The multiagency approach to Sudden Unexpected Infant Deaths (SUID): eleven years' experience in the Tuscany Region.

BACKGROUND: The Sudden Unexpected Infant Death Syndrome (SUID) is one of the leading causes of mortality in the first year of life. The aim of this work was the retrospective evaluation of the incidence of SUID and the effectiveness of the multiagency approach to this phenomenon in the Tuscany Region. METHODS: Data were obtained from the regional registry of SUID cases in the period 2009-2019. The registry contains both sudden unexpected deaths in the first week of life (Sudden Unexpected Early Neonatal Deaths - SUEND), and those occurring after the first week up to 1 year of age (SUID). RESULTS: In this timeframe a total of 73 sudden unexpected deaths occurred in our region; 32 were Unexplained (i.e. Sudden Infant Death Syndrome - SIDS), 24 Explained, 10 Undetermined, and 7 SUEND. Autopsies were performed in 91% of cases, and in 95% of these by three groups of selected pathologists according to our protocol. We found a low incidence of SUID (0.21 ‰), and SIDS deaths accounted for 0.1‰ of live births (48% of cases) with a high prevalence of infants of non-Italian ethnicity (38% of cases). Bereaved families were able to receive psychological support from mental health professionals and have contact with the family association, Seeds for SIDS. Audits were organized when post-mortem examinations were not carried out or carried out incorrectly in procedural terms, and when the diagnosis was particularly uncertain. CONCLUSIONS: This paper first provides data on SUID mortality based on complete post-mortems in an Italian region. According to these findings we can state that our approach is effective both in terms of correctly performed autopsies and support for bereaved families. Future efforts are necessary to further reduce the incidence of SUID especially among non- Italian infants. An improvement action is also recommended for ensuring a more accurate and consistent picture of the circumstances of death. The final approval of the National Protocol for the management of SUID cases is therefore strongly advocated in order to improve surveillance in this specific field and abolish disparities among the Italian regions.

Can we still do something-and what? - for a seemingly missing syndrome?: "Yes we can".

In this letter, the authors compare the incidence of SUDI and SIDS in the Tuscany Region to the incidence reported by Campi and Bonati in their paper "Can we still do something-and what?- for a seemingly missing syndrome?" that was recently published in this journal. The Tuscany data are directly gathered from the autopsies while the others from the death certificates that are often not reilable, thus causing an understimation of the phenomenon. The real picture of the extent of SIDS is crucial to evaluate the effectiveness of back to sleep campaigns.

Right Diaphragmatic Peak Motion Velocities on Pulsed Wave Tissue Doppler Imaging in Neonates: Method, Reproducibility, and Reference Values.

OBJECTIVES: To test the reproducibility and report the reference ranges of the right diaphragmatic excursion's peak velocities recorded by pulsed wave tissue Doppler imaging in healthy term neonates. METHODS: We formerly assessed intraobserver and interobserver variability of the method for the right hemidiaphragm in a small group of neonates, including ventilated neonates. We did not attempt to test the approach for the left hemidiaphragm because of the recognized high failure rate of visualization. Next, we recorded the peak velocities of both hemidiaphragms throughout inspiration and expiration in 229 healthy term neonates near birth to establish weight-dependent reference ranges for the measurements. RESULTS: The study population included 116 male and 113 female neonates. The reproducibility of the technique was excellent even in neonates supported by ventilation. We always recorded the right diaphragmatic peak velocities in the normative study group, whereas the left ones were only recorded in 110 of 229 (48%) and 148 of 229 (65%) neonates from the anterior and lateral views, respectively. The modality of delivery and sex showed no influence on diaphragmatic kinetics. The mean inspiratory peak velocities ± SD were 1.4 ± 0.2 cm/s for the right hemidiaphragm and 1.5 ± 0.3 cm/s for the left hemidiaphragm. The mean expiratory peak velocities were 1.3 ± 0.2 cm/s for the right hemidiaphragm and 1.4 ± 0.3 cm/s for the left hemidiaphragm. CONCLUSIONS: Measurement of right diaphragmatic kinetics as assessed by pulsed wave tissue Doppler imaging was found to be a reliable technique. Its clinical applicability for the prompt diagnosis and effective management of neonatal respiratory failure deserves further investigation.

Soy-Based Infant Formula: Are Phyto-Oestrogens Still in Doubt?

Although Scientific Societies have stated that there are very few indications for the use of soy-based formula (SF) in infant nutrition, their utilization rates have been repeatedly found to be higher than expected. It is likely that a significant role in this regard is played by the belief that the use of SF during infancy can reduce the risk of the development of several diseases later in life. Although no definitive data that can substantiate these claims have been collected, many people perceive soy consumption to confer significant health benefits and might also use soy for infant nutrition. However, not all the problems regarding safety of SF in infants have been definitively solved. Among risks, the potentially toxic role of the phyto-oestrogens contained in SF is not definitively established. In vitro and animal studies have raised suspicions that SF could have potentially negative effects on sexual development and reproductive function, neurobehavioral development, immune function, and thyroid function. Several studies in humans have aimed to assess whether the results of animal studies can be applied to humans and whether SF can be used in infants following the official recommendations. The results are somewhat conflicting. The aim of this narrative review is to discuss what is presently known regarding the impact of phyto-oestrogens in SF on early and late child development. PubMed was used to search for the studies published from January 1980 to June 2017 using the keywords: "soy," "soy formula," "child," "phytoestrogens." Analysis of the literature showed that a global evaluation of the impact of modern SFs on human development seems to suggest that their use is not associated with relevant abnormalities. Only children with congenital hypothyroidism need adequate monitoring of thyroid function.

Epicutaneous immunotherapy in rhino-conjunctivitis and food allergies: a review of the literature.

BACKGROUND: Epicutaneous immunotherapy (EPIT) is a new way of allergen administration that has a high rate of adherence and safety. The aim of this manuscript is to review clinical trials on EPIT for respiratory and food allergies published in the last 10 years, taking into account how different variables (i.e., dose, patch application duration, skin preparation, and efficacy and safety evaluation) have influenced study results. MAIN BODY: From a review of the literature, we identified eight placebo-controlled, double-blind trials conducted on children and adults, including four studies on grass pollen rhino-conjunctivitis, one on cow's milk allergy and three on peanut allergy. Different methods for skin pre-treatment, such as skin abrasion and tape stripping or stratum corneous hydration by an occlusive system, different endpoints and cumulative allergen doses, and different durations of patch application and tape stripping, were used in the rhino-conjunctivitis studies. A visual analogue system was used for the efficacy evaluation. Several local skin reactions (eczema) and some systemic adverse reactions were reported at higher rates in the active group compared to placebo in one study, but this was not shown by other authors. Local eczema reactions were correlated to the times for applying the tape stripping, while systemic side effects were correlated to the deepness of scraping. In the food allergy trials, differences in the food challenge thresholds, endpoints and allergen sites of the cutaneous patch application influenced the study results. A slight dose-dependent efficacy was found in the peanut allergy studies, which was confirmed by a more significant increase in the following progressive open study. Few adverse events and high adherence in all of the food allergen trials were reported. CONCLUSIONS: Overall, the EPIT study results, even if they were affected by great heterogeneity among the methodologies applied, have shown not only the high safety and adherence with this kind of immunotherapy but also suggested the possibility for obtaining definitive evidence of the efficacy of EPIT, especially for food allergies.

Childhood Asymmetry Labium Majus Enlargement (CALME): Description of Two Cases.

Background: Childhood asymmetry labium majus enlargement (CALME) is an uncommon, benign condition that occurs in pre- and early pubertal girls and is characterized by a painless, fluctuating, non-tender labial swelling with normal overlying skin. Recognition of this benign condition is essential. Differentiation with several other diseases that mimic CALME and require different diagnostic and therapeutic approaches is mandatory. Two cases of CALME are described in this report. Differential diagnoses and therapeutic approaches are highlighted. Case presentation: The first case was an 11-year-old Caucasian girl referred to our hospital for the evaluation of right labium majus, which showed a palpable, painless, soft, non-tender, non-erythematous enlargement measuring approximately 2 cm with indistinct borders. Ultrasound showed a mass 23 × 18 × 12 mm in diameter. Surgical excision of the mass was performed and in the histopathological evaluation, the tissue specimens were composed of haphazardly arranged vascular channels, adipose tissue and nervous elements that were components of the vulvar soft tissue and were compatible with the diagnosis of CALME. Case 2 was a 6-year-old Caucasian girl who presented a post-traumatic painless mass of left labium majus swelling that progressively increased in volume. Ultrasound study evidenced an ill-defined heterogeneous echotexture mass 26 × 15 × 10 mm in diameter and magnetic resonance imaging confirmed these findings. Histopathological examination was performed after bioptic sampling evidencing normal constituents of vulvar soft tissue, including fibroblast, collagen, adipose tissue, blood vessels and nerves compatible with CALME. Conclusions: CALME is a particular clinical condition that occurs mainly in pre-pubertal girls and has a benign course but poses numerous problems in differential diagnosis that can be solved only with careful clinical observation and with a careful use of radiological imaging techniques. Our cases, in agreement with recent literature, suggest that radical excision is not recommended and that surgical biopsy should be taken into consideration only in cases of doubt.

Inflamed Phylloides Tumour in a Girl: A Challenging Diagnosis in Paediatric Breast Lesions.

Introduction: Phylloides tumours (PTs) are rare fibroepithelial neoplasms that account for 0.3⁻0.9% of all breast tumours. These tumours typically occur in women aged 30⁻70 years. The occurrence of these tumours in older children and adolescents poses particular diagnostic and therapeutic problems. However, early diagnosis is mandatory because although most of the cases of PTs in children are benign, the borderline and malignant cases with potential negative outcomes cannot be excluded. Case presentation: A 12-year-old girl presented at the Paediatric Emergency Department for hyperaemia and warmth of the left breast that occurred a few days prior without fever. The girl experienced menarche 8 months previously. She experienced no previous trauma and she had no family history of breast cancer. On physical examination, the left breast was painful, enlarged and tender. The overlying skin was erythematous and warm. A breast ultrasonography (US) revealed a large mass with features of an abscess, including a hyperechoic wall, scattered internal echoes and hypoechoic peripheral lacunae of apparent colliquative nature. After 4 days of unsuccessful antibiotic therapy, surgical drainage was performed due to the suspicion of a mammary abscess. At the surgical incision site, the lesion was not-well circumscribed and lacked a capsule. In addition, purulent material was not detected. Histological examination revealed that the tissue alterations were compatible with benign PT. With this diagnosis, the girl underwent definitive surgical removal of the lesion. The postoperative period passed without negative events. An US performed 6 months later revealed that no new mass was present at this time, suggesting no recurrence of the tumour. Conclusion: This case shows that in the presence of a clinical picture suggesting the inflammation of the breast in adolescent females, PT should be considered as a possible diagnosis and US-guided core biopsy should be considered to confirm this suspicion. Thereafter, when surgical excision is performed, particular attention must be paid to both the preservation of all the normal breast parenchyma and future aesthetic problems.

The Role of the Microbiome in Asthma: The Gut⁻Lung Axis.

Asthma is one of the most common chronic respiratory diseases worldwide. It affects all ages but frequently begins in childhood. Initiation and exacerbations may depend on individual susceptibility, viral infections, allergen exposure, tobacco smoke exposure, and outdoor air pollution. The aim of this review was to analyze the role of the gut⁻lung axis in asthma development, considering all asthma phenotypes, and to evaluate whether microbe-based therapies may be used for asthma prevention. Several studies have confirmed the role of microbiota in the regulation of immune function and the development of atopy and asthma. These clinical conditions have apparent roots in an insufficiency of early life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts. Commensal microbes are necessary for the induction of a balanced, tolerogenic immune system. The identification of commensal bacteria in both the gastroenteric and respiratory tracts could be an innovative and important issue. In conclusion, the function of microbiota in healthy immune response is generally acknowledged, and gut dysbacteriosis might result in chronic inflammatory respiratory disorders, particularly asthma. Further investigations are needed to improve our understanding of the role of the microbiome in inflammation and its influence on important risk factors for asthma, including tobacco smoke and host genetic features.

Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) plays a key role in the management of thalassemia major patients, but few data are available in pediatric population. This study aims at a retrospective multiparametric CMR assessment of myocardial iron overload, function, and fibrosis in a cohort of pediatric thalassemia major patients. METHODS AND RESULTS: We studied 107 pediatric thalassemia major patients (61 boys, median age 14.4 years). Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. All scans were performed without sedation. The 21.4% of the patients showed a significant myocardial iron overload correlated with lower compliance to chelation therapy (P<0.013). Serum ferritin ≥2000 ng/mL and liver iron concentration ≥14 mg/g/dw were detected as the best threshold for predicting cardiac iron overload (P=0.001 and P<0.0001, respectively). A homogeneous pattern of myocardial iron overload was associated with a negative cardiac remodeling and significant higher liver iron concentration (P<0.0001). Myocardial fibrosis by late gadolinium enhancement was detected in 15.8% of the patients (youngest children 13 years old). It was correlated with significant lower heart T2* values (P=0.022) and negative cardiac remodeling indexes. A pathological magnetic resonance imaging liver iron concentration was found in the 77.6% of the patients. CONCLUSIONS: Cardiac damage detectable by a multiparametric CMR approach can occur early in thalassemia major patients. So, the first T2* CMR assessment should be performed as early as feasible without sedation to tailor the chelation treatment. Conversely, late gadolinium enhancement CMR should be postponed in the teenager age.

Fast generation of T2* maps in the entire range of clinical interest: application to thalassemia major patients.

T2* maps obtained by the processing of multiecho MR sequences can be useful in several clinical applications. T2* map generation procedures should join a processing time compatible with on-line image analysis with a good precision in the entire T2* range of clinical interest. Fast generation of T2* maps can be achieved by the estimation of the T2* values by the weighted linear fitting of the logarithm of the signal (WLSL) method. This approach fails if the signal decay diverges from a pure exponential decay, as happens at low T2* values where the rapid decay in the signal intensity leads to a plateau in the later echo times (TE). The proposed method implements the automatic truncation of the signal decay curves to be fitted in order to compensate for the signal collapse at low T2* values, allowing the extension of the WLSL method through the entire clinical range of T2* values. Validation was performed on synthetic images and on 60 thalassemia major patients with different levels of myocardial iron overload. Phantom experiments showed that a 5% fitting error threshold represented the best compromise between T2* value measurement precision and processing time. A good agreement was found between T2* map pixel-wise measurements and ROI-based measurements performed by expert readers (CoV=1.84% in global heart T2*, CoV=5.8% in segmental analysis). In conclusion, the developed procedure was effective in generating correct T2* maps for the entire T2* clinical range.

Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major.

BACKGROUND: The multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. METHODS: We considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. RESULTS: We identified 4 groups of patients: 138 with homogeneous MIO (all segments with T2* < 20 ms), 97 with heterogeneous MIO (some segments with T2* < 20 ms, others with T2* ≥ 20 ms) and significant global heart iron (global heart T2* < 20 ms), 238 with heterogeneous MIO and no significant global heart iron, and 339 with no MIO (all segments with T2* ≥ 20 ms). Compared to patients with no MIO, patients with homogeneous MIO were more likely to have cardiac complications (odds ratio-OR = 2.67), heart failure (OR = 2.54), LV dysfunction (OR = 5.59), and RV dysfunction (OR = 2.26); patients with heterogeneous MIO and significant global heart iron were more likely to have heart failure (OR = 2.38) and LV dysfunction (OR = 2.39). CONCLUSIONS: Cardiac complications, heart failure and dysfunction were correlated with MIO distribution with an increasing risk from the TM patients with no MIO to those with homogeneous MIO. Using a segmental approach, early iron deposit or homogeneous MIO patterns can be characterized to better tailor chelation therapy.

Preferential patterns of myocardial iron overload by multislice multiecho T*2 CMR in thalassemia major patients.

T*(2) multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty-three thalassemia major patients underwent cardiac MR. Three short-axis views of the left ventricle were acquired and analyzed using a 16-segment standardized model. The T*(2) value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (global T*(2) <26 ms), subsequently divided into two groups: severe (global T*(2) <10 ms) and mild to moderate (global T*(2) between 10 and 26 ms) myocardial iron overload. A preferential pattern of iron store in anterior and inferior regions was detected in both groups. This pattern was preserved among the slices. The pattern could not be explained by additive susceptibility artifacts, negligible in heavily iron-loaded patients. A significantly higher T*(2) value in the basal slice was found in patients with severe iron overload. In conclusion, a segmental T*(2) cardiac MR approach could identify early iron deposit, useful for tailoring chelation therapy and preventing myocardial dysfunction in the clinical setting.