Search

Biofilms, aggregates of bacteria enclosed in a self-produced matrix, have been implicated in various pediatric respiratory infections, including acute otitis media (AOM), otitis media with effusion (OME), adenoiditis, protracted bacterial bronchitis, and pulmonary exacerbations in cystic fibrosis. These infections are prevalent in children and often associated with biofilm-producing pathogens, leading to recurrent and chronic conditions. Biofilms reduce antibiotic efficacy, contributing to treatment failure and disease persistence. This narrative review discusses biofilm production by respiratory pathogens such as Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus. It examines their mechanisms of biofilm formation, antibiotic resistance, and the challenges they present in clinical treatment. Various antibiofilm strategies have shown promise in vitro and in animal studies, including the use of N-acetylcysteine, enzymes like dispersin B, and agents disrupting quorum sensing and biofilm matrix components. However, their clinical application, particularly in children, remains limited. Traditional treatments for biofilm-associated diseases have not significantly evolved, even with biofilm detection. The transition from experimental findings to clinical practice is complex and requires robust clinical trials and standardized biofilm detection protocols. Addressing biofilms in pediatric respiratory infections is crucial for improving treatment outcomes and managing recurrent and chronic diseases effectively. [ABSTRACT FROM AUTHOR]

Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) is a relatively uncommon autoantibody demyelinating disorder of the central nervous system (CNS) with heterogeneous clinical manifestations and magnetic resonance imaging (MRI) findings. In recent years, a rare MOGAD subtype characterized by distinct clinical and MRI findings has been described. Seizures and cortical hyperintensities best seen on MRI T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences, associated with headache and cerebral spine fluid (CSF) pleocytosis, are the most important characteristics of this MOGAD entity that is named FLAMES (FLAIR hyperintense cortical lesions in MOG-associated encephalitis with seizures). Because of its rarity and the peculiarities of the brain damage and clinical manifestations, it can be under-recognized and confused with focal viral encephalitis, meningitis, subarachnoid hemorrhage, CNS vasculitis, or mitochondrial cytopathy. We described the case of a 4-year-old previously healthy girl who was admitted for focal-onset, tonic-clonic seizures, fever, and headache, combined with optic neuritis. MRI was characterized by FLAIR imaging showing hyperintense cortical lesions, and a mild leukocytosis in the CSF was detected. Efficacy and rapid response to steroid therapy was observed, and no recurrences of neurological problems or further seizures were reported in the following 12 months. This case report can help in understanding FLAMES characteristics in pediatrics in order to favor early diagnosis and prompt therapy. [ABSTRACT FROM AUTHOR]

In recent years, the use of smartphones and other wireless technology in medical care has developed rapidly. However, in some cases, especially for pediatric medical problems, the reliability of information accessed by mobile health technology remains debatable. The main aim of this paper is to evaluate the relevance of smartphone applications in the detection and diagnosis of pediatric medical conditions for which the greatest number of applications have been developed. This is the case of smartphone applications developed for the diagnosis of acute otitis media, otitis media with effusion, hearing impairment, obesity, amblyopia, and vision screening. In some cases, the information given by these applications has significantly improved the diagnostic ability of physicians. However, distinguishing between applications that can be effective and those that may lead to mistakes can be very difficult. This highlights the importance of a careful application selection before including smartphone-based artificial intelligence in everyday clinical practice. [ABSTRACT FROM AUTHOR]

With the introduction of the influenza vaccine in the official immunization schedule of most countries, several data regarding the efficacy, tolerability, and safety of influenza immunization were collected worldwide. Interestingly, together with the confirmation that influenza vaccines are effective in reducing the incidence of influenza virus infection and the incidence and severity of influenza disease, epidemiological data have indicated that influenza immunization could be useful for controlling antimicrobial resistance (AMR) development. Knowledge of the reliability of these findings seems essential for precise quantification of the clinical relevance of influenza immunization. If definitively confirmed, these findings can have a relevant impact on influenza vaccine development and use. Moreover, they can be used to convince even the most recalcitrant health authorities of the need to extend influenza immunization to the entire population. In this narrative review, present knowledge regarding these particular aspects of influenza immunization is discussed. Literature analysis showed that the specific effects of influenza immunization are great enough per se to recommend systematic annual immunization of younger children, old people, and all individuals with severe chronic underlying diseases. Moreover, influenza immunization can significantly contribute to limiting the emergence of antimicrobial resistance. The problem of the possible nonspecific effects of influenza vaccines remains unsolved. The definition of their role as inducers of trained immunity seems essential not only to evaluate how much they play a role in the prevention of infectious diseases but also to evaluate whether they can be used to prevent and treat clinical conditions in which chronic inflammation and autoimmunity play a fundamental pathogenetic role. [ABSTRACT FROM AUTHOR]

Antibiotic-related adverse events are common in both adults and children, and knowledge of the factors that favor the development of antibiotic-related adverse events is essential to limit their occurrence and severity. Genetics can condition the development of antibiotic-related adverse events, and the screening of patients with supposed or demonstrated specific genetic mutations may reduce drug-related adverse events. This narrative review discusses which genetic variations may influence the risk of antibiotic-related adverse events and which conclusions can be applied to clinical practice. An analysis of the literature showed that defined associations between genetic variations and specific adverse events are very few and that, at the moment, none of them have led to the implementation of a systematic screening process for patients that must be treated with a given antibiotic in order to select those at risk of specific adverse events. On the other hand, in most of the cases, more than one variation is implicated in the determination of adverse events, and this can be a limitation in planning a systematic screening. Moreover, presently, the methods used to establish whether a patient carries a "dangerous" genetic mutation require too much time and waiting for the result of the test can be deleterious for those patients urgently requiring therapy. Further studies are needed to definitively confirm which genetic variations are responsible for an increased risk of a well-defined adverse event. [ABSTRACT FROM AUTHOR]

Among emergent climate-sensitive infectious diseases, some mosquito-vectored arbovirus infections have epidemiological, social, and economic effects. Dengue virus (DENV), West Nile virus (WNV), and Chikungunya virus (CHIKV) disease, previously common only in the tropics, currently pose a major risk to global health and are expected to expand dramatically in the near future if adequate containment measures are not implemented. The lack of safe and effective vaccines is critical as it seems likely that emerging mosquito-vectored arbovirus infections will be con-trolled only when effective and safe vaccines against each of these infections become available. This paper discusses the clinical characteristics of DENV, WNV, and CHIKV infections and the state of development of vaccines against these viruses. An ideal vaccine should be able to evoke with a single administration a prompt activation of B and T cells, adequate concentrations of protecting/neutralizing antibodies, and the creation of a strong immune memory capable of triggering an effective secondary antibody response after new infection with a wild-type and/or mutated infectious agent. Moreover, the vaccine should be well tolerated, safe, easily administrated, cost-effective, and widely available throughout the world. However, the development of vaccines against emerging mosquito-vectored arbovirus diseases is far from being satisfactory, and it seems likely that it will take many years before effective and safe vaccines for all these infections are made available worldwide. [ABSTRACT FROM AUTHOR]

Polymorphisms of genes encoding drug metabolizing enzymes and transporters can significantly modify pharmacokinetics, and this can be associated with significant differences in drug efficacy, safety, and tolerability. Moreover, genetic variants of some components of the immune system can explain clinically relevant drug-related adverse events. However, the implementation of drug dose individualization based on pharmacogenomics remains scarce. In this narrative review, the impact of genetic variations on the disposition, safety, and tolerability of the most commonly prescribed drugs is reported. Moreover, reasons for poor implementation of pharmacogenomics in everyday clinical settings are discussed. The literature analysis showed that knowledge of how genetic variations can modify the effectiveness, safety, and tolerability of a drug can lead to the adjustment of usually recommended drug dosages, improve effectiveness, and reduce drug-related adverse events. Despite some efforts to introduce pharmacogenomics in clinical practice, presently very few centers routinely use genetic tests as a guide for drug prescription. The education of health care professionals seems critical to keep pace with the rapidly evolving field of pharmacogenomics. Moreover, multimodal algorithms that incorporate both clinical and genetic factors in drug prescribing could significantly help in this regard. Obviously, further studies which definitively establish which genetic variations play a role in conditioning drug effectiveness and safety are needed. Many problems must be solved, but the advantages for human health fully justify all the efforts. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has entailed consequences on any type of physical activities, mainly due to the social restriction measures applied to reduce the spreading of SARS-CoV-2. When public health policies progressively reduced limitations and resuming a normal life was possible, the return to previous physical activity and sports was not only requested by people who had deeply suffered from limitations, but was also recommended by experts as a means of reducing the physical and psychological consequences induced by the pandemic. The aim of this narrative review is to summarize the available evidence on the return to play in children after SARS-CoV-2 infection, suggesting an algorithm for clinical practice and highlighting priorities for future studies. Criteria to identify subjects requiring laboratory and radiological tests before returning to physical activity are severity of COVID-19 and existence of underlying disease. Children of any age with asymptomatic infection or mild disease severity, i.e., the great majority of children with previous COVID-19, do not need a cardiologic test before resumption of previous physical activity. Only a visit or a telephonic contact with the primary care pediatricians should be established. On the contrary, children with moderate COVID-19 should not exercise until they are cleared by a physician and evaluated for resting electrocardiogram, exercise testing, and echocardiogram. Finally, in those with severe COVID-19, return to play should be delayed for several months, should be gradual and should be performed only after a cardiologist's clearance. Further studies are needed to assess the risks of returning to sports activity in pediatric age, including careful age-adjusted risk stratification, in order to improve the cost–benefit ratio of specific screenings. [ABSTRACT FROM AUTHOR]

Neonatal sepsis is a bacterial bloodstream infection leading to severe clinical manifestations frequently associated with death or irreversible long-term deficits. Antibiotics are the drug of choice to treat sepsis, regardless of age. In neonates, the lack of reliable criteria for a definite diagnosis and the supposition that an early antibiotic administration could reduce sepsis development in children at risk have led to a relevant antibiotic overuse for both prevention and therapy. The availability of biomarkers of neonatal sepsis that could alert the physician to an early diagnosis of neonatal sepsis could improve the short and long-term outcomes of true sepsis cases and reduce the indiscriminate and deleterious use of preventive antibiotics. The main aim of this narrative review is to summarize the main results in this regard and to detail the accuracy of currently used biomarkers for the early diagnosis of neonatal sepsis. Literature analysis showed that, despite intense research, the diagnosis of neonatal sepsis and the conduct of antibiotic therapy cannot be at present decided on the basis of a single biomarker. Given the importance of the problem and the need to reduce the abuse of antibiotics, further studies are urgently required. However, instead of looking for new biomarkers, it seems easier and more productive to test combinations of two or more of the presently available biomarkers. Moreover, studies based on omics technologies should be strongly boosted. However, while waiting for new information, the use of the clinical scores prepared by some scientific institutions could be suggested. Based on maternal risk factors and infant clinical indicators, sepsis risk can be calculated, and a significant reduction in antibiotic consumption can be obtained. [ABSTRACT FROM AUTHOR]

Pain is a biopsychosocial experience characterized by sensory, physiological, cognitive, affective, and behavioral components. Both acute and chronic pain can have short and long-term negative effects. Unfortunately, pain treatment is often inadequate. Guidelines and recommendations for a rational approach to pediatric pain frequently differ, and this may be one of the most important reasons for the poor attention frequently paid to pain treatment in children. This narrative review discusses the present knowledge in this regard. A literature review conducted on papers produced over the last 8 years showed that although in recent years, compared to the past, much progress has been made in the treatment of pain in the context of the pediatric emergency room, there is still a lot to do. There is a need to create guidelines that outline standardized and easy-to-follow pathways for pain recognition and management, which are also flexible enough to take into account differences in different contexts both in terms of drug availability and education of staff as well as of the different complexities of patients. It is essential to guarantee an approach to pain that is as uniform as possible among the pediatric population that limits, as much as possible, the inequalities related to ethnicity and language barriers. [ABSTRACT FROM AUTHOR]

To face the COVID-19 outbreak, a wide range of non-pharmaceutical interventions (NPIs) aimed at limiting the spread of the virus in communities, such as mask-wearing, hand hygiene, social distancing, travel restrictions, and school closures, were introduced in most countries. Thereafter, a significant reduction of new asymptomatic and symptomatic COVID-19 cases occurred, although there were differences between countries according to the type and duration of the NPIs. In addition, the COVID-19 pandemic has been accompanied by significant variations in the global incidence of diseases due to the most common non-SARS-CoV-2 respiratory viruses and some bacteria. In this narrative review, the epidemiology of the most common non-SARS-CoV-2 respiratory infections during the COVID-19 pandemic is detailed. Moreover, factors that could have had a role in modifying the traditional circulation of respiratory pathogens are discussed. A literature analysis shows that NPIs were the most important cause of the general reduction in the incidence of influenza and respiratory syncytial virus infection in the first year of the pandemic, although the different sensitivity of each virus to NPIs, the type and duration of measures used, as well as the interference among viruses may have played a role in modulating viral circulation. Reasons for the increase in the incidences of Streptococcus pneumoniae and group A Streptococcus infections seem strictly linked to immunity debt and the role played by NPIs in reducing viral infections and limiting bacterial superimposed infections. These results highlight the importance of NPIs during pandemics, the need to monitor the circulation of infectious agents that cause diseases similar to those caused by pandemic agents, and the need to make efforts to improve coverage with available vaccines. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is an extremely virulent pathogen that is capable of quickly evolving and developing antibiotic resistance. To overcome this problem, new antibiotics have been developed. Some of these have been licenced for use in clinical practice, mainly for the treatment of adults with acute skin and soft tissue infections, in addition to both community-acquired pneumonia (CAP) and nosocomial pneumonia (hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia). In this paper, the main characteristics and clinical use of new licenced anti-staphylococcal drugs have been discussed. In vitro studies have demonstrated that some new anti-staphylococcal antibiotics have better antimicrobial activity and, at least in certain cases, more favourable pharmacokinetic properties and higher safety and tolerability than the presently available anti-staphylococcal drugs. This suggests that they may have a potential use in reducing the risk of failure of S. aureus therapy. However, an in-depth analysis of microbiological and clinical studies carried out with these new drugs seems to indicate that further studies need to be conducted before the problem of resistance of S. aureus to the antibiotics available today can be completely solved. Considering the overall available research, the drugs that are active against S. aureus appear to present a great therapeutic opportunity for overcoming resistance to traditional therapy. There are advantages in the pharmacokinetic characteristics of some of these drugs and they have the potential to reduce hospital stays and economic costs associated with their use. [ABSTRACT FROM AUTHOR]

Although vaccines are the safest and the most effective measure to prevent disease, disability, and death from various pediatric infectious diseases, parental vaccine hesitancy is a common and increasing phenomenon worldwide. To contribute to improving our knowledge on parental willingness and hesitancy toward COVID-19 vaccine administration in children aged 5–11 years, an anonymous online questionnaire was disseminated in Italy after the COVID-19 vaccine's authorization for this age group. An online survey was conducted using the Crowd Signal platform from 15 December 2021 to 15 January 2022 in Italy among parents of children 5–11 years old. A total of 3433 questionnaires were analyzed. Overall, a "Favorable" position was observed in 1459 (42.5%) parents, a "Doubtful" one in 1223 (35.6%) and a "Hesitant/Reluctant" one in 751 (21.9%). The univariate multinomial logistic regression analysis and the multivariate multinomial logistic regression analysis showed that the Hesitant/Reluctant parents were younger than 40 years of age, mostly female, with a secondary or middle school degree, an annual income below EUR 28,000, more than one child in the age range from 5 to 11 years, an underestimated consideration of the severity of COVID-19's effects, and concern regarding the COVID-19 vaccines in general. These results show that in Italy, most parents of children aged 5 to 11 were doubtful or hesitant/reluctant to vaccinate their children against the COVID-19 virus. Poor trust in health institutions as well as poor consideration of the epidemiological and clinical relevance of COVID-19 in children seem to have played the biggest roles in forming these attitudes. Moreover, the negative attitude of several parents who previously agreed to immunize their children against other childhood illnesses according to the official national pediatric immunization schedule clearly indicates that only the COVID-19 vaccine was put in doubt or rejected. All these findings lead us to conclude that to improve COVID-19 vaccination coverage in children aged 5 to 11, health authorities should increase parental education on the true clinical relevance of COVID-19 and on the importance of its prevention to hinder the evolution of the pandemic in pediatric subjects and the emergence of new variants, and its relative weight in influencing the efficacy of vaccines. [ABSTRACT FROM AUTHOR]

Tuberculosis remains (TB) to be one of the most common causes of child morbidity and mortality. Abdominal TB is not frequently diagnosed and, although its incidence is not definitively established, there are data that seem to indicate that it accounts for approximately 1–3% of all pediatric TB cases and for no more than 10% of those with extrapulmonary manifestations. It seems, however, that abdominal TB is significantly more common than usually thought as signs and symptoms are non-specific and may mimic other diseases. The delayed or wrong diagnosis of pediatric abdominal TB can have dramatic consequences as they can lead to untreated TB with miliary dissemination, unnecessary surgery, or dangerous drug therapies. This report describes five cases of abdominal TB diagnosed among 216 pediatric patients admitted for TB in Italy from 2011 to 2021. Our cases evidence that abdominal TB is a complex and potentially very severe disease that, when not appropriately diagnosed, may be associated with severe complications and prolonged anti-TB therapy. Discussion among specialists is crucial to achieve an early diagnosis and to promptly start the anti-TB treatment. Further studies are needed to clarify the appropriate duration of therapy as well as management of MDR abdominal TB cases. [ABSTRACT FROM AUTHOR]

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19. [ABSTRACT FROM AUTHOR]

Vitamin D (VD) is a pro-hormone that has long been known as a key regulator of calcium homeostasis and bone health in both children and adults. In recent years, studies have shown that VD may exert many extra-skeletal functions, mainly through a relevant modulation of the innate and adaptive immune system. This has suggested that VD could play a fundamental role in conditioning development, clinical course, and treatment of several autoimmune disorders, including celiac disease (CD) and inflammatory bowel diseases (IBDs). The main aim of this review is to evaluate the relationships between VD, CD, and IBDs. Literature analysis showed a potential impact of VD on CD and IBDs can be reasonably assumed based on the well-documented in vitro and in vivo VD activities on the gastrointestinal tract and the immune system. The evidence that VD can preserve intestinal mucosa from chemical and immunological damage and that VD modulation of the immune system functions can contrast the mechanisms that lead to the intestinal modifications characteristic of gastrointestinal autoimmune diseases has suggested that VD could play a role in controlling both the development and the course of CD and IBDs. Administration of VD in already diagnosed CD and IBD cases has not always significantly modified disease course. However, despite these relevant problems, most of the experts recommend monitoring of VD levels in patients with CD and IBDs and administration of supplements in patients with hypovitaminosis. [ABSTRACT FROM AUTHOR]

In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary. [ABSTRACT FROM AUTHOR]

Sudden infant death syndrome (SIDS) is defined as the sudden death of an infant younger than one year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. About 90% of SIDS occur before six months of age, the peak incidence is between two and four months, and the median age for death is elven weeks. The clinical, social, and economic relevance of SIDS, together with the evidence that prevention of this syndrome was possible, has significantly stimulated research into risk factors for the development of SIDS in the hope of being able to introduce new effective preventive measures. This narrative review discusses the potential relationships between apparent life-threatening events (ALTE) or brief resolved unexplained events (BRUE) and SIDS development, and when a home cardiorespiratory monitor is useful for prevention of these conditions. A literature analysis showed that home cardiorespiratory monitoring has been considered a potential method to identify not only ALTE and BRUE but SIDS also. ALTE and BRUE are generally due to underlying conditions that are not detectable in SIDS infants. A true relationship between these conditions has never been demonstrated. Use of home cardiorespiratory monitor is not recommended for SIDS, whereas it could be suggested for children with previous ALTE or severe BRUE or who are at risk of the development of these conditions. However, use of home cardiorespiratory monitors assumes that family members know the advantages and limitations of these devices after adequate education and instruction in their use. [ABSTRACT FROM AUTHOR]

Ocular surgery encompasses a wide range of procedures, including surgery of the tear ducts, eyelid, cornea and conjunctiva, lens, ocular muscle, and vitreoretinal and iris surgery. Operations are also performed for the removal of tumors, repairs of ocular trauma and, finally, corneal transplantation. Antibiotic prophylaxis for the prevention of surgical site infections (SSIs) in ocular surgery is a complex field in which shared lines of action are absent. In light of the scarcity of shared evidence in the use of ocular antimicrobial prophylaxis for the pediatric population, this consensus document aims to provide clinicians with a series of recommendations on antimicrobial prophylaxis for patients of neonatal and pediatric age undergoing eye surgery. The following scenarios are considered: (1) intraocular surgery; (2) extraocular surgery; (3) ocular trauma; (4) ocular neoplasm; (5) ocular surface transplantations; (6) corneal grafts. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding clinical actions in the peri-operative environment in eye surgery. The application of uniform and shared protocols aims to improve surgical practice, through the standardization of procedures, with a consequent reduction of SSIs, also limiting the phenomenon of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Deep neck infections (DNIs) include all the infections sited in the potential spaces and fascial planes of the neck within the limits of the deep layer of the cervical fascia. Parapharyngeal and retropharyngeal infections leading to parapharyngeal abscess (PPA) and retropharyngeal abscess (RPA) are the most common. DNIs remain an important health problem, especially in children. The aim of this narrative review is to describe the management of peritonsillar, retropharyngeal and parapharyngeal abscesses in pediatric age. Despite relatively uncommon, pediatric DNIs deserve particular attention as they can have a very severe course and lead to hospitalization, admission to the intensive care unit and, although very rarely, death. They generally follow a mild upper respiratory infection and can initially present with signs and symptoms that could be underestimated. A definite diagnosis can be made using imaging techniques. Pus collection from the site of infection, when possible, is strongly recommended for definition of diseases etiology. Blood tests that measure the inflammatory response of the patient may contribute to monitor disease evolution. The therapeutic approach should be targeted toward the individual patient. Regardless of the surgical treatment, antibiotics are critical for pediatric DNI prognosis. The diagnostic-therapeutic procedure to be followed in the individual patient is not universally shared because it has not been established which is the most valid radiological approach and which are the criteria to be followed for the differentiation of cases to be treated only with antibiotics and those in which surgery is mandatory. Further studies are needed to ensure the best possible care for all children with DNIs, especially in this era of increased antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Bronchiolitis (BR), a lower respiratory tract infection mainly caused by respiratory syncytial virus (RSV), can be very severe. Presently, adequate nutritional support and oxygen therapy remain the only interventions recommended to treat patients with BR. For years, mild BR cases were treated with noninvasive standard oxygen therapy (SOT), i.e., with cold and poorly or totally nonhumidified oxygen delivered by an ambient headbox or low-flow nasal cannula. Children with severe disease were intubated and treated with invasive mechanical ventilation (IMV). To improve SOT and overcome the disadvantages of IMV, new measures of noninvasive and more efficient oxygen administration have been studied. Bi-level positive air way pressure (BiPAP), continuous positive airway pressure (CPAP), and high-flow nasal cannula (HFNC) are among them. For its simplicity, good tolerability and safety, and the good results reported in clinical studies, HFNC has become increasingly popular and is now widely used. However, consistent guidelines for initiation and discontinuation of HFNC are lacking. In this narrative review, the role of HFNC to treat infants with BR is discussed. An analysis of the literature showed that, despite its widespread use, the role of HFNC in preventing respiratory failure in children with BR is not precisely defined. It is not established whether it can offer greater benefits compared to SOT and when and in which infants it can replace CPAP or BiPAP. The analysis of the results clearly indicates the need for multicenter studies and official guidelines. In the meantime, HFNC can be considered a safe and effective method to treat children with mild to moderate BR who do not respond to SOT. [ABSTRACT FROM AUTHOR]

For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen. [ABSTRACT FROM AUTHOR]

Malformations of the cerebral cortex are an important cause of developmental disabilities and epilepsy. Neurological disorders caused by abnormal neuronal migration have been observed to occur with mutations in tubulin genes. The α- and β-tubulin genes encode cytoskeletal proteins, which play a role in the developing brain. TUBA1A mutations are associated with a wide spectrum of neurological problems, which are characterized by peculiar clinical details and neuroradiologic patterns. This manuscript describes the case of a nine-year-old girl with microcephaly, mild facial dysmorphisms, epileptic seizures, and severe developmental delay, with a de novo heterozygous c.320A>G [p.(His 107 Arg)] mutation in TUBA1A gene, and the clinical aspects and neuroimaging features of "lissencephaly syndrome" are summarized. This case shows that TUBA1A mutations lead to a variety of brain malformations ranging from lissencephaly with perisylvian pachygyria to diffuse posteriorly predominant pachygyria, combined with internal capsule dysgenesis, cerebellar dysplasia, and callosal hypotrophy. This peculiar neuroradiological pattern, in combination with the usually severe clinical presentation, suggests the need for future molecular studies to address the mechanisms of TUBA1A mutation-induced neuropathology. [ABSTRACT FROM AUTHOR]

Eating problems in adolescents with type 1 diabetes (T1D) can be divided into two groups. The first includes the diagnosed eating disorders (EDs), i.e., diseases specifically identified by defined signs and symptoms for which a degree of severity has been established, such as anorexia nervosa, bulimia nervosa, binge-eating disorder, pica, and rumination. The second is the group of disordered eating symptoms (DES), which include behaviors such as dieting for weight loss, binge eating, self-induced vomiting, excessive exercise, and laxative or diuretic use; these behaviors cannot be categorized as complete diseases, and, although apparently mild, they must be closely evaluated because they can evolve into true EDs. In this review, present knowledge about the clinical relevance of EDs and DES and the possible preventive and therapeutic measures used to reduce their impact on the course of T1D will be discussed. As adolescents with diabetes are at higher risk of eating disturbances and consequently for higher rates of disease complications, care providers should pay attention to clinical warning signs that raise suspicion of disturbed eating to refer these patients early to an expert in nutrition and mental health disorders. To ensure the best care for adolescents with T1D, diabetes teams should be multidisciplinary and include a pediatric diabetologist, a skilled nurse, a dietician, and a psychologist. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon- protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) places a considerable burden on society. A substantial number of pediatric and adult CAP cases are due to Streptococcus pneumoniae, but fortunately there are effective vaccines available that have a significant impact on CAP-related medical, social, and economic problems. The main aim of this paper is to evaluate the published evidence concerning the impact of pneumococcal vaccines on the prevention of CAP in children and adults. Available data indicate that pneumococcal conjugate vaccines (PCVs) are effective in children, reducing all-cause CAP cases and bacteremic and nonbacteremic CAP cases. Moreover, at least for PCV7 and PCV13, vaccination of children is effective in reducing the incidence of CAP among adults. Recently use of PCV13 in adults alone or in combination with the pneumococcal polysaccharide vaccine has been suggested and further studies can better define its effectiveness in this group of subjects. The only relevant problem for PCV13 is the risk of a second replacement phenomenon, which might significantly reduce its real efficacy in clinical practice. Protein-based pneumococcal vaccines might be a possible solution to this problem. [ABSTRACT FROM AUTHOR]

In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease. [ABSTRACT FROM AUTHOR]

In children, infectious discitis (D) and infectious spondylodiscitis (SD) are rare diseases that can cause significant clinical problems, including spinal deformities and segmental instabilities. Moreover, when the infection spreads into the spinal channel, D and SD can cause devastating neurologic complications. Early diagnosis and treatment may reduce these risks. The main aim of this paper is to discuss recent concepts regarding the epidemiology, microbiology, clinical presentation, diagnosis, and treatment of pediatric D and SD. It is highlighted that particular attention must be paid to the identification of the causative infectious agent and its sensitivity to antibiotics, remembering that traditional culture frequently leads to negative results and modern molecular methods can significantly increase the detection rate. Several different bacterial pathogens can cause D and SD, and, in some cases, particularly those due to Staphylococcus aureus, Kingella kingae, Mycobacterium tuberculosis, Brucella spp., the appropriate choice of drug is critical to achieve cure. [ABSTRACT FROM AUTHOR]

In order to compare the last version of the Respiratory Virus Panel (RVP) Fast assay for human Adenovirus (hAdv) detection with a specific real-time polymerase chain reaction (qPCR), which is considered the gold standard for hAdv detection, nasopharyngeal samples collected from 309 children (age range, four months to eight years) with respiratory tract infection were tested using the RVP Fast v2 assay (Luminex Molecular Diagnostics, Inc., Toronto, ON, Canada) and a specific TaqMan qPCR to identify hAdv DNA. The RVP Fast v2 assay detected 30/61 (49.2%) hAdv infections that had been identified by real-time qPCR, demonstrating a significantly lower detection rate (p < 0.001). The sensitivity of the RVP Fast v2 assay in comparison to qPCR was lower in younger children (42.9% vs. 57.7%; Cohen's kappa coefficient, 0.53); in samples with co-infections (40.0% vs. 56.7%; Cohen's kappa coefficient, 0.52); and in samples with hAdv type C (45.9% vs. 57.1%; Cohen's kappa coefficient, 0.60). Samples with lower viral loads were associated with a significantly lower sensitivity of the RVP Fast v2 assay (35.1% vs. 68.2%, p = 0.01; Cohen's kappa coefficients, 0.49). The RVP Fast v2 assay has important limitations for the detection of hAdv and cannot be used to evaluate whether hAdvs are the main etiologic agent responsible for an outbreak or when epidemiological studies are performed. [ABSTRACT FROM AUTHOR]

First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many reports from different countries have described an increasing number of patients with respiratory diseases due to EV-D68 associated with relevant clinical severity. In particular, an unexpectedly high number of children have been hospitalized for severe respiratory disease due to EV-D68, requiring intensive care such as intubation and mechanical ventilation. Moreover, EV-D68 has been associated with acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the community. As no specific antiviral therapy is available, treatment is mainly supportive. Moreover, because no vaccines are available, conventional infection control measures (i.e., standard, for contacts and droplets) in both community and healthcare settings are recommended. However, further studies are required to fully understand the real importance of this virus. Prompt diagnosis and continued surveillance of EV-D68 infections are essential to managing and preventing new outbreaks. Moreover, if the association between EV-D68 and severe diseases will be confirmed, the development of adequate preventive and therapeutic approaches are a priority. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs) represent a potential complication in surgical procedures, mainly because clean/contaminated surgery involves organs that are normally colonized by bacteria. Dental, maxillo-facial and ear-nose-throat (ENT) surgeries are among those that carry a risk of SSIs because the mouth and the first respiratory tracts are normally colonized by a bacterial flora. The aim of this consensus document was to provide clinicians with recommendations on surgical antimicrobial prophylaxis in neonates (<28 days of chronological age) and pediatric patients (within the age range of 29 days–18 years) undergoing dental, maxillo-facial or ENT surgical procedures. These included: (1) dental surgery; (2) maxilla-facial surgery following trauma with fracture; (3) temporo-mandibular surgery; (4) cleft palate and cleft lip repair; (5) ear surgery; (6) endoscopic paranasal cavity surgery and septoplasty; (7) clean head and neck surgery; (8) clean/contaminated head and neck surgery and (9) tonsillectomy and adenoidectomy. Due to the lack of pediatric data for the majority of dental, maxillo-facial and ENT surgeries and the fact that the recommendations for adults are currently used, there is a need for ad hoc studies to be rapidly planned for the most deficient areas. This seems even more urgent for interventions such as those involving the first airways since the different composition of the respiratory microbiota in children compared to adults implies the possibility that surgical antibiotic prophylaxis schemes that are ideal for adults may not be equally effective in children. [ABSTRACT FROM AUTHOR]

The main aim of surgical antimicrobial prophylaxis (SAP) in urologic procedures is to prevent bacteraemia, surgical site infections (SSIs), and postoperative urinary tract infections (ppUTIs). Guidelines for SAP in paediatric urology are lacking. Only some aspects of this complex topic have been studied, and the use of antibiotic prophylaxis prior to surgical procedures seems to be more often linked to institutional schools of thought or experts' opinions than to rules dictated by studies demonstrating the most correct and preferred management. Therefore, the aim of this Consensus document realized using the RAND/UCLA appropriateness method is to provide clinicians with a series of recommendations on SAP for the prevention of bacteraemia, SSIs, and ppUTIs after urologic imaging and surgical procedures in paediatric patients. Despite the few available studies, experts agree on some basilar concepts related to SAP for urologic procedures in paediatric patients. Before any urological procedure is conducted, UTI must be excluded. Clean procedures do not require SAP, with the exception of prosthetic device implantation and groin and perineal incisions where the SSI risk may be increased. In contrast, SAP is needed in clean-contaminated procedures. Studies have also suggested the safety of eliminating SAP in paediatric hernia repair and orchiopexy. To limit the emergence of resistance, every effort to reduce and rationalize antibiotic consumption for SAP must be made. Increased use of antibiotic stewardship can be greatly effective in this regard. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs) represent a potential complication in any type of surgery and can occur up to one year after the procedure in the case of implant placement. In the field of orthopedic and hand surgery, the rate of SSIs is a relevant issue, considering the need for the placement of synthesis devices and the type of some interventions (e.g., exposed fractures). This work aims to provide guidance on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing orthopedic and hand surgery in order to standardize the management of patients and to reduce, on the one hand, the risk of SSI and, on the other, the development of antimicrobial resistance. The following scenarios were considered: (1) bloodless fracture reduction; (2) reduction of unexposed fracture and grade I and II exposed fracture; (3) reduction of grade III exposed fracture or traumatic amputation; (4) cruel fracture reduction with percutaneous synthesis; (5) non-traumatic amputation; (6) emergency intact skin trauma surgery and elective surgery without synthetic media placement; (7) elective orthopedic surgery with prosthetic and/or synthetic media placement and spinal surgery; (8) clean elective hand surgery with and without bone involvement, without use of synthetic means; (9) surgery of the hand on an elective basis with bone involvement and/or with use of synthetic means. This manuscript has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding the behavior to be adopted in the peri-operative setting in neonatal and pediatric orthopedic and hand surgery. The specific scenarios developed are aimed at guiding the healthcare professional in practice to ensure the better and standardized management of neonatal and pediatric patients, together with an easy consultation. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs), i.e., surgery-related infections that occur within 30 days after surgery without an implant and within one year if an implant is placed, complicate surgical procedures in up to 10% of cases, but an underestimation of the data is possible since about 50% of SSIs occur after the hospital discharge. Gastrointestinal surgical procedures are among the surgical procedures with the highest risk of SSIs, especially when colon surgery is considered. Data that were collected from children seem to indicate that the risk of SSIs can be higher than in adults. This consensus document describes the use of preoperative antibiotic prophylaxis in neonates and children that are undergoing abdominal surgery and has the purpose of providing guidance to healthcare professionals who take care of children to avoid unnecessary and dangerous use of antibiotics in these patients. The following surgical procedures were analyzed: (1) gastrointestinal endoscopy; (2) abdominal surgery with a laparoscopic or laparotomy approach; (3) small bowel surgery; (4) appendectomy; (5) abdominal wall defect correction interventions; (6) ileo-colic perforation; (7) colorectal procedures; (8) biliary tract procedures; and (9) surgery on the liver or pancreas. Thanks to the multidisciplinary contribution of experts belonging to the most important Italian scientific societies that take care of neonates and children, this document presents an invaluable reference tool for perioperative antibiotic prophylaxis in the paediatric and neonatal populations. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs), which are a potential complications in surgical procedures, are associated with prolonged hospital stays and increased postoperative mortality rates, and they also have a significant economic impact on health systems. Data in literature regarding risk factors for SSIs in pediatric age are scarce, with consequent difficulties in the management of SSI prophylaxis and with antibiotic prescribing attitudes in the various surgical procedures that often tend to follow individual opinions. The lack of pediatric studies is even more evident when we consider surgeries performed in subjects with underlying conditions that may pose an increased risk of complications. In order to respond to this shortcoming, we developed a consensus document to define optimal surgical antimicrobial prophylaxis (SAP) in neonates and children with specific high-risk conditions. These included the following: (1) colonization by methicillin-resistant Staphylococcus aureus (MRSA) and by multidrug resistant (MDR) bacteria other than MRSA; (2) allergy to first-line antibiotics; (3) immunosuppression; (4) splenectomy; (5) comorbidity; (6) ongoing antibiotic therapy or prophylaxis; (7) coexisting infection at another site; (8) previous surgery in the last month; and (9) presurgery hospitalization lasting more than 2 weeks. This work, made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, represents, in our opinion, the most up-to-date and comprehensive collection of recommendations relating to behaviors to be undertaken in a perioperative site in the presence of specific categories of patients at high-risk of complications during surgery. The application of uniform and shared protocols in these high-risk categories will improve surgical practice with a reduction in SSIs and consequent rationalization of resources and costs, as well as being able to limit the phenomenon of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Several studies have shown that in recent years incidence of acute otitis media (AOM) has declined worldwide. However, related medical, social, and economic problems for patients, their families, and society remain very high. Better knowledge of potential risk factors for AOM development and more effective preventive interventions, particularly in AOM-prone children, can further reduce disease incidence. However, a more accurate AOM diagnosis seems essential to achieve this goal. Diagnostic uncertainty is common, and to avoid risks related to a disease caused mainly by bacteria, several children without AOM are treated with antibiotics and followed as true AOM cases. The main objective of this manuscript is to discuss the most common difficulties that presently limit accurate AOM diagnosis and the new approaches and technologies that have been proposed to improve disease detection. We showed that misdiagnosis can be dangerous or lead to relevant therapeutic mistakes. The need to improve AOM diagnosis has allowed the identification of a long list of technologies to visualize and evaluate the tympanic membrane and to assess middle-ear effusion. Most of the new instruments, including light field otoscopy, optical coherence tomography, low-coherence interferometry, and Raman spectroscopy, are far from being introduced in clinical practice. Video-otoscopy can be effective, especially when it is used in association with telemedicine, parents' cooperation, and artificial intelligence. Introduction of otologic telemedicine and use of artificial intelligence among pediatricians and ENT specialists must be strongly promoted in order to reduce mistakes in AOM diagnosis. [ABSTRACT FROM AUTHOR]

Maternal immunization against some infectious diseases can offer significant advantages for women, preventing maternal morbidity and mortality, or for offspring, preventing fetal disease and conferring passive immunity to neonates. Recently, clinical trials specifically to evaluate the immunogenicity, safety, and tolerability of some of the available coronavirus disease 2019 (COVID-19) vaccines in pregnant and lactating women have been planned, initiated and, in some cases, completed. This paper discusses whether the immunization of pregnant women against COVID-19 is justified and presents knowledge about the immunogenicity and safety of mRNA COVID-19 vaccines for these subjects. The results of recent studies indicate that pregnant women are at increased risk of developing severe disease compared with nonpregnant women of the same age. Studies carried out with mRNA vaccines indicate that the immunogenicity, safety and tolerability of these preventive measures in pregnant women are not different from those in nonpregnant women of the same age. Moreover, antibodies are efficiently transferred through the placenta and can be detected in breastmilk, suggesting a potential prevention of infection in the child. All these findings authorize the use of mRNA vaccines in pregnant women to protect both the mother and the child. However, further studies with larger sample size and with follow-up of the pregnant women vaccinated during different periods of pregnancy and their children are needed to better characterize the immune response of pregnant women, to define when these vaccines should be administered to obtain the best protection, and to measure vaccine efficacy against virus variants in both mothers and infants. COVID-19 vaccines based on different technological platforms cannot presently be used, and their role in pregnant women should be clarified. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is the most common cause of congenital infection and non-genetic sensorineural hearing loss in childhood. Up to 2% of neonates, with the highest percentages found in developing countries, are congenitally infected with CMV. At birth, most of these infants are asymptomatic. However, approximately 10% have signs and symptoms of the disease, and 40–60% of symptomatic neonates will later develop permanent neurologic sequelae. To reduce congenital CMV (cCMV) infection, a vaccine able to prevent primary infection is essential. In this narrative review, actual ongoing research about the development of a CMV vaccine is discussed. The progressive increase in knowledge on the ways in which the host's immune system and CMV relate has made it possible to clarify that the development of a vaccine that is certainly capable of reducing the risk of cCMV infection, and preventing both primary and nonprimary infections is extremely difficult. Many of the ways in which the virus evades the immune system and causes cCMV infection are not yet fully understood, especially in cases of nonprimary infection. Moreover, the schedule that should be recommended and that subjects must be vaccinated to obtain the greatest effect have not been precisely defined. Further studies are needed before the problem of cCMV infection and its related challenges can be totally solved. [ABSTRACT FROM AUTHOR]

Incidence of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Children with IBDs have a dysfunctional immune system and they are frequently treated with immunomodulating drugs and biological therapy, which significantly impair immune system functions and lead to an increased risk of infections. Vaccines are essential to prevent at least part of these infections and this explains why strict compliance to the immunization guidelines specifically prepared for IBD patients is strongly recommended. However, several factors might lead to insufficient immunization. In this paper, present knowledge on the use of vaccines in children with IBDs is discussed. Literature review showed that despite a lack of detailed quantification of the risk of infections in children with IBDs, these children might have infections more frequently than age-matched healthy subjects, and at least in some cases, these infections might be even more severe. Fortunately, most of these infections could be prevented when recommended schedules of immunization are carefully followed. Vaccines given to children with IBDs generally have adequate immunogenicity and safety. Attention must be paid to live attenuated vaccines that can be administered only to children without or with mild immune system function impairment. Vaccination of their caregivers is also recommended. Unfortunately, compliance to these recommendations is generally low and multidisciplinary educational programs to improve vaccination coverage must be planned, in order to protect children with IBD from vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

In most cases, infection due to Bartonella henselae causes a mild disease presenting with a regional lymphadenopathy frequently associated with a low-grade fever, headache, poor appetite and exhaustion that spontaneously resolves itself in a few weeks. As the infection is generally transmitted by cats through scratching or biting, the disease is named cat scratch disease (CSD). However, in 5–20% of cases, mainly in immunocompromised patients, systemic involvement can occur and CSD may result in major illness. This report describes a case of systemic CSD diagnosed in an immunocompetent 4-year-old child that can be used as an example of the problems that pediatricians must solve to reach a diagnosis of atypical CSD. Despite the child's lack of history suggesting any contact with cats and the absence of regional lymphadenopathy, the presence of a high fever, deterioration of their general condition, increased inflammatory biomarkers, hepatosplenic lesions (i.e., multiple abscesses), pericardial effusion with mild mitral valve regurgitation and a mild dilatation of the proximal and medial portion of the right coronary artery, seroconversion for B. henselae (IgG 1:256) supported the diagnosis of atypical CSD. Administration of oral azithromycin was initiated (10 mg/kg/die for 3 days) with a progressive normalization of clinical, laboratory and US hepatosplenic and cardiac findings. This case shows that the diagnosis of atypical CSD is challenging. The nonspecific, composite and variable clinical features of this disease require a careful evaluation in order to achieve a precise diagnosis and to avoid both a delayed diagnosis and therapy with a risk of negative evolution. [ABSTRACT FROM AUTHOR]

The history of Streptococcus pneumoniae diseases dramatically changed with the introduction into the immunization schedule of infants and children of the first pneumococcal conjugate vaccine, the one containing 7 (PCV7) of the most common pneumococcal serotypes (STs) causing invasive pneumococcal diseases (IPDs). Where PCV7 was largely used, incidence of both IPDs and non-invasive pneumococcal diseases (nIPDs) in vaccinated children and in unvaccinated subjects of any age, mainly the elderly, significantly decreased. Unfortunately, the impact of PCV7 administration was slightly lower than expected, as the reduction in infections due to vaccine serotypes (STs) was accompanied by a significant increase in the number of IPDs and nIPDs due to STs not included in the vaccine. To overcome this problem, two PCVs containing 10 (PCV10) and 13 (PCV13) STs, chosen among those emerging, were developed and licensed. However, ST replacement occurred again. Moreover, the new PCVs showed little effectiveness in the prevention of infection due to non-encapsulated STs and to ST3. Next-generation S. pneumoniae vaccines able to prevent pneumococcal infections regardless of infecting ST are urgently needed. For the moment, the use of available PCVs remains fundamental because their benefits far outweigh any concerns for emerging STs. [ABSTRACT FROM AUTHOR]

The need to cope with the medical, social, and economic storm due to the new coronavirus 2019 (COVID-19) pandemic as quickly as possible has led to the very rapid development of a huge number of vaccines. All these vaccines have been mainly developed in healthy adults and, in some cases, in the elderly. Children were marginally involved as, according to the clinical trial registry Clinical Trials.gov, only very few studies have included children among subjects to enroll, although just a few weeks after the pandemic declaration, the US Food and Drug Administration had highlighted the importance of vaccine evaluation in pediatrics. Availability of an effective and safe pediatric COVID-19 vaccine appears mandatory for several clinical and epidemiological reasons. However, as the development of an effective and safe pediatric vaccine seems far from easy, strong cooperation among governments, researchers, and pharmaceutical companies is highly desirable. [ABSTRACT FROM AUTHOR]