Abstract
In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-γ production in ...216 PLWH on ART with advanced disease (CD4 count <200 cell/mm
3
and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm
3
(20–122), 93% HIV-RNA < 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (>2 log
2
difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.
Co-infections during COVID-19 may worsen patients’ outcomes. This study reports the results of a screening assessing the presence of co-infections among patients hospitalized for SARS-CoV-2 infection ...in the Infectious Diseases-Ward of the Policlinico Tor Vergata Hospital, Rome, Italy, from 1 January to 31 December 2021. Data on hepatitis B and C virus, urinary antigens for legionella pneumophila and streptococcus pneumoniae, pharyngeal swab for respiratory viruses, QuantiFERON®-TB Gold Plus assay (QFT-P), blood cultures and pre-hospitalization antibiotic prescription were recorded. A total of 482 patients were included, 61% males, median age of 65 years (IQR 52–77), median Charlson comorbidity index of 4 (IQR 2–5). The mortality rate was 12.4%; 366 patients needed oxygen supply. In total, 151 patients (31.3%) received home antibiotics without any association with the outcome. No significant association between mortality and the positivity of viral hepatitis markers was found. Out of 442 patients, 125 had an indeterminate QFT-P, associated with increased mortality. SARS-CoV-2 was the only respiratory virus detected among 389 pharyngeal swabs; 15/428 patients were positive for S. pneumoniae; none for L. pneumophila. In total, 237 blood cultures were drawn within 48 h from hospital admission: 28 were positive and associated with increased mortality. In our cohort, bacterial and viral co-infections in COVID-19 hospitalized patients were rare and not associated with higher mortality.
Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus (HIV) epidemic, people living ...with HIV have represented most cases for more than a decade. With the diffusion of highly active antiretroviral therapy, this group progressively decreased in favor of patients undergoing treatment with targeted therapy/immunomodulators. In this systematic review and meta-analysis, the objective was to assess which drugs are most frequently related to PML development, and report the incidence of drug-induced PML through a meta-analytic approach.
The electronic databases MEDLINE, EMBASE, ClinicalTrials.gov, Web of Science and the Canadian Agency for Drugs and Technologies in Health Database (CADTH) were searched up to May 10, 2022. Articles that reported the risk of PML development after treatment with immunomodulatory drugs, including patients of both sexes under the age of 80 years, affected by any pathology except HIV, primary immunodeficiencies or malignancies, were included in the review. The incidence of drug-induced PML was calculated based on PML cases and total number of patients observed per 100 persons and the observation time. Random-effect metanalyses were conducted for each drug reporting pooled incidence with 95% confidence intervals (CI) and median (interquartile range IQR) of the observation time. Heterogeneity was measured by I
statistics. Publication bias was examined through funnel plots and Egger's test.
A total of 103 studies were included in the systematic review. In our analysis, we found no includible study reporting cases of PML during the course of treatment with ocrelizumab, vedolizumab, abrilumab, ontamalimab, teriflunomide, daclizumab, inebilizumab, basiliximab, tacrolimus, belimumab, infliximab, firategrast, disulone, azathioprine or danazole. Dalfampridine, glatiramer acetate, dimethyl fumarate and fingolimod show a relatively safe profile, although some cases of PML have been reported. The meta-analysis showed an incidence of PML cases among patients undergoing rituximab treatment for multiple sclerosis (MS) of 0.01 cases/100 persons (95% CI - 0.08 to 0.09; I
= 20.4%; p = 0.25) for a median observation period of 23.5 months (IQR 22.1-42.1). Treatment of MS with natalizumab carried a PML risk of 0.33 cases/100 persons (95% CI 0.29-0.37; I
= 50%; p = 0.003) for a median observation period of 44.1 months (IQR 28.4-60) and a mean number of doses of 36.3 (standard deviation SD ± 20.7). When comparing data about patients treated with standard interval dosing (SID) and extended interval dosing (EID), the latter appears to carry a smaller risk of PML, that is, 0.08 cases/100 persons (95% CI 0.0-0.15) for EID versus 0.3 cases/100 persons (95% CI 0.25-0.34) for SID.
A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents.
Anticancer therapies cannot be included in a one-size-fits-all scenario; it is imperative to adapt therapies to the tumor molecular profile and most importantly to develop target-specific ...therapeutics. Nanotherapeutics can combine molecular imaging with molecular therapy in order to provide the maximum benefit to patients in terms of disease prevention, identification, and treatment. Nanotechnology applied to therapy provides numerous advantages in diagnostics and in drug delivery, especially for those malignant cells that are difficult to target or for drugs with poor bioavailability, such as those used for multiple myeloma (MM). This review summarizes the recent advances in the development of nanoparticle-based systems for the treatment of MM, taking into account the methods used for their functionalization, biocompatibility, and anticancer activity.
Solid tumors are a leading cause of cancer-related deaths globally, being characterized by rapid tumor growth and local and distant metastases. The failures encountered in cancer treatment are mainly ...related to the complicated biology of the tumor microenvironment. Nanoparticles-based (NPs) approaches have shown the potential to overcome the limitations caused by the pathophysiological features of solid cancers, enabling the development of multifunctional systems for cancer diagnosis and therapy and allowing effective inhibition of tumor growth. Among the different classes of NPs, 2D graphene-based nanomaterials (GBNs), due to their outstanding chemical and physical properties, easy surface multi-functionalization, near-infrared (NIR) light absorption and tunable biocompatibility, represent ideal nanoplatforms for the development of theranostic tools for the treatment of solid tumors. Here, we reviewed the most recent advances related to the synthesis of nano-systems based on graphene, graphene oxide (GO), reduced graphene oxide (rGO), and graphene quantum dots (GQDs), for the development of theranostic NPs to be used for photoacoustic imaging-guided photothermal–chemotherapy, photothermal (PTT) and photodynamic therapy (PDT), applied to solid tumors destruction. The advantages in using these nano-systems are here discussed for each class of GBNs, taking into consideration the different chemical properties and possibility of multi-functionalization, as well as biodistribution and toxicity aspects that represent a key challenge for their translation into clinical use.
Summary
Background
The World Health Organization estimated that 90% of the infected people need to be diagnosed and 80% need to be treated to reach the aim of hepatitis C virus (HCV) elimination by ...2030. For this reason, all possible strategies to detect and treat HCV‐infected people need to be carefully evaluated to implement the best one.
Aim
To review and synthesise the economic evaluations of HCV screening programs conducted in the era of direct‐acting antiviral agents regimens.
Methods
A systematic literature review was conducted until April 2018 to provide information on the costs and effectiveness of HCV screenings in direct‐acting antiviral agents era. A critical assessment of the quality of economic evaluations retrieved was conducted.
Results
The literature search identified 716 references; 17 of them assessed cost and effectiveness of screening programs and antiviral treatments in different populations: general population (n = 7), drug users (n = 5), high‐risk populations (n = 4) and other populations (n = 3). The HCV screening and direct‐acting antiviral agents treatment appear to be good value for money, both in general and high‐risk populations, if a cost per quality adjusted life years of $50 000 is set as willingness to pay threshold. Some studies showed the value of including lower stage of fibrosis in the treatment selection criteria.
Conclusions
Several HCV screening strategies plus direct‐acting antiviral agents treatments resulted cost‐effectiveness in different populations. However, there is still need of country and population‐specific evaluations within the different HCV screening and treatment strategies available, in order to assess their cost‐effectiveness and sustainability and fully support an evidence‐informed policy for HCV elimination.
To investigate the feasibility, image quality, and clinical implications of a combined ECG-gated and helical acquisition mode in a computed tomography angiography (CTA) protocol in patients scheduled ...for transcatheter aortic valve implantation (TAVI) using a fixed, low-volume, contrast medium injection.
Between July and October 2019, 43 TAVI candidates underwent investigation with CTA using a 64-slice CT scanner. Images obtained were prospectively evaluated. 65 mL of low iodine dose contrast medium (CM), followed by 25 mL of saline, were administered using a fixed multiphasic injection protocol in all patients. Patients were divided into three groups based on BMI: Group 1 (n = 9) with BMI < 22 kg/m2; Group 2 (n = 22) with BMI 22−29 kg/m2; Group 3 (n = 12) with BMI > 29 kg/m2. Images were evaluated for image quality, vessel attenuation (HU), Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and estimated radiation dose. Image quality of the aortic root and iliac-femoral vessels was diagnostic in all patients.
Vascular attenuation was > 200 HU and CNR > 3 at all vessel levels.
Data from our study suggest that it is possible to image the aortic annulus and aorto-iliac anatomy and obtain high image quality in all patients by using a combined ECG-gated and helical acquisition mode in a computed tomography angiography (CTA) protocol with a fixed low-volume contrast medium injection (65 mL). This allows for accurate CT measurements of the aortic annulus, recruitment of patients for TAVI and facilitates pre-procedural planning in these high surgical risk patients.
To explore the feasibility and image quality of ultra-low volume contrast-saline mixture injection with dual-flow injection technique in a computed tomography angiography (CTA) protocol in patients ...scheduled for transcatheter aortic valve implantation (TAVI).
Forty (40) TAVI candidates underwent investigation with CTA using a third-generation dual-source CT scanner between September and November 2020. Different volumes of a monophasic contrast-saline mixture at an 80:20 ratio were administered at an infusion rate of 3 mL/s in 20 patients (group A). The injected volume was based on patient body mass index (BMI): 50 mL if BMI <29 kg/m2 and 63 mL if BMI >29 kg/m2. The other 20 patients (group B)—the control cases—received a total of 65 mL of contrast medium (CM), in multiphasic injections at different flow rates, followed by 10 mL of saline. The images that were obtained were prospectively evaluated for image quality, vessel attenuation (HU), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and estimated radiation dose.
Image quality of the aortic root and ilio-femoral vessels was diagnostic in all patients. Vascular attenuation was >200 HU and CNR >3 at any vessel level.
Data from this study suggest that a monophasic ultra-low volume contrast-saline mixture injection with a dual-flow technique can provide clear visualisation of the aortic root and ilio-femoral vessels in pre-TAVI CTA, which is comparable with a standard multiphasic volume injection protocol.
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