Recurrent Respiratory Infections in Children with Down Syndrome: A Review.

Down Syndrome (DS) is the most common chromosomal abnormality compatible with life. The life of patients suffering from DS can be strongly impacted by Recurrent Respiratory tract Infections (RRIs), leading to an increased rate of hospitalisation, a higher need for intensive care and fatality. With a literature review, we summarise here the main etiological factors for RRI in this category of patients, particularly focusing on airway malformations such as tracheomalacia, tracheal bronchus and bronchomalacia, comorbidities associated with the syndrome, like congenital heart diseases, dysphagia, gastroesophageal reflux, musculoskeletal involvement and obesity, and immunologic impairments, involving both innate and adaptive immunity. For these patients, a multidisciplinary approach is imperative as well as some preventive strategies, in particular vaccinations in accordance with their national schedule for immunization.

Allogeneic Mesenchymal Stromal Cells as a Global Pediatric Prospective Approach in the Treatment of Respiratory Failure Associated with Surfactant Protein C Dysfunction.

Mesenchymal stromal cells (MSCs) have been proposed as a new therapeutic strategy to treat congenital and acquired respiratory system diseases. We describe a case report of an 18-month-old male patient with progressive chronic respiratory failure, associated with mutations of the surfactant protein C gene (SFTPC) due to c.289G > T variant p.Gly97Ser (rs927644577) and c.176A > G variant (p.His59Arg), submitted to repeated intravenous infusions of allogeneic bone marrow (BM) MSCs. The clinical condition of the patient was monitored. Immunologic studies before and during MSC treatment were performed. No adverse events related to the MSC infusions were recorded. Throughout the MSC treatment period, the patient showed a growth recovery. Starting the second infusion, the patient experienced an improvement in his respiratory condition, with progressive adaptation to mechanical ventilation. After the third infusion, five hours/die of spontaneous breathing was shown, and after infusion IV, spontaneous ventilation for 24/24 h was recorded. A gradual decrease of lymphocytes and cell subpopulations was observed. No variations in the in vitro T cell response to PHA were determined by MSC treatment as well as for the in vitro B cell response. A decrease in IFN-γ, TNF-α, and IL-10 levels was also detected. Even though we cannot exclude an improvement of pulmonary function due to the physiological maturation, the well-known action of MSCs in the repair of lung tissue, together with the sequence of events observed in our patient, may support the therapeutic role of MSCs in this clinical condition. However, further investigations are necessary to confirm the result and long-term follow-up will be mandatory to confirm the benefits on the pulmonary condition.

Hypertensive pneumothorax with cystic lesions: Pleuropulmonary blastoma in an infant.

Pleuropulmonary blastoma (PPB) is a rare primitive malignant lung cancer that occurs in pediatric age. Its main differential diagnosis is congenital cystic pulmonary malformation (CPAM). A 30-day-old infant with respiratory failure obtained a chest x-ray and a computed tomography scan (CT) which revealed hypertensive pneumothorax with multifocal bilateral cysts. After thoracic drainage, the patient underwent multiple thoracoscopic pulmonary resections. The first histological diagnosis was of type 2 CPAM. During the radiological follow-up, an increase in the number and dimension of the lesions was detected. Thus, a histological revision was performed, leading to the diagnosis of type I PPB, at nine months. The patient subsequently underwent chemotherapy. At the five-year follow-up appointment, chest magnetic resonance (MR) and CT scans showed a dimensional increase in size of the lesions, with the risk of recurrent pneumothorax. An upper right lobectomy and wedge resection of the residual cysts were performed. Control MR scans showed normalization of the lung parenchyma and the patient showed substantial clinical improvement.

Congenital Lung Malformations: Clinical and Functional Respiratory Outcomes after Surgery.

Congenital lung malformations (CLMs) involve anomalies of the lungs and respiratory tree such as congenital pulmonary airway malformation (CPAM), pulmonary sequestration (PS), bronchogenic cysts, congenital lobar emphysema, and bronchial atresia (BA). Although symptomatic lesions require surgical resection, the appropriateness of surgery for patients with asymptomatic malformations is a matter of ongoing debate. Limited data are available concerning the long-term follow-up of affected subjects. In this study, we sought to evaluate the long-term clinical and functional respiratory outcomes in children with CLMs who underwent surgical resection. We carried out a retrospective analysis of 77 children with CLMs who underwent pulmonary resection with at least one year of follow-up. The most common diagnoses were CPAM (50.65%), hybrid lesions (25.97%), lobar emphysema (11.69%), and PS (5.19%). The most common surgical approaches were lobectomy (61.3%), segmentectomy (10.7%), and pneumonectomy (5.3%). Acute post-surgery complications occurred in 31.2% of children. In addition, 73.7% experienced long-term complications, and we found no correlation between the presence of these complications and the sex of the patients, their age at time of surgery, the type of surgery undergone, the presence of symptoms prior to intervention, or acute complications after surgery. Pulmonary function tests revealed FEV1 Z-scores of <−2 SDs in 16 patients, and we found a significant correlation between pneumonectomy and the development of lung function deficit (p = 0.031). In conclusion, clinical and functional respiratory complications may occur in children with CLMs who undergo surgical resection. Long-term monitoring is needed to improve the management of asymptomatic patients.

Non-Occlusive Mesenteric Ischemia in Children With Diabetic Ketoacidosis: Case Report and Review of Literature.

Introduction: Despite the use of technology, recurrent diabetic ketoacidosis (DKA) prevention remains an unmet need in children and adolescents with T1D and may be accompanied by life-threatening acute complications. We present a rare case of non-occlusive mesenteric ischemia (NOMI) with overt manifestation after DKA resolution and a discussion of recent literature addressing DKA-associated NOMI epidemiology and pathogenesis in children and adolescents. Case Presentation: A 13-year-old female with previously diagnosed T1D, was admitted at our emergency department with hypovolemic shock, DKA, hyperosmolar state and acute kidney injury (AKI). Mildly progressive abdominal pain persisted after DKA correction and after repeated ultrasound evaluations ultimately suspect for intestinal perforation, an intraoperative diagnosis of NOMI was made. Conclusion: The diagnosis of DKA-associated NOMI must be suspected in pediatric patients with DKA, persistent abdominal pain, and severe dehydration even after DKA resolution.

Six-month multidisciplinary follow-up in multisystem inflammatory syndrome in children: An Italian single-center experience.

Background: A severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 has been described after infection. A limited number of reports have analyzed the long-term complications related to pro-inflammatory status in MIS-C. We evaluated multiorgan impairment at the 6-month follow-up in MIS-C. Methods: We enrolled 33 pediatric patients consecutively hospitalized for MIS-C and monitored for almost 6 months. The inter-relationship of patient's features and disease severity at admission with long term complications was studied by multivariate analysis. Results: Endo-metabolic derangement, cardiac injury, respiratory, renal and gastrointestinal manifestations and neurological involvement are part of the initial presentation. The most abnormalities appear to resolve within the first few weeks, without significant long term dysfunction at the 6-months follow-up, except for endocrine (non-thyroidal illness syndrome in 12.1%, insulin resistance in 21.2%) and neurological system (27.3% cognitive or psychological, behavioral, adaptive difficulties). Endocrine and heart involvement at admission represent a significant factor on the long term sequelae; however no association between severity score and long-term outcome was noted. Conclusions: The severity of initial clinical presentation may be associated to organ domain, however it is not related to long term sequelae. The prevalent organ restoration supports a predominant indirect immune-mediated injury triggered by a systemic inflammatory response; however a direct damage due to the viral entry could be not excluded. Eventhought our preliminary results seem to suggest that MIS-C is not a long-term risk condition for children health, a longer follow-up is mandatory to confirm this hypothesis.

Agreement between magnetic resonance imaging and computed tomography in the postnatal evaluation of congenital lung malformations: a pilot study.

OBJECTIVES: To compare postnatal magnetic resonance imaging (MRI) with the reference standard computed tomography (CT) in the identification of the key features for diagnosing different types of congenital lung malformation (CLM). METHODS: Respiratory-triggered T2-weighted single-shot turbo spin echo (ss-TSE), respiratory-triggered T1-weighted turbo field echo (TFE), balanced fast field echo (BFFE), and T2-weighted MultiVane sequences were performed at 1.5 T on 20 patients prospectively enrolled. Two independent radiologists examined the postnatal CT and MRI evaluating the presence of cysts, hyperinflation, solid component, abnormal arteries and/or venous drainage, and bronchocele. Diagnostic performance of MRI was calculated and the agreement between the findings was assessed using the McNemar-Bowker test. Interobserver agreement was measured with the kappa coefficient. RESULTS: CT reported five congenital pulmonary airway malformations (CPAMs), eight segmental bronchial atresias, five bronchopulmonary sequestrations (BPS), one congenital lobar overinflation, one bronchogenic cyst, and three hybrid lesions. MRI reported the correct diagnosis in 19/20 (95%) patients and the malformation was correctly classified in 22/23 cases (96%). MRI correctly identified all the key findings described on the CT except for the abnormal vascularization (85.7% sensitivity, 100% specificity, 100% PPV, 94.1% NPV, 95% accuracy for arterial vessels; 57.1% sensitivity, 100% specificity, 100% PPV, 84.2% NPV, 87% accuracy for venous drainage). CONCLUSIONS: MRI can represent an effective alternative to CT in the postnatal assessment of CLM. In order to further narrow the gap with CT, the use of contrast material and improvements in sequence design are needed to obtain detailed information on vascularization, which is essential for surgical planning. KEY POINTS: • Congenital lung malformations (CLMs) can be effectively studied by MRI avoiding radiation exposure. • Crucial features of CLM have similar appearance when comparing CT with MRI. • MRI performs very well in CLM except for aberrant vessel detection and characterization.

Viable phenotype of ILNEB syndrome without nephrotic impairment in siblings heterozygous for unreported integrin alpha3 mutations.

BACKGROUND: Integrin α3 (ITGA3) gene mutations are associated with Interstitial Lung disease, Nephrotic syndrome and Epidermolysis bullosa (ILNEB syndrome). To date only six patients are reported: all carried homozygous ITGA3 mutations and presented a dramatically severe phenotype leading to death before age 2 years, from multi-organ failure due to interstitial lung disease and congenital nephrotic syndrome. The involvement of skin and cutaneous adnexa was variable with sparse hair and nail dysplasia combined or not to skin lesions ranging from skin fragility to epidermolysis bullosa-like blistering. RESULTS: We report on two siblings of 13 and 9 years born to non-consanguineous healthy parents, who display growth delay, severe pulmonary fibrosis with fatigue, dyspnea on exertion and wheezing, atrophic skin with erythematosus lesions, rare eyelashes/eyebrows and pachyonychia. By exome sequencing, we identified two unreported ITGA3 missense mutations, c.373G>A (p.(G125R)) in exon 3 and c.821G>A (p.(R274Q)) in exon 6, affecting highly conserved residues in the integrin α3 extracellular N-terminal ß-propeller domain. Homology modelling of α3ß1 heterodimer fragment, encompassing the mutation sites, showed that G125 plays a pivotal structural role in the ß-propeller, while R274 might prevent the interaction between integrin and urokinase complex. CONCLUSION: We report a variant of ILNEB syndrome in two siblings differing from the previously reported patients in the lack of nephrotic impairment and survival beyond childhood. Our siblings are the first reported compound heterozygous for ITGA3 mutations; this state as well as the hypomorphic nature of their p.(R274Q) mutation likely account for their survival.

Pulmonary Malformations: Predictors of Neonatal Respiratory Distress and Early Surgery.

OBJECTIVES: The objective of our study is to retrospectively analyze a single-centre series of antenatally detected pulmonary malformations (PM) and to evaluate their postnatal outcome. MATERIALS AND METHODS: We retrospectively reviewed all prenatally diagnosed PM patients referred to our Centre in the period between January 1999 and December 2014. All cases were diagnosed by one of our Maternal-Fetal Specialists by US examination. Congenital pulmonary airway malformation (CPAM) volume ratio (CVR), development of fetal complications, need for fetal therapy, need for neonatal resuscitation and timing of surgery were analyzed. RESULTS: A total of 70 fetuses were diagnosed with a PM in the period of study. An initial CVR higher than 1.6 was found in 16/70 patients (22.8%); 14/16 developed fetal complications (p less than .0001). Fifty-six fetuses (80%) did not develop any complications during pregnancy. To all complicated cases a prenatal treatment was offered, carried out in 12 (1 termination, 1 refusal). Survival rate was 100%. Sixty-three fetuses (90%) were asymptomatic at birth and did not require any neonatal resuscitation. Six patients submitted to fetal therapy and one untreated presented with neonatal respiratory distress, required mechanical ventilation at birth and early surgery in the neonatal period (7/70, 10%). CONCLUSION: CVR > 1.6 and the presence of fetal complications can be considered as predictors of respiratory distress at birth and of the need for early surgery. Nevertheless, the vast majority of PM are asymptomatic at birth and only a small group of fetuses require prenatal and postnatal treatment and support.

Fetal-MRI prenatal diagnosis of severe bilateral lung hypoplasia: alveolar capillary dysplasia case report.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung that affect both acinar structure and the intrinsic pulmonary vasculature. We report prenatal and postnatal imaging with histopathological findings of this rare condition. We, first, describe MR imaging features and discuss its role in prenatal imaging.

Magnetic resonance imaging of renal involvement in genetically studied patients with tuberous sclerosis complex.

PURPOSE: To evaluate renal involvement in tuberous sclerosis complex (TSC). MATERIALS AND METHODS: A series of 24 TSC patients (19 with genetically demonstrated disease), underwent abdominal 1.0-T MR imaging with axial/coronal T1- and T2-weighted scans, with/without fat saturation. We looked for angiomyolipomas (AMLs) and cysts in 47 kidneys of 24 patients. We evaluated the percentage of parenchymal involvement by manual contouring on the coronal scans in 39 kidneys of 20 patients. RESULTS: We detected AMLs in 15/24 (63%) patients and in 27/47 (57%) kidneys, cysts in 14/24 (58%) and in 26/47 (55%); respectively. AMLs were found in 2/4 TSC1 and in 11/15 TSC2 patients, cysts were found in 2/4 TSC1 and in 9/15 TSC2 patients. The global renal involvement ranged from 0 to 32% (median, 18%) in TSC1 and from 0 to 100% (median, 39%) in TSC2 patients. A fair correlation (r=.464) was found between patient's age and renal involvement, a good correlation (r=0.655) between renal involvement and creatinine clearance. CONCLUSION: Renal parenchyma of TSC patients can be evaluated with MR imaging. A detectable renal involvement was found in 83% of patients, higher in TSC2 than in TSC1. Renal function seems to correlate with renal involvement quantified with MR imaging.

Brain apparent diffusion coefficient decrease during correction of severe hypernatremic dehydration.

We report on the brain diffusion MR imaging findings in a neonate with severe hypernatremic dehydration, which resulted in cerebral edema (osmotic edema) and in apparent diffusion coefficient decrease, despite a careful and slow rehydration. This report provides in vivo insight into nervous cell response to osmotic challenge.

Prenatal magnetic resonance imaging of rhombencephalosynapsis and associated brain anomalies: report of 3 cases.

Rhombencephalosynapsis (RES) is a rare congenital abnormality characterized by vermian agenesis and fusion of the cerebellar hemispheres. In the 3 cases reported here, prenatal magnetic resonance imaging clearly depicted cerebellar features characteristic of RES, allowing a definite diagnosis.

Magnetic resonance imaging in prenatal diagnosis of dacryocystocele: report of 3 cases.

The presence of cystic dilation of the lacrimal drainage system (dacryocystocele) in the fetus must be differentiated from less benign paraocular masses. Three cases of dacryocystocele studied during fetal life by ultrasound and magnetic resonance (MR) imaging are reported. The accuracy of prenatal MR imaging facilitated a definite diagnosis depicting the characteristic triad of dacryocystocele: paraocular cystic mass in the medial canthus region, nasolacrimal duct enlargement, and intranasal cyst.

Early prenatal MR imaging diagnosis of polymicrogyria.

The case of a 24-week-old fetus that showed features suggestive of focal cortical developmental anomaly at prenatal MR imaging is presented. The anomaly was confirmed to be polymicrogyria by 34-week prenatal and the 3-day postnatal MR imaging studies. The report demonstrates that the development of polymicrogyria can be assessed throughout different stages by prenatal MR imaging. In the case reported, the additional presence of periventricular heterotopia strongly suggests that a neuronal migration alteration coexisted with a postmigrational disorder.

Prenatal magnetic resonance imaging evaluation of ischemic brain lesions in the survivors of monochorionic twin pregnancies: report of 3 cases.

The death of 1 twin of monochorionic pairs is associated with a significant risk of brain hypoxic-ischemic damage in the survivor. Ultrasound may diagnose cerebral anomalies only a few weeks after the event. We report 3 cases of single survivors of monochorionic-twin pregnancies in which prenatal magnetic resonance imaging detected brain changes earlier and with better definition of the brain abnormalities than ultrasound.