Investigating Acute Hepatitis after SARS-CoV-2 Vaccination or Infection: A Genetic Case Series.

(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a case series of patients who experienced the onset of acute hepatitis, with or without autoimmune features, following SARS-CoV-2 vaccination or infection and to hypothesize a genetic susceptibility in the pathogenesis. (2) Methods: A group of patients with acute onset hepatitis following SARS-CoV-2 vaccination or infection were evaluated in our hepatology outpatient clinic, where they underwent biochemical and autoimmune tests. Hepatitis A (HAV), B (HBV), and C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV) infections were excluded. Patients with a diagnosis of autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) underwent HLA typing and histological testing. (3) Results: Five patients experienced new-onset AIH after COVID-19 vaccination, one of which developed mild symptoms after vaccination that strongly worsened during subsequent SARS-CoV-2 infection. One patient had AIH relapse after COVID-19 vaccination while on maintenance immunosuppressive treatment. All of them had HLA DRB1 alleles known to confer susceptibility to AIH (HLA DRB1*03,*07,*13,*14), and in three of them, HLA DRB1*11 was also detected. Two patients developed acute hepatitis without autoimmune hallmarks which resolved spontaneously, both positive for HLA DRB1*11. (4) Conclusions: An association between AIH and COVID-19 vaccine or infection can be hypothesized in individuals with a genetic predisposition. In patients without autoimmune features and spontaneous improvement of hypertransaminasemia, the diagnosis of drug-induced liver injury (DILI) is probable. Further studies are needed to determine the presence of an actual association and identify a possible role of HLA DRB1*11 in the pathogenesis of acute liver injury after SARS-CoV2 vaccination or infection.

Early atrial fibrillation detection is associated with higher arrhythmic burden in patients with loop recorder after an embolic stroke of undetermined source.

Background: After an embolic stroke of undetermined source (ESUS), long-term monitoring is recommended to start an anticoagulation therapy in patients with documented atrial fibrillation (AF). Literature is sparse about the AF burden following an ESUS, although this might have significant implications in terms of clinical management and therapeutic strategy. Our primary aim was to evaluate a possible association between early detection of AF (within 90 days from the ILR implantation) and higher AF burden. Methods: This is a retrospective single-center study of 129 consecutive patients who received implantable loop recorders (ILRs) after an ESUS for detection of subclinical AF and their AF burden. Results: Mean age was 70.3 ± 10.4 years old (males: 51.9%). Atrial fibrillation was found in 40.3% of patients. Patients with AF were older, presented a higher CHAD2S2-Vasc Score and greater left atrial volume compared with patients without AF. The median AF burden was 1.2%; 59% of patients had the first AF episode within 90 days from the ILR implant while 41% experienced the first episode later than 90 days. The AF burden was significantly higher in the former group. Of note, the univariate analysis showed that only early AF detection was significantly associated with AF burden >1% (OR 20.0; 95% CI 1.68-238.6, p = 0.01). Conclusions: The early AF detection was found to be significantly associated with a higher burden of AF.

Virological Treatment Monitoring for Chronic Hepatitis B.

More than 250 million people worldwide are currently infected with hepatitis B, despite the effectiveness of vaccination and other preventive measures. In terms of treatment, new therapeutic approaches are rapidly developing, promising to achieve the elimination of infected cells and the complete cure of infection. The on-treatment monitoring of these innovative antiviral treatments will require the implementation of new virological tools. Therefore, new biomarkers are being evaluated besides the traditional virological and serological assays in order to obtain information on different steps of the viral replication cycle and to monitor response to therapy more accurately. The purpose of this work is to describe both standard and innovative tools for chronic hepatitis B treatment monitoring, and to analyse their potential and feasibility.

Venous thromboembolism prevention with low molecular weight heparin may reduce hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Subcutaneous heparin at a prophylactic dose (SHPD) is a rather common treatment in ischemic stroke, but whether it confers an increased risk of hemorrhagic transformation of cerebral infarct (HT) and whether its reduction or discontinuation favors HT regression are presently poorly understood. METHODS: Two samples of ischemic stroke patients with a cerebral lesion diameter ≥ 3 cm on brain CT scan, admitted over 7 years to our stroke unit, were retrospectively examined: (1) patients treated or not treated with SHPD (enoxaparin 4000 U/day), with subsequent assessment of possible HT appearance (N = 267, mean age 75.9 ± 12.8 years) and (2) patients treated with SHPD, with HT and subsequent reduction/discontinuation or maintenance of the initial dose, and subsequent assessment of HT evolution (N = 116, mean age 75.7 ± 11.1 years). HT severity was quantified according to the ECASS study (HT score). RESULTS: In the first sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and other possible confounders, SHPD was inversely associated with HT appearance (hazard ratio 0.62, 95% CI 0.39-0.98, P = 0.04). In the second sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and initial HT severity, SHPD reduction/discontinuation had an inverse effect on both HT score improvement (odds ratio 0.42, 95% CI 0.18-0.99, P = 0.049) and HT improvement according to neuroradiological reports (odds ratio 0.34, 95% CI 0.14-0.82, P = 0.015). CONCLUSIONS: This retrospective study suggests that SHPD may play a protective role in HT appearance and evolution, which requires verification by a randomized clinical trial.

Efficacy and safety in pharmacological cardioversion of recent-onset atrial fibrillation: a propensity score matching to compare amiodarone vs class IC antiarrhythmic drugs.

The acute management of recent-onset (<48 h) atrial fibrillation (AF) is still debated. Aim of our study was to compare efficacy and safety of intravenously administered class IC antidysrhythmic agents vs amiodarone in a propensity score matched series of patients acutely treated for AF in the emergency department. During a 3-year period, we retrospectively evaluated all episodes of recent-onset (<48 h) AF pharmacologically treated for sinus rhythm restoration in the emergency department. By means of a propensity score matching considering the main statistically different covariates, we selected two accurately matched treatment groups. We analysed the differences between amiodarone and class IC group in terms of efficacy and safety that is conversion to sinus rhythm rates within 12 and 48 h after starting treatment, time to conversion, and adverse drug effects. An overall number of 817 episodes of recent-onset AF were collected (amiodarone group = 406, class IC group = 411). After matching, we obtained 358 episodes equally divided (amiodarone group = 179 and class IC group = 179). Conversion rates within 12 h were 139 (53.1 %) in amiodarone group and 95 (72.6 %) in class IC group (p < 0.05). Median time for cardioversion was 420 min (331.6-508.3 CI 95 %) in amiodarone and 55 min (44.9-65.1 CI 95 %) in class IC group (p < 0.05). The incidence of adverse events in both groups was very low and equally distributed (p = ns). Intravenously administration of class IC agents, when compared with amiodarone, proved to be more rapid and effective, and equally safe in the acute management of recent-onset AF.

New automated and high-throughput quantitative analysis of urinary ketones by multifiber exchange-solid phase microextraction coupled to fast gas chromatography/negative chemical-electron ionization/mass spectrometry.

The present research is focused on automation, miniaturization, and system interaction with high throughput for multiple and specific Direct Immersion-Solid Phase Microextraction/Fast Gas Chromatography analysis of the urinary ketones. The specific Mass Spectrometry instrumentation, capable of supporting such the automated changeover from Negative Chemical to Electron Ionization mode, as well as the automation of the preparation procedure by new device called MultiFiber Exchange, through change of the fibers, allowed a friendly use of mass spectrometry apparatus with a number of advantages including reduced analyst time and greater reproducibility (2.01-5.32%). The detection limits for the seven ketones were less than 0.004 mg/L. For an innovative powerful meaning in high-throughput routine, the generality of the structurally informative Mass Spectrometry fragmentation patterns together with the chromatographic separation and software automation are also investigated.

Atrial asynchrony and function before and after electrical cardioversion for persistent atrial fibrillation.

AIMS: The relation between left atrial (LA) electrical and mechanical activity is a challenging field of investigation. The availability of echocardiographic strain analysis techniques has enhanced our ability to non-invasively assess LA wall mechanical synchrony and performance. The aim of our study was to investigate how new strain analysis tools describe the improvement in LA mechanical function after sinus rhythm (SR) restoration as a result of electrical cardioversion (CV) and how such improvement mirrors endocrine profile changes. METHODS AND RESULTS: Seventy-three patients, with persistent atrial fibrillation (AF) who underwent successful electrical CV, were prospectively studied with transthoracic echocardiography 1 week before CV and 1 month after SR. Speckle-tracking 2D-strain evaluation and asynchrony quantification were performed according to the standard deviation of time-to-peak (TP-SD) of deformation of six segments automatically located along the perimeter of the LA cavity, as imaged in an apical four-chamber view. We also calculated classic echocardiograhic parameters such as mitral regurgitation (MR) jet area, LA volume, LV diastolic and systolic volumes, as well as E-wave velocity and deceleration time (DT) on transmitral pulsed wave Doppler. Specimens for plasmatic brain natriuretic peptide (BNP) were also obtained before and 1 month after CV. After 1 month of SR, we detected a significant reduction in TP-SD (from 17.5 +/- 7.4 to 15.2 +/- 7.5%, P = 0.022), this being the expression of improved LA asynchrony, together with a marked increase in LA deformation (peak strain from 11.4 +/- 5.2 to 17.2 +/- 7.5%, P < 0.001) and a reduction in LA volume (-4.5 +/- 36%, P = 0.012). BNP decreased by one-third (from 127 +/- 96 to 86 +/- 89 pg/mL, P = 0.01). We also noticed improved ventricular pump performance [LV ejection fraction (EF) from 53 +/- 10 to 57 +/- 8%, P = <0.001] due to a 20 +/- 42% (P < 0.001) increase in LV diastolic volume (without variations in LV systolic volume and mass), a better diastolic profile (DT 34 +/- 64%, P = 0.003), and a reduction in MR jet area (-1.0 +/- 2.0 cm(2), P < 0.001). These findings are compatible with reverse LA remodelling secondary to SR maintenance, with a favourable effect on LV function that appears modulated by the atrium itself. A significant correlation (r = 0.40, P < 0.001) was demonstrated between TP-SD and peak strain data pre-post CV. At multivariate analysis, a significant capacity for the TP-SD/peak strain ratio to predict AF recurrence at 1-year follow-up (P = 0.013) was shown. CONCLUSION: Our novel noninvasive approach appears to be able to describe the LA mechanical behaviour during AF and how this ameliorates after 1 month of SR, together with an improved endocrine profile. LA mechanical data pre-CV can predict AF recurrence 1-year post CV.

Transradial versus transfemoral approach for percutaneous coronary procedures.

Selective coronary angiography was originally performed through open brachial arteriotomy. Thereafter, the percutaneous Seldinger technique and the use of preformed Judkins-type catheters popularized the femoral approach. More recently, after the first report of successful coronary angiography by the transradial approach in 1989, the radial artery has been increasingly used as an alternative access site. The main advantage offered by the transradial approach is represented by the very low (< 1%) incidence of relevant vascular access site complications, which on the contrary occur in about 3% to 7% of patients undergoing procedures through the femoral route. The main disadvantage is a higher incidence of procedural failure that leads to a crossover to the femoral route. In this review, we examine the available evidence on transradial and transfemoral approach advantages, disadvantages, and complications in coronary angiography and intervention. Their use in the acute myocardial infarction setting and other situations is described. Vascular closure device usefulness is also considered.

Mean platelet volume and the extent of coronary artery disease: results from a large prospective study.

BACKGROUND: Platelets play a central role in the pathogenesis of coronary artery disease. Mean platelet volume (MPV) is an indicator of platelet activation, and has been demonstrated to be correlated with platelet reactivity. The aim of the current study was to investigate whether mean platelet volume is associated with the extent of coronary artery disease. METHODS: We measured MPV in 1411 consecutive patients undergoing coronary angiography. All angiograms were analyzed by two investigators blinded of clinical data. Significant coronary artery disease was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. The relationship between MPV and platelet aggregation was evaluated by PFA-100 in 50 consecutive patients who were not taken any antiplatelet therapy, and in a cohort of patients who were on aspirin by PFA-100 (n=161) and Multiplate (n=94). RESULTS: Patients were divided into three groups according to tertiles of MPV. Patients with higher MPV were slightly older (p=0.038), with larger prevalence of diabetes (p<0.0001), hypertension (p=0.008), previous CVA (p=0.041), less often with stable angina (p=0.043) and family history of CAD (p=0.011), more often on statins (p=0.012), and diuretics (p=0.007). MPV was associated with baseline glycaemia (p<0.0001) and red blood cell count (p=0.056), but inversely related to platelet count (p<0.0001). MPV was not associated with the extent coronary artery disease (p=0.71) and carotid IMT (p=0.9). No relationship was found between MPV and platelet aggregation. CONCLUSION: This study showed that MPV is not related to platelet aggregation, the extent of coronary artery disease and carotid IMT. Thus, this parameter cannot be considered as a marker of platelet reactivity or a risk factor for coronary artery disease.

A multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) - study design and rationale.

BACKGROUND: Several randomized trials and registries have shown a reduction of restenosis after coronary angioplasty with drug-eluting stents (DESs) compared with bare metal stents (BMSs). However, cost-efficacy analysis and long-term outcome of DESs compared to BMSs deserve further assessment. Moreover, concern has been raised regarding adverse clinical events occurring late after DES implantation, in particular, late stent thrombosis related to the suspension of dual antiplatelet therapy. The use of a short-cycle oral treatment with prednisone at immunosuppressive dose after BMS implantation has shown remarkable efficacy in reducing restenosis in nondiabetic patients, with very low additional cost and without the need for long-term dual antiplatelet therapy. Such results are however limited by small sample size. STUDY DESIGN: Cortisone plus BMS or DES versus BMS alone to Eliminate Restenosis is an independent, prospective, multicenter, randomized study. It will randomize 375 nondiabetic patients with coronary artery disease in three different arms to BMS (control group), DES (DES group) or BMS followed by a 40-day prednisone treatment (prednisone group). The DES and the prednisone groups will be compared to the control group to investigate the expected clinical advantage. The primary endpoint of the study is the event-free survival of cardiovascular death, myocardial infarction and recurrence of ischemia-needing repeated target vessel revascularization at 1 year. Secondary endpoints are the event-free survival analysis at 2 and 3 years, the restenosis rate at 9 months, and cost-effectiveness at 1, 2 and 3 years. SAMPLE SIZE: The expected primary endpoint rates are 90% for DESs and for prednisone-treated patients and 77% for BMSs. The study was designed as a superiority trial, to compare DES, and BMS and prednisone, with BMS alone. A sample size of 118 patients per group provides an 80% power, assuming a complete 12-month follow-up information available for each patient. To obviate for cases of drop out, the sample size was increased to 375 patients to be enrolled in five Italian hospitals. CONCLUSION: This study will provide a magnitude of the net clinical and economic benefits of DES and of the safety and efficacy of BMS and cortisone compared to the standard use of BMS alone in nondiabetic patients with coronary artery disease.

Intravenous contrast echocardiography after myocardial infarction: relationship among residual myocardial perfusion, contractile reserve and long-term remodelling.

OBJECTIVE: Previous studies have shown the potential role played by intracoronary myocardial contrast echocardiography (MCE) in predicting long-term remodelling and function after myocardial infarction (MI). Scanty data, however, are available on the role of intravenous MCE in this regard. The aim of this study was to assess the role of residual myocardial blood volume in the asynergic region in modulating ventricular volume changes over time post-MI. METHODS: Thirty-two consecutive patients with anterior MI were studied predischarge using low-dose dobutamine echocardiography (Dob) and intravenous triggered MCE. Videointensity plots were generated from the apical approach and fitted exponentially. Volumes were assessed at baseline, during Dob and at 8 months. RESULTS: Baseline volumes, which appeared related to the extent of the asynergic region (P < 0.01) but showed no relation with videointensity in that area, did not change at follow-up, although Dob had elicited significant contractile reserve. However, videointensity in the asynergic region showed a significant interaction (P = 0.044) with the change in diastolic volume over time, with patients with the highest videointensity reverting remodelling (n = 11, from 69 +/- 16 to 65 +/- 16 ml/m) as compared with the remaining population (n = 21, from 68 +/- 16 to 73 +/- 21 ml/m). This was not seen when Dob-derived parameters were used. Multivariate analysis ranked videointensity second (P = 0.066), after baseline stroke volume (P = 0.005), in predicting changes in volumes over time. CONCLUSIONS: Unlike inotropic reserve, residual myocardial blood volume in the dysfunctioning muscle, as assessed by predischarge quantitative intravenous MCE, has the potential to modulate remodelling in patients who suffered an anterior MI.