The quest for a cure for chronic hepatitis B from an HTA perspective:lessons learned from chronic hepatitis c

Despite the availability of treatments and vaccines, chronic hepatitis B (CHB) is among the world's deadliest infectious diseases and a global public health concern. This thesis focuses on the quest for curative treatments for CHB from a Health Technology Assessment (HTA) perspective and the evidence/data required by HTA and reimbursement bodies to evaluate new products. New direct antivirals have recently been introduced for hepatitis C and this experience can be built on in hepatitis B, although there are both similarities and differences between hepatitis C and B viruses and related chronic diseases. The second and third chapters focus on hepatitis C with possible directions for future research and development on CHB. Chapter 4 concerns an analysis of data on US Veterans patients, showing the high clinical and economic burden of CHB in this population. Chapter 5 highlights that self-stigma and social stigma are common among patients living with CHB. Chapter 6 addresses patient preferences and shows that one of the main desired attributes of new treatments is limited duration and the ability to achieve sustained HBsAg loss. Chapters 7 and 8 describe a network meta-analysis of clinical trials in CHB, and a systematic review of the literature about health economics models; these findings can be used to adapt cost-effectiveness models. Adequate collection and provision of the data required by HTA agencies and payers and learning from experience in hepatitis C will optimize patient access to new treatments for HBV and accelerate WHO's ambitious goal of eliminating viral hepatitis

Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants

Abstract Introduction The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants. Methods We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed. Result For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was € 6,244.20 with palivizumab and € 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was € 15,568.65 and € 8,676.74, respectively. Conclusion This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants.</p

Peri-procedural brain lesions prevention in CAS (3PCAS). Randomized trial comparing CGuard™ stent vs. wallstent

Background: Aim of this study was to evaluate peri-procedural incidence of new diffusion-weighted-magneticresonance- imaging (DWMRI) brain lesions in CAS patients treated by carotid mesh stent (CGuard™) or closed-cell stent (Wallstent™). Methods: Consecutive patients with asymptomatic carotid stenosis ≥ 70% were submitted to preoperative DWMRI scan, to exclude the presence of preoperative silent cerebral lesions. Patients were randomized to CGuard orWallstent. DWMRI was performed immediately after the intervention and at 72-hour postoperatively. Moreover, pre and postoperative Mini-Mental-State-Examination Test (MMSE) and aMontreal-Cognitive-Assessment (MoCA) test were conducted, and S100β and NSE neurobiomarkers were measured at 5-time points (preoperatively, 2, 12, 24, and 48 h postoperatively). Results: From January 2015 to October 2016, sixty-one consecutive eligible patients were submitted to preoperative DWMRI scan. Three patients were excluded because of preoperative silent cerebral lesions. In 29 CGuard patients, 1 developed a minor stroke and 8 silent newlesionswere observed in the 72 h-DWMRI (31%): 4 lesions were ipsilateral, and 4 lesions were contra or bilateral. In 29 Wallstent patients, 7 clinically-silent new lesions were found in the 72 h-DWMRI (24.1%; p = 0.38). In 4 cases lesions were ipsilateral and in 3 cases contra or bilateral. S100B values doubled at 48 h in 24 patients, and among them 12 presented new DWMRI lesions. 48-h S100B increase was significantly related to 72-h DWMRI lesions (p= 0.012). Conclusions: In our experience both stents showed an acceptable rate of subclinical neurological events with no significant differences at 72-hour DWMRI between groups. Bilateral/contralateral lesions suggest that periprocedural neurological damage may have extra-carotid sources

SARS-CoV-2 and extracellular vesicles: An intricate interplay in pathogenesis, diagnosis and treatment

Extracellular vesicles (EVs) are widely recognized as intercellular communication mediators. Among the different biological processes, EVs play a role in viral infections, supporting virus entrance and spread into host cells and immune response evasion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an urgent public health issue with significant morbidity and mortality worldwide, being responsible for the current COVID-19 pandemic. Since EVs are implicated in SARS-CoV-2 infection in a morphological and functional level, they have gained growing interest for a better understanding of SARS-CoV-2 pathogenesis and represent possible diagnostic tools to track the disease progression. Furthermore, thanks to their biocompatibility and efficient immune activation, the use of EVs may also represent a promising strategy for the development of new therapeutic strategies against COVID-19. In this review, we explore the role of EVs in viral infections with a focus on SARS-CoV-2 biology and pathogenesis, considering recent morphometric studies. The common biogenesis aspects and structural similarities between EVs and SARS-CoV-2 will be examined, offering a panoramic of their multifaceted interplay and presenting EVs as a machinery supporting the viral cycle. On the other hand, EVs may be exploited as early diagnostic biomarkers and efficient carriers for drug delivery and vaccination, and ongoing studies will be reviewed to highlight EVs as potential alternative therapeutic strategies against SARS-CoV-2 infection

Urgent carotid endarterectomy to prevent recurrence and improve neurologic outcome in mild-to-moderate acute neurologic events

Objectives: This study evaluated the safety and benefit of urgent carotid endarterectomy (CEA) in patients with carotid disease and an acute stable neurologic event. Methods: The study involved patients with acute neurologic impairment, defined as >= 4 points on the National Institutes of Health Stroke Scale (NIHSS) evaluation related to a carotid stenosis >= 50% who underwent urgent CEA. Preoperative workup included neurologic assessment with the NIHSS on admission or immediately before surgery and at discharge, carotid duplex scanning, transcranial Doppler ultrasound imaging, and head computed tomography or magnetic resonance imaging. End points were perioperative (30-day) neurologic mortality, significant NIHSS score improvement or worsening (defined as a variation >= 4), and hemorrhagic or ischemic neurologic recurrence. Patients were evaluated according to their NIHSS score on admission (4-7 or >= 8), clinical and demographic characteristics, timing of surgery (before or after 6 hours), and presence of brain infarction on neuroimaging. Results: Between January 2005 and December 2009, 62 CEAs were performed at a mean of 34.2 +/- 50.2 hours (range, 2-280 hours) after the onset of symptoms. No neurologic mortality nor significant NIHSS score worsening was detected. The NIHSS score decreased in all but four patients, with no new ischemic lesions detected. The mean NIHSS score was 7.05 +/- 3.41 on admission and 3.11 +/- 3.62 at discharge in the entire group (P = 8 on admission had a bigger score reduction than those with a lower NIHSS score (NIHSS 4-7; mean 4.95 +/- 1.03 preoperatively vs 1.31 +/- 1.7 postoperatively, NIHSS >= 8 10.32 +/- 1.94 vs 4.03 +/- 3.67; P < .001). Conclusions: In patients with acute neurologic event, a high NIHSS score does not contraindicate early surgery. To date, guidelines recommend treatment of symptomatic carotid stenosis <= 2 weeks from onset of symptoms to minimize the neurologic recurrence. Our results suggest that minimizing the time for intervention not only reduces the risk of recurrence but can also improve neurologic outcome. (J Vasc Surg 2011;53:622-8.

Radiolabeled native low-density lipoprotein injected into patients with carotid stenosis accumulates in macrophages of atherosclerotic plaque

BACKGROUND: Accumulation of LDL within the arterial wall appears to play a crucial role in the initiation and progression of . The dynamic sequence of this event has not been fully elucidated in humans. METHODS AND RESULTS: In 7 with previous transient ischemic attack or stroke and critical (>70%) , autologous [(125)I]-labeled LDL or [(125)I]-labeled human serum albumin were 24 to 72 hours before endarterectomy. specimens obtained at endarterectomy were analyzed by autoradiography and immunohistochemistry. Autoradiographic study showed that LDL was localized prevalently in the foam cells of plaques, whereas the accumulation in the lipid core was negligible. Immunohistochemistry revealed that foam cells that had accumulated LDL were mostly CD68 positive, whereas a small number were alpha-actin positive. No accumulation of the radiotracer was detected in plaques after injection of human serum albumin. In 3 treated for 4 weeks with vitamin E (900 mg/d), an almost complete suppression of LDL uptake by was observed. CONCLUSIONS: This study shows that circulating LDL rapidly in human . The prevalent accumulation of LDL by provides strong support to the hypothesis that these cells play a crucial role in the pathogenesis of atherosclerosis

Early Carotid Endarterectomy after Ischemic Stroke: The Results of a Prospective Multicenter Italian Study

ObjectivesTo evaluate safety of early carotid endarterectomy (CEA) in patients with acute brain ischemia presenting to the emergency department stroke units (EDSU).MethodsThe neurologists, neuroradiologists and vascular surgeons on duty in emergency departments enrolled 96 patients who underwent very early CEA according to a predefined protocol within two years. The protocol included evaluation of neurological status by National Institute of Health Stroke Scale (NIHSS), neuroimaging assessment, ultrasound of the carotid arteries and Transcranial Doppler. Patients with NIHSS>22 or whose neuroimaging showed brain infarct >2/3 of the middle cerebral artery territory were excluded. All eligible patients underwent CEA as soon as possible. Primary end points of the study were mortality, neurological morbidity by NIHSS and postoperative hemorrhagic conversion on neuroimaging. Statistical analysis was performed by univariate analysis.ResultsThe mean time elapsing between the onset of stroke and endarterectomy was 1.5 days (±2 days). The overall 30-day morbidity mortality rate was 7.3% (7/96). No neurological mortality occurred. On hospital discharge, three patients (3%) experienced worsening of the neurological deficit (NIHSS score 1 to 2, 1 to 3 and 9 to 10 respectively). Postoperative CT demonstrated there were no new cerebral infarcts nor hemorrhagic transformation. At hospital discharge 9/96 patients (9%) had no improvement in NHISS scores, 37 were asymptomatic and 45 showed a median decrease of 4.5 NIHSS points (range 1–18). By univariate analysis none of the considered variables influenced the clinical outcome.ConclusionOur protocol selected patients who can safely undergo very early (<1.5 days) surgery after acute brain ischemia. Large randomized multicenter prospective trials are warranted to compare very early CEA versus best medical therapy

Surprising complication of intussusception after colonoscopy. a case report and a review of the literature

This study discusses a case with a history of ileal-caecal intussusception post colonoscopy requiring urgent surgical intervention and a systematic review explores the literature on post-colonoscopy intussusception. A systematic review was conducted according to PRISMA guidelines. Studies reporting entero-enteric, ileo-colic, or colo-colic intussusception after colonoscopy, published in English before June 2023, were included. Data was extracted on patient demographics, indications for colonoscopy, procedural details, clinical symptoms, and management. Overall, 19 cases were identified from 17 studies. The median age was 48 years and 53 % were male. History of abdominal surgery was reported in 42% of cases. Symptoms typically appeared within a week of the procedure. The majority of cases required surgical intervention (63%), while others were managed conservatively (34%). The case report is an 85-year-old man with a history of diabetes, cardiopathy and abdominal surgery presented to the Emergency Department with 2 days of abdominal pain and vomiting after colonoscopy. A Computer Tomography abdomen revealed findings concerning for a small-bowel volvulus. Subsequent laparotomy revealed ileo-caecal intussusception, requiring surgical resection. Histology examination revealed a small-bowel intramucosal adenocarcinoma. The patient recovered and was discharged on postoperative day 7. The etiology of post-colonoscopy intussusception is multifactorial, with potential contributing factors including adhesions, altered bowel motility, and gas insufflation. Patients with a history of abdominal surgery should be considered at increased risk and prompt identification is crucial to reduce morbidity and mortality

A comparative network meta-analysis of standard of care treatments in treatment-naive chronic hepatitis B patients

Objective:Published network meta-analyses of chronic hepatitis B (CHB) treatments are either out-of-date or excluded key treatments. Therefore, we aimed to comprehensively update the efficacy evidence for the following end points: Hepatitis B surface antigen (HBsAg) loss, hepatitis B early antigen (HBeAg) seroconversion and hepatitis B virus DNA (HBV DNA) suppression.Materials & methods:Approved treatments in CHB and their combinations were evaluated. A systematic literature review was conducted to identify all randomized controlled trials in treatment-naive CHB patients. Included studies reported at least one of the end points of interest. A frequentist probability network meta-analysis was performed for each end point. The choice of fixed effect or random-effect model was based on the I-square statistic, a measure of variation in study outcomes between studies. The analyses were performed separately for HBeAg-positive and HBeAg-negative patients. For the primary analyses, end points measured 48 +/- 4 weeks after treatment initiation were considered.Results:A total of 47 randomized controlled trials (13,826 patients), covering 23 unique treatment regimens, were included: a total of 29 reported HBsAg loss, 36 reported HBeAg seroconversion and 37 reported HBV DNA suppression. For both HBsAg loss and HBeAg seroconversion, pegylated interferon-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. On the other hand, for HBV DNA suppression, nucleosides-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients.Conclusion:Our findings confirm available evidence around the comparative efficacy of available CHB treatments. Therefore, they can be used to update relevant cost-effectiveness analyses and clinical guidelines