Risultati per: L’eparina inibisce la proteina spike del virus SARS-Cov-2

Oncologi, ‘subito un piano di recupero per la prevenzione’

Annals of Internal Medicine, Ahead of Print.

Introduction
Janus kinase (JAK) inhibitors are an important therapeutic option in the treatment of rheumatoid arthritis, but increase the risk of developing herpes zoster. Although a dry recombinant zoster vaccine (RZV) that can be used under immunosuppressive conditions has recently been developed, its optimal use and appropriate timing in patients scheduled to start JAK inhibitors is still unclear. The present study is designed to clarify the appropriate timing of JAK inhibitor initiation to measure varicella zoster virus (VZV)-specific IgG titers and VZV-specific T cell response in patients with rheumatoid arthritis who start tofacitinib at the first RZV vaccination or at the second one.

Methods and analysis
STOP HZ (Effectiveness and S afe T y O f P rophylactic Recombinant H erpes Z oster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) study is a multicentre, open-label, randomised, comparative study in patients with rheumatoid arthritis who are scheduled to start tofacitinib. This study enrols 60 study subjects in 12 sites. Enrolled subjects receive RZV two times on day 1 and week 8 and initiate tofacitinib 5 mg two times a day at the time of their first RZV (day 1, group A) or second RZV (week 8, group B) based on randomisation. The random assignment is performed centrally in a 1:1 ratio. Patients in Group B continue the same treatment until the start of tofacitinib treatment. Primary endpoint is VZV-specific IgG antibody titers at week 12 compared with those at baseline in each group. Secondary endpoints include comparison of VZV-specific IgG antibody between the groups, changes in disease activity of rheumatoid arthritis, VZV-specific T cell response and adverse events.

Ethics and dissemination
The study has been approved by the Certified Review Board of Keio (No. 2022008), and conforms to the Declaration of Helsinki and good clinical practice guidelines. Written informed consent is obtained from participants prior to enrolment. The results of this study are planned to be submitted for publishment in relevant peer-review journals.

Trial registration number
jRCTs031230329.

New England Journal of Medicine, Volume 391, Issue 19, Page 1863-1864, November 14, 2024.

New England Journal of Medicine, Ahead of Print.

Chronic hepatitis B virus (HBV) infection remains a significant global health burden, affecting over 250 million people worldwide who are at risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Currently available nucleos(t)ide analogues (NAs) are effective in controlling viraemia; however, functional cure, defined as loss of hepatitis B surface antigen (HBsAg), is rare and difficult to achieve and likely requires robust immune responses, reflecting the need for innovative therapeutic strategies.1 Thus, the future of treating chronic HBV infections relies on combination therapies that include both direct-acting antiviral agents and immunomodulatory agents.2 In this context, selgantolimod (SLGN), an agonist of Toll-like receptor 8 (TLR8), could be a promising candidate. Its efficacy in the treatment of chronic HBV infections has been investigated in preclinical models and clinical trials,3–5 but there remains limited understanding of its impact on immune effectors within the…

Circulation, Volume 150, Issue Suppl_1, Page A4143264-A4143264, November 12, 2024. Background:R-on-T phenomenon occurs when an electrical stimulus is delivered at a critical point during ventricular repolarization. This can initiate ventricular arrhythmias like polymorphic ventricular tachycardia (PMVT). We describe a case of ventricular pacemaker spikes delivered on the T wave causing PMVT.Case:A 53-year-old female with CAD s/p stent, postpartum cardiomyopathy s/p Bi-V CRT-D (Boston Scientific G124), and paroxysmal atrial fibrillation presented for elective endoscopy and colonoscopy to evaluate her dysphagia and abdominal pain. Her CRT-D was reprogrammed from DDD pacing with lower rate limit (LRL) 50 bpm to an asynchronous Bi-V DOO mode at 50 bpm (‘electrocautery mode’) for the procedure (tachy therapy disabled). Her LV-RV offset was 40 msec. Prior to receiving sedation or medications, she was found unresponsive. Telemetry showed Spike-on-T phenomenon which initiated PMVT. She was externally defibrillated with 200J and received magnesium and an IV amiodarone bolus. She returned to sinus rhythm, but one minute later had another Spike-on-T event initiating PMVT. She was successfully defibrillated with 360J. Post-shock EKG showed an asynchronous Bi-V paced rhythm at 50 bpm.Decision Making:The patient was admitted to the CCU for post-resuscitation care. Her electrolytes and cardiac enzymes were unremarkable. Her CRT-D was reprogrammed to DDD 80-140 bpm. Transthoracic echocardiogram showed normal biventricular systolic function. Cardiac catheterization did not show obstructive CAD. After reprogramming of her device, she had no further events. After initial treatment with IV amiodarone load, she was discharged home on oral magnesium gluconate.Discussion:The only intervention prior to her procedure was device reprogramming (DDD 50 bpm to DOO 50 bpm). Telemetry showed pacer spikes initiating PMVT. Given the LV-RV offset of 40 msec, she would have received these two tightly coupled pacemaker spikes in an asynchronous mode, in this unfortunate instance during her T wave. While her bowel preparation may have led to electrolytes abnormalities, post-resuscitation electrolytes were normal. Fortunately, she received prompt therapy and was reprogrammed with increased LRL.Conclusion:We described a case of Spike-on-T PMVT prior to colonoscopy without obvious provocation other than asynchronous pacemaker spikes. Reprogramming devices in DOO mode with increased LRL may prevent PVCs and asynchronous pacemaker spikes from triggering PMVT.

Circulation, Volume 150, Issue Suppl_1, Page A4144514-A4144514, November 12, 2024. Introduction:Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era.Case Report:A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device.Discussion:Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.

Circulation, Volume 150, Issue Suppl_1, Page A4123849-A4123849, November 12, 2024. Background:Older adults and adults with comorbidities are at increased risk for severe respiratory syncytial virus (RSV) disease and related complications.Aims:To estimate the risk of myocardial infarction (MI) and all−cause mortality among adults aged ≥50 years hospitalized with RSV compared to those with no recent acute respiratory illness (ARI) and those hospitalized with influenza.Methods:Data from Optum’s de−identified Clinformatics® Data Mart Database were analyzed (October 2015–June 2023) in this retrospective cohort study. Adults aged ≥50 years with ≥12 months of continuous enrollment were assigned to cohorts based on RSV or influenza hospitalization (from ICD−10 codes; RSV and flu cohorts) or no recent ARI (control cohort). Index dates for RSV and flu cohorts were the start of an ARI that included hospitalization. Baseline characteristics were measured in the 12 months pre−index. MI (from ICD−10 codes) and all−cause mortality were measured during follow−up and compared between cohorts using time−varying coefficient multivariable adjusted Cox models (MI results accounted for the competing risk of death).Results:In the RSV cohort (n=14,759), mean age (76.5 years) and mean Charlson comorbidity index (CCI; 3.3) were higher than the flu (n=77,468; 75.4 years, CCI=2.9) and control (n=73,795; 69.5 years, CCI=1.0) cohorts. Adjusted HRs (95% CI) for MI and all−cause mortality risk were significantly higher in the RSV vs control cohort across follow−up, ranging from 30.96 (26.22–36.54) within 30 days post−index to 2.26 (2.04–2.51) >365 days post−index for MI and 10.77 (9.19–12.63) within 30 days post−index to 2.29 (2.18–2.42) >365 days post−index for mortality. Compared to the flu cohort, adjusted MI and mortality risk in the RSV cohort were lower during the 30 days post−index (MI: 0.87 [0.82–0.92]; mortality: 0.84 [0.78–0.90]) but higher >365 days post−index (MI: 1.11 [1.01–1.22]; mortality: 1.05 [1.01–1.10]).Conclusion:MI and all−cause mortality risk were higher for hospitalized RSV cases compared to controls. Smaller differences in outcomes were observed when comparing hospitalized RSV cases with hospitalized influenza cases, with varying direction over time. With existing evidence of increased MI and mortality risk after influenza and these findings on MI and mortality risk after RSV, future research should aim to further understand the impact of RSV on cardiovascular outcomes and assess the role of RSV prevention in lowering the risk of MI and mortality.

Circulation, Volume 150, Issue Suppl_1, Page A4140628-A4140628, November 12, 2024. Introduction:Human immunodeficiency virus (HIV) infection increases the risk of heart failure, particularly Heart Failure with Reduced Ejection Fraction (HFrEF). Guideline-directed medical therapy (GDMT), including beta-blockers (BB), renin-angiotensin system inhibitors (RASi), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), has been shown to decrease morbidity and mortality in patients with HFrEF.Hypothesis:Lower GDMT prescription rates would be associated with higher 30-day readmission or mortality rates in patients with HIV and HFrEFAims:To assess GDMT prescription rates and their impact on short-term morbidity and mortality in patients with HIV and HFrEF.Methods:Patients diagnosed with HIV and HFrEF who were admitted with acute heart failure within Emory Healthcare from 2010 to 2020 were identified using ICD codes. Diagnoses were confirmed by physician review. Baseline demographics, CD4 count, viral load (VL), prescriptions for GDMT and antiretroviral medications at the time of admission were assessed. A simple GDMT score was created, assigning 1 point for each medication prescribed (0-3, excluding SGLT2i given the study timeframe). Multivariable logistic regression was used to determine the association of the GDMT score with 30-day readmission or death, adjusting for age, sex, race, hypertension, diabetes, estimated glomerular filtration rate (eGFR), and VL.Results:The study included 161 patients (mean age 56 years, 22.9% women, 86.3% Black, 55% with VL

Circulation, Volume 150, Issue Suppl_1, Page A4144823-A4144823, November 12, 2024. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have become a significant healthcare burden. Sustained increases in prothrombotic markers have been reported in hospitalized acute COVID-19 patients. However, whether patients with less severe acute infection also endure a persistent prothrombotic state remains uncertain. We tested for a prothrombotic state in this cohort and examined potential mediators. We enrolled 70 adult patients with prior mild acute SARS-CoV-2 infection and sustained PASC symptoms (per WHO criteria). A control healthy group matched for age and sex was also enrolled who were not previously diagnosed with COVID-19. Markers of platelet activation and platelet-neutrophil aggregates (PNA) were quantified using whole-blood flow cytometry. Markers of extracellular traps (citrullinated histones [H3Cit] and cell-free DNA [cfDNA]), anti-dsDNA IgG, and thrombin generation potential were measured in plasma. At recruitment (6 weeks to 3 years post infection), there was increased potential for thrombin generation in the plasma from PASC compared to control reflected by increased peak and velocity index (P

Circulation, Volume 150, Issue Suppl_1, Page A4138507-A4138507, November 12, 2024. Background:SARS-CoV2 infection has been associated with cardiovascular consequences, including myocarditis and cardiac arrhythmias. Myocarditis secondary to SARS-CoV2 infection and cardiac arrhythmias may often go unrecognized and can present with late and nonspecific symptoms. Predicting those at risk allows for prompt treatment and prevention of their potentially life-threatening consequences.Methods:The National COVID Cohort Collaborative (N3C) database was used to identify patients aged 0-30 years with COVID-19 index date between 1/1/2020 and 3/31/2022, whose sites provided data for at least six months beyond the index date. Outcomes included myocarditis and new arrythmias within 6 months of the index visit. Patients with known cardiac comorbidities were excluded. Predictors included gender, race, COVID severity as an ordinal scale, vaccination status, clinical comorbidities, and Area Deprivation Index (ADI). The data were stratified by age groups (0-4, 5-17, 18-30). Random forest models were used for data analysis and SHapley Additive exPlanations (SHAP) method was applied to optimize results. These analyses were conducted using the NCATS N3C Data Enclave.Results:Of the 1,487,741 patients in our study population, 4,105 (0.28%) had the measured outcomes; 404 had myocarditis only, 3,634 had arrhythmia only and 67 had both. Severity of COVID (SHAP 0.2344 for 0-4 years, 0.2114 for 5-17, 0.1370 for 18-30) was identified as the most important risk factor for de-novo myocarditis and arrhythmias overall. Increase in ADI (indicating lower socioeconomic status) was the second most important risk factor for the 0-4 and 5-17 age groups (SHAP: 0.0370, 0.0223). Among the 18-30 age group, race (SHAP 0.0321) and gender (SHAP 0.0289) were the second and third most important risk factors, with White and Black patients more likely to develop an event and Hispanic patients less likely. Women were less likely to develop a cardiac outcome than men.Conclusion:The severity of COVID was identified as the most important risk factor for the occurrence of myocarditis or cardiac arrhythmia within 6 months of infection. ADI, race, and gender were also identified as important, though less influential, risk factors.

Introduction
Hepatitis C virus (HCV) infection is a silent epidemic that needs a comprehensive and contextualised approach to manage. Access to readily available, affordable and acceptable HCV point-of-care (POC) in vitro diagnostics (IVDs) is equally required to meet the global HCV goals. However, most guidelines for evaluating these IVDs such as the WHO prequalification process and country-specific standards disproportionately focus on diagnostic performance. The real-time connectivity, ease of specimen collection, affordability, sensitivity, specificity, user-friendliness, rapidity and robustness, equipment-free or simplicity and deliverability to end-users (REASSURED) criteria provide a holistic and user-oriented evaluation of the IVDs in the populations they are meant to be used. Therefore, as part of a multinational study in sub-Saharan Africa, we will conduct an evaluation of the Bioline HCV POC test for diagnosing HCV infection in primary healthcare settings of Ghana using the REASSURED criteria.

Methods and analysis
This field evaluation will be conducted in three phases. The first phase will use a cross-sectional field evaluation study design to evaluate the diagnostic performance of the Bioline HCV POC test. The second phase will use mixed methods to ascertain operational characteristics and users’ perceptions. In the third phase, a cross-sectional survey will be used to estimate the costs of accessing HCV diagnostics services using three proposed HCV testing models to inform the affordability of the testing pathways and linkage to care in the primary healthcare clinics. This phase will run concurrently with the second phase of the study. Thematic content analysis and quantitative data analysis will be performed using ATLAS.ti V.23.0.6 and StataCorp LLC’s Stata statistical software V.16.0, respectively.

Ethics and dissemination
The study protocol has been reviewed and fully approved by the Faculty of Health Sciences Research Ethics Committee, University of Pretoria (281/2023) and the Ghana Health Service Ethics Review Committee (GHS-ERC013/08/23). This diagnostic trial has also been registered in the Pan African Clinical Trial Registry (PACTR202410837698664). The findings of the study will be presented in relevant peer-reviewed journals, at local and international conferences, and to all stakeholders involved.