Therapeutic eradication choices in Helicobacter pylori infection in children.

Current recommendations on Helicobacter pylori (H. pylori) eradication in children differ from adults. In H. pylori-infected adults, the eradication is always recommended because of the risk to develop gastrointestinal and non-gastrointestinal associated diseases. Instead, before treating infected children, we should consider all the possible causes and not merely focus on H. pylori infection. Indeed, pediatric international guidelines do not recommend the test and treat strategy in children. Therefore, gastroscopy with antimicrobial susceptibility testing by culture on gastric biopsies should be performed before starting the eradication therapy in children to better evaluate all the possible causes of the symptomatology and to increase the eradication rate. Whether antibiotic susceptibility testing is not available, gastroscopy is anyway recommended to better set any possible cause of symptoms and not simply focus on the presence of H. pylori. In children the lower antibiotics availability compared to adults forces to treat based on antimicrobial susceptibility testing to minimize the unsuccessful rates. The main antibiotics used in children are amoxicillin, clarithromycin, and metronidazole in various combinations. In empirical treatment, triple therapy for 14 days based either on local antimicrobial susceptibility or on personal antibiotic history is generally recommended. Triple therapy with high dose of amoxicillin is a valid alternative choice, either in double resistance or in second-line treatment. Moving from therapeutic regimens used in adults, we could also select quadruple therapy with or without bismuth salts. However, all the treatment regimens often entail unpleasant side effects and lower compliance in children. In this review, the alternative and not yet commonly used therapeutic choices in children were also analyzed.

Is Helicobacter pylori Anyway Pathogen in Children?

Helicobacter pylori (H. pylori) infection is a continuous challenge for both gastroenterologists and pediatricians. The international guidelines regarding diagnostic and treatment pathways differ between adults and children. The pediatric guidelines are more restrictive because children are rarely affected by serious consequences, particularly in Western countries. Therefore, infected children should be treated only after a careful case-by-case evaluation by a pediatric gastroenterologist. In any case, recent studies are confirming an increasingly all-around pathological role of H. pylori even in asymptomatic children. For these reasons, following the current evidence, we feel that H. pylori-infected children could be treated starting in pre-adolescence, particularly in Eastern countries, because their stomachs have already begun to develop the biomarkers of gastric damage. Therefore, we believe that H. pylori is anyway pathogen in children. Nevertheless, the possible beneficial role of H. pylori in humans has not yet been conclusively disproved.

Role of Artificial Intelligence in Fighting Antimicrobial Resistance in Pediatrics.

Artificial intelligence (AI) is a field of science and engineering concerned with the computational understanding of what is commonly called intelligent behavior. AI is extremely useful in many human activities including medicine. The aim of our narrative review is to show the potential role of AI in fighting antimicrobial resistance in pediatric patients. We searched for PubMed articles published from April 2010 to April 2020 containing the keywords "artificial intelligence", "machine learning", "antimicrobial resistance", "antimicrobial stewardship", "pediatric", and "children", and we described the different strategies for the application of AI in these fields. Literature analysis showed that the applications of AI in health care are potentially endless, contributing to a reduction in the development time of new antimicrobial agents, greater diagnostic and therapeutic appropriateness, and, simultaneously, a reduction in costs. Most of the proposed AI solutions for medicine are not intended to replace the doctor's opinion or expertise, but to provide a useful tool for easing their work. Considering pediatric infectious diseases, AI could play a primary role in fighting antibiotic resistance. In the pediatric field, a greater willingness to invest in this field could help antimicrobial stewardship reach levels of effectiveness that were unthinkable a few years ago.

An Atypical Presentation of Primary Hyperparathyroidism in an Adolescent: A Case Report of Hypercalcaemia and Neuropsychiatric Symptoms Due to a Mediastinal Parathyroid Adenoma.

Psychiatric disorders are rare clinical manifestations of hypercalcaemia in the pediatric population, are relatively more frequent during adolescence and are often overlooked in cases of severe hypercalcaemia. We described the case of a 17-year-old girl affected by anorexia nervosa, depression and self-harm with incidental detection of moderate hypercalcaemia. Clinical, laboratory and instrumental tests demonstrated that hypercalcaemia was secondary to primary hyperparathyroidism (PHPT) due to a mediastinal parathyroid adenoma in the thymic parenchyma. After parathyroidectomy with robot-assisted surgery, we observed the restoration of calcium and PTH levels in addition to an improvement in psychiatric symptoms. This case demonstrates that serum calcium concentration should be evaluated in adolescents with neurobehavioural symptoms and in cases of hypercalcaemia PHPT should be excluded. Surgery represents the cornerstone of the management of PHPT and may contribute to improving quality of life and psychological function in these patients. However, the complexity of neurological involvement in cases of hypercalcaemia due to PHPT requires further investigations to establish the real impact of this condition on the neurocognitive sphere.

Improving the Quality of Hospital Antibiotic Use: Impact on Multidrug-Resistant Bacterial Infections in Children.

Antimicrobial resistance (AMR) is considered a rapidly growing global public health emergency. Neonates and children are among patients for whom antibiotics are largely prescribed and for whom the risk of AMR development is high. The phenomenon of increasing AMR has led to the need to develop measures aimed at the rational and effective use of the available drugs also in children and antimicrobial stewardship (AS), which is one of the measures that in adults has showed the highest efficacy in reducing antibiotic abuse and misuse, appears as an attractive approach. The aim of this manuscript is to analyze the basic principles and strategies of pediatric AS. To this end, we searched in PubMed articles published in years 2000 to 2019 containing "antimicrobial resistance," "antibiotic use," "antimicrobial stewardship," and "children" or "pediatric" as keywords. Our review showed that the balance between multi-resistant organisms and new antimicrobials is extremely precarious. The AS tools are the most important weapon at our disposal to stem the phenomenon. Careful monitoring of prescriptions, continuous training of prescribing physicians and collaboration with highly qualified multidisciplinary staff, creation of local and national guidelines, use of rapid diagnostic tests, technological means of support, and research activities by testing new broad-spectrum antibiotics are mandatory. However, all of these measures must be supported by adequate investment by national and international health organizations. Only by making AS daily practice, through the use of financial resources and dedicated staff, we can fight AMR to ensure safe and effective care for our young patients.

Gut Microbiota in Celiac Disease: Is There Any Role for Probiotics?

Celiac disease (CD) is an immune-mediated disorder initiated by the ingestion of gluten in genetically predisposed individuals. Recent data shows that changes in the gut microbiome composition and function are linked with chronic inflammatory diseases; this might also be the case for CD. The main aim of this manuscript is to discuss our present knowledge of the relationships between gut microbiota alterations and CD and to understand if there is any role for probiotics in CD therapy. PubMed was used to search for all of the studies published from November 2009 to November 2019 using key words such as "Celiac Disease" and "Microbiota" (306 articles), "Celiac Disease" and "Gastrointestinal Microbiome" (139), and "Probiotics" and "Celiac Disease" (97 articles). The search was limited to articles published in English that provided evidence-based data. Literature analysis showed that the gut microbiota has a well-established role in gluten metabolism, in modulating the immune response and in regulating the permeability of the intestinal barrier. Promising studies suggest a possible role of probiotics in treating and/or preventing CD. Nevertheless, human trials on the subject are still scarce and lack homogeneity. A possible role was documented for probiotics in improving CD-related symptoms, modulating the peripheral immune response and altering the fecal microbiota, although the results were not consistent in all of the studies. No evidence was found that probiotic administration might prevent CD onset. Knowledge of the role of intestinal bacteria in the development of CD opens new possibilities for its treatment through probiotic administration, even though further studies are needed to better clarify whether probiotics can help treat or prevent the disease and to define which probiotics to use, at what dose and for how long.

Case report of a familial triple: a syndrome and review of the literature.

RATIONALE: Triple-A syndrome, or Allgrove syndrome (AS), is a rare autosomal recessive disorder characterized by the alacrimia, achalasia, and adrenal insufficiency triad. Alacrimia usually starts at early infancy, while achalasia and adrenal insufficiency appear later during childhood or adulthood. Some patients may also present with the so-called Double-A syndrome (i.e., alacrimia and achalasia, or alacrimia and adrenal insufficiency); adrenal insufficiency usually represents a life-threatening event due to severe hypoglycemia. Many patients may also present other associated manifestations, such as neurological disorders. We describe, here, 2 sisters of non-consanguineous parents. PATIENT CONCERNS: An 8-year-old girl was admitted to the Pediatric Care Unit of Parma after an episode characterized by seizure with loss of consciousness and generalized hypertonia lasting a few minutes. Her sister, a 6-year-old girl, presented with recurrent episodes of vomiting and failure to thrive. DIAGNOSES: Both children were investigated by laboratory tests, esophagogastroduodenoscopy, and imaging. The first patient had the complete triad of AS (alacrimia, achalasia, adrenal insufficiency), while the second one presented only alacrimia and achalasia. Both resulted from a mutation in the achalasia, addisonianism, alacrimia syndrome gene. INTERVENTIONS: Both patients were treated with oral hydrocortisone for Addison disease, and with artificial tears in the first case. After many pneumatic endoscopic dilations and therapy with nifedipine, both patients underwent surgical Heller myotomy for achalasia. OUTCOMES: A rapid and favorable recovery to normal diet and with improvement of growth parameters was obtained. These cases are also compared with the literature data, reported in a brief review. LESSONS: AS is a rare multisystemic disorder. The longer diagnosis is delayed, the greater extent to which this syndrome may be life-threatening, mainly because of hypoglycemia due to adrenal insufficiency. In AS, the red-flag symptom of alacrimia should instigate investigation for achalasia, Addison disease, and achalasia, addisonianism, alacrimia syndrome gene mutation.

An Unusual Dysphagia for Solids in a 17-Year-Old Girl Due To a Lusoria Artery: A Case Report and Review of the Literature.

Background: Dysphagia is a condition that can have many underlying causes, often different between adults and children and its early diagnosis is crucial especially during childhood and adolescence, given the importance of proper nutritional intake to ensure adequate growth and development. Case report: We described the case of a 17-year-old girl reporting dysphagia for solids for approximately one month. No symptoms were previously referred. Oesophagogastroduodenoscopy was performed, detecting an image of ab extrinseco compression at the level of the mid-cervical oesophagus. An upper gastrointestinal tract radiography confirmed an oesophageal impression above the arch of the aorta suggestive of vascular abnormality. Computed tomography angiography and three-dimensional reconstruction techniques showed the presence of a lusoria artery that originated from the medial margin of the descending aorta and crossed the trachea and oesophagus posteriorly to the distal third. The lusoria artery was transected via a left thoracotomy and re-implanted into the right common carotid artery with complete symptom resolution. Conclusions: Dysphagia lusoria is an impairment of swallowing due to compression from an aberrant right subclavian artery. The diagnosis is always difficult, as the symptoms are often nonspecific. It is imperative to accurately identify and properly manage dysphagia in pediatric age and this is only possible with an anamnestic, clinical and instrumental process that takes into account an adequate differential diagnosis.

Updated Management Guidelines for Clostridioides difficile in Paediatrics.

Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile. Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations.

Primary Antimicrobial Susceptibility Changes in Children with Helicobacter pylori Infection over 13 Years in Northern Italy.

The eradication therapy of Helicobacter pylori (H. pylori) infection is still a challenge for gastroenterologists. One of the main causes of failure in H. pylori eradication is the antibiotic resistance mainly to clarithromycin. Culture from biopsies is maybe the most used method among the antimicrobial susceptibility techniques. In this study, we compared the antimicrobial susceptibility changes in children with H. pylori infection over 13 years and we confirmed that clarithromycin resistance has been increased (16% versus 26%) though with no statistically signficant value. Therefore, clarithromycin should not be used in empiric treatment of H. pylori eradication therapy in children, but its use should be limited only to children with known antimicrobial susceptibility. On the other hand, metronidazole resistance has decreased over this time period in statistically significant manner (56% versus 33%, p = 0.014). Furthermore, ampicillin resistance has been confirmed to be very rare (3% versus 0%) in children with H. pylori infection. In conclusion, in H. pylori infection, if we do not know the antibiotic susceptibility of patients, we should recommend an eradication therapy based on the local distribution of antibiotic resistance rates trying to limit the therapeutic failures.

Childhood Crohn's disease presenting as chronic constipation.

Inflammatory bowel disease (IBD) include Crohn's disease (CD) and ulcerative colitis (UC). In children signs and symptoms of IBD are often non-specific, diagnosis is more difficult than in adults and systemic manifestation as growth failure and delayed puberty are common. While abdominal pain, rectal bleeding and diarrhoea are usual symptoms, constipation represents an unusual presentation of CD or UC. We report a 9-years-old girl with severe constipation, worsening abdominal pain, intermittent fever, diagnosed as CD. To our knowledge, this is a rare case of CD presenting as chronic constipation in children; we can find, in reviewed recent literature, only few report of similar condition.