current consumption and never smoking, respectively, were not statistically significantly associated with CRC recurrence (Alcohol - HR: 0.95. 95% CI: 0.71-1.29; Ever smoking - HR: 0.98, 95% CI: 0.75-1.29) or CRC-specific mortality (Alcohol - HR: 0.95. 95% CI: 0.74-1.22; Ever smoking - HR: 0.98, 95% CI: 0.77-1.24). No associations were observed between alcohol and smoking at diagnosis and clinical outcomes in this well-annotated longitudinal cohort. Our cohort study reports no significant associations; however, limiting alcohol use and avoiding smoking are health behaviors recommended for CRC survivors for prevention of other cancers and chronic conditions.