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The ongoing COVID-19 pandemic has significantly impacted special populations, including immunocompromised individuals, people living with HIV (PLWHIV), pediatric patients, and those with chronic liver disease (CLD). This scoping review aims to map the clinical outcomes of these vulnerable groups when infected with various SARS-CoV-2 variants. The review identifies trends and patterns, noting that early variants, such as Alpha and Delta, are associated with more severe outcomes, including higher hospitalization and mortality rates. In contrast, the Omicron variant, despite its increased transmissibility, tends to cause milder clinical manifestations. The review highlights the necessity for ongoing surveillance and tailored healthcare interventions due to the heterogeneity of patient populations and the evolving nature of the virus. Continuous monitoring and adaptive healthcare strategies are essential to mitigate the impact of COVID-19 on these high-risk groups. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) can be primary or secondary, with significant associated morbidity and mortality. Primary bloodstream infections (BSIs) are defined as infections where no clear infection source is identified, while secondary BSIs originate from a localized infection site. This study aims to compare patterns, outcomes, and medical costs between primary and secondary BSIs and identify associated factors. Conducted at the University Hospital of Patras, Greece, from May 2016 to May 2018, this single-center retrospective cohort study included 201 patients with confirmed BSIs based on positive blood cultures. Data on patient characteristics, clinical outcomes, hospitalization costs, and laboratory parameters were analyzed using appropriate statistical methods. Primary BSIs occurred in 22.89% (46 patients), while secondary BSIs occurred in 77.11% (155 patients). Primary BSI patients were younger and predominantly nosocomial, whereas secondary BSI was mostly community-acquired. Clinical severity scores (SOFA, APACHE II, SAPS, and qPitt) were significantly higher in primary compared to secondary BSI. The median hospital stay was longer for primary BSI (21 vs. 12 days, p < 0.001). Although not statistically significant, mortality rates were higher in primary BSI (43.24% vs. 26.09%). Total care costs were significantly higher for primary BSI (EUR 4388.3 vs. EUR 2530.25, p = 0.016), driven by longer hospital stays and increased antibiotic costs. This study underscores the distinct clinical and economic challenges of primary versus secondary BSI and emphasizes the need for prompt diagnosis and tailored antimicrobial therapy. Further research should focus on developing specific management guidelines for primary BSI and exploring interventions to reduce BSI burden across healthcare settings. [ABSTRACT FROM AUTHOR]

Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19. [ABSTRACT FROM AUTHOR]

Background: Ceftaroline fosamil is approved for the treatment of complicated skin and soft tissue infections (cSSTI) and community-acquired pneumonia (CAP); however, data on its real-world use and effectiveness in Europe and Latin America are currently limited. This retrospective observational study assessed ceftaroline fosamil use and treatment outcomes in adults hospitalized with cSSTI or CAP treated with ceftaroline fosamil in a usual care setting in Europe and Latin America. Results for patients with cSSTI are reported. Methods: Data from patients with cSSTI who received ≥ 4 consecutive intravenous ceftaroline fosamil doses up to May 31, 2019, were collected from sites in Brazil, Colombia, France, Greece, Italy, and Spain. Patient characteristics, clinical management, hospitalization information, microbiological diagnosis, and clinical responses were summarized descriptively. Healthcare resource use variables were evaluated by clinical response to ceftaroline fosamil. Results: Data for 132 patients were included (58.3% male; mean age 58.5 years). Most common lesions were cellulitis/fasciitis (62.1%), abscess (34.1%), and post-surgical wounds (19.7%). Pathogens most frequently identified were methicillin-resistant (18.2%) and methicillin-susceptible Staphylococcus aureus (17.4%). Median (range) ceftaroline fosamil treatment duration was 8 (2– 60) days (daily doses of 1200 [400– 2400] mg); 78 patients (59.1%) received monotherapy. In total, 75 (56.8%) patients had additional antibiotics after ceftaroline fosamil. Clinical response occurred in 118 (89.4%) patients. All-cause 30-day readmission occurred in 13 (9.8%) patients, and all-cause 30-day mortality in 7 (5.3%). Clinical response to ceftaroline was associated with > 25% shorter length of hospital and intensive care stay, and with ~40% lower hospital costs, versus non-responders. Conclusion: Ceftaroline fosamil was effective in treating adults with cSSTI and clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders, in Europe and Latin America. Clinicaltrials.gov Identifier: NCT04198571. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) poses significant health concerns worldwide, particularly among people living with HIV (PLWHIV), due to an increased risk of chronic infection and progression to cirrhosis in individuals with low CD4 cell counts. This study aimed to investigate the prevalence, chronicity potential, and risk factors of HEV infection among PLWHIV in Greece, where data are currently absent. A synchronic multicentric study encompassing five major Greek university hospitals was executed over 24 months, recruiting 696 PLWHIV participants. The prevalence of HEV IgG antibodies was 16.5%, with 8.6% showing evidence of acute HEV infection (HEV IgM). Active viral replication (HEV RNA) was present in 2.3% of the study population. Longitudinal analysis revealed that of the 25 initially anti-HEV IgM-positive individuals, only 3 seroconverted to IgG positivity, and among those with prior HEV RNA positivity (16), none showed evidence of active replication in subsequent tests. Comparative subgroup analysis highlighted the lack of significant differences in HIV-related parameters between HEV seropositive and seronegative individuals. Laboratory evaluations generally showed no significant disparities across most parameters; however, a higher seropositivity for Hepatitis A was observed in the HEV-positive subgroup. Our findings highlight a considerable prevalence of HEV among PLWHIV in Greece, with no observed cases of chronicity. [ABSTRACT FROM AUTHOR]

The Tuning-Medicine Project produced a set of "level one" and "level two" learning outcomes/competences to be met by European medical graduates. In the learner-centered era self-assessment becomes more and more important. Our aim was to develop a self-completion questionnaire ("iCAN!") evaluating graduates' learning outcomes. The Tuning "level two" learning outcomes were transformed to a 104 closed items questionnaire, tested with a convenient sample of 512 graduates from the seven Greek medical schools during the 2009-2011 graduation cohorts, 21 practitioners, and seven different undergraduate student groups. Cronbach alpha, factor analysis, and mean score comparisons were used to check internal consistency, construct validity, and sensitivity respectively. Question mean scores were used to differentiate weak and strength areas of competence. Among graduates, all overall alphas were >0.95 and all subscale alphas higher than expected, indicating an at least acceptable internal consistency. Factor analysis produced one factor per "level one outcome", except for "practical procedures" which was split in two meaningful factors. Overall mean score was 44.4%, 52.2%, 61.2%, 73.4%, 81.4% among 2nd-year, 4th-year, 6th-year students, graduates, and practitioners respectively (p<0.001); improvement through progressively matured groups suggest good sensitivity, indicating also good responsiveness. Among graduates, question mean scores ranged from very weak (blood transfusion, 39%) to very strength (measuring blood pressure, 95%), indicating good differentiation of strengths and weaknesses. A consistent, well-structured, and sensitive version of a questionnaire is hereby released for graduates' abilities and professionalism self-assessment and differentiation of strengths and weaknesses that could be used for informed SWOT policy.

Introduction: Clinical disadvantages of initiating ART at low CD4 counts have been clearly demonstrated but whether any excess risk remains even after reaching relatively high/safe CD4 levels remains unclear. We explore whether individuals starting ART with <500 CD4 cells/μL who increased their CD4 count above this level, have, from this point onwards, similar risk of clinical progression to serious AIDS/non-AIDS events or death with individuals starting ART with ≥500 CD4 cells/μL. Methods: Data were derived from a multicenter cohort (AMACS). Adults, starting PI, NNRTI or INSTI based ART, in or after 2000 were eligible, provided they started ART with ≥500 ("High CD4") or started with CD4 <500 cells/μL but surpassed this threshold while on ART ("Low CD4"). Baseline was the date of ART initiation ("High CD4") or of first reaching 500 CD4 cells/μL ("Low CD4"). Survival analysis, allowing for competing risks, was used to explore the risk of progression to study's endpoints. Results: The study included 694 persons in the "High CD4" and 3,306 in the "Low CD4" group. Median (IQR) follow-up was 66 (36, 106) months. In total, 257 events (40 AIDS related, 217 SNAEs) were observed. Rates of progression did not differ significantly between the two groups but the subgroup of those initiating ART with <200 CD4 cells/μL had significantly higher risk of progression after baseline, compared to those in the "High CD4" group. Conclusions: Individuals starting ART with <200 cells/μL remain on increased risk even after reaching 500 CD4 cells/μL. These patients should be closely followed. [ABSTRACT FROM AUTHOR]

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination's prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory. [ABSTRACT FROM AUTHOR]