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Background and Aims: Drug-eluting stents (DES) are not designed for overexpansion to supra-nominal diameters or intentional stent fracture (ISF). The optimal dilation technique to minimize stent shortening (SS) and achieve ISF to accommodate pediatric somatic growth has not been described., Methods: Three sizes of two commonly used DES were implanted within a silicone model to simulate blood vessels. Each stent was serially dilated in 1 mm increments under fluoroscopy using three techniques: 2 cm length, semi-compliant balloons (Technique 1), 2 cm, noncompliant balloons straddling the entire stent (Technique 2), or noncompliant balloons in an "inside-out" manner (balloon shorter than stent or 2 cm balloon aligned with distal end of stent (no straddle); (Technique 3). Technique 1 crossed over to noncompliant balloons once stent "napkin-ringed" (NR). Percent SS = (L nominal  - L final )/L nominal  * 100., Results: Technique 1 resulted in the greatest SS (median 85%, IQR 82, 87) and universal napkin ringing. Technique 2 caused less SS (median 14%, IQR 7, 15), and Technique 3 caused the least SS (median 7%, IQR 3, 11). ISF was achieved in all, however, the inside-out technique caused ISF at smaller stent diameters (median 114% recommended postdilation limit vs. 122%-131%) and lower inflation pressures (median 15 vs. 28-29 ATM). ISF was achieved in Technique 1 after napkin ringing but required larger noncompliant balloons than other techniques (median 8.5 vs. 7 mm)., Conclusion: Inside-out dilation resulted in less SS and fracture at smaller diameters with lower inflation pressures. This technique may improve the ISF success rate of DES in pediatric patients., (© 2025 Wiley Periodicals LLC.)

Background/Objectives : To face antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been implemented in the pediatric age, but the area of urgency remains understudied. We aimed to assess the impact of an educational program on optimizing antibiotic appropriateness in a pediatric ED. Methods : We conducted a pre-post observational study with an audit, intervention, and feedback given to prescribers. We recorded all systemic antibiotic prescriptions for children attending our pediatric ED from January to March and from July to September 2020. The study's team assigned a score to each prescription, regarding the appropriate molecule, dose, and duration of therapy, according to the diagnosis. From April to June 2020, we held weekly meetings focusing on different pediatric infectious diseases, with interaction between one to three ED physicians and the infectious disease (ID) specialist of the study's team. We then distributed synthetic digital guidelines adapted to our reality to all prescribers. Results : Optimal antibiotic prescriptions increased after the intervention, with statistical significance ( p < 0.001) in four main aspects (overall adequacy: 13% PRE vs. 43% POST; need of antibiotics: 53% vs. 68%; adequacy of the spectrum: 55% vs. 63%; adequacy of the chosen molecule: 54% vs. 62%). We observed an improvement in all the main infectious diseases and concerns all the ED physicians. The prescription of first-choice drugs increased in specific and common illnesses such as otitis and pharyngotonsillitis. Conclusions : An antimicrobial stewardship program is a relevant method for improving the appropriateness of antimicrobial use also in the complex setting of a pediatric ED.

Synthetic bone models have increasing utility in orthopaedic research due to their low cost and low variability and have been shown to be biomechanically equivalent to human bones in a variety of ways. The rise in additive manufacturing (AM) for orthopaedic applications presents an opportunity to construct synthetic whole-bone models for biomechanical testing applications, but there is a lack of research comparing these AM models to cadaveric or commercially available bone surrogates. This study compares the mechanical properties of 3D printed clavicle models to commercially available (4th generation Sawbones) and human cadaveric clavicles via nondestructive cyclic 4-point bending, axial compression, and torsion, and a final axial compression test to failure. Commercially available synthetic clavicles had 57.8-203% higher superior-inferior bending rigidity (p < 0.0001), 80.9-198% higher axial stiffness (p < 0.001), and 314-557% higher torsional rigidity (p < 0.05) on average than AM and cadaveric clavicles. Cadaveric and AM clavicles printed from a BoneMatrix/VeroWhite composite material had similar failure mechanisms under axial compression while AM VeroWhite clavicles experienced catastrophic failure, but these groups did not have significantly different ultimate failure loads. Together, these results demonstrate that current commercially available synthetic clavicles may be too rigid to emulate the mechanical properties of elderly cadaveric clavicles, and that AM bone models can closely mimic these cadaveric bones in a variety of biomechanical loading schemes. These results show promising applications for future work using 3D printed bone surrogates for biomechanical analysis of orthopaedic implants and other surgical repair techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background & Aims: Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC., Methods: This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data., Results: Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment., Conclusions: This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: Atrioventricular valve regurgitation (AVVR) is a devastating complication in children and young adults with congenital heart disease (CHD), particularly in patients with single ventricle physiology. Transcatheter edge-to-edge repair (TEER) is a rapidly expanding, minimally invasive option for the treatment of AVVR in adults that avoids the morbidity and mortality associated with open heart surgery. However, application of TEER in in CHD and in children is quite novel. We describe the development of a peri-procedural protocol including image-derived pre-intervention simulation, with successful application to four patients., Aims: To describe the initial experience using the MitraClip system for TEER of dysfunctional systemic atrioventricular valves in patients with congential heart disease within a pediatric hospital., Methods: A standardized screening and planning process was developed using cardiac magnetic resonance imaging, three dimensional echocardiography and both virtual and physical simulation. Procedures were performed using the MitraClip G4 system and patients were clinically followed post-intervention., Results: A series of four CHD patients with at least severe AVVR were screened for suitability for TEER with the MitraClip system: three patients had single ventricle physiology and Fontan palliation, and one had repair of a common atrioventricular canal defect. Each patient had at least severe systemic AVVR and was considered at prohibitively high risk for surgical repair. Each patient underwent a standardized preprocedural screening protocol and image-derived modeling followed by the TEER procedure with successful clip placement at the intended location in all cases., Conclusions: The early results of our protocolized efforts to introduce TEER repair of severe AV valve regurgitation with MitraClip into the CHD population within our institution are encouraging. Further investigations of the use of TEER in this challenging population are warranted., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, Pantoea species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on a few anecdotal reports. (2) Methods: We conducted this five-year (2018-2023) single-center study aimed at investigating the prevalence and clinical and microbiological findings of Pantoea species bloodstream infections. (3) Results: Among the 4996 bloodstream infection Gram-negative isolates collected during the study period, Pantoea species accounted for 0.4% (n = 19) of isolates from 19 different patients, 5 of them being pediatric cases. Among Pantoea species isolates, P. agglomerans was the most frequently detected (45%; n = 9) followed by P. eucrina (30%; n = 6) and P. septica (15%; n = 3). Malignancy (35.7%) in adults and malignancy (40%) and cerebrovascular disease following meconium aspiration (40%) in pediatric patients as comorbidities and shivering and/or fever following parenteral infusion (36.8%) as a symptom/sign of Pantoea species bloodstream infection onset were the most frequently observed clinical features. Among adults, primary bloodstream infection was the most frequent (50%), whereas among pediatric patients, the most commonly identified sources of infection were catheter-related (40%) and the respiratory tract (40%). Overall, Pantoea species bloodstream infection isolates displayed high susceptibility to all the antibiotics except for ampicillin (63.2%), fosfomycin (73.7%), and piperacillin/tazobactam (84.2%). Targeted antibiotic treatment was prescribed as monotherapy for adults (71.4%) and combination therapy for pediatric patients (60%). The most prescribed antibiotic regimens were piperacillin/tazobactam (21.4%) in adults and meropenem- (40%) and aminoglycoside-containing (40%) antibiotics in pediatric patients. The overall 28-day all-cause mortality rate was 5.3% (n = 1). (4) Conclusions: The prevalence and 28-day mortality rate of Pantoea species bloodstream infections were low. The prescription of targeted therapy including broad-spectrum antibiotics could indicate an underestimation of the specific involvement of the Pantoea species in the onset of the disease, warranting further studies defining their pathogenic potential.

Objectives: We summarized the clinical and radiological characteristics of meningitis-retention syndrome (MRS), its therapeutic options, and urological outcome, to better understand the pathogenesis of this syndrome and to evaluate the effectiveness of corticosteroids in reducing the period of urinary retention., Methods: We reported a new case of MRS in a male adolescent. We also reviewed the previously 28 reported cases of MRS, collected from inception up to September 2022., Results: MRS is characterized by aseptic meningitis and urinary retention. The mean length of the interval between the onset of the neurological signs and the urinary retention was 6.4 days. In most cases, no pathogens were isolated in cerebrospinal fluid, except for 6 cases in which Herpesviruses were detected. The urodynamic study resulted in a detrusor underactivity, with a mean period for urination recovery of 4.5 weeks, regardless of therapies., Discussion: Neurophysiological studies and electromyographic examination are not pathological, distinguishing MRS from polyneuropathies. Although there are no encephalitic symptoms or signs, and the magnetic resonance is often normal, MRS may represent a mild form of acute disseminated encephalomyelitis, without radiological detectable medullary involvement, due to the prompt use of steroids. It is believed that MRS is a self-limited disease, and no evidence suggests the effectiveness of steroids, antibiotics, and antiviral treatment in its clinical course., (© 2023. The Author(s).)

Objective: To describe the development and implementation of a process for creating accurate Pediatric genitourinary 3D modeling and printing with multiphase postcontrast imaging for surgical planning., Materials and Methods: Additive manufacturing and 3D model present opportunities to support clinical planning, this manuscript's specific process and considerations for creating pediatric genitourinary 3D modeling to support urology. The process for creating the 3D models and prints covers 3 key aspects from image acquisition, imaging review and selection, and segmentation and modification (as needed). Each step is outlined with the key roles and procedures., Results: The described case had digital and printed models prepared with references to the optimized imaging sequence for 3D modeling of Pediatric genitourinary. Case shared include complex genitourinary reconstruction and Kideny with Wilms tumors., Conclusion: The processes described have become a standard of practice for complex kidney tumors and exstrophy planning. The team continues to work on ever-changing improvements to make the best possible models to support clinical and surgical planning., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transcatheter edge-to-edge valve repair (TEER) is a complex procedure requiring delivery and alignment of the device to the target valve, which can be challenging in atypical or surgically palliated anatomy. We demonstrate application of virtual and physical simulation to plan optimal TEER access and catheter path in normal and congenitally abnormal cardiac anatomy., Methods: Three heart models were created from three-dimensional (3D) images and 3D printed, including two with congenital heart disease. TEER catheter course was simulated both virtually and physically using a commercial TEER system., Results: We demonstrate application of modeling in three patients, including two with congenital heart disease and a Fontan circulation. Access site and pathway to device delivery was simulated by members of a multidisciplinary valve team. Virtual and physical simulation were compared., Conclusions: Virtual and physical simulation of TEER using 3D printed heart models is feasible and may be beneficial for planning and simulation, particularly in patients with complex anatomy. Future work is required to demonstrate application in the clinical setting.

Purpose: Stroke is a leading cause of long-term disability with high mortality rate in the first year after the event. In Campania, mechanical thrombectomy treatment significantly increases in the last 3 years, as well as hospitals delivering acute stroke treatments. The aim of this study is to demonstrate how a full opening of our stroke network improves stroke management and stroked patients' survival in Campania., Material and Methods: In Federico II University Hospital of Naples acting as a HUB center of 7 peripheral SPOKE hospitals in regional territory, 68 patients with acute ischemic stroke were evaluated with NIHSS and m-RS clinical scores and neuroradiological ASPECT scores, from January 1 to December 31, 2021. At hospital discharge, NIHSS score and three months after m-RS score were re-assessed to evaluate the therapeutic effects., Results: Forty-two of 68 patients (63%) admitted to our hub center had ischemic acute stroke at CT evaluation; 29 patients had ASPECT score > 7 (69%), and 6 a score < 7 (14%). At admission, NIHSS score mean value was 10.75, and m-RS score mean value was 0.74. At discharge, NIHSS score mean value was 7.09. After three months, m-RS score mean value was 0.74., Discussion: The inter-company agreement between Federico II University and several peripheral hospitals allows an absolute and relative increase in endovascular mechanical thrombectomy and intravenous thrombolysis procedures, with a relative prevalence of mechanical thrombectomy. A regional implementation of the stroke multi-disciplinary care system is hardly needed to ensure the optimum treatment for the largest number of patients, improving patient's outcome., (© 2023. The Author(s).)

Background: Like most hospitals, our hospital experienced COVID-19 pandemic-related supply chain shortages. Our additive manufacturing lab's capacity to offset these shortages was soon overwhelmed, leading to a need to improve the efficiency of our existing workflow. We undertook a work system analysis guided by the Systems Engineering Initiative for Patient Safety (SEIPS) construct which is based on human factors and quality improvement principles. Our objective was to understand the inefficiencies in project submission, review, and acceptance decisions, and make systematic improvements to optimize lab operations., Methods: Contextual inquiry (interviews and workflow analysis) revealed suboptimal characteristics of the system, specifically, reliance on a single person to facilitate work and, at times, fractured communication with project sponsors, with root causes related to the project intake and evaluation process as identified through SEIPS tools. As interventions, the analysis led us to: 1) enhance an existing but underused project submission form, 2) design and implement an internal project scorecard to standardize evaluation of requests, and 3) distribute the responsibility of submission evaluation across lab members. We implemented these interventions in May 2021 for new projects and compare them to our baseline February 1, 2018 through - April 30, 2021 performance (1184 days)., Results: All project requests were submitted using the enhanced project submission form and all received a standardized evaluation with the project scorecard. Prior to interventions, we completed 35/79 (44%) of projects, compared to 12/20 (60%) of projects after interventions were implemented. Time to review new submissions was reduced from an average of 58 days to 4 days. A more distributed team responsibility structure permitted improved workflow with no increase in staffing, allowing the Lab Manager to devote more time to engineering rather than administrative/decision tasks., Conclusions: By optimizing our workflows utilizing a human factors approach, we improved the work system of our additive manufacturing lab to be responsive to the urgent needs of the pandemic. The current workflow provides insights for labs aiming to meet the growing demand for point-of-care manufacturing., (© 2022. The Author(s).)

Background: Surgical and catheter-based interventions for congenital heart disease require precise understanding of complex anatomy. The use of three-dimensional (3D) printing and virtual reality to enhance visuospatial understanding has been well documented, but integration of these methods into routine clinical practice has not been well described. We review the growth and development of a clinical 3D modeling service to inform procedural planning within a high-volume pediatric heart center., Methods: Clinical 3D modeling was performed using cardiac magnetic resonance (CMR) or computed tomography (CT) derived data. Image segmentation and post-processing was performed using FDA-approved software. Patient-specific anatomy was visualized using 3D printed models, digital flat screen models and virtual reality. Surgical repair options were digitally designed using proprietary and open-source computer aided design (CAD) based modeling tools., Results: From 2018 to 2020 there were 112 individual 3D modeling cases performed, 16 for educational purposes and 96 clinically utilized for procedural planning. Over the 3-year period, demand for clinical modeling tripled and in 2020, 3D modeling was requested in more than one-quarter of STAT category 3, 4 and 5 cases. The most common indications for modeling were complex biventricular repair (n = 30, 31%) and repair of multiple ventricular septal defects (VSD) (n = 11, 12%)., Conclusions: Using a multidisciplinary approach, clinical application of 3D modeling can be seamlessly integrated into pre-procedural care for patients with congenital heart disease. Rapid expansion and increased demand for utilization of these tools within a high-volume center demonstrate the high value conferred on these techniques by surgeons and interventionalists alike., (© 2022. The Author(s).)

Malaria is not endemic in Italy, however every year about 600-700 imported cases are detected in people born or living in Italy who return from a stay in their country of origin (visiting friends and relatives - VFR). Children account for 20% of this population and they have an higher risk of severe disease. Socio-economic problems and deficiencies in the doctor-patient relationship often lead to a lack of awareness of the importance of prophylaxis, making the category of VFRs at increased risk of disease. The aim of this study is to analyze the characteristics of pediatric imported malaria, with a specific focus on prevention and risk factors for severe malaria. All malaria cases diagnosed from 2007 to 2019 in Ospedale Infantile Regina Margherita in Turin were retrospectively observed. Epidemiological and clinical data were described. A total of 72 patients were reported: 98.6% had African origins and 73.6% traveled as VFRs. Plasmodium falciparum was the species most commonly isolated (94.4%). Twenty-four patients (33.3%) underwent chemoprophylaxis and never appropriately. Patients not undergoing prophylaxis and those undergoing incomplete prophylaxis showed not statistically significant difference in term of disease severity (p = 0.26). Nineteen cases were considered severe, including 3 with cerebral malaria. High levels of parasitemia were statistically significantly correlated with severe anemia (p = 0.049) and severe thrombocytopenia (p = 0.036). In 25% of cases the first diagnosis was incorrect. The therapeutic use of artemisinin derivatives has resulted in a significant shortening of the parasitemia clearance time compared to the use of other drugs (p < 0.001). Families have to be educated about the serious implications of a malaria infection and the importance of a correct and complete prophylaxis. Clinicians should always consider malaria in the differential diagnoses in patients with fever and a history of a recent travel to an endemic area. Prompt diagnosis and use of appropriate drugs, according to the latest guidelines, could guarantee a better outcome for patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic produced unprecedented challenges to healthcare and medical device manufacturing (e.g. personal protective device and replacement part shortages). Additive manufacturing, 3D printing, and the maker community were uniquely positioned to respond to these needs by providing in-house design and manufacturing to meet the needs of clinicians and hospitals. This paper reviews the pandemic response of Children's Hospital of Philadelphia CHAMP 3D Lab, a point-ofcare3D printing team that supports clinical and research projects across the hospital network. The CHAMP team responded to a variety of COVID-19 healthcare needs including providing protective eyewear and ventilator components, creating a transport hook, and designing a novel transparent facemask. This case series details our response to these needs, describing challenges experienced and lessons learned in overcoming them so that others may learn from our experiences. Challenges to responding to the pandemic included the need to handle urgent pandemic related requests in addition to our standard fare. This required us to not only expand our capacity without additional resources, but also to develop a system of prioritization. Specific changes made included: streamlining workflows, identifying safety review processes, and developing/enlisting a network of collaborators. Further, we consider how to transition to a future, post-pandemic world without losing the cohesive drive of emergency-induced innovation. This paper aims to share what we have learned and to encourage both teams currently engaged in the printing community and those looking to join it., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Despite efforts made to prevent the spread of multi-drug-resistant bacteria, carbapenemase-producing Enterobacteriaceae (CPE) has become one of the most dangerous threat worldwide. However, data on the epidemiology of CPE and on the correlation between CPE colonization and infection are scanty. The objectives of this study were first to describe the epidemiologic characteristics of colonizations and invasive CPE infections in the pediatric population, and second, to apply the Giannella Risk Score (GRS) to the pediatric population for the assessment of the risk of invasive CPE infection in patients with already known colonization., Methods: Pediatric patients with evidence of colonization by CPE were retrospectively enrolled. For each colonized patient, the subsequent development of an infection by CPE was then assessed for a 90-day period after the first CPE isolation; GRSs were compared between patients who had developed any type of CPE infection and those without infection., Results: A total of 215 patients (113 males and 102 females) with at least 1 isolation of CPE during hospitalization were analyzed. Median age was 5.6 years [interquartile range (IQR), 1.89-12.2 years]. Overall, 28 CPE infections (13%) were documented: 23 blood stream infections and 5 complicated urinary tract infections. The 30-day mortality of invasive CPE infections was 34.8%. The GRS values in patients with any CPE infection were statistically higher than in noninfected patients: median GRS 9 (IQR, 4-12.5) versus 4 (IQR, 2-4), respectively; P < 0.0001. The analysis of the receiver operating characteristic curves identified a GRS cut-off value ≥8 as the best predictor of CPE infection. The likelihood ratio of the results was <2 and the informedness of the test had a value <0.50., Conclusions: Our study confirms that the spread of CPE is an impelling problem also in the pediatric population, with a high mortality rate of invasive infections. However, the application of the GRS appears to be poorly informative in the pediatric setting; it might sometimes help to identify patients at very low-risk of CPE infection, in whom it is reasonable to spare targeted antimicrobial treatments., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The role of contrast-enhanced ultrasound (CEUS) imaging is being widely explored by various groups for its use in the pediatric population. Clinical implementation of new diagnostic or therapeutic techniques requires extensive and meticulous preclinical testing and evaluation. The impact of CEUS will be determined in part by the extent to which studies are oriented specifically toward a pediatric population. Rather than simply applying principles and techniques used in the adult population, these studies are expected to advance and augment preexisting knowledge with pediatric-specific information. To further develop this imaging modality for use in children, pediatric-focused preclinical research is essential. In this paper we describe the development and implementation of the pediatric-specific preclinical animal and phantom models that are being used to evaluate CEUS with the goal of clinical translation to children., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The quality of contrast-enhanced ultrasound (CEUS) imaging performed with high-frequency convex and linear transducers is often suboptimal. A common solution to improving the microbubble signal is by increasing the volume of the ultrasound contrast agent being administered. An alternative technique to improve the signal from the contrast agent is to adjust the mechanical index (MI). This study aimed to compare the manufacturer's default MI to an optimal MI (as determined by the best contrast-to-tissue ratio) for improving the CEUS image quality using linear and convex transducers. This study found that in most cases, the default CEUS MI setting by the manufacturer is often suboptimal, and increasing the MI is necessary to improve the contrast-to-tissue ratio and image quality. The MI can be modified by the clinician during the study to improve the quality of the clinical CEUS examination., (© 2020 American Institute of Ultrasound in Medicine.)

Antimicrobial resistance is one of the most relevant threats in public health worldwide. Strategies as antimicrobial stewardship programs, aiming to preserve our antibiotic armamentarium, have been implemented since 2007 in adult and paediatric patients. We aim to describe the first experience of a paediatric antimicrobial stewardship program. We conducted a retrospective observational study in a tertiary care children's hospital. A team composed of a microbiologist, an infectious diseases physician, and a paediatrician led the project. All positive blood and cerebrospinal fluid cultures and other biological samples yielding multi-drug-resistant bacteria were collected and reviewed through a prospective-audit-with-feedback strategy. We recorded patient characteristics and worth monitoring prescribed antibiotics. The antimicrobial stewardship audit could end in intervention (step-up/step-down and broadening/narrowing) or recommendation(s). We then checked out wards staff compliance. The team performed 192 interventions out of 584 reviews, mostly suggesting discontinuation of antibiotics (in 76.0% of cases and 39.7% of running molecules). The antibiotic spectrum was more likely tapered than expanded (p < 0.0001), and we ordered more narrow-spectrum antibiotic molecules than local medical staff straightaway did (p = 0.0113). Interventions were most likely needed in case of documented infections (p < 0.0001) and in surgical patients (p = 0.0002). In 85.9% of interventions, ward teams fully agreed with our argument. This study demonstrated an antimicrobial stewardship program to be a suitable method for improving the appropriateness of antimicrobial use in hospitalized children., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For mastering bronchoscope handling, positioning, and directing of the bronchoscope in response to the intraluminal view provided by the bronchoscope camera, sufficient training is necessary, especially in infants and toddlers who have smaller airways, faster respiratory rates, and higher airway collapsibility. With the use of three-dimensional printing, we aimed to develop a set of anatomically accurate and low-cost airway models for teaching and training of bronchoscopy technique and foreign body removal: a translucent airway box model, a static airway model, and a dynamic airway model consisting of a flexible tree model connected to a pump that allows simulation of airway collapsibility during breathing. Computed tomography (CT) patient data of three different ages (1, 5, and 18 years of age) was imported into Materialise Mimics, segmented, and printed using VisoClear and soft Tango+ material. The models were evaluated by three pediatric pulmonology attendings for anatomical accuracy and usefulness for teaching and training. The translucent airway box model was preferred for the initial presentation of bronchoscope handling and learning anatomy in three dimensions. The static and flexible tree models were used to train bronchoscope handling and foreign body removal. The dynamic model provided the most realistic representation of a pediatric airway throughout the respiratory cycle with increased patency during inspiration and relative collapse during exhalation. Objective verification of anatomical accuracy and physiology of breathing motion was obtained by comparing CT scans of the model with original images and by application of 4D dynamic CT airway imaging protocols, respectively., (© 2021 The Authors. Pediatric Pulmonology Published by Wiley Periodicals LLC.)

Lithium is the milestone of psychiatric patients' therapy, in particular in bipolar disorder. Despite its high therapeutic efficacy, there are several side effects (renal, thyroid, parathyroid, dermatological) and management problems linked to its narrow therapeutic range, which exposes patients to a high risk of toxicity. We describe the case of a male patient with bipolar disorder in therapy with lithium sulfate who developed a severe acute-on-chronic intoxication. He came to our attention in a somnolent state with lithemia >3 mEq/L and therefore underwent hemodialysis. In view of the high toxicity of lithium, a timely and correct therapeutic choice is important to improve the patient's outcome. In this context, considering lithemia, but also kidney function and the patient's clinical status, it is necessary to consider extracorporeal treatments, of which hemodialysis is the most preferable., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Objectives: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to <18 years old) with CHC in the real-world setting., Methods: Prospective, open-label, multicentre study involving 12 Italian centres. Patients received the fixed-dose combination of SOF/LDV (400/90 mg) once daily ± ribavirin as per EMA approval and recommendations. The key efficacy endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) as per intention-to-treat analysis. Safety was assessed by adverse events and clinical/laboratory data., Results: Seventy-eight consecutive adolescents (median age 15.2 years, range 12-17.9; girls 53.8%) were enrolled and treated between June 2018 and December 2019. Genotype distribution was as follows: genotype 1 (82.1%), 3 (2.5%), and 4 (15.4%). Seventy-six (97.4%) patients completed treatment and follow-up. Overall, SVR12 was 98.7%. One patient was lost to follow-up after 4 weeks of treatment; 1 patient completed treatment and missed the follow-up visit. No virological breakthrough or relapse were observed. No patient experienced grade 3 to 4 adverse event or serious adverse event., Conclusions: The results of this real-world study confirmed the high efficacy and the optimal safety profile of SOF/LDV for treatment of CHC in adolescents., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Little is known about the sequelae of SARS-CoV-2 infection in children. In a COVID-19 dedicated clinic, we followed-up for 4 months 25 children previously hospitalized for COVID-19, performing clinical, laboratory, and lung ultrasound evaluation. Mid-term sequelae were rarely observed in our COVID-19 children's cohort.

Pediatric radiology departments across the globe face unique challenges in the midst of the current COVID-19 pandemic that have not been addressed in professional guidelines. Providing a safe environment for personnel while continuing to deliver optimal care to patients is feasible when abiding by fundamental recommendations. In this article, we review current infection control practices across the multiple pediatric institutions represented on the Society for Pediatric Radiology (SPR) Quality and Safety committee. We discuss the routes of infectious transmission and appropriate transmission-based precautions, in addition to exploring strategies to optimize personal protective equipment (PPE) supplies. This work serves as a summary of current evidence-based recommendations for infection control, and current best practices specific to pediatric radiologists.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Chronic hepatitis C virus (HCV) infection is associated with several hepatic and extrahepatic complications, including cancers and autoimmune disorders, whose frequency is reduced but not abolished after drug-induced viral clearance. The causes of these complications and of their persistence are ill-defined. Human endogenous retroviruses (HERVs) are remnants of ancestral infections and constitute 8% of the human genome. Most HERV elements are inactive, but some are transcribed. HERV overexpression is associated with many cancers and autoimmune diseases with a putative pathogenetic role. Several viral infections trigger HERV activation, but there are no studies on HCV-infected subjects. We assessed, through a PCR real-time amplification assay, the transcription levels of the pol genes of HERV-H, -K, and -W, and of their repressor TRIM28 in white blood cells (WBCs) of vertically infected children, both before and after therapy with direct-acting antivirals (DAAs). The results documented significantly higher expressions of HERV-H-pol and HERV-K-pol, not of HERV-W-pol, in HCV-infected subjects as compared to age-matched controls. HERV RNA levels remained unchanged after DAA-driven viral clearance. No significant variations in transcription levels of TRIM28 were observed in infected subjects. Our findings demonstrate HERV-H-pol and HERV-K-pol overexpression in subjects with chronic HCV infection, without variations after a positive response to DAAs; this might justify their predisposition to cancers and autoimmune disorders that persist after a DAA-induced resolution of viremia.

Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in adults. Considering its potent bactericidal activity against Pseudomonas aeruginosa , it might represent an important option also for treating children with exacerbations of cystic fibrosis due to Pseudomonas aeruginosa when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis., (Copyright © 2020 Garazzino, Altieri, Silvestro, Pruccoli, Scolfaro and Bignamini.)

Over the last few decades, there has been growing interest in the application of additive manufacturing (AM) or 3D printing for medical research and clinical application. Imaging phantoms offer clear benefits in the way of training, planning, and quality assurance, but the model's availability per catalog tend to be suited for general testing purposes only. AM, on the contrary, offers flexibility to clinicians by enabling custom-built phantoms based on specific interests or even individual patient needs. This study aims to quantify the radiographic properties (ultrasound, magnetic resonance imaging, and computed tomography) of common additive manufacturing technologies and to discuss potential opportunities to fabricate imaging phantoms. Test phantoms were composed of samples from the three most common AM styles, namely PolyJet, fused deposition modeling (FDM), and stereolithography (SLA). Test imaging of the phantoms was performed on ultrasound, MRI, and CT and reviewed and evaluated with radiology software. The ultrasound images showed clearly defined upper and lower edges of the material but did not demonstrate distinct differences in internal echogenicity between materials. The MR scans revealed a distinct signal intensity difference between the model (17 grayscale value) and the printer support (778 grayscale value). Finally, the CT images showed a slight variation between the plastic (82 HU) and rubber (145 HU) materials. The radiographic properties of AM offer a clear opportunity to create basic two- or three-material phantoms. These would be high-accuracy and cost-effective models. Although the materials currently available are not suitable for complex multi-material applications as realistic as true human anatomy, one can easily foresee the development of new materials with broader density in the near future.

Background: The prevalence of neuropsychiatric symptoms (NPS) diminishes the quality of life and increases the care burden in patients with dementia. Despite the clinical importance of dementia-associated NPS, no protocols for treating NPS are already well established. Attention has turned to the effectiveness of nonpharmacological treatments for NPS since their potential safe alternative to pharmacotherapy., Objective: This study is aimed to compare the effects in older individuals with dementia living in a residential care, of two intervention programs, the gesture-verbal treatment (GVT), a treatment implemented by us on a previous method for word retrieval in individuals with aphasia, and the better-known doll therapy (DT). The GVT would act on both receptive and expressive language skills, the DT on attachment and emotional connections., Methods: We evaluated NPS by the neuropsychiatric inventory in a total of 30 patients divided into 3 groups, the GVT, the DT, and control groups, using a pre-post design. The treatment groups completed 12-week nonpharmacological interventions in addition to standard rehabilitative therapies, while the control group participated only in standard rehabilitative therapies., Results: The DT group showed significant improvements in agitation, irritability, apathy, depression, and delusions relative to controls. The GVT group showed significant improvements in apathy and depression with respect to controls. The DT intervention ameliorated symptoms of agitation compared to the GVT intervention whereas the GVT intervention improved apathy compared to the DT intervention., Conclusion: Improved understanding of the potential therapeutic benefits of different treatments for neuropsychiatric symptoms is crucial for establishing nonpharmacological interventions in dementia., (© 2018 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.)

Three-dimensional (3-D) printing is gaining terrain in medical education, presurgical evaluation and recently as forensic evidence in court. Physicians, including radiologists, often provide expert testimony in court cases involving children with rib fractures and other injuries concerning for child physical abuse. Effectively communicating the complexities of fractures and other skeletal findings to nonmedical personnel using standard radiology studies can be challenging, especially during medical courtroom testimony. For this reason, we printed two 3-D models of the rib cage from the chest computed tomography (CT) scans of two patients with suspected non-accidental injury. The patients also had available chest radiographs. The DICOM (Digital Imaging and Communications in Medicine) data were 3-D reconstructed and segmented using two attenuation thresholds. We removed unwanted structures and printed them on a commercially available scanner. A pediatric radiologist, blinded to clinical data, reviewed both 3-D models, identified all rib lesions and classified them according to their healing stage. We compared the 3-D models and the chest radiograph against the chest CT as the standard of care. We convened a meeting with the Child Protection Team at out institution to get their feedback and opinions about the models. From our observations of our experts, three spontaneous interactions were observed. Instinctively, the experts picked up and grasped the models, rotating them, feeling them and angling them to better visualize the fractures from multiple angles. The experts expressed a willingness to consider using the models in court.

Although few cases of bacteremia or sepsis caused by probiotics have been reported, it is important to consider their pathogenic potential, especially in some categories of patients. We report a case of Bifidobacterium spp bacteremia in a child with heart disease, undergoing probiotic supplementation to prevent antibiotic-associated diarrhea.

Mastering the technical skills required to perform pediatric cardiac valve surgery is challenging in part due to limited opportunity for practice. Transformation of 3D echocardiographic (echo) images of congenitally abnormal heart valves to realistic physical models could allow patient-specific simulation of surgical valve repair. We compared materials, processes, and costs for 3D printing and molding of patient-specific models for visualization and surgical simulation of congenitally abnormal heart valves. Pediatric atrioventricular valves (mitral, tricuspid, and common atrioventricular valve) were modeled from transthoracic 3D echo images using semi-automated methods implemented as custom modules in 3D Slicer. Valve models were then both 3D printed in soft materials and molded in silicone using 3D printed "negative" molds. Using pre-defined assessment criteria, valve models were evaluated by congenital cardiac surgeons to determine suitability for simulation. Surgeon assessment indicated that the molded valves had superior material properties for the purposes of simulation compared to directly printed valves (p < 0.01). Patient-specific, 3D echo-derived molded valves are a step toward realistic simulation of complex valve repairs but require more time and labor to create than directly printed models. Patient-specific simulation of valve repair in children using such models may be useful for surgical training and simulation of complex congenital cases.

Aim: To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS)., Methods: The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported., Results: 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment and 17 (31%) did not. 177/247 (72%) women were put on heparin plus LDA. Thrombosis appeared in two during pregnancy and in 14 during the puerperium. 7 (3%) women evolved to complete SLE., Conclusions: OAPS shows differential characteristics than classical APS. All laboratory test categories are needed to avoid false-negative diagnoses. In some cases, complement levels could act as a serological marker. OAPS has very good foetal-maternal outcomes when treated. Thrombosis and progression to SLE in mothers with OAPS are scarce compared with "classical APS", suggesting that they have different aPL-mediated pathogenic mechanisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have poor prognosis, and pulmonary endarterectomy (PEA) is considered the treatment of choice for this condition. We report a case and review the literature of successful PEA for CTEPH due to antiphospholipid syndrome associated with systemic lupus erythematosus. The definitive and decisive approach needed to treat this high-risk patient with a history of comorbidity, long-term illness and poor compliance was found with a therapy of PEA.

We report the experience from the Antiphospholipid Antibodies (aPL) Regional Consortium in northwest Italy, meant to support clinical research and foster collaboration among health professionals regarding the diagnosis and management of antiphospholipid syndrome (APS) patients. This cohort-study (APS Piedmont Cohort) was designed to register the clinical characteristics at inception and associated immunological manifestations at diagnosis (if any) of patients who strictly fulfilled the current criteria for APS, all recruited at the Piedmont and Valle d'Aosta regions. Clinical and laboratory data from 217 APS patients (171 with vascular events, 33 with pregnancy morbidity and 13 with both), from 16 centres within the geographical area were collected. Venous thrombosis was recorded in 45.6% of patients, arterial thrombosis in 35%, small-vessel thrombosis in 1.12% and mixed arterial and venous thrombosis in the remaining 19.4% of the cases. Pregnancy morbidity included 19 patients with unexplained fetal death beyond the 10th week of pregnancy, 17 with premature birth before the 34th week and 10 with three or more unexplained spontaneous abortions before the 10th week of gestation. This consortium represents an instrument by which to audit clinical practice, to provide counselling to local centres and to sustain future basic and clinical APS research.

There is increasing evidence suggesting a relationship between cytokine levels and disease pathogenesis, which has led to interest in analyzing multiple cytokines in biological fluids and culture supernatants for various research and clinical studies. The introduction of methodologies allowing simultaneous measurement of interrelated biomarkers/cytokines has further revolutionized this process. In contrast to tissue culture supernatant, the measurement of cytokines in serum has proven to be difficult to characterize in multiplexed formats because of the presence of large dynamic concentration ranges of proteins and other interfering factors that are present in this matrix. In the present study, we have used the microsphere-based multiplex method to simultaneously quantitate and compare six analytes, encompassing a representation of the Th1/Th2 cytokine panel (interleukin (IL)-2, IL-4, IL-5, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-10), in both serum and culture supernatants from peripheral blood mononuclear cells (PBMCs). A detailed validation procedure for these determinations is described along with a comparative analysis of the performance of the multiplexed assay in serum and culture supernatant matrices. Our results indicate that precision of the multiplexed assay is comparable in both culture supernatant and serum. However, the accuracy of quantification of cytokines in the serum matrix but not in culture supernatant may be compromised depending upon the cytokine being analyzed. Therefore, one must use caution when interpreting data from such complex matrices. Nevertheless, this assay format is appropriate to profile cytokines in clinical trial samples.

We report on a sibship in which three members were affected by Gaucher disease. Molecular analysis of the patients showed homozygosity for a novel mutation (C5390G) of the beta-glucocerebrosidase gene, resulting in the substitution of the arginine 353 with a glycine. Western blot analysis showed a reduced amount of beta-glucocerebrosidase-related polypeptides in fibroblasts. The phenotype resulting from this mutation is characterized by visceral and skeletal manifestations. In addition, the presence of seizures and electrophysiological abnormalities only in the 3 patients and in none of the other unaffected sibs suggests that the mutation is responsible for neurologic involvement.

We have studied motor, somatosensory, brainstem auditory and visual evoked potentials in two patients with ML III without overt neurologic symptoms. Both our patients showed abnormal central motor functions upon magnetic cortical stimulation; in addition, in one of them, we observed a decreased conduction velocity of the nervous impulse in the central tract of the upper limb somatosensory pathway, from the cervical spinal cord to sensory cortex. Our results suggest that central motor pathways are affected in both children and also that the central somatosensory system is involved in one of them. We propose that the electrophysiological techniques might be of help to detect, locate and monitor minimal neurological lesions of mild lysosomal disorders like ML III.