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.

Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying a TINF2 Variant.

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αß+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.

Haploidentical Stem Cell Transplantation After TCR-αß+ and CD19+ Cells Depletion In Children With Congenital Non-Malignant Disease.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a valuable alternative for children with nonmalignant disease and ex vivo negative selection of TCR-αß+ cells is an emerging graft manipulation option that carries several potential advantages in terms of reduced risk of graft-versus-host disease (GvHD) and improved immune reconstitution. We report all consecutive patients with a diagnosis of nonmalignant disease who received a TCR-αß+ and CD19+depleted haplo-HSCT at "IRCCS Istituto Giannina Gaslini" from 2013 to 2019; the conditioning regimen was myeloablative or non-myeloablative, depending on underlying disease; all patients received antithymocyte globulin and rituximab. No post-transplantation GvHD prophylaxis was given in presence of a TCR-αß+ cell dose in the graft lower than the threshold of 1 × 105/kg of the recipient's weight. Among 20 HSCTs, engraftment occurred in 17 (85%) after a median of 14 and 12 days from graft infusion for neutrophils and platelets, respectively. Primary graft failure was diagnosed in 3 (15%) patients, and 2 (10%) experienced secondary rejection; all of these patients underwent a second HSCT. The cumulative incidence of a-GvHD and c-GvHD was 15% (2 = grade 1, 1 = grade 4) at 90 days and 5% (1 = grade 1) at 7 months, respectively. Cytomegalovirus reactivation requiring pre-emptive treatment was observed in 9 patients (45%). One patient developed a JC virus-related progressive multifocal leukoencephalopathy, successfully managed with donor-derived virus-specific T-cell infusions. A complete immunological recovery was reached in most patients within 6 months. After a median follow-up of 4 years, 18 patients are alive, with a cumulative survival probability of 90%. Haplo-HSCT after ex vivo TCR-αß+/CD19+ negative selection may be considered a good option for children with nonmalignant diseases because it ensures a high engraftment rate with an acceptable risk of graft failure, very low incidence of significant GvHD, and good immune reconstitution with low frequency of severe virus-related disease. However, the control of viral infection/reactivation should be kept high to promptly provide pre-emptive treatments and approaches of antiviral adoptive immunotherapy.

Longitudinally Extensive Transverse Myelitis (LETM) and Myopericarditis in a 7-Month-Old Child with SARs-CoV-2 Infection.

INTRODUCTION: In the last few months, some pediatric cases with neurological and neuroradiological pictures related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported, often associated with multisystem inflammatory syndrome (MIS-C). The most frequently encountered pediatric neurological complications seem to be postinfectious immune-mediated acute disseminated encephalomyelitis (ADEM)-like changes of the brain, myelitis, neural enhancement, and splenial lesions. Concomitant neurological and cardiac involvement has been reported only in MIS-C, although specific clinical details are often not fully available. METHODS: In this case report, a very young child infected with SARs-CoV-2 and diagnosed as longitudinal extensive transverse myelitis with concomitant myo-pericarditis is presented. RESULTS: A previously healthy 7-month-old girl presented with abrupt onset of generalized weakness with inability to sit up. She had had mild respiratory symptoms 1 week earlier. Spinal magnetic resonance imaging (MRI) showed a T2-hyperintense intramedullary lesion extending from C4 to T2, compatible with acute longitudinally extensive transverse myelitis (LETM). Cerebrospinal fluid analysis was negative.Echocardiography and blood tests were suggestive for myo-pericarditis. Real time polymerase chain reaction for SARS-CoV-2 on nasopharyngeal swab sample tested positive. She was promptly treated with high dose of steroids and immunoglobulin with satisfactory clinical response. CONCLUSION: To the evolving literature of neurological complications of SARs-CoV-2 infection, we add the youngest patient described to date with isolated LETM and concomitant cardiac involvement. Our case suggests that clinicians should be aware of this association, although difficult to recognize in infants. Practitioners are encouraged to consider aggressive first-line immunotherapies with the final aim to prevent permanent disability.