Risultati per: Long COVID: principali risultati, meccanismi e raccomandazioni

Introduction
Globally, long-distance truck drivers’ (LDTDs) risk of exposure to HIV infections is higher compared with other populations in transit. Thus, several HIV prevention interventions have been implemented, though to a narrower extent compared with other most at-risk populations. Consequently, the effectiveness of such interventions is not well understood. Therefore, a review is warranted to inform policymakers on the most effective HIV prevention interventions targeted for LDTDs.

Methods and analysis
The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines were followed. Original peer-reviewed interventional studies involving LDTDs of either gender aged above 18 years, and reporting findings on HIV prevention interventions from any part of the world will be included. Non-empirical research studies like systematic reviews, literature reviews and scoping reviews will be excluded. A comprehensive search will be done from PubMed, Cumulated Index to Nursing and Allied Health Literature and other five databases to identify eligible studies. The Rayyan online platform will be used for the screening of titles and abstracts. For the meta-analysis, a random-effects meta-analysis using the ‘metafor’ package in R software will be done. Where specific studies may not report adequate data for meta-analysis, their findings will be presented qualitatively. The Cochrane Collaboration tool and Joanna Brigs Checklist will be used to assess the quality and risk of bias in the included studies.

Ethics and dissemination
A formal ethical approval is not required for this systematic review and meta-analysis. The findings will be presented at scientific conferences and published in open-access peer-reviewed journals to reach policymakers, stakeholders and the scientific community.

PROSPERO registration number
CRD42024505542.

Background
Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration.

Methods
We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching

Objectives
To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

Design
A population-based longitudinal cohort study using real-time user data.

Setting
35 specialised long COVID clinics in the UK.

Participants
4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.

Main outcome measures
Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.

Results
The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was –0.86 (95% CI –1.32, –0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.

Conclusions
Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

New England Journal of Medicine, Volume 391, Issue 19, Page 1860-1862, November 14, 2024.

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

Annals of Internal Medicine, Ahead of Print.

Objective
In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse ( >6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy).

Design
In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).

Results
In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76–0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66–0.68 vs 0.61 vs 0.52 vs 0.59, respectively).

Conclusion
In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.

Trial registration number
NCT00571337 and NCT02177071.

Circulation, Volume 150, Issue Suppl_1, Page A4128491-A4128491, November 12, 2024. Introduction:N-3 very-long-chain polyunsaturated fatty acids (VLCPUFA; C≥24), which are found primarily in retina and a few other select tissues, are known to play critical roles in specific biological systems. Although n-3 PUFA, such as eicosapentanoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), may confer cardiovascular benefits, they did not improve age-related macular degeneration (AMD), a leading cause of blindness worldwide, in clinical trials. The activity of ELOVL fatty acid elongase 2 (ELOVL2), an enzyme that converts EPA into tetracosapentaenoic acid (TPA, C24:5 n-3), is known to decrease in the retina with age due to promoter methylation.Hypothesis:We hypothesized that dietary VLCPUFA may delay or prevent AMD, by bypassing the ELOVL2-mediated lipid elongation step. We also hypothesize that VLCPUFA may benefit cardiometabolic health like shorter-chain n-3 PUFA through similar mechanisms.Aims:We aimed to investigate the effect of dietary VLCPUFA on retinal function and cardiometabolic risk factors in mice.Methods:We have produced a new fish oil that contains ~40% (w/w) of C24-C28-rich VLCPUFA. We fed 9-month-old ApoE -/- mice with normal or VLCPUFA fortified diet (1% or 3% (w/w)) for 8 weeks, and age-matched C57BL/6J mice were used as control. We conducted electroretinography (ERG) and cognitive ability tests at the end of feeding period. Inin vitrostudies, we performed PPAR reporter assay and investigated the anti-inflammatory effects of TPA in lipopolysaccharide-stimulated RAW264.7 cells.Results:Supplementation of VLCPUFA showed a significant and dose-dependent improvement in ERG response. Like EPA and DHA, we also observed favorable cardiometabolic changes and decreased atherosclerotic plaque area due to dietary VLCPUFA. Intriguingly, VLCPUFA supplemented aging mice exhibit better cognitive performance compared with control. Transcriptome analysis revealed that VLCPUFA-enriched fish oil favorably regulated genes involved in nuclear receptor signaling pathways, lipid metabolism and inflammation. Furthermore, purified TPA potently activates PPARs, and suppressed inflammation in macrophage cells.Conclusions:Overall, our studies revealed for the first time several potential health benefits for our new VLCPUFA-enriched fish oil in several age-related diseases and support its future development as a new dietary supplement.

Circulation, Volume 150, Issue Suppl_1, Page A4144521-A4144521, November 12, 2024. Background:There is conflicting evidence on whether racial disparities still exist in heart transplant (HT) outcomes, with prior studies focusing primarily on differences in short-term mortality. We examined disparities in HT survival over a longer follow-up duration alongside a broader range of post-HT outcomes.Methods:Using the United Network for Organ Sharing (UNOS) database, we evaluated adult HT recipients between 2017 and 2022 and classified each according to race as either Black, non-Hispanic White and Other. The primary outcome was graft survival and secondary outcomes included rejection, renal dysfunction, and post-transplant diabetes. Chi-squared tests were used to compare baseline clinical factors and selected outcomes by racial group. Kaplan-Meier and Cox proportional hazards analyses were performed to compare risks of the primary outcome by race.Results:Among 15,873 recipients (63% non-Hispanic White, 23% Black, 14% Other), Black recipients were more often female, less often college educated, and more often had public (vs. private) insurance. Blacks had higher use of durable ventricular assist devices (VAD) and intra-aortic balloon pump (IABP) at the time of HT. Graft survival at one year did not differ by race (91.8% for Blacks vs. 91.1% for non-Blacks), but at three years was significantly lower for Blacks (83.4%) than non-Blacks (85.7%). Blacks had higher risk of graft failure after adjustment for baseline socioeconomic status (SES) and clinical variables (HR 1.28, CI 1.17 – 1.41). Blacks also had significantly higher prevalences of acute rejection (12.4% vs. 10.2%), diabetes (10.8% vs. 7.1%), and progression of renal dysfunction at 3-years post HT (40.9% vs. 37.1%; p < 0.05 for all).Conclusions:Racial disparities in graft survival after HT remain in the contemporary era but are only evident after longer-term follow-up. These survival disparities could be mediated by concurrent disparities in shorter term outcomes such as development of acute rejection, chronic kidney disease, and new onset diabetes.

Circulation, Volume 150, Issue Suppl_1, Page A4120583-A4120583, November 12, 2024. Background:First generation drug eluting stents (DES) with thick polymers may contribute to local vascular inflammation and late stent thrombosis. Thinner-strut DES (ultrathin), particularly those with biodegradable polymers, aim to reduce this risk by minimizing flow disturbance and vascular injury. However, the long-term safety and efficacy of ultrathin biodegradable polymer sirolimus eluting stents (BP-SES) compared to durable polymer everolimus eluting stents (DP-EES) are still uncertain. Thus, we performed a meta analysis to compare outcomes of these two stents.Methods:Inclusion criteria comprised randomized controlled trials comparing ultrathin BP SES and thin DP EES in patients undergoing percutaneous coronary interventions with long term follow-up of at least 3 years. We excluded cohort studies, case reports, editorials, conference abstracts, and animal studies. Primary outcomes were target lesion failure (TLF), cardiac death (CD), target-vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (CI-TLR). We systematically searched PubMed, Cochrane CENTRAL, and Scopus. Cochrane’s ROB 2.0 tool assessed trial quality, and RevMan software (5.4) performed the meta-analysis.Results:Our analysis included ten RCTs, totaling 16,216 patients, with 9,108 in the BP SES group and 7,108 in the DP EES group. TLF occurred in 905 patients (9.94%) in the BP-SES group and 821 patients (11.55%) in the DP-EES group, with no statistically significant differences between the groups (RR = 0.92, 95% CI = 0.85 to 1.01, p = 0.08). Additionally, there were no significant differences in cardiac death (RR = 1.00, 95% CI = 0.84 to 1.19, p = 1.00), TV-MI (RR = 0.91, 95% CI = 0.78 to 1.05, p = 0.19), and CI-TLR (RR = 0.88, 95% CI = 0.78 to 1.01, p = 0.06) between the two groups.Conclusion:The use of BP-SES did not result in higher rates of TLF, CD, TV-MI, or CI-TLR compared to DP-DES. These findings suggest that both BP-SES and DP-DES are viable options for PCI procedures, with comparable long-term safety profiles. However, some trials used strut thicknesses exceeding 70µm in cases requiring wider diameters, similar to the strut thickness in the DP-EES group. This makes it challenging to assess whether, in addition to biodegradable polymers, lower strut thickness contributes to reducing target lesion-related events. Further research may be needed to explore other relevant outcomes and to confirm these findings in diverse patient populations.

Circulation, Volume 150, Issue Suppl_1, Page A4141445-A4141445, November 12, 2024. Introduction:Bicuspid aortic valve (BAV) is associated with progressive ascending aorta (AAo) dilation, often leading to aneurysms, dissections, and ruptures. Thus, current guidelines recommend preventive surgery for AAo dilation. Recent 4D flow MRI studies show that BAV morphology causes abnormal transvalvular flow patterns, increasing wall shear stress (WSS), a trigger of aortic growth. Further studies have delineated areas of abnormally high WSS by comparing to estimates of matched controls, and show promise in detecting risk for aortic growth. However, since the long-term prognostic significance of this marker is unclear, we aimed to quantify WSS in BAV patients to assess its value in predicting the need for aortic surgery up to 10 years post-4D flow MRI acquisition.Methods:BAV patients without prior surgical intervention scanned before April 1, 2014 were identified. Using medical records, patients were categorized as ‘operated’ if they underwent aortic surgery post-scan and ‘non-operated’ if they were surgery-free for at least 10 years post-scan. 4D flow MRIs were processed with an AI pipeline, including 3D segmentation of the aorta, followed by peak velocity (PV) and WSS quantification in the AAo (Fig. 1A-C). Patient-specific WSS heatmaps were computed relative to a map based on the WSS of 10 or more sex and age-matched controls. Relative areas of elevated WSS in the AAo were then calculated (Fig. 1D-F).Results:115 patients were included, with 73 non-operated (age: 42.5±11.5y, 49M) and 42 operated patients (age: 53.5±12.1y, 34M). The mean baseline mid-AAo diameters for non-operated and operated patients were 3.8±0.6 cm and 4.1±0.5 cm, respectively. Among operated patients, the mean scan to surgery time was 5.7±3.3y. All three 4D flow metrics were significantly higher in operated compared to non-operated patients: PV: 2.6±0.6 vs. 1.7±0.4 m/s (p

Circulation, Volume 150, Issue Suppl_1, Page A4144529-A4144529, November 12, 2024. Introduction:Cardiac hypertrophy is a known adverse prognostic marker in various non-transplant pathologies. In heart transplant patients, due to many confounders, it has been controversial on the relevance and timing of cardiac hypertrophy as an adverse remodeling vs acute injury pattern in an immunologically hostile environment. Previous studies have shown prognostication of hypertrophy on echocardiogram at 1-year post-heart transplant.Research Questions:Does cardiac hypertrophy within a year after transplant have long-term prognostic implications?Methods:We collected relevant clinical variables for all heart transplants using EPIC EHR’s Clarity database. Hypertrophy was defined based on LV Mass Indexed to body surface area where LV Mass = 0.8 x (1.04 x (((LVIDD + IVSd + PWd)3- LVIDD3))) + 0.6. Relative Wall Thickness was defined as RWT = 2 x PWd / LVIDD. We used a rule-based natural language processing program validated by correlation with manual readings by trained cardiologists (r=0.96, p=0.007) to abstract echo variables.Results:Inclusion criteria were heart transplants performed from 2015 to 2023 at our center, with an echocardiogram closest to 6 months (+/- 1 month). Ten percent (n=33) showed hypertrophy on echocardiograms at 6 months (Table 1). Of these, 20 (61%) had mild, 3 (9%) severe, and 10 (30%) moderate hypertrophy. Of 33 patients, 28 (85%) had concentric, and 5 (15%) had eccentric hypertrophy. Patients with hypertrophy at 6 months had significantly worse survival at 5 years (p=0.01) and 10 years (p=0.05) compared to patients without hypertrophy (Fig 1). Survival at 5 and 10 years was not statistically different for patients with hypertrophy at 3 months (5 yrs p=0.17, 10 yrs p=0.06), 12 months (5 yrs p=0.38, 10 yrs p=0.30), and 18 months (5 yrs p=0.15, 10 yrs p=0.08) compared to those without hypertrophy.Conclusion:Cardiac hypertrophy on echocardiogram at 6 months predicts adverse long-term survival, while other time points did not.

Circulation, Volume 150, Issue Suppl_1, Page A4140117-A4140117, November 12, 2024. Background:Catheter ablation is a most common treatment for atrial fibrillation (AF), but rhythm outcome after AF ablation in long-standing persistent atrial fibrillation (LS-PerAF) is still poor. Left atrial low-voltage areas (LVAs) is associated with poor rhythm outcome after catheter ablation. However, the predictors of LVAs presence have not been fully elucidated in patients with LS-PerAF.Purpose:The purpose of this study was to establish a novel predictive score for the prevalence of LVAs in patients with LS-PerAF ablation.Methods:In total, 109 consecutive patients who underwent initial ablation for LS-PerAF were included. LS-PerAF was defined as AF whose duration was more than 1 year. LVA was defined as areas with bipolar peak-to-peak voltage of < 0.50mV. A clinical risk score was obtained as the total number of independent predictors analyzed by multivariate logistic regression analysis. AF recurrence after the catheter ablation was followed for 24 months.Results:Of 109 patients with LS-PerAF, LVAs existed in 26 (24%) patients. A novel predictive score, named DESK score, consisted of diabetes mellitus (odds ratio [OR] 3.7, [95% confidence interval {CI} 2.2–11], p = 0.02), age ≥ 70 years (OR 3.8, [95% CI 1.4-10], p = 0.007), female sex (3.0 [95% CI 1.04-8.4], p = 0.04), AF duration ≥ 3.7 years (44 months) (OR 3.7, [95% CI 1.3-11], p =0.02). LVAs were more frequently found in patients with a higher DESK score (OR, 3.5 [95% CI, 1.9–6.5], p < 0.001) (Figure 1A). On receiver operating characteristic curve analysis, DESK score was a moderate predictor of LVAs presence (area under the curve, 0.750; Figure 1B). The optimal cut-off of DESK score was 3 points, corresponding to a 38.5% sensitivity, 97.6% specificity, and 83.5% predictive accuracy. Freedom from AF recurrence was significantly lower in patients with DESK score ≥ 3 than in those with DESK score < 3 (10.4% vs. 43.5%, p = 0.008).Conclusions:In patients who underwent LS-PerAF ablation, the DESK score correlated with the prevalence of LVAs, and associated with poor rhythm outcome.

Circulation, Volume 150, Issue Suppl_1, Page A4120534-A4120534, November 12, 2024. Background:Sex is a vital prognostic factor in patients with coronary heart disease, however, the data on sex-treatment interaction among real-world patients with three-vessel coronary disease (TVD) are limited.Objectives:This study aimed to investigate the long-term outcomes after medication therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass grafting surgery (CABG) according to sex in patients with TVD.Methods:Consecutive 8943 patients with TVD [2421 (27.1%) MT, 3825 (42.8%) PCI, and 2697 (30.2%) CABG] were enrolled from April 2004 to February 2011 at Fu Wai Hospital. The primary endpoint was cardiac death and major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction (MI), stroke or repeat revascularization. The secondary endpoints were the components of MACCE.Results:Among 8943 TVD patients, 7122 (79.6%) were men and 1821 (20.4%) were women. While the number of women undergoing PCI was comparable to men, women opted for more MT and fewer CABG (Figure 1). During a median 6.6-year follow-up, CABG showed a lower risk of MACCE compared to PCI, with a similar treatment effect for women and men (female HR: 0.76; 95% CI: 0.60 to 0.97; male HR: 0.61, 95% CI: 0.55 to 0.69; p for interaction=0.222) (Figure 2 and Figure 3). CABG also showed lower risks of all-cause death, MI, and repeat revascularization, and a higher risk of stroke, which had no significant interaction with sex. PCI, compared to MT, was associated with lower risks of MACCE, all-cause death, and stroke and a higher risk of MI and repeat revascularization, without significant gender disparities. CABG versus MT was associated with lower risks of MACCE, all-cause death, MI and repeat revascularization and a higher risk of stroke, with a similar treatment effect for female and male patients (Figure 3).Conclusion:There was no significant sex differences in the risks of long-term outcomes of PCI vs. CABG, PCI vs. MT, and CABG vs. MT in real-world TVD patients.

Circulation, Volume 150, Issue Suppl_1, Page A4139196-A4139196, November 12, 2024. Introduction:The mavaCamten ObservationaL evIdence Global cOnsortium in hypertrophic cardiomyopathy (COLLIGO-HCM; ClinicalTrials.gov ID NCT06372457) is a multinational, multicenter observational research initiative aiming to describe the real-world outcomes of mavacamten for the treatment of obstructive HCM.Aims:Describe the real-world effectiveness and safety of mavacamten, measured by echo measurements and NYHA class.Methods:This retrospective study used data from medical records from two participating HCM centers in the US. Patient-level data was extracted to assess the effectiveness and safety of mavacamten post-treatment initiation through 60 weeks. Patient characteristics and outcomes were described, including echocardiogram measurements, New York Heart Association (NYHA) functional class, and safety.Results:A total of 93 patients were treated with mavacamten (mean age 60.6 ± 13.9 years, 23.7% black, 57.0% female, and 77.4% NYHA class III at baseline) with a mean follow-up of 37.0 ± 28.1 weeks (Table). From baseline to week 60, 3 (3.2%) patients experienced temporary treatment discontinuation, and 3 (3.2%) discontinued mavacamten due to left ventricular ejection fraction (LVEF)