The usefulness of point-of-care ultrasound in dehydrated patients in a pediatric emergency department.

BACKGROUNDS: Dehydration is among the most common causes of Pediatric Emergency Department admission; however, no clinical signs, symptoms, or biomarkers have demonstrated sufficient sensitivity, specificity, or reliability to predict dehydration. METHODS: We conducted a prospective, monocentric, observational study at Giannina Gaslini Hospital, a tertiary care pediatric hospital. Our study aimed to compare inferior vena cava ultrasound measurement with volume depletion biomarkers to understand if point-of-care ultrasound could help grade, evaluate, and better manage dehydration in children presenting to the pediatric emergency department. We enrolled patients under the age of 14 who required blood tests in the suspect of dehydration; for each patient, we collected values of venous pH, natremia, bicarbonatemia, uric acid, chloremia, and blood urea nitrogen. For each patient, we performed two ultrasound scans to calculate the Inferior Vena Cava/Aorta area ratio and to assess the IVC collapsibility index; moreover, we described the presence of the "kiss sign" (100% IVC walls collapsing during the inspiratory phase). RESULTS: Patients with the "kiss sign" (25/65 patients, 38.5% of the total) showed worse blood tests, in particular, uric acid levels (p = 0.0003), bicarbonatemia (p = 0.001) and natriemia (p = 0.0003). Moreover, patients with the "kiss sign" showed a high frequency of ≥ 2 pathological blood tests (p = 0.0002). We found no statistical significant difference when comparing the IVC/Ao ratio and IVC-CI with the considered blood tests. CONCLUSIONS: The "kiss sign" seems to be related to worse hydration state, whereas IVC/Ao and IVC-CI are not. In an emergency setting, where physicians must take diagnostic-therapeutic decisions quickly, the presence of the "kiss sign" in patients suspected to be dehydrated can be a helpful tool in their management.

Difficult Intravascular Access in Pediatric Emergency Department: The Ultrasound-Assisted Strategy (DIAPEDUS Study).

Vein line positioning represents one of the first diagnostic and therapeutic steps in Pediatric Emergency Department (PED); however, the outcome of this maneuver is frequently not as expected, especially for difficult-to-access (DIVA) patients. The standard technique (visual-palpatory) has a low success rate; hence ultrasound (US) assistance has been suggested for DIVA patients, although controversial results have been obtained. Our study compared the success rate of an intravascular (IV) access procedure at the first attempt, with and without ultrasound assistance, in pediatric DIVA patients. Secondary objectives were the global success rate, the mean procedural time, the IV device's life span, and the complications rate. We conducted an observational, prospective, monocentric, no-profit cohort study enrolling 110 patients presenting to our ED, aged 0-21 years. All the patients were considered difficult-to-access patients according to the DIVA score (≥4) or history of previous difficult intravascular access. They were randomized into two homogeneous groups: 50 patients with the standard and 60 with the US-assisted technique. We obtained a significantly higher success rate at first attempt with the US-guided technique (90% vs 18%, p ≤ .00001). Moreover, the overall success rate was higher in the US group (95% vs 46%, p < .00001). The mean procedural time resulted significantly less in the US group (2.7 ± 2.2 min vs 10 ± 6.4 min, p < .0001), as well as the overall number of attempts to obtain a stable IV line (1.09 ± 0.34 attempts vs 2.38 ± 1.09 attempts, p < .0001). We experienced some post-procedural complications without differences in the two groups, although none were severe. Our study showed that bedside ultrasound assisting implantation of peripheral venous access in pediatric DIVA patients improves first-time success rate, overall success rate, procedural time, and patient comfort, reducing the number of attempts to obtain a stable IV line.

Individual, environmental and demographic factors may play a role in the prognosis of fatal and non-fatal paediatric drowning.

AIM: Drowning is a leading cause of unintentional death. Ongoing efforts are dedicated to preventing these tragic incidents. Our aim was to evaluate whether demographic, environmental and epidemiological characteristics of drowned children influence their prognosis. METHODS: Single-centre retrospective study spanning 12 years. Each patient's record included: age, sex, place of residence, presence of siblings, season of incident, location of event, associated trauma, loss of consciousness, need for cardiopulmonary resuscitation, intubation, admission to intensive care unit, length of stay and mortality. RESULTS: We enrolled 60 patients, with a mean age of 5.9 ± 3.4 years; 63.5% were male. Children who did not reside near the sea were significantly older than those who did (p = 0.01) and faced a higher risk of experiencing sea-related drowning (p = 0.05). No patients died. Loss of consciousness and need for cardiopulmonary resuscitation were recorded in 30 and 19 patients respectively. Seven patients sustained trauma. Only one patient requiring intubation. Pool-related drowning were associated with a higher incidence of needing cardiopulmonary resuscitation (p = 0.02). The need for cardiopulmonary resuscitation (p = 0.05) and the occurrence of trauma (p = 0.02) were identified as risk factors for a longer hospitalisation. CONCLUSION: Prevention and early initiation of cardiopulmonary resuscitation are essential for achieving a favourable prognosis. Identifying demographic and environmental risk factors may help identify other effective preventive measures.

Kidney Involvement in PSTPIP1 Associated Inflammatory Diseases (PAID): A Case Report and Review of the Literature.

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, and the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome are two distinct clinical conditions caused by heterozygous mutations of the PSTPIP1 gene. While skin and joint involvements are shared by both conditions, PAMI is characterized by hepatosplenomegaly, pancytopenia, and growth failure. Kidney involvement is exceptional in PSTPIP1-mediated disorders. The two missense PSTPIP1 variants associated with PAMI syndrome are p.E250K and p.E257K. Long-term treatment with interleukin (IL)-1 inhibitors is effective to control inflammatory manifestations and is usually well-tolerated. We report a case of a patient carrying the PSTPIP1 p.E250K mutation who developed a late-onset kidney involvement despite a long treatment with canakinumab and anakinra. Kidney biopsy showed focal segmental glomerulosclerosis that was treated with tacrolimus (0.1 mg/kg/day in two doses). A literature revision with the aim to assess the proportion and type of kidney involvement in PAMI syndrome revealed that heterogeneous nephropathies may be part of the clinical spectrum. Our study supports the importance of a periodic diagnostic work-up, including kidney laboratory tests and kidney biopsy, in individuals affected with PAMI syndrome. Kidney and liver functions may be impaired regardless of anti-cytokines treatments and additional therapy approaches (i.e., multi-drugs, hematopoietic stem cell transplantation) should be carefully considered.

Second Wave Antibodies in Autoimmune Renal Diseases: The Case of Lupus Nephritis.

Clinical Trial registry name and registration number: Zeus study, NCT02403115.

Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study.

OBJECTIVES: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. METHODS: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. RESULTS: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. CONCLUSIONS: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. TRIAL REGISTRATION: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Failure of anti Interleukin-1 ß monoclonal antibody in the treatment of recurrent pericarditis in two children.

BACKGROUND: Recurrent pericarditis (RP) is a complication (15-30%) of acute pericarditis with an unknown etiology. Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, with the addition of corticosteroids in resistant or intolerant cases. In the last decade anakinra was shown as an effective treatment in patients with colchicine resistant and steroid-dependent RP, initially in anecdotal reports in children and more recently in a randomized trial. Canakinumab is a monoclonal antibody selectively blocking IL-1ß and its use is only anecdotally reported to treat pericarditis. We report two pediatric patients with refractory recurrent pericarditis, who presented an optimal response to anakinra treatment but prompt relapse after switch to canakinumab. CASE PRESENTATION: The first patient is a girl with Recurrent Pericarditis started in April 2015, after heart surgery. NSAIDs and oral steroids were started, with prompt relapse after steroid suspension. The child showed a steroid-dependent RP; anakinra was therefore started with excellent response, but discontinued after 2 weeks for local reactions. In July 2016 therapy with canakinumab was started. She experienced four relapses during canakinumab therapy despite dosage increase and steroid treatment. In January 2018 a procedure of desensitization from anakinra was performed, successfully. Anakinra as monotherapy is currently ongoing, without any sign of flare. The second patient is a girl with an idiopathic RP, who showed an initial benefit from NSAIDs and colchicine. However, 10 days after the first episode a relapse occurred and therapy with anakinra was established. Two months later, while being in complete remission, anakinra was replaced with canakinumab due to patient's poor compliance to daily injections. She experienced a relapse requiring steroids 10 days after the first canakinumab injection. Anakinra was subsequently re-started with complete remission, persisting after 24 months follow-up. CONCLUSIONS: We describe two cases of failure of the treatment with anti-IL-1ß monoclonal antibodies in steroid- dependent idiopathic RP. This anecdotal and preliminary observation suggests a different efficacy of the two IL-1 blockers in the management of RP and support a possible pivotal role of IL-1α in the pathogenesis of this condition.

An Update on Antibodies to Necleosome Components as Biomarkers of Sistemic Lupus Erythematosus and of Lupus Flares.

Systemic lupus erythematosus (SLE) is an autoimmune disease with variable clinical expression. It is a potentially devastating condition affecting mostly women and leading to clinically unpredictable outcomes. Remission and flares may, in fact, alternate over time and a mild involvement limited to few articular sites may be followed by severe and widespread organ damage. SLE is the prototype of any autoimmune condition and has, for this reason, attracted the interest of basic immunologists. Therapies have evolved over time and clinical prognosis has, in parallel, been improved. What clinicians still lack is the possibility to use biomarkers of the disease as predictors of outcome and, in this area, several studies are trying to find solutions. Circulating autoantibodies are clearly a milestone of clinical research and the concrete possibility is to integrate, in the future, classical markers of activation (like C3) with target organ autoantibodies. Anti-dsDNA antibodies represent a basic point in any predictive attempt in SLE and should be considered the benchmark for any innovative proposal in the wide field of target organ pathologies related to SLE. DNA is part of the nucleosome that is the basic unit of chromatin. It consists of DNA wrapped around a histone octamer made of 2 copies each of Histone 2A, 2B, 3, and 4. The nucleosome has a plastic organization that varies over time and has the potential to stimulate the formation of antibodies directed to the whole structure (anti-nucleosome) or its parts (anti-dsDNA and anti-Histones). Here, we present an updated review of the literature on antibodies directed to the nucleosome and the nucleosome constituents, i.e., DNA and Histones. Wetriedto merge the data first published more than twenty years ago with more recent results to create a balanced bridge between old dogma and more recent research that could serve as a stimulus to reconsider mechanisms for SLE. The formation of large networks would provide the chance of studying large cohorts of patients and confirm what already presented in small sample size during the last years.

Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome.

AIMS: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions. METHODS: We investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid-dependent and steroid/calcineurin inhibitor-dependent disease) treated at a national referral centre over a 9-year period (400 treatments; follow-up 1-9 years). RESULTS: Infusion reactions were mainly absent in children with steroid-dependent disease. Rash, dyspnoea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion, respectively) were resolved by using premedication with salbutamol. Other short-term reactions (up to 3 months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3-9 months following infusion, were similarly common in the two groups and resolved with targeted therapies [antibiotic, fluconazole, immunoglobulins (Igs), etc.]. The number of circulating CD19/20 cells fell to 0 at month 1 and were reconstituted at month 3; circulating IgG antibodies remained within the normal range for 1 year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein-Barr virus and John Cunningham virus activation markers were occasionally observed. CONCLUSION: Overall, the toxicity of anti-CD20 monoclonal antibodies was limited to post-infusion side effects in children with more complex disease. The relatively safe profile of anti-CD20 antibodies supports their use as steroid-sparing agents in children with INS.

Management of Lyme Disease in European Children: a Review for Practical Purpose.

PURPOSE OF REVIEW: Lyme disease is a tick-borne zoonosis transmitted through a bite of a tick carrying a spirochete belonging to Borrelia species. In the last 20 years, the reported incidence of Lyme disease is increased by three times in Europe. Clinically, the illness develops through a primary stage with a typical skin rash (erythema marginatum), then a secondary stage with possible neurologic or cardiac involvement. The last stage (chronic Lyme disease) is mainly represented by arthritis or late neurological complications but nowadays is rarely seen due to precocious antibiotic use. RECENT FINDINGS: The diagnosis of Lyme disease is essentially based on history in agreement with tick exposure (living/recent traveling in endemic area or tick bite) and clinical findings compatible with the disease. At present, no laboratory diagnostic tool available can neither establish nor exclude the diagnosis of Lyme disease. The management of Lyme disease should comprise a prophylactic administration of antibiotic in selected population (patients exposed to a tick bite in endemic regions) in which the typical signs of Lyme disease are not yet appeared; conversely, patients with current signs of Lyme disease should undergo a standard therapeutic course. First-line therapy should be oral tetracycline or oral penicillin/cephalosporin (in pediatric populations, beta-lactamic drugs are preferred). In severe courses, intravenous route should be preferred. The aim of this review is to provide an updated guide to the management of pediatric Lyme patients, from prophylaxis to first- and second-line therapy in European setting.

Ofatumumab-associated acute pneumonitis: Not new but still the first case.

Ofatumumab is an anti-CD20 humanized monoclonal antibody utilized in the treatment of several clinical conditions resistant to other treatments. In spite there was a general expectation that ofatumumab was less toxic compared to rituximab, side effects have been reported that resemble those of its anti-CD20 chimeric precursor. Here, we describe the first case of Ofatumumab associate lung injury occurring in a 14-year-old boy affected by nephrotic syndrome dependent to prednisone plus cyclosporine A who had been treated with the dose of drug utilized in nephrotic syndrome (1500 mg/173 m2). The patient developed the full blown picture of rituximab associated lung injury (RALI) after 45 days from ofatumumab infusion at the end of the steroid tapering: severe exertional dyspnea, mild fever and cyanosis, with CT scan showing diffuse ground glass areas in both lungs and DLCO (diffusing capacity of transfer factor of the lung for carbon monoxide) test suggestive for reduction of CO diffusion. Clinical outcome was good with rapid improvement and normalization of all parameters without any specific therapy. After 60 days, chest CT and CO diffusion tests were normal. In conclusion, we describe here the first case of acute pneumonitis associated with ofatumumab that presents the same clinical, laboratory, and radiology features of the lung injury reported for rituximab. Like RALI occurring in patients treated for nephrotic syndrome, this case had a mild clinical expression and recovered in a few months.

A Long-Term Psychological Observation in an Adolescent Affected with Gardner Diamond Syndrome.

Gardner-Diamond syndrome (GDS) is an uncommon disease clinically characterized by a wide spectrum of psycho-emotive symptoms associated with painful ecchymoses/purpuric lesions and positivity of auto-erythrocyte sensitization skin test. Herein, a perspective clinical and psychological observation of an adolescent GDS is firstly reported focusing on her psychological features long-term monitored for a 1-year period. The administration of a standardized tools battery allowed us to define psychological features of the young patient over time and to monitored clinical course and response to treatment.

Cytomegalovirus-related necrotising vasculitis mimicking Henoch-Schönlein syndrome.

Viral vasculitides have been previously reported in the literature, the role of infections in their pathogenesis ranging from direct cause to trigger event. Here we report the case of a 3-year-old immunocompetent girl who developed a systemic vasculitis leading to ileal perforation, mimicking a full blown picture of Henoch-Schönlein purpura. High dosage steroid treatment was started, with good response. The anatomopathological examination of the resected gastrointestinal tract showed features of necrotising vasculitis and cytomegalovirus (CMV)-related inclusion bodies in the endothelial cells, with direct correlation to vascular damage. The causative role of viral infection was revealed by the presence of CMV DNA in patient's blood and positive IgG titer against the virus. Steroid therapy was then tapered: the patient achieved clinical remission, which still persists after a six-months follow-up. Our report suggests that CMV vasculitis is probably more frequent than previously thought, even in immunocompetent patients, with a protean clinical presentation, mimicking other types of vasculitides.

Long-term efficacy of interleukin-1 receptor antagonist (anakinra) in corticosteroid-dependent and colchicine-resistant recurrent pericarditis.

OBJECTIVE: To evaluate the long-term response and safety of interleukin-1 receptor antagonist (anakinra) in recurrent pericarditis. STUDY DESIGN: Fifteen patients (12 children, 3 adults) were enrolled in a multicenter retrospective study. All the patients were corticosteroid-dependent and 14 had received colchicine. Anakinra was given at 1-2 mg/kg/d. The primary outcome of the study was a reduction of at least 70% of disease flares after anakinra treatment compared with the pretreatment period. Secondary outcomes were: (1) number of complete or partial responders to anakinra and time for complete response; (2) number of patients who discontinued other ongoing treatments (non-steroidal anti-inflammatory drugs, corticosteroid, colchicine) and time needed for discontinuation; (3) number of relapses during continuous anakinra treatment; and (4) number of relapses during anakinra tapering or discontinuation. RESULTS: All patients treated had a complete response within a few days and were able to rapidly withdraw concomitant treatments, including corticosteroids. During daily treatment, no patient had a relapse of the disease; 14 patients started tapering and 6 of them experienced a relapse, with a prompt response after anakinra reintroduction. Overall, after a median follow-up of 39 months (range 6-57), a 95% reduction of flares was observed compared with pretreatment period. CONCLUSION: The long-term use of anakinra in monotherapy is associated with persistent control of recurrent pericarditis.

Primary red ear syndrome associated with cochleo-vestibular symptomatology: a paediatric case report.

BACKGROUND: Red ear syndrome (RES), first described by Lance in 1996 in an adult series, may be primary or associated with headache syndromes, upper cervical disorders or vascular anomalies. Clinically the disease is characterised by recurrent episodes of reddening and burning pain in the auricle, usually elicited by different triggers. The prevalence of RES in the paediatric age group remains poorly understood. Several therapeutic approaches have been tried with heterogeneous clinical response. CASE RESULTS: We report a paediatric patient suffering from primary RES associated with debilitating cochleo-vestibular symptomatology causing severe discomfort. Three years after the disease onset, the patient also developed headache, with clinical features of migraine. DISCUSSION: The temporal and spatial association could suggest shared pathogenetic features between neurological (cochleo-vestibular) and vascular (red and burning ear) symptomatology, likely related to trigeminal autonomic reflex activation, although further studies are required for full comprehension of RES pathogenesis.