Therapy of parapneumonic empyema in children: a protocol for a scoping review of the literature [version 2; peer review: 2 approved]

Background Empyema (the presence of pus in the pleural space) is a severe complication of community-acquired pneumonia and significant cause of morbidity, but, fortunately, not mortality in children. Between 0.6 and 2% of pneumonias are complicated by empyema and the three main pathogens involved are Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus 1,2,3,4. Optimal management in children, especially the choice of antibiotics, method of administration and duration of therapy, pleural dranage or surgery, are still a matter of debate and currently, lack of strong specific recommendations. This paper displays the study protocol for a scoping review that aims to summarize the available literature on the microbiological epidemiology, the medical and surgical treatment options, and the outcomes of pleural empyema in pediatric population. Methods Comprehensive research combining the terms pediatric (children aged 0 to 18 years) and pleural empyema will be performed on PubMed and SCOPUS to identify all eligible studies. At first, two reviewers will screen the abstract and then their full text to determine the articles that meet the inclusion criteria. This work will be carried out independently, everyone on a different Excel spreadsheet and each researcher will be blinded to the decision of the other researcher. When the process is completed, in case of discordance, any disagreement will be identified and resolved through discussion or with help of a third author. Dissemination The findings of this review will be published in a peer-reviewed journal

Management of Pediatric Urinary Tract Infections: A Delphi Study

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis

OltreMare - Un progetto per il futuro della Biodiversità del Mediterraneo

Osservatorio e comunicazione. Questo progetto narra dello sguardo degli artisti dell’Accademia di Belle Arti di Palermo sul lavoro di ricerca portato avanti dall’IAS - CNR (ex IAMC) riguardo all’osservazione e alla tutela della Biodiversità e costituisce uno strumento eccellente di comunicazione per un pubblico quanto mai ampio. La divulgazione della scienza è un’attività complessa e sicuramente necessita di competenze e attitudini multidisciplinari oltreché di motivazione ed entusiasmo. La comunicazione delle tematiche scientifiche, di per sè ostiche nella traduzione al grande pubblico, grazie alla forza e all’immediatezza tipica dell’espressione artistica diventa prodigioso spunto di riflessione e di osservazione, sia per i giovani che per la comunità intera. Grazie al progetto Osservatorio della Biodiversità Siciliana, sono state realizzate da partners con competenze istituzionali complementari , quali l’Accademia di Belle Arti di Palermo e l’IAS - CNR di Capo Granitola, delle azioni didattiche e creative di valore scientifico espresse con straordinaria forza e bellezza. La sinergia creata, nata da un rapporto consolidato ormai da tempo, ha portato ad uno scambio tra ricercatori e professori che si sono messi in gioco in uno sforzo congiunto per avvicinare le proprie competenze. In seguito ad un’intensa attività di coordinamento e pianificazione dei lavori, si è riusciti a portare avanti un progetto ambizioso e imponente, coinvolgendo moltissimi ambiti scientifici e altrettante cattedre, sensibilizzando così gli artisti ai temi della Biodiversità. Le opere prodotte, accompagnate da schede scientifiche, hanno dunque acquisito un valore, oltreché artistico, didattico, e restano come testimonianze oggettive, nel percorso culturale, per i visitatori dell’Osservatorio. Questa collaborazione conferma l’importanza e l’opportunità di unire arte e scienza per esaltare la percezione della ricerca scientifica da parte della comunità e ,ancora una volta, si conferma come, per fare “cose straordinarie”, siano più importanti i rapporti umani piuttosto che le competenze tecniche. A tal proposito, un ringraziamento sentito al Prof. Calogero Piro che, con passione e dedizione, ha reso possibile questa esperienza, e al gruppo di Comunicazione EDU Lab dell’IAS - CNR, che è stato, per me, un supporto indispensabile per la realizzazione di questo complesso progetto

Multidrug-resistant tuberculosis in children: Are the same therapy options available worldwide?

The spread of drug-resistant tuberculosis (TB) encouraged the development of new medicines and the reappraisal of old drugs rarely used in recent years. Providing access for children with drug-resistant TB to appropriate treatments is a cornerstone of strategies to reduce the burden of TB worldwide. Aim of this perspective was to describe the availability of child-friendly medicines to treat drug-resistant TB at the global level. We showed that the development of child-friendly formulations of second-line drugs should be encouraged to promote adherence to recommended treatment regimens and consequently to increase the success rate and to prevent the development of additional mycobacterial resistances. This is even more crucial, considering the long duration of antitubercular therapies. Importantly, companies and policy makers are called to more efforts in facilitating their prompt availability in every contest because drug-resistant pediatric TB is a worldwide medical problem

Duration of immunity to SARS-CoV-2 in children after natural infection or vaccination in the omicron and pre-omicron era: A systematic review of clinical and immunological studies

Background Duration of humoral and cellular memory in children previously infected SARS-CoV-2 or vaccinated and subsequent risk of reinfection is still not fully elucidated.Methods Systematic review of studies retrieved from medical databases and article reference lists.Results From 2420 identified articles, 24 met the inclusion criteria. Children infected during the pre-omicron era developed long lasting (at least 10-12 months) humoral and cellular immunity against pre-Omicron SARS-CoV-2 variants, but have reduced in vitro cross-reactivity against Omicron. Conversely, although vaccination has a limited efficacy in preventing new infection with pre-Omicron and Omicron variants, in vitro studies suggested that vaccine-induced immunity provides better in vitro cross-neutralization against pre-Omicron and Omicron variants. Preprints published after the period of inclusion of our review suggested that overall risk of infection after Omicron infection is reduced, but children developed weak neutralizing responses in about half cases.Conclusions Available evidence, although limited, suggested a long-lasting but unperfect protection of previous infections or vaccination against pre-Omicron and Omicron variants. Based on our findings, it might be reasonable to offer families of children infected before Omicron a booster vaccination. A similar indication should be proposed also for those infected with Omicron, specifically for more fragile children at higher risk of COVID-19-related complications, based on better cross-variant neutralisation induced by vaccination

Parapneumonic empyema in children: a scoping review of the literature

Abstract Community-acquired pneumonia can lead to a serious complication called empyema, which refers to pus within the pleural space. While it poses a significant threat to morbidity, particularly in children, it is fortunately not associated with high mortality rates. However, determining the best course of management for children, including decisions regarding antibiotic selection, administration methods, and treatment duration, remains a topic of ongoing debate. This scoping review aims to map the existing literature on empyema in children, including types of studies, microbiology, therapies (both antimicrobial and surgical) and patient outcomes. We systematically searched PubMed and SCOPUS using the terms “pediatric” (encompassing children aged 0 to 18 years) and “pleural empyema” to identify all relevant studies published since 2000. This search adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA ScR) checklist. A total of 127 studies was included. Overall, 15 attempted to compare medical treatments (alone or in combination with pleural drainage or fibrinolysis) with more invasive surgical approaches, and six studies compared diverse surgical interventions. However, the diversity of study designs makes it difficult to derive firm conclusions on the optimal approach to pediatric empyema. The heterogeneity in inclusion criteria, pharmacological/surgical approaches and settings limit the ability to draw definitive conclusions. Overall, 78 out of 10,896 children (0.7%) included in the review died, with mortality being higher in Asia and Africa. Our scoping review highlights important gaps regarding several aspects of empyema in children, including specific serotypes of the most common bacteria involved in the etiology, the optimal pharmacological and surgical approach, and the potential benefits of newer antibiotics with optimal lung penetration. New trials, designed on a multi-country level a higher number of patients and more rigorous inclusion criteria and designs, should be urgently funded

Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications

Silence of the Lambs: The Immunological and Molecular Mechanisms of COVID-19 in Children in Comparison with Adults

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19

Antibiotic Prophylaxis for the Prevention of Urinary Tract Infections in Children: Guideline and Recommendations from the Emilia-Romagna Pediatric Urinary Tract Infections (UTI-Ped-ER) Study Group

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency