New Approaches and Technologies to Improve Accuracy of Acute Otitis Media Diagnosis

: 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

Preclinical and clinical characterization of fibroblast-derived neuregulin-1 on trastuzumab and pertuzumab activity in HER2-positive breast cancer

[Purpose]: To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab.[Experimental Design]: Characterization of NRG1 expression in tumor cell lines, in tumor specimens, and in cancer-associated fibroblasts (CAFs). Patient-derived CAFs were used to investigate NRG1 impact on the activity of trastuzumab with or without pertuzumab in HER2-positive breast cancer cells. The relationship between NRG1 expression and pathologic response to anti-HER2–based neoadjuvant therapy was assessed in a retrospective patient cohort and in the NeoSphere trial.[Results]: NRG1 was expressed in HER2-positive breast cancer–derived fibroblasts at significantly higher levels than in cancer cells. NRG1 and the conditioned media (CM) from CAFs phosphorylated HER3 and AKT in cancer cells and mediated trastuzumab resistance. Stable genetic depletion of NRG1 from CAFs overcame trastuzumab resistance. Pertuzumab effectively suppressed trastuzumab resistance mediated by either NRG1 or CAF's CM. NRG1 engaged an epithelial-to-mesenchymal transition that was prevented by trastuzumab and pertuzumab. In clinical samples, stromal and/or tumor cell expression of NRG1 determined by immunohistochemistry was uncommon (13.2%) yet significantly linked with residual disease following trastuzumab-based neoadjuvant therapy. In the NeoSphere trial, the magnitude of the difference of pathologic complete response rates favoring the pertuzumab arm was higher in the NRG1-high group.[Conclusions]: CAF-derived NRG1 mediates trastuzumab resistance through HER3/AKT, which might be reverted by pertuzumab. In patients with HER2-positive breast cancer, high expression of NRG1 was associated to poor response to trastuzumab, but not in combination with pertuzumab.This work is supported by ISCIII (CIBERONC CB16/12/00481, CB16/12/00241, PI18/00382, PI18/00006, PI18/01219 and by Generalitat de Catalunya (2017 SGR 507). S. Menendez is supported by Department de Salut, Generalitat de Catalunya (PERIS SLT006/17/00040). MARBiobanc is supported by ISCiii/FEDER (PT17/0015/0011) and by “Xarxa de Bancs de tumors” sponsored by Pla Director d’ Oncologia de Catalunya (XBTC) and Fundacion Jimenez Díaz Biobanks Platform by PT13/0010/0012 grant. Ministry of Economy and Competitiveness of Spain (BFU2015-71371-R) and the CRIS Cancer Foundation provides support to A. Pandiella. Work carried out in our laboratories receive support from the European Community through the Regional Development Funding Program (FEDER). J.C. Montero is funded by the ISCIII through a Miguel Servet program (CPII17/00015) and receives research support from the same institution (PI18/00796). J. Albanell is supported by Breast Cancer Research Foundation (BCRF20-08), Instituto de Salud Carlos III Project Reference number AC15/00062 and the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181), and Asociacion Espanola Contra el Cáncer (AECC)

Antimicrobial Prophylaxis in Neonates and Children Undergoing Dental, Maxillo-Facial or Ear-Nose-Throat (ENT) Surgery: A RAND/UCLA Appropriateness Method Consensus Study

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

Surgical Antimicrobial Prophylaxis in Patients of Neonatal and Pediatric Age Undergoing Orthopedic and Hand Surgery: A RAND/UCLA Appropriateness Method Consensus Study

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

Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5\u20139 years and lymphopenia were statistically related to ICU admission (p < 0.05). Garazzino et al. SARS-CoV-2 in Children and Adolescents Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission

Surgical Antimicrobial Prophylaxis in Neonates and Children Undergoing Neurosurgery: A RAND/UCLA Appropriateness Method Consensus Study

Pediatric neurosurgery is a highly specialized branch of surgery in which surgical site infections (SSIs) are potentially serious complications that can also adversely affect a good surgical outcome, compromising functional recovery and, in some cases, even putting the patient's life at risk. The main aim of this consensus document is to provide clinicians with a series of recommendations on antimicrobial prophylaxis for neonates and children undergoing neurosurgery. The following scenarios were considered: (1) craniotomy or cranial/cranio-facial approach to craniosynostosis; (2) neurosurgery with a trans-nasal-trans-sphenoidal approach; (3) non-penetrating head injuries; (4) penetrating head fracture; (5) spinal surgery (extradural and intradural); (6) shunt surgery or neuroendoscopy; (7) neuroendovascular procedures. Patients undergoing neurosurgery often undergo peri-operative antibiotic prophylaxis, with different schedules, not always supported by scientific evidence. This consensus provides clear and shared indications, based on the most updated literature. 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 on the behavior to be held in the peri-operative setting in this type of intervention, in order to guide physicians in the management of the patient, standardize approaches and avoid abuse and misuse of antibiotics

Peri-Operative Prophylaxis in Patients of Neonatal and Pediatric Age Subjected to Cardiac and Thoracic Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs) represent a potential complication of surgical procedures, with a significant impact on mortality, morbidity, and healthcare costs. Patients undergoing cardiac surgery and thoracic surgery are often considered patients at high risk of developing SSIs. This consensus document aims to provide information on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing cardiac and non-cardiac thoracic surgery. The following scenarios were considered: (1) cardiac surgery for the correction of congenital heart disease and/or valve surgery; (2) cardiac catheterization without the placement of prosthetic material; (3) cardiac catheterization with the placement of prosthetic material; (4) implantable cardiac defibrillator or epicardial pacemaker placement; (5) patients undergoing ExtraCorporal Membrane Oxygenation; (6) cardiac tumors and heart transplantation; (7) non-cardiac thoracic surgery with thoracotomy; (8) non-cardiac thoracic surgery using video-assisted thoracoscopy; (9) elective chest drain placement in the pediatric patient; (10) elective chest drain placement in the newborn; (11) thoracic drain placement in the trauma setting. This consensus provides clear and shared indications, representing the most complete and up-to-date collection of practice recommendations in pediatric cardiac and thoracic surgery, in order to guide physicians in the management of the patient, standardizing approaches and avoiding the abuse and misuse of antibiotics

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered