Managing low-level HIV viraemia in antiretroviral therapy: a systematic review and meta-analysis

objective: HIV-1 management has advanced significantly with antiretroviral therapy (ART), yet challenges persist, including low-level HIV-1 viraemia (LLV). LLV presents a complex scenario, with varied definitions in the literature, reflecting uncertainties in its clinical interpretation. questions arise regarding the underlying mechanisms of LLV, whether it signifies ongoing viral replication or stems from other factors. this study aimed to systematically review strategies for LLV management, providing insights into optimal clinical approaches. methods: MEDLINE, EMBASE, cochrane library, web of science and canadian agency for drugs and technologies in health were searched for relevant literature on LLV management. We included studies published between 2004 and 2024, assessing interventions such as ART modification, genotypic resistance testing, adherence assessment, performing therapeutic drug monitoring, testing for chronic coinfections and assessing the viral reservoir via HIV DNA quantification. meta-analyses were conducted where feasible. results: the systematic review identified 48 eligible records. findings indicated limited evidence supporting the effectiveness of ART regimen modification in achieving virological suppression among individuals with LLV. however, studies assessing genotypic resistance testing revealed a significant association between resistance-associated mutations and virological suppression during LLV. adherence to ART emerged as a critical determinant of treatment efficacy, with interventions showing promise in achieving viral suppression. the clinical utility of therapeutic drug monitoring in managing LLV remained inconclusive. gaps in the literature were identified regarding follow-up scheduling, managing concurrent chronic infections and assessing inflammatory markers in LLV management. conclusions: While ART modification may not consistently achieve virological suppression, genotypic resistance testing may offer insights into treatment outcomes. adherence to ART emerged as a crucial factor, necessitating tailored interventions. however, further research is needed to elucidate the clinical utility of therapeutic drug monitoring and other management strategies. the study highlights the importance of ongoing research to refine therapeutic approaches and improve patient outcomes in LLV management. prospero registration number: CRD42024511492

Association between adverse childhood experiences and suicidal behavior in schizophrenia spectrum disorders: A systematic review and meta-analysis

Assessing and managing suicide behaviors is highly relevant to individuals with schizophrenia spectrum disorders. Our study aims to assess the association between adverse childhood experiences and suicidal behaviors in individuals with schizophrenia spectrum disorders. We included observational studies comparing the probability of suicide behaviors in adults with schizophrenia spectrum disorders exposed and unexposed to adverse childhood experiences. Odds ratio estimates were obtained by pooling data using a random-effects pairwise meta-analysis. Standardized criteria were used to assess the strength of the association of the pooled estimate. We found 21 eligible studies reporting outcomes for 6257 individuals from 11 countries. The primary outcome revealed an association between any suicidal behavior and adverse childhood experiences, which resulted "highly suggestive" according to validated Umbrella Criteria. Similarly, a positive association was confirmed for suicidal ideation and suicide attempt and for any subtype of adverse childhood experience. This meta-analysis showed that exposure to adverse childhood experiences strongly increases the probability of suicide behaviors in people with schizophrenia spectrum disorders

The Impact of Viral and Bacterial Co-Infections and Home Antibiotic Treatment in SARS-CoV-2 Hospitalized Patients at the Policlinico Tor Vergata Hospital, Rome, Italy

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

Vaccine-Induced Subacute Thyroiditis (De Quervain’s) after mRNA Vaccine against SARS-CoV-2: A Case Report and Systematic Review

De Quervain’s thyroiditis, sometimes referred to as subacute thyroiditis (SAT), is the most common granulomatous disease of the thyroid, typically found after a viral infection in middle-aged women. The mRNA encoding for the angiotensin-converting enzyme-2 (ACE-2) receptor is expressed in follicular thyroid cells, making them a potential target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides infection, SARS-CoV-2 vaccines have also been implicated in SAT pathogenesis. We present a case of a woman developing SAT following vaccination with Comirnaty by Pfizer Inc. (New-York, USA). We performed a systematic review of similar cases available in the literature to provide a better understanding of the topic. We searched the databases PubMed and Embase and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patient records were then sorted according to the type of administered vaccine and a statistical analysis of the extracted data was performed. No statistically significant difference between mRNA vaccines and other vaccines in inducing SAT was found, nor was any found in terms of patient demographics, symptoms at presentation, initial, or follow-up blood tests. In our case report, we described the possible association between SARS-CoV-2 mRNA-based vaccine Comirnaty and SAT

Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis

introduction 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. methodsthe electronic databases MEDLINE, EMBASE, clinical trials.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 I2 statistics. publication bias was examined through funnel plots and Egger's test.ResultsA 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; I2 = 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; I2 = 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. conclusions 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

Brain abscess caused by Actinomyces turicensis in a non-immunocompromised adult patient: a case report and systematic review of the literature

abstract background actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis, therefore delaying the correct identification and treatment. Here we report a case of a 55-year-old immunocompetent adult with brain abscess caused by a. turicensis. a systematic review of a. turicensis infections was performed. methods a systematic review of the literature was performed according to the preferred reporting Items for systematic reviews and meta-analyses (PRISMA) guidelines. the databases MEDLINE, Embase, web of science, CINAHL, clinicaltrials.gov and canadian agency for drugs and technology in health (CADTH) were searched for all relevant literature. results search identified 47 eligible records, for a total of 67 patients. a. turicensis infection was most frequently reported in the anogenital area (n = 21), causing acute bacterial skin and skin structure infections (ABSSSI) including fournier’s gangrene (n = 12), pulmonary infections (n = 8), gynecological infections (n = 6), cervicofacial district infections (n = 5), intrabdominal or breast infections (n = 8), urinary tract infections (n = 3), vertebral column infections (n = 2) central nervous system infections (n = 2), endocarditis (n = 1). Infections were mostly presenting as abscesses (n = 36), with or without concomitant bacteremia (n = 7). fever and local signs of inflammation were present in over 60% of the cases. treatment usually involved surgical drainage followed by antibiotic therapy (n = 51). antimicrobial treatments most frequently included amoxicillin (+clavulanate), ampicillin/sulbactam, metronidazole or cephalosporins. eighty-nine percent of the patients underwent a full recovery. two fatal cases were reported. conclusions to the best of our knowledge, we hereby present the first case of a brain abscess caused by a. turicensis and p. mirabilis. brain involvement by a. turicensis is rare and may result from hematogenous spread or by dissemination of a contiguous infection. the infection might be difficult to diagnose and therefore treatment may be delayed. nevertheless, the pathogen is often readily treatable. diagnosis of actinomycosis is challenging and requires prompt microbiological identification. surgical excision and drainage and antibiotic treatment usually allow for full recovery

Additional file 1 of Brain abscess caused by Actinomyces turicensis in a non-immunocompromised adult patient: a case report and systematic review of the literature

Additional file 1