Timeline of diagnosed pain causes in children with severe neurological impairment.

Objective: Pain's causes in children with severe cognitive impairment may be challenging to diagnose. This study aimed to investigate if there is a relationship between pain causes and the age of children. Methods: We conducted a multicenter retrospective study in three Italian Pediatric Units. Eligible subjects were patients from 1 to 18 years with severe neurological impairment. We collected data regarding diagnoses, pain causes and medical or surgical procedures. The timing of pain episodes was categorized into age-related periods: infants and toddlers (0-24 months), preschool children (3-5 years), schoolchildren (6-12 years), and adolescents (13-17 years). Results: Eighty children with severe neurological impairment were enrolled. The mean age was 11 years (±5.8). Gastroenterological pain was most common in the first years of life (p = 0.004), while orthopaedic and tooth pain was the most typical in schoolchildren and adolescents (p = 0.001 and p = 0.02). Concerning surgical procedures, PEG placement and gastric fundoplication were significantly more common in the first 5 years of age (p = 0.03), and heart surgery was typical of infants (p = 0.04). Orthopaedic surgery was more commonly reported in older children and adolescents (p < 0.001). Conclusions: Some causes of pain are more frequent in children with severe neurological impairment in defined age-related periods. Specific age-related pain frequencies may help physicians in the diagnostic approach.

Italian pediatric intensive care units admitting critically ill cancer children: results from a national survey.

BACKGROUND: Pediatric patients affected by oncologic disease have a significant risk of clinical deterioration that requires admission to the intensive care unit. This study reported the results of a national survey describing the characteristics of Italian onco-hematological units (OHUs) and pediatric intensive care units (PICUs) that admit pediatric patients, focusing on the high-complexity treatments available before PICU admission, and evaluating the approach to the end-of-life (EOL) when cared in a PICU setting. METHODS: A web-based electronic survey has been performed in April 2021, involving all Italian PICUs admitting pediatric patients with cancer participating in the study. RESULTS: Eighteen PICUs participated, with a median number of admissions per year of 350 (IQR 248-495). Availability of Extracorporeal Membrane Oxygenation therapy and the presence of intermediate care unit are the only statistically different characteristics between large or small PICUs. Different high-level treatments and protocols are performed in OHUs, non depending on the volume of PICU. Palliative sedation is mainly performed in the OHUs (78%), however, in 72% it is also performed in the PICU. In most centers protocols that address EOL comfort care and treatment algorithms are missing, non depending on PICU or OHU volume. CONCLUSIONS: A non-homogeneous availability of high-level treatments and in OHUs is described. Moreover, protocols addressing EOL comfort care and treatment algorithms in palliative care are lacking in many centers.

Photobiomodulation for Lowering Pain after Tonsillectomy: Low Efficacy and a Possible Unexpected Adverse Effect.

BACKGROUND: Tonsillectomy is one of the most common surgical procedures performed in children as a treatment for obstructive sleep apnea due to tonsil hypertrophy or highly recurrent tonsillitis. Odynophagia, associated with food refusal for the first few days, is a common post-operative complaint. Available drugs for pain management, while efficacious, present some drawbacks, and a novel strategy would be welcome. Photobiomodulation (PBMT), in this context, can represent a possible choice, together with pharmacological therapy. The aim of this study was to evaluate PBMT effects compared to standard pain therapy on nociceptive sensation at different time points and administration of painkiller. METHODS: A registered, controlled, randomized, double-blind clinical trial was performed. Twenty-two patients were recruited and divided into laser-treated (T) or untreated (UT) groups, based on random assignment. In T group, immediately after tonsillectomy, performed with cold dissection technique, laser light was applied to the surgery site (using a Cube 4 from Eltech K-Laser s.r.l., Treviso, Italy), and then hemostasis was performed using bismuth subgallate paste. In C group, the same procedure was performed, except that laser light was switched off. The primary outcome was the difference in pain scores between subject receiving photobiomodulation (PBMT) and subjects receiving standard care after 24 h; the secondary outcomes were pain scores at awakening and at 48 h together with distress (delirium) at awakening. RESULTS: Two patients from the T group experienced a post-surgery bleeding, and one of them required revision of the hemostasis under general anesthesia. A preliminary analysis of pain sensation reported by the patients or caregivers did not show differences between treated and untreated subjects. CONCLUSION: These data suggest that PBMT could increase post-surgical bleeding.

In vitro effects of photobiomodulation therapy on 50B11 sensory neurons: evaluation of cell metabolism, oxidative stress, mitochondrial membrane potential (MMP), and capsaicin-induced calcium flow.

The analgesic properties of photobiomodulation therapy (PBMT) have been raising increasing interest in the clinical community due to the positive effects observed on patients, nevertheless the mechanistic basis of its action on peripheral sensory neurons remains still elusive. In this study, the effect of near-infrared (NIR) PBMT at 800 and 970 nm of wavelength was investigated on the 50B11 immortalized nociceptive sensory neuronal cell line by evaluating capsaicin-induced calcium flow and different markers correlated to mitochondria, that is, ATP, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP). Calcium peak stimulated by capsaicin, the ligand of TRPV1 channel, was decreased in neurons pre-irradiated with the combination of the two wavelengths. Furthermore, delivering the 800 and 970 nm separately an increment of ATP, as well as MMP hyperpolarization were detected; notably, the 800 nm wavelength also increased ROS and O2- levels. Our findings, obtained on an in vitro model of nociception, show the positive effect of PBMT on two potential photo-targets of NIR light, namely the TRPV1 channel and the mitochondria.

Proteomic Study Identifies Glycolytic and Inflammation Pathways Involved in Recurrent Otitis Media.

Recurrent acute otitis media (RAOM) in children is clinically defined as the occurrence of at least three episodes of acute otitis media over a course of 6 months. A further common pathological condition of interest in the context of pediatric otolaryngology is adenotonsillar hypertrophy (ATH), a common cause of obstructive sleep apnea syndrome. Aimed at unraveling the differential modulation of proteins in the two pathologies and at understanding the possible pathways involved in their onset, we analyzed the proteomic profile of the adenoids from 14 RAOM and ATH patients by using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). The 2-DE coupled with MS allowed us to identify 23 spots with significant (p-value < 0.05) changes in protein amount, recognizing proteins involved in neutrophil degranulation and glycolysis pathways.

Efficacy and safety of exogenous surfactant therapy in patients under 12 months of age invasively ventilated for severe bronchiolitis (SURFABRON): protocol for a multicentre, randomised, double-blind, controlled, non-profit trial.

INTRODUCTION: Some evidence indicates that exogenous surfactant therapy may be effective in infants with acute viral bronchiolitis, even though more confirmatory data are needed. To date, no large multicentre trials have evaluated the effectiveness and safety of exogenous surfactant in severe cases of bronchiolitis requiring invasive mechanical ventilation (IMV). METHODS AND ANALYSIS: This is a multicentre randomised, placebo-controlled, double-blind study, performed in 19 Italian paediatric intensive care units (PICUs). Eligible participants are infants under the age of 12 months hospitalised in a PICU, suffering from severe acute hypoxaemic bronchiolitis, requiring IMV. We adopted a more restrictive definition of bronchiolitis, including only infants below 12 months of age, to maintain the population as much homogeneous as possible. The primary outcome is to evaluate whether exogenous surfactant therapy (Curosurf, Chiesi Pharmaceuticals, Italy) is effective compared with placebo (air) in reducing the duration of IMV in the first 14 days of hospitalisation, in infants suffering from acute hypoxaemic viral bronchiolitis. Secondary outcomes are duration of non-invasive mechanical ventilation in the post-extubation phase, number of cases requiring new intubation after previous extubation within 14 days from randomisation, PICU and hospital length of stay (LOS), duration of oxygen dependency, effects on oxygenation and ventilatory parameters during invasive mechanical respiratory support, need for repeating treatment within 24 hours of first treatment, use of other interventions (eg, high-frequency oscillatory ventilation, nitric oxide, extracorporeal membrane oxygenation), mortality within the first 14 days of PICU stay and before hospital discharge, side effects and serious adverse events. ETHICS AND DISSEMINATION: The trial design and protocol have received approval by the Italian National Agency for Drugs (AIFA) and by the Regional Ethical Committee of Verona University Hospital (1494CESC). Findings will be disseminated through publication in peer-reviewed journals, conference/meeting presentations and media. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, issue date 22 May 2019. NCT03959384.

Case Report: Use of Anakinra in Multisystem Inflammatory Syndrome During COVID-19 Pandemic.

During COVID-19 outbreak, a large number of children with severe inflammatory disease has been reported. This condition, named Pediatric Multi-inflammatory Syndrome temporally associated with COVID-19 (PIMS-TS) or Multisystem Inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C), shares some clinical features with Kawasaki disease and is frequently complicated by myocarditis or shock. It has been suggested that MIS-C belongs to the group of cytokine storm syndromes triggered by SARS-CoV-2 infection. So far, intravenous immunoglobulin (IVIG) and systemic glucocorticoids are the most common therapeutic approaches reported in this group of patients. However, the use of anakinra in patients with severe forms of COVID-19 is showing promising results. Here we reported two patients with multisystem inflammatory syndrome complicated with shock. Both the patients presented a poor response to IVIG and systemic glucocorticoids and received anakinra. Treatment with IL-1 receptor antagonist showed a rapid improvement of clinical conditions and biochemical analysis in both patients and demonstrated a good safety profile. Thus, we look forward for future controlled clinical trials with the aim to demonstrate the effectiveness of anakinra in patients with MIS-C and established precise criteria for its use.