Possible role of vitamin D in Covid-19 infection in pediatric population.

PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. METHODS: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and ß-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.

Posture and movement in healthy preterm infants in supine position in and outside the nest.

OBJECTIVE: To evaluate whether lying in a nest affects the posture and spontaneous movements of healthy preterm infants. METHOD: 10 healthy preterm infants underwent serial video recording in the supine position, when lying in a nest and outside it, at three ages: 30-33 weeks postmenstrual age (PMA) (early preterm), 34-36 weeks PMA (late preterm) and 37-40 weeks PMA (term). The nest was shell-shaped, made by putting two rolled blankets in a form of an oval. Posture was assessed both before and after general movements by scoring the predominant postural pattern. Movements towards and across the midline, elegant wrist movements, abrupt hand and/or limb movements, rolling to side, and frozen postures of the arms and legs were assessed during four general movements. All data relating to motor and postural items were normalised into frequencies of events per minute because the general movements varied in duration. RESULTS: When lying in the nest, the infants more often displayed a flexed posture with shoulder adduction and elbow, and hip and knee flexion, and the head was frequently in the midline. The nest was also associated with an increase in elegant wrist movements and movements towards and across the midline and a reduction in abrupt movements and frozen postures of the limbs. The nest did not affect the occurrence of asymmetrical tonic neck posture. CONCLUSIONS: A nest promotes a flexed posture of the limbs with adduction of shoulders, facilitates elegant wrist movements and movements towards and across the midline and reduces abrupt movements and frozen postures of the arms and legs.

Non-specific febrile illness by Coxsackievirus A16 in a 6-day-old newborn.

A case of non-specific febrile illness by Coxsackievirus A 16 (CA 16) in a 6-day-old newborn whose mother had developed hand, foot and mouth disease manifestations 2 days after delivery is reported. Notwithstanding the concurrence of negative circumstances like the presence of the enterovirus genome in the cerebrospinal fluid, absence of type specific neutralizing antibody and a few days of life, the newborn recovered 3 days after the onset of fever. This case, also characterized by the absence of mucosal and cutaneous erythematous manifestations typical of CA16 infection, draws attention to the possibility that non-specific febrile illness in newborns usually suspected of bacterial origin may have an enteroviral cause.

General movements detect early signs of hemiplegia in term infants with neonatal cerebral infarction.

Background. Studies have reported that infants with hemiplegia of congenital origin may have a period between birth and up to 12 months when clinical signs of hemiplegia are not evident. The aim of this study was to establish whether the assessment of general movements (GMs) may help in the earlier detection of signs of hemiplegia. Subjects and Methods. Eleven infants with cerebral infarction on brain MRI, and eleven normal controls were enrolled in the study. Quality of GMs was assessed from videotapes between 3 and 6 weeks and between 9 and 16 weeks. Neurological outcome was evaluated at least at two years. Results. Seven of the 11 infants had an assessment performed between 3 and 6 weeks: abnormal GMs were observed in all the infants who developed hemiplegia, but one child had abnormal GMs and a normal outcome. All 11 infants had a scorable assessment between 9 and 16 weeks. In all a specific type of GMs, fidgety movements (FMs), were predictive of neurological outcome. The presence of early asymmetries at both 3 - 6 and 9 - 16 weeks was also significantly associated with later signs of hemiplegia. Conclusions. The assessment of GMs after the neonatal period appears to be very useful in the early identification of hemiplegia in infants with cerebral infarction. Whilst the prediction of hemiplegia should be possible from early neonatal MRI brain scans, this facility is not always available. Observation of GMs is a bedside clinical approach that allows confirmation of early prediction from MRI, early rehabilitation if needed and reassurance that neurological outcome will be good where that is appropriate.

The early markers for later dyskinetic cerebral palsy are different from those for spastic cerebral palsy.

Qualitative abnormalities of spontaneous motor activity in newborns and young infants are early predictive markers for later spastic cerebral palsy. Aim of this research was to identify which motor patterns may be specific for later dyskinetic cerebral palsy. In a large, prospectively performed longitudinal study involving four European hospitals we identified twelve cases with the relatively rare condition of dyskinetic cerebral palsy and compared their early motor development with twelve spastic cerebral palsy cases and twelve controls. From birth to the fifth month post-term, all infants were repeatedly videoed and their spontaneous motor patterns, including general movements, were assessed. Until the second month post-term, the infants that later became dyskinetic displayed a poor repertoire of general movements, "arm movements in circles" and finger spreading. Abnormal arm and finger movements remained until at least five months and were then concurrent with a lack of arm and leg movements towards the midline. Later dyskinetic infants share with later spastic infants the absence of fidgety movements, a spontaneous movement pattern that is normally present from three to five months. Qualitative assessment of spontaneous motor patterns enabled us to identify infants at high risk for dyskinetic cerebral palsy early in life. Additionally, we were able to discriminate them from those infants at high risk for later spastic cerebral palsy. This is a matter of significant clinical relevance because the two types of cerebral palsy ask for different management and early intervention.

Cramped synchronized general movements in preterm infants as an early marker for cerebral palsy.

OBJECTIVE: To ascertain whether specific abnormalities (ie, cramped synchronized general movements [GMs]) can predict cerebral palsy and the severity of later motor impairment in preterm infants affected by brain lesions. DESIGN: Traditional neurological examination was performed, and GMs were serially videotaped and blindly observed for 84 preterm infants with ultrasound abnormalities from birth until 56 to 60 weeks' postmenstrual age. The developmental course of GM abnormalities was compared with brain ultrasound findings alone and with findings from neurological examination, in relation to the patient's outcome at age 2 to 3 years. RESULTS: Infants with consistent or predominant (33 cases) cramped synchronized GMs developed cerebral palsy. The earlier cramped synchronized GMs were observed, the worse was the neurological outcome. Transient cramped synchronized character GMs (8 cases) were followed by mild cerebral palsy (fidgety movements were absent) or normal development (fidgety movements were present). Consistently normal GMs (13 cases) and poor repertoire GMs (30 cases) either lead to normal outcomes (84%) or cerebral palsy with mild motor impairment (16%). Observation of GMs was 100% sensitive, and the specificity of the cramped synchronized GMs was 92.5% to 100% throughout the age range, which is much higher than the specificity of neurological examination. CONCLUSIONS: Consistent and predominant cramped synchronized GMs specifically predict cerebral palsy. The earlier this characteristic appears, the worse is the later impairment.

Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator.

OBJECTIVES: To determine the incidence of catheter related thrombosis and to test the efficacy of recombinant tissue type plasminogen activator (rt-PA) in preterm infants. STUDY DESIGN: From January 1995 to December 1998, echocardiography was performed in the first few days of life in 76 very low birthweight (< or = 1500 g) infants out of a total of 147 having an umbilical catheter placed. When intracardiac thrombosis was diagnosed, rt-PA infusion was performed. RESULTS: Four infants (5%) developed an intracardiac thrombosis during the first few days of life. In three of them, rt-PA at a dose of 0.4-0.5 mg/kg in a 20-30 minute bolus led to dissolution of the clot. One patient received a three hour infusion after the bolus, at a dose of 0.1 mg/kg/h, with resolution of the thrombus. No systemic effects were observed after rt-PA infusion. CONCLUSIONS: Early thrombosis may occur as a complication of umbilical catheterisation in preterm infants; early echocardiographic detection of this disorder allows complete, safe, and rapid lysis with rt-PA.

Early neurological signs in preterm infants with unilateral intraparenchymal echodensity.

UNLABELLED: The aim of the study was to document the early developmental course of neurological signs in a group of preterm infants at risk for hemiplegia due to unilateral intraparenchymal echodensity (UIPE). Sixteen preterm infants with UIPE and sixteen controls were given serial neurological examinations, according to the protocols currently adopted in the different NICUs of the project. Moreover, the quality assessment of their general movements (GMs) was assessed subsequently from videotapes, from birth until around four months postterm. At two years, 12 of the UIPE infants showed hemiplegia and one suffered from asymmetrical diplegia. The findings of the traditional neurological examination were abnormal for the large majority of the UIPE infants, although normal findings were also recorded in some cases, especially during the preterm period. Asymmetries were found after term age in nine UIPE and in two control infants. From the first observation onwards, all infants with UIPE showed bilaterally abnormal GMs and in those with unfavourable outcome fidgety movements (FMs) were absent. At the FMs period (9-16 weeks postterm), all infants with subsequent hemiplegia showed asymmetry of distal segmental movements which were reduced or absent on the side contralateral to the lesion. CONCLUSIONS: Unilateral brain lesions induce clear neurological signs and abnormal GMs in particular, although these abnormalities are not initially asymmetrical. A reduction of segmental movements on one side of the body during the third month postterm is highly predictive of hemiplegia.

[Neonatal cystic fibrosis: report of 2 cases]. / Fibrosi Cistica ad esordio neonatale: descrizione di due casi.

Cystic fibrosis is the most common life-limiting recessive genetic disorder in Caucasian. It is caused by mutations of CFTR gene (cystic fibrosis transmembrane conductance regulator); at present over 500 mutations are known. Cystic fibrosis as a cause of respiratory distress in the neonate is quite rare. In neonatal period the most important clinical manifestations are meconium ileum and much rarely cholestatic jaundice. We present two cases of cystic fibrosis in newborns. In the first one, we point out the strict association between meconium ileum and cystic fibrosis. The patient underwent a surgical treatment for meconium ileum and the diagnosis was rapidly confirmed by genetic analysis and sweat test. The second one had intestinal obstruction from birth caused by meconium ileum associated with ileal atresia; besides, he developed cholestatic jaundice, severe and rapidly progressive respiratory disease. He died at 102 degrees day of age for cardiac failure. The diagnosis of cystic fibrosis, supported by typical clinical features and high level of serum trypsin, unfortunately wasn't confirmed by genetic analysis (lambda F508/neg), in addition, the sweat test wasn't reliable because an inadequate quantity of sweat was collected.

[Intra-arterial antiblastic treatment of breast carcinoma]. / Terapia antiblastica per via intrarteriosa del carcinoma della mammella.

PURPOSE: To report our personal experience with the locoregional treatment of breast cancer. MATERIAL AND METHODS: Eighteen patients aged 33-67 years (mean: 54 years) were treated with 31 sessions of intra-arterial antiblastic infusion, 5 of them for neoadjuvant purposes (Group 1), 5 for palliation in unresectable tumors (Group 2) and 8 for cutaneous recurrences after mastectomy (Group 3). RESULTS: 2/5 CR and 3/5 PR were obtained in Group 1; 2/5 lesions were made resectable and 3/5 RP obtained in stage III or unresectable lesions (Group 2). Finally, 3/8 CR, 3/8 PR, 1/8 SD and 1/8 PD were observed in Group 3. An objective response according to WHO criteria was demonstrated in 15/18 cases (88%). We had no post-treatment hematologic complications, but one patient presented focal subcutaneous sclerosis and one cutaneous necrosis. CONCLUSIONS: The morphological efficacy of intraarterial antiblastic infusion in our series was similar to that of other series. No definitive conclusions can be drawn yet about clinical results and long-term survival. This poorly invasive and low risk procedure, which should be combined with other treatments, permits to reduce the extent of surgery and to treat skin recurrences.

Electroclinical correlation in neonatal seizures.

A dissociation between clinical and electroencephalographic phenomena is often observable in neonatal seizures. This finding raises important questions, including those related to the management of these patients. Another characteristic of neonatal convulsions is represented by their increased tendency towards status epilepticus. In order to examine the electroclinical correlation and its possible relationship to the occurrence of status epilepticus, recorded video-electroencephalograms of 17 newborns were submitted to detailed analysis. Time of onset, duration and other characteristics of all clinical and electrical events were noted. Five degrees of correlation were observed, from constant concurrence to complete dissociation. Examining the role of different parameters, it was observed that the incidence of electric discharges related significantly to the occurrence of electroclinical dissociation.

[Results of flow-controlled antiblastic perfusions (stop-flow technique) carried out with percutaneous technique: 30-month experience]. / Risultati delle perfusioni antiblastiche con controllo del flusso (tecniche stop-flow) eseguite con tecnica percutanea: 30 mesi di esperienza.

PURPOSE: We report the morphological and clinical results in a series of patients with advanced thoracopulmonary, abdominal, pelvic and lower limb tumors treated with stop-flow perfusion (SFP). MATERIAL AND METHODS: We performed 77 SFPs with the percutaneous angiographic technique in 55 patients (25 women and 30 men; mean age: 53 years). Eighteen thoracic perfusions with aortocaval block (ASI) were performed in 11 patients, 33 abdominal hypoxic perfusions (HAP) in 26 patients, 17 hypoxic pelvic perfusion (HPP) in 11 patients and 9 hypoxic lower limb perfusions (HILP) in 7 patients. 42/77 procedures were followed by hemofiltration. RESULTS: No technical complications were observed. Twenty-eight patients in our series are still alive (mean follow-up: 14 months) and 23 have died (mean survival: 8 months), 20/23 of them (87%) for disease progression. Three of 77 patients (3.8%) died within 7 days of the procedure (2 AS, 1 HAP). At CT or MR follow-up, responses > 50% were observed in 56% of the procedures and clinical CR was achieved in 53/77 patients (69%). In the subgroups classified by procedure, positive responses were observed in 56, 48, 59 and 78%, respectively for ASI, HAP, HPP and HLP. Clinical CR was observed in 67, 67, 71 and 78%, respectively. The death rate for disease progression relative to the overall death rate was 100, 86, 75 and 100%. Hematologic toxicity according to WHO criteria (mean: 2) was observed in 77% of the whole of procedures (59/77). Statistical analysis showed no relationship between morphological responses and type of antiblastic drug or previous antiblastic treatments. CONCLUSIONS: SF procedures permit the effective control of many advanced tumors which cannot be treated otherwise, with a high rate of positive morphological and of complete clinical responses. The best results were obtained in hypoxic perfusion of the lower limb. The results were not correlated with previous antiblastic treatments. However, the high rate of sequels and the low hematologic tolerance of those procedures must be emphasized.

[Antiblastic hypoxic stop-flow perfusion in the treatment of liver metastasis: preliminary results]. / Perfusione antiblastica ipossica con blocco del flusso nella terapia delle metastasi epatiche: risultati preliminari.

PATIENTS AND METHODS: 27 patients (14 men and 13 women aged 35 to 71 years; average: 59 years), with 3-11 months' follow-up (average: 5 months) were treated for hepatic metastases (17/22 from colorectal, 10/22 from other primary tumors) with hypoxic locoregional hepatic perfusion. Sixteen of 22 patients had been pretreated with resection, systemic chemotherapy or freeflow locoregional infusion. Our protocol consists in blocking arterial flow with an occlusion balloon catheter inflated in the hepatic artery; the main catheter channel is connected with a pump system and 250-300 ml saline with 30-40 mg Mitomycin C are perfused in the arterial hepatic system. Embolization with a gelatin sponge is performed after the end of perfusion. RESULTS: 19/27 patients are still alive, and 8/27 are dead but death was caused by the progression of intrahepatic disease in only 2/27 (7%). Iatrogenic lesions of the arterial wall were shown at follow-up DSA in 15/22 patients (56%). Thirteen CR (48%) and 9 PR (33%) were demonstrated at CT follow-up, amounting to 81% of objective responses. Follow-up showed a clinical CR in 12/18 symptomatic patients (66%). No case of hematologic toxicity was observed. Mean CEA values changed from 129 to 10.60. Twelve of 27 patients exhibited mild posttreatment sequels, none of them lasting longer than three days; ischemic cholecystitis was seen in 3/15 cases (14%). CONCLUSIONS: The occlusion catheters on the market are not optimal for this procedure; the axillary percutaneous approach is advantageous. CR rate was very high in our series but the objective response rate doses do not differ from those in the series with free-flow procedures. The highest CR rate was observed in untreated patients and in hypervascularized lesions; the rate of clinical sequels was low, clinical CR rates were high and there was no hematologic toxicity. This well-tolerated procedure provides good local disease control, but the high rate of deaths from extrahepatic progression suggests that systemic chemotherapy and long-step intraarterial perfusion be combined.

[Antiblastic locoregional perfusion with control of the aorto-caval flow: technique of percutaneous access]. / Perfusione locoregionale antiblastica con controllo del flusso aorto-cavale: tecnica dell'accesso percutaneo.

The authors introduce a new technique for performing aortic stop-flow infusion (ASI) or hypoxic abdominal perfusion (HAP) to treat advanced thoracoabdominal tumors, via an angiographic percutaneous approach. To date, the maneuver has always been performed with surgical exposure of vascular sites in the groins. The materials available on the market were initially used and then dedicated materials have been developed, such as 11-F vascular sheaths, 8-F catheters, latex balloons with maximum phi's of 4 cm and maximum capacity of 70 ml. We performed 72 maneuvers in 56 patients during 22 months. No technical or instrumental complications occurred and all treatments were successful. Three patients (6%) died within 12 hours, two because of ARDS following thoracic perfusion and one for acute renal failure and disseminated intravascular coagulation following abdominal perfusion. The percutaneous approach provides the same mechanical-occlusive efficacy for aortocaval occlusion and therefore the same therapeutic results as surgery, but it has fewer risks of technical complications and no technical failures. Moreover, this technique is more repeatable and less expensive than surgery and its hospital stay and recovery time are shorter. To conclude, the ASI/HAP procedure is an interesting therapeutic chance in otherwise untreatable advanced cancer patients offering several prospects of technical and pharmacologic development to further increase its efficacy.

Which better predicts later outcome in full-term infants: quality of general movements or neurological examination?

The qualitative assessment of general movements (GMs) has been shown to be a better predictor of neurological outcome than the traditional neurological examination in brain-damaged preterm infants. The aim of this study was to compare the results of the two techniques in term infants. Off-line assessment of GMs from videorecordings and neurological examinations were carried out, from birth till about 6 months of postterm age, in a group of 58 term infants, the majority of which were affected by mild to severe hypoxic-ischaemic encephalopathy. The agreement between the two techniques and their predictive power, with respect to the neurological outcome at 2 years, were evaluated for four age groups. The range of agreement between neurological and GM findings was between 78 and 83%. At all ages the results of GM observation correlated highly with the neurological outcome; their sensitivity and specificity with respect to outcome were consistently slightly superior to those of neurological examination. In infants normalize after an initial period of transient abnormalities, GMs normalize earlier than the neurological results.

Posture, spontaneous movements, and behavioural state organisation in infants affected by brain malformations.

Posture, quantity of spontaneous movement patterns, quality of general movements (GMs), and behavioural state organisation were studied in nine infants affected by documented brain malformations. A single 1 h video recording of five infants and two or more serial video recordings of another four infants were performed after birth. The graphic representation of single movement patterns (actogram) and of behavioural states of one video recording was performed in eight out of nine infants. The quality of GMs was assessed according to Prechtl's method in all video recordings. All nine infants showed a less variable posture than normal newborn infants and an unusual resting posture was detected in seven infants. Poor behavioural state organisation without sleep cycles was common to the nine infants and excessive wakefulness was observed in six infants. As for the quantity of single movement patterns, six infants lacked one or two movement patterns normally present in healthy newborn infants. An abnormal quality of GMs was noted in all nine infants and distinct motor abnormalities were observed in single infants. A monotonous and sometimes stereotyped sequence of different body parts involved in the movement (i.e. poor repertoire GMs) was common to all infants. In the four infants of whom two or more video recordings were available, initial poor repertoire GMs were followed by a further deterioration in movement quality. No relationship was found between the quantity of defective brain tissue, lack of a specific part of the brain, type and severity of GM and posture abnormalities.

[Locoregional therapy with hypoxic liver perfusion in malignant neoplasms of the gallbladder. Preliminary experience]. / Terapia locoregionale con perfusione ipossica epatica delle neoplasie maligne della colecisti. Esperienza preliminare.

PURPOSE: We report four cases of advanced malignant cancer of the gallbladder treated with hypoxic hepatic perfusion. MATERIAL AND METHODS: Hypoxic hepatic perfusion is currently used to treat diffuse hepatic metastases: the common hepatic artery is occluded with a balloon catheter and then a large amount of antiblastic solution is infused into the liver. Hypoxia and slow flow increase the effect of the drug on neoplastic tissue. Two sessions were performed in three patients with an interval ranging 2-4 months, while one patient underwent a single session. The drug was Mitomycin C, whose dose ranged 20-40 mg (mean: 30 mg). Blood filtration was performed after one of the six procedures only and can be considered unnecessary. RESULTS: Acute gastric bleeding appeared in a patient after the embolization of the right gastric artery with bucrylate during the first session performed to avoid drug reflux into gastric wall arteries. No other technical or clinical complications occurred. An objective morphological response (tumor necrosis or reduction in size > 50%) was observed in all patients after the first session. CT findings were stable in two of three patients submitted to a second session, while local progression was observed in the other patient. Complete clinical response was achieved in all symptomatic patients. No WHO toxicity was observed. DISCUSSION AND CONCLUSIONS: The rate of positive morphological and/or clinical responses after hypoxic perfusion was very high in our experience, even though our series was small. Recurrences were found in two patients some months later, which suggests the need of long-term follow-up. Hypoxic perfusion can be nevertheless considered as a new and interesting therapeutic approach for advanced malignant gallbladder cancer, with a strong short-term effect on the lesion and good results on clinical symptoms.