Statins in Children with Neurofibromatosis Type 1: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Statins, apart from their plasma-cholesterol-lowering ability, exert several pleiotropic effects, making them a potential treatment for other diseases. Animal studies have showed that statins, through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, can affect the Ras/MAPK pathway, thus providing impetus to examine the efficacy of statins in the pediatric population with neurofibromatosis type 1 (NF1). We aimed to systematically address all relevant evidence of statin treatment in children with NF1. METHODS: We searched PubMed and Cochrane Library resources up to 2 June 2023 for randomized controlled trials (RCTs) written in English and evaluating statins versus placebo in children with NF1 (PROSPERO registration number: CRD42023439424). RESULTS: Seven RCTs were suitable to be included in this qualitative synthesis, with a total participation of 336 children with NF1. The duration of the studies ranged from 12 to 52 weeks. The mean age of the pediatric population was 10.9 years old. Three studies investigated the role of simvastatin, while four studies examined lovastatin. According to our analysis, neither simvastatin nor lovastatin improved cognitive function, full-scale intelligence, school performance, attention problems, or internalizing behavioral problems when compared with placebo in children with NF1. Statins were well tolerated in all included RCTs. CONCLUSION: Although safe, current evidence demonstrates that statins exert no beneficial effect in cognitive function and behavioral problems in children with NF1.

Lomentospora prolificans Disseminated Infections: A Systematic Review of Reported Cases.

BACKGROUND: Lomentospora prolificans, a rare, highly virulent filamentous fungus with high rates of intrinsic resistance to antifungals, has been associated with different types of infections in immunocompromised as well as immunocompetent individuals. OBJECTIVE: To systematically address all relevant evidence regarding L. prolificans disseminated infections in the literature. METHODS: We searched Medline via PubMed and Scopus databases through July 2022. We performed a qualitative synthesis of published articles reporting disseminated infections from L. prolificans in humans. RESULTS: A total of 87 studies describing 142 cases were included in our systematic review. The pathogen was most frequently reported in disseminated infections in Spain (n = 47), Australia (n = 33), the USA (n = 21), and Germany (n = 10). Among 142 reported cases, 48.5% were males. Underlying conditions identified for the majority of patients included malignancy (72.5%), hemopoietic stem cell transplantation (23.2%), solid organ transplantation (16%), and AIDS (2%). Lungs, central nervous system, skin, eyes, heart and bones/joints were the most commonly affected organs. Neutropenia was recorded in 52% of patients. The mortality rate was as high as 87.3%. CONCLUSIONS: To the best of our knowledge, this is the first systematic review conducted on disseminated infections due to this rare microorganism. Physicians should be aware that L. prolificans can cause a diversity of infections with high mortality and primarily affects immunocompromised and neutropenic patients.

Acute acalculous cholecystitis due to infectious causes.

Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder not associated with the presence of gallstones. It usually occurs in critically ill patients but it has also been implicated as a cause of cholecystitis in previously healthy individuals. In this subgroup of patients, infectious causes comprise the primary etiology. We, herein, discuss the pathophysiological mechanisms involved in AAC, focusing on the infectious causes. AAC associated with critical medical conditions is caused by bile stasis and gallbladder ischemia. Several mechanisms are reported to be involved in AAC in patients without underlying critical illness including direct invasion of the gallbladder epithelial cells, gallbladder vasculitis, obstruction of the biliary tree, and sequestration. We emphasize that multiple pathogenic mechanisms may concurrently contribute to the development of AAC in varying degrees. Awareness of the implicated pathogens is essential since it will allow a more focused examination of the histopathological specimens. In conclusion, additional research and a high degree of clinical suspicion are needed to clarify the complex spectrum of mechanisms that are involved in the pathogenesis of AAC.

Fever of unknown origin caused by infectious diseases in the era of migrant and refugee crisis.

Concern exists in Europe about the possibility of importation of infectious diseases due to the recent influx of migrants and refugees after 2011. In this retrospective 6-year study, we examined the epidemiology of fever of unknown origin (FUO) in Greece over the past years. Forty-eight patients with classical FUO were included. The proportion of infectious causes of FUO (29.2%) was similar to previous studies in Greece and all infections were endemic to the area. Disease-related mortality was 12.5% and no deaths due to infection were recorded. In conclusion, none of the diagnosed infectious causes of FUO raised concerns about the possibility of imported diseases or pathogens. These results re-inforce the perception that migrants and refugees are not carriers of communicable diseases that can cause public health problems to European countries.

Assessing the knowledge, attitudes and perceptions of junior doctors on antimicrobial use and antimicrobial resistance in Greece.

OBJECTIVES: Understanding antimicrobial prescribing attitudes and perceptions, especially in the early stages of medical training, is an important driver for appropriate interventions. This study examined junior doctors' knowledge, attitudes and perceptions regarding antimicrobial use and antimicrobial resistance in Greece. METHODS: A self-administered, internet-based questionnaire survey was completed by trainees and residents of all primary care centres and hospitals in Crete, Greece. RESULTS: From the 313 invited junior doctors, 214 (68.4%) fully completed the questionnaire. The mean correct knowledge score (four items) was 60%. The highest confidence rates with prescribing were recorded in accurately diagnosing an infection that needs antimicrobial treatment, selecting an appropriate administration route, and selecting the appropriate dosage. The lowest confidence rates were recorded in modifying antimicrobial treatment based on clinical and/or microbiological evidence, prescribing antimicrobial combinations and not prescribing an antimicrobial in a febrile patient without severity criteria and uncertain diagnosis of infection. Use of guidelines and expert consultation were perceived as the most important factors influencing antimicrobial prescribing practices. Most participants were aware of the antimicrobial resistance problem in Greece, and considered excessive prescribing of antimicrobials and broad-spectrum antimicrobials to be the most important causes. Availability of local and national guidelines and antimicrobial resistance data, senior consultation and infectious diseases specialist consultation were the preferred interventions to improve antimicrobial prescribing. CONCLUSIONS: The findings of this study will contribute to the design of appropriate interventions, based on local evidence, for the establishment of antimicrobial stewardship programs in a country characterised by excessive use of antimicrobials and high resistance rates.

Non-typhoidal Salmonella myocarditis in an immunocompetent young adult with diarrhea.

Myocarditis is the inflammation of the heart muscle and it is caused by a wide range of infectious and non-infectious conditions. Non-typhoidal Salmonella infection, a common foodborne illness worldwide, only rarely causes myocarditis. We describe a case of an immunocompetent adult with Salmonella enterica serovar Typhimurium myocarditis who had a favorable outcome due to early recognition of the causative factor and prompt initiation of appropriate treatment.