Masked or not, I smile to you: Exploring full-term and preterm infants' social smiles to adults wearing a protective facemask.

The early emergence of social smiles is an important milestone of infants' socio-emotional development. Our aim was to assess how the use of protective facemasks by adults affects the display of social smiles in preterm (PT) and full-term (FT) infants at 3 months (corrected age for prematurity). We enrolled 30 FT and 30 PT infants (gestational age ≤ 32 weeks). Infants' social smiles displays were assessed at 2-3-month-age (corrected) across a three-episode (masked mother; unmasked mother; masked adult female stranger) videotaped interactive task. During each episode, the adult was instructed to maintain specific facial expressions (happy-smiling, sad-frowning, neutral-unresponsive) for 15 second windows and then instructed to interact spontaneously for 45 s (of which the first 15 s were coded). FT and PT infants did not differ in the display of social smiles. In both groups, social smiles were mostly exhibited in response to happy/smiling and spontaneously interacting partners. Overall, no effect of wearing a protective facemask emerged. The use of protective facemasks did not result in a lower display of social smiles. The findings suggest that FT and PT might be equally sensitive to their adult interactive partners in terms of social smiles displays at 2-3-month-age.

Expanding the Natural History of SNORD118-Related Ribosomopathy: Hints from an Early-Diagnosed Patient with Leukoencephalopathy with Calcifications and Cysts and Overview of the Literature.

Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive disorder showing a pediatric or adult onset. First described in 1996 by Labrune and colleagues, it was only in 2016 that bi-allelic variants in a non-protein coding gene, SNORD118, were found as the cause for LCC, differentiating this syndrome from coats plus (CP). SNORD118 transcribes for a small nucleolar RNA, which is necessary for correct ribosome biogenesis, hence the classification of LCC among ribosomopathies. The syndrome is characterized by a combination of white matter hyperintensities, calcifications, and cysts on brain MRI with varying neurological signs. Corticosteroids, surgery, and recently bevacizumab, have been tried with unclear results since the natural history of the disease remains elusive. To date, 67 patients with a pediatric onset of disease have been described in the literature, with a clinical-radiological follow-up carried out in only eleven of them. We described the clinical-radiological follow-up from birth to almost five years of age of a late-preterm patient diagnosed with LCC and carried out a thorough overview of pediatric patients described in the literature. It is important to gather serial clinical-radiological data from other patients to depict the natural history of this disease, aiming to deeply depict genotype-phenotype correlations and make the role of new therapeutics clearer.

Ketosis and migraine: a systematic review of the literature and meta-analysis.

Introduction: Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising approach is ketogenic therapy, which replaces the brain's glucose fuel source with ketone bodies, potentially reducing the frequency or severity of headaches. Aim: This study aims to conduct a systematic review of the scientific literature on the impact of ketosis on migraine, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Results: After a careful selection process and bias evaluation, 10 articles were included in the review, primarily from Italy. The bias assessment indicated that 50% of the selected articles had a low risk of bias in all domains, with the randomization process being the most problematic domain. Unfortunately, the evaluation of ketosis was inconsistent between articles, with some assessing ketonuria, some assessing ketonemia, and some not assessing ketosis levels at all. Therefore, no association could be made between the level of ketosis and the prevention or reduction of migraine attacks. The ketogenic therapies tested in migraine treatments included the very low-calorie ketogenic diet (VLCKD, n = 4), modified Atkins diet (MAD, n = 3), classic ketogenic diet (cKDT, n = 2), and the administration of an exogenous source of beta-hydroxybutyrate (BHB). The meta-analysis, despite reporting high heterogeneity, found that all interventions had an overall significant effect (Z = 9.07, p < 0.00001; subgroup differences, Chi2 = 9.19, dif = 3, p = 0.03; I2, 67.4%), regardless of the type of endogenous or exogenous induction of ketosis. Conclusion: The initial findings of this study suggest that metabolic ketogenic therapy may provide some benefit in treating migraines and encourage further studies, especially randomized clinical trials with appropriate and standardized methodologies. The review strongly recommends the use of the adequate measurement of ketone levels during ketogenic therapy to monitor adherence to the treatment and improve knowledge of the relationship between ketone bodies and efficacy. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022330626.

Chest-to-arm tunneling technique for central venous access devices in neonates.

BACKGROUND: Chest-to-arm (CTA) tunneling technique has been described recently as an alternative option to exit site of the catheter in the infraclavicular area. METHOD: We report our experience with ultrasound-guided centrally inserted central catheters (CICCs) placed using CTA tunneling in six neonates. All central venous catheters were positioned with ultrasound guidance and real-time tip location. RESULTS: There were no insertion-related complications; all devices were correctly positioned at the first attempt. During the follow-up, we found no catheter-related thrombosis, infections, or catheter malfunction. No tip position-related complications. Only one case of secondary malposition was reported. CONCLUSION: In our experience, the CTA tunneling technique is reliable, safe, and feasible in the neonate even from the first hours of life, as well as for preterm newborns; it could be a valid alternative to the usual exit site.

A novel variant in NEUROD2 in a patient with Rett-like phenotype points to Glu130 codon as a mutational hotspot.

BACKGROUND: NEUROD2, encoding the neurogenic differentiation factor 2, is essential for neurodevelopment. To date, heterozygous missense variants in this gene have been identified in eight patients (from six unrelated families) with epileptic encephalopathy and developmental delay. CASE REPORT: We describe a child with initial clinical suspicion of Rett/Rett-like syndrome, in whom exome sequencing detected a novel de novo variant (c.388G > A, p.Glu130Lys) in NEUROD2. Interestingly, a missense change affecting the same codon, c.388G > C (p.Glu130Gln), was previously identified in other two patients. CONCLUSIONS: Our results suggest that Glu130 might represent a potential mutational hotspot of NEUROD2. Furthermore, the clinical findings (especially the absence of clinically overt seizures) strengthen the NEUROD2-phenotypic spectrum, implying that developmental delay may also manifest isolatedly. We suggest inclusion of NEUROD2-associated developmental and epileptic encephalopathies (DEEs) in the differential diagnosis of atypical Rett syndrome as well as gene panels related to autism spectrum disorder.

Long peripheral catheters in neonates: filling the gap between short peripheral catheters and epicutaneous-caval catheters?

INTRODUCTION: Non-critically ill neonates at times require venous access to provide peripherally compatible infusions for a limited period (more than 3 days). In such a situation, short peripheral cannulas are not appropriate as their average duration is about 2 days, while-on the other hand-epicutaneous-caval catheters may be too invasive. In these patients, insertion of long peripheral cannulas may be an effective option. METHODS: In this observational retrospective study, we revised all "long" peripheral catheters (4 and 6 cm long) inserted by direct Seldinger technique in our neonatal intensive care unit when peripheral venous access was required for more than 3 days. RESULTS: We inserted 52 2Fr polyurethane catheters, either 4 cm long (n = 25) or 6 cm long (n = 27) in 52 patients. Mean dwelling time was 4.17 days (range 1-12). Most devices were inserted in the cephalic vein (n = 18, 35%), and the rest in the saphenous vein (n = 11, 21%) and other superficial veins. There was no significant correlation between the duration of the device and type of infusion (p = 0.40). The main complications were infiltration (n = 16, 31%) and phlebitis (n = 8, 15%). The rate of removal due to complications was significantly higher (p < 0.01) in neonates with bodyweight <2000 g at the time of insertion. CONCLUSION: In our experience, 2 Fr 4-6 cm long peripheral catheters may be a valid option for neonates requiring peripherally compatible infusions for more than 3 days. The limits of this study are the necessity of training in the technique of insertion and the small size of our sample. The longest dwell was observed in neonates weighing >2000 g at the time of LPC insertion.

Recurrent idiopathic carotid and coronary artery vasospasm treated by stent implantations.

Arterial vasospasm is a well known cause of ischemia and, if prolonged, of parenchymal infarction. The clinical presentation varies according to the involved arterial district. We describe a rare case, which occurred in a young lady, of recurrent and multisystem vasospasm, resulting in multiple cerebral and myocardial infarctions. Our patient was resistant to medical therapy, requiring stent implantation of the involved vessels.

Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

Introduction: Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Methods: Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally. Results: Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content. Conclusion: In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA in vivo and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort.

Nutrition and Exercise in a Case of Carnitine Palmitoyl-Transferase II Deficiency.

In the mild subtype of inherited carnitine palmitoyltransferase II (CPTII) deficiency, muscular mitochondrial fatty acid ß-oxidation is impaired. In this condition, interventions involve daily dietary restriction of fats and increase of carbohydrates, whereas physical exercise is commonly contraindicated due to the risk of muscle pain and rhabdomyolysis. We present the case of a 14-year-old female with CPTII deficiency who underwent a 1-h session of unsupervised exercise training for 6 months, 3 days per week, including interval and resistance exercises, after diet assessment and correction. Before and after intervention, the resting metabolic rate (RMR) and respiratory quotient (RQ) were measured by indirect calorimetry, and a cardiopulmonary exercise test (CPET, 10 W/30 s to exhaustion) was performed. Interval training consisted of a 1 min run and a 5 min walk (for 15 min progressively increased to 30 min). During these efforts, the heart rate was maintained over 70% HR max corresponding to respiratory exchange ratio (RER) of 0.98. Resistance training included upper/lower split workouts (3 sets of 8 repetitions each, with 2 min rest between sets). Blood CK was checked before and 36 h after two training sessions chosen randomly without significant difference. After training, RMR increased (+8.1%) and RQ lowered into the physiological range (from 1.0 to 0.85). CPET highlighted an increase of peak power output (+16.7%), aerobic performance (VO2 peak, 8.3%) and anaerobic threshold (+5.7%), oxygen pulse (+4.5%) and a much longer isocapnic buffering duration (+335%). No muscle pain or rhabdomyolysis was reported. Results from our study highlight that training based on short-duration high-intensity exercise improves overall metabolism and aerobic fitness, thus being feasible, at least in a case of CPTII deficiency.

Novel insight into GLUT1 Deficiency Syndrome: screening for emotional and behavioral problems in youths following ketogenic diet.

BACKGROUND: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1DS) is a rare disorder with a broad spectrum of neurological manifestations. The ketogenic diet (KD) is, to date, the gold standard treatment. Behavioral problems, well recognized in patients with chronic conditions, have not been, so far, deeply investigated in GLUT1DS patients. We performed an exploratory study to assess the risk of emotional and behavioral problems and investigated the potential role of influencing factors related to the pathology itself or KD treatment. METHODS: This was a mono-center retrospective study involving youths patients with GLUT1Ds treated with KD and a group of migraine patients age- and gender-matched. Patients were included if the main caregiver completed the Child Behavior Check List 6-18 (CBCL). Descriptive statistics for demographic and clinical data and questionnaire scores were computed. Correlational analyses were used to assess the potential associations of clinical variables and age and time from KD introduction with CBCL scores in GLUT1DS patients. RESULTS: We enrolled nine youths with GLUT1DS and 9 with migraine. In the GLUT1DS group, none of the mean scores of the CBCL items fell within the borderline/clinical range, except for social problems located in the borderline range. Investigation for influencing factors revealed the patient's age related to withdrawn/depressive (r=.709, p=.032) and social problems (r=.684, p=.042). Time from the introduction of KD was related to social problems (r=.827, p=.006). From the comparison with the scores obtained from migraine patients, significantly higher scores emerged in the latter group in internalizing problems (Z= -2.48, p = .01), externalizing problems (Z= -3.49, p < .001), anxious/depressed subscale (Z= -2.37, p=.014), somatic complaints subscale (Z= -2.624, p=.008), aggressive behavior subscale (Z= -2.539, p=.011). CONCLUSIONS: Although highly exploratory in its nature, this study provides a novel insight into GLUT1DS. Our data suggested that the risk for internalizing problems in GLUT1DS youths was related to higher age and higher time elapsed from KD introduction. They occurred at a sub-clinical level, making them difficult to detect, if not expressly and systematically investigated.

Migraine Symptoms Improvement During the COVID-19 Lockdown in a Cohort of Children and Adolescents.

Background: Pediatric migraine is among the most common primary or comorbid neurologic disorders in children. Psychological stressors are widely acknowledged as potential triggers involved in recurring episodes of pediatric migraine. As the COVID-19 emergency may have affected the levels of stress perceived by children and adolescents with migraine, the present study was aimed to understand the effect of COVID-19 emergency on symptoms intensity and frequency in pediatric patients. Methods: A cohort of 142 child and adolescent patients with a diagnosis of migraine was enrolled at the Child Neurology and Psychiatry Unit of the IRCCS Mondino Foundation in Pavia (Italy). Socio-demographic and clinical characteristics were obtained from medical records. An on-line survey was used to collect information on COVID-19 exposure, stress response to the lockdown period, anxious symptoms during COVID-19 emergency, as well as migraine symptoms intensity and frequency before and during the lockdown. Results: The great majority were outpatients (n = 125, 88.0%), 52 (36.6%) had migraine with aura, whereas, 90 (63.4%) had migraine without aura. All the patients reporting worsening symptoms progression before COVID-19, had reduced intensity during the lockdown (χ2 = 31.05, p < 0.0001). Symptoms frequency reduction was observed in 50% of patients presenting worsening symptoms before the lockdown, 45% of those who were stable, and 12% of those who were already improving. All patients who had resolved symptoms before COVID-19 were stable during the lockdown (χ2 = 38.66, p < 0.0001). Anxious symptomatology was significantly associated with greater migraine symptoms frequency (χ2 = 19.69, p < 0.001). Repeating the analysis separately for individuals with and without aura did not affect the findings and significant associations were confirmed for both the patients' subgroups. Discussion: A significant reduction of migraine symptoms intensity and frequency was observed in pediatric patients during the COVID-19 lockdown phase in northern Italy. The improvement in both intensity and frequency of the migraine symptoms was especially significant in patients who were stable or worsening before the lockdown. The reduction of symptoms severity during a period of reduced environmental challenges and pressures further highlights the need of providing effective training in stress regulation and coping for these patients.

[An unusual presentation of cardiac involvement during the COVID-19 pandemic]. / COVID-19 e coinvolgimento cardiaco: una presentazione inusuale.

Severe acute respiratory syndrome coronavirus 2 may affect the cardiovascular system and cause acute cardiac injury. Other authors described cases of myocarditis with reduced systolic function and/or a life-threatening presentation. We describe the clinical course of an unusual presentation with isolated reversible high degree atrioventricular block in a patient with COVID-19. In this case, a "wait and see approach" avoided an unnecessary permanent pacemaker implantation.

Subcutaneously Anchored Sutureless Device for Securement of Chest Tubes in Neonates with Pleural Effusion: Three Case Reports.

We report the clinical cases of three neonates, all of them premature, requiring the placement of a chest tube for drainage of a massive pleural effusion. In all three patients, the chest tube was secured using a new subcutaneously anchored sutureless system. This new securement device was easy to insert and to remove, and highly effective in preventing dislodgment. Also, it was not associated to any undesired effect: no sign of pain and/or discomfort and no skin inflammation. The securement device proved to be comfortable and harmless even in fragile patients as neonates, including the frailest ones, the premature. To our best knowledge, this is the first report describing the use of such a device for this purpose.

Self-expanding transcatheter aortic valve implantation for degenerated small Mitroflow bioprosthesis: early and midterm outcomes.

AIMS: The aim of this study was to report clinical outcomes of self-expanding transcatheter aortic valve implantation (TAVI) for failed small Mitroflow (MF) bioprostheses. METHODS AND RESULTS: Between January 2013 and July 2016, 15 symptomatic patients (NYHA Class ≥III) with degenerated small MF (≤23 mm) underwent CoreValve (CV) or Evolut R (EvR) implantation due to high/prohibitive risk for surgical redo. The MF size was 19 or 21 mm (off-label in Europe) in eight patients. A "preventive" left main (LM) stenting was successfully performed in one patient. Early LM obstruction occurred in two cases requiring stenting. Late LM obstruction was observed in one subject. A significant correlation between virtual left transcatheter valve-to-coronary ostia (VTC) distance and left sinus of Valsalva (LSV) diameter was observed (R=0.652; p=0.012). However, only left VTC was significantly smaller in patients who experienced LM obstruction compared to those who did not (p=0.002). No cases of moderate/severe stenosis were observed in either on- or off-label procedures. No death or other major events occurred up to the one-year follow-up. CONCLUSIONS: CV or EvR implantation for failed small MF has favourable early and midterm outcomes if a careful risk evaluation and preventive measures for coronary obstruction are adopted. Low gradients can be achieved regardless of MF size.

Reference intervals of citrated-native whole blood thromboelastography in premature neonates.

BACKGROUND: Bleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated. AIMS: To evaluate TEG in preterm neonates, and to assess their reference ranges. METHODS: One hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates. RESULTS: Comparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values. CONCLUSIONS: These results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning.

Mitraclip therapy in patients with functional mitral regurgitation and missing leaflet coaptation: is it still an exclusion criterion?

AIMS: The aim of this study was to investigate the feasibility, safety, and efficacy of Mitraclip therapy in patients with functional mitral regurgitation (MR) and missing leaflet coaptation (MLC). METHODS AND RESULTS: Out of 62 consecutive patients with functional MR undergoing Mitraclip implantation, 22 had MLC defined as the presence of a 'gap' between two mitral leaflets or insufficient coaptation length (<2 mm), according to the EVEREST II criterion. Compared with the control group, the MLC population had a significantly higher effective regurgitant orifice area (0.67 ± 0.31 vs. 0.41 ± 0.13 cm2 ; P = 0.019) and sphericity index (0.80 ± 0.11 vs. 0.71 ± 0.10; P = 0.003). MLC patients were treated with pharmacological/mechanical support in order to improve leaflet coaptation and to prepare the mitral valve apparatus for grasping. Implantation of >1 clip and device time were comparable in patients with and without MLC (61.9% vs. 47.5%; P = 0.284 and 101 ± 39 vs. 108 ± 69 min; P = 0.646, respectively). No significant differences were observed between the two cohorts in technical success (95.5% vs. 97.5%, P = 0.667), 30-day device success (85.7% vs. 78.9%; P = 0.525), procedural success (81.8% vs. 75%; P = 0.842), and 1-year patient success (52.9% vs. 44.1%; P = 0.261), defined according to the MVARC (Mitral Valve Academic Research Consortium) criteria. The long-term composite endpoint of cardiovascular death and heart failure hospitalization was similar in the two groups (49.9% vs. 44.4%; P = 0.348). A significant improvement of MR and NYHA functional class and a lack of reverse remodelling were observed up to 2 years in both arms. CONCLUSION: The Mitraclip procedure could be extended to patients with functional MR who do not fulfil the coaptation length EVEREST II criterion and who would otherwise be excluded from this treatment.