Propranolol as first-line treatment for life-threatening diffuse infantile hepatic hemangioma: a case report

[No abstract available

Evaluation of esophageal motility using multichannel intraluminal impedance in healthy children and children with gastroesophageal reflux: comments

Abstract OBJECTIVE: : Multichannel intraluminal impedance (MII) directly evaluates esophageal bolus transport. There is a good correlation between MII and manometry in healthy adults, but there are no reports concerning children.The aim of the present study was to determine normal values of esophageal motility using only impedance measurements in healthy children and in a pediatric population with gastroesophageal reflux (GER). PATIENTS AND METHODS: : We described in the present study 60 children submitted to pH-MII for 24 hours for suspected GER. Patients were divided into 2 different groups on the basis of their pH-MII report. Group 1 patients showed acid GER, whereas group 2 patients had negative pH-MII analysis for GER despite symptoms. We described impedance reflux and motility parameters on 10 standardized swallows: number of reflux, mean acid clearing time, median bolus clearing time, bolus presence time, total bolus transit time, segmental transit time, and total propagation velocity. RESULTS: : In group 1, the median mean acid clearing time was 151 seconds, whereas the median mean bolus clearing time was 25 seconds. In group 2 patients, all of the reflux parameters were normal. In group 1 the median bolus presence time at each measuring site, the median total bolus transit time, and the median segmental transit time were significantly greater and total propagation velocity lower than values reported in group 2 (P < 0.001), if compared with those described for adult patients. CONCLUSIONS: : The pH-MII is an ideal test in children because it studies GER with its characteristics and motility pattern. Our report summarizes for the first time impedance motility parameters in healthy children

Topographic and biomechanical changes after application of corneal cross-linking in recurrent keratoconus

Background: Recurrent keratoconus (RKC) develops as a progressive thinning of the peripheral and the inferior cornea after keratoplasty, in both graft and host, causing secondary astigmatism, refractive instability, and reduced visual acuity. We evaluated the effectiveness of corneal cross-linking (CXL) in patients diagnosed with RKC. Methods: Accelerated-CXL via the epi-off technique was performed in15 patients (18 eyes) diagnosed with RKC. Topographic and biomechanical changes were assessed at 12 months. Results: Differences in maximum keratometry, thinnest corneal thickness, and biomechanical parameters (deformation amplituderatio, inverse concave radius, applanation 1 velocity, and applanation 2 velocity, stiffness A1) versus baseline were statistically significant (p &lt; 0.05).Best corrected visual acuity was improved in 13 eyes and unchanged in 4;manifest refractive spherical equivalent was reduced in 13 eyes, increased in 3,and unchanged in 1 eye; topographic astigmatism was reduced in 9 eyes, remained stable in 1 eye, and increased in 7 eyes. Conclusions: Improved topographic and biomechanic indexes at 1 year after CXL suggest it's potential as first-line therapy for RKC, as it is for KC

Maternal depression and attachment: the evaluation of mother–child interactions during feeding practice

Internal working models (IWMs) of attachment can moderate the effect of maternal depression on mother-child interactions and child development. Clinical depression pre-dating birthgiving has been found to predict incoherent and less sensitive caregiving. Dysfunctional patterns observed, included interactive modes linked to feeding behaviors which may interfere with hunger-satiation, biological rhythms, and the establishment of children's autonomy and individuation. Feeding interactions between depressed mothers and their children seem to be characterized by repetitive interactive failures: children refuse food through oppositional behavior or negativity. The aim of this study was to investigate parenting skills in the context of feeding in mothers with major depression from the point of view of attachment theory. This perspective emphasizes parents' emotion, relational and affective history and personal resources. The sample consisted of 60 mother-child dyads. Mothers were divided into two groups: 30 with Major Depression and 30 without disorders. Children's age ranged between 12 and 36 months The measures employed were the Adult Attachment Interview and the Scale for the Evaluation of Alimentary Interactions between Mothers and Children. Insecure attachment prevailed in mothers with major depression, with differences on the Subjective Experience and State of Mind Scales. Groups also differed in maternal sensitivity, degrees of interactive conflicts and negative affective states, all of which can hinder the development of adequate interactive patterns during feeding. The results suggest that IWMs can constitute an indicator for the evaluation of the relational quality of the dyad and that evaluations of dyadic interactions should be considered when programming interventions

Tumor derived Microvesicles enhance cross-processing ability of clinical grade Dendritic Cells

Tumor cells release extracellular microvesicles (MVs) in the microenvironment to deliver biological signals to neighbouring cells as well as to cells in distant tissues. Tumor-derived MVs appear to play contradictory role promoting both immunosuppression and tumor growth and both evoking tumor specific immune response. Recent evidences indicate that tumor-derived MVs can positively impact Dendritic Cells (DCs) immunogenicity by reprogramming DC antigen processing machinery and intracellular signaling pathways, thus promoting anti-tumor response. DCs are considered pivot cells of the immune system due to their exclusive ability to coordinate the innate and acquired immune responses, cross-present exogenous antigens and prime naïve T cells. DCs are required for the induction and maintenance of long-lasting anti-tumor immunity and their exploitation has been extensively investigated for the design of anti-tumor vaccines. However, the clinical grade culture conditions that are required to generate DCs for therapeutic use can strongly affect their functions. Here, we investigated the immunomodulatory impact of MVs carrying the MUC1 tumor glycoantigen (MVsMUC1) as immunogen formulation on clinical grade DCs grown in X-VIVO 15 (X-DCs). Results indicated that X-DCs displayed reduced performance of the antigen processing machinery in term of diminished phagocytosis and acidification of the phagosomal compartment suggesting an altered immunogenicity of clinical grade DCs. Pulsing DCs with MVsMUC1 restored phagosomal alkalinization, triggering ROS increase. This was not observed when a soluble MUC1 protein was employed (rMUC1). Concurrently, MVsMUC1 internalization by X-DCs allowed MUC1 cross-processing. Most importantly, MVsMUC1 pulsed DCs activated IFNγ response mediated by MUC1 specific CD8+ T cells. These results strongly support the employment of tumor-derived MVs as immunogen platforms for the implementation of DC-based vaccine

Efficacy of periportal infiltration and intraperitoneal instillation of ropivacaine after laparoscopic surgery in children

Postoperative pain is less intense after laparoscopic than after open surgery. However, minimally invasive surgery is not a a pain-free procedure. Many trials have been done in adults using intraperitoneal and/or incisional local anesthetic, but similar studies have not yet been reported in the literature in children. Aim: The aim of this study was to evaluate the analgesic effect of periportal infiltration and intraperitoneal instillation of ropivacaine in children undergoing laparoscopic surgery. Materials and Methods: Thirty patients who underwent laparoscopic surgery were randomly allocated to one of three groups. Group A (n 10) received local infiltration of port sites with 10 mL of ropivacaine. Group B (n 10) received both an infiltration of port sites with 10 mL of ropivacaine and an intraperitoneal instillation of 10 mL of ropivacaine. Group C did not receive any analgesic treatment. The local anesthetic was always administered at the end of surgery. The degree of postoperative abdominal parietal pain, abdominal visceral pain, and shoulder pain was assessed by using a Wong-Baker pain scale and a Visual Analog Scale (VAS) at 3, 6 12, and 24 hours postoperatively. The following parameters were also evaluated: rescue analgesic treatment, length of hospital stay, and time of return to normal activities. Results: Three hours after operation, patients had low pain scores. Six and 12 hours postoperatively, the abdominal parietal pain was significantly higher (P 0.0005) in group C than in the other two groups, both treated with an infiltration at the trocar sites; mean intensity of abdominal visceral pain was significantly lower (P 0.0005) in group B than in groups A and C; the overall incidence of shoulder pain was significantly lower (P 0.0005) in group B patients than in patients of groups A and C. At 20 hours postoperatively, pain scores were significantly reduced of intensity in all groups. Rescue analgesic treatment was significantly higher in group C, if compared to groups A and B 12 hours after the operation. No statistically significant difference was found in length of hospital stay, but children who received analgesic treatment had a more rapid return to normal activities than untreated patients (P 0.0005). Conclusions: Our study demonstrates that the combination of local infiltration and intraperitoneal instillation of ropivacaine is more effective for pain relief in children after laparoscopic surgery than the administration of ropivacaine only at the trocar sites

Immunological backbone of uveal melanoma: is there a rationale for immunotherapy?

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease

Identification of murine phosphodiesterase 5A isoforms and their functional characterization in HL-1 cardiac cell line

Phosphodiesterase 5A (PDE5A) specifically degrades the ubiquitous second messenger cGMP and experimental and clinical data highlight its important role in cardiac diseases. To address PDE5A role in cardiac physiology, three splice variants of the PDE5A were cloned for the first time from mouse cDNA library (mPde5a1, mPde5a2 and mPde5a3). The predicted amino acidic sequences of the three murine isoforms are different in the N-terminal regulatory domain. mPDE5A isoforms were transfected in HEK293T cells and they showed high affinity for cGMP and similar sensitivity to sildenafil inhibition. RT-PCR analysis showed that mPde5a1, mPde5a2 and mPde5a3 had differential tissue distribution. In the adult heart, mPde5a1 and mPde5a2 were expressed at different levels whereas mPde5a3 was undetectable. Overexpression of mPDE5As induced an increase of HL-1 number cells which progress into cell cycle. mPDE5A1 and mPDE5A3 overexpression increased the number of polyploid and binucleated cells, mPDE5A3 widened HL-1 areas and modulated hypertrophic markers more efficiently respect to the other mPDE5A isoforms. Moreover, mPDE5A isoforms had differential subcellular localization: mPDE5A1 was mainly localized in the cytoplasm, mPDE5A2 and mPDE5A3 were also nuclear localized. These results demonstrate for the first time the existence of three PDE5A isoforms in mouse and highlight their potential role in the induction of hypertrophy. This article is protected by copyright. All rights reserved

AAV-mediated transcription factor EB (TFEB) gene delivery ameliorates muscle pathology and function in the murine model of Pompe Disease

Pompe disease (PD) is a metabolic myopathy due to acid alpha-glucosidase deficiency and characterized by extensive glycogen storage and impaired autophagy. We previously showed that modulation of autophagy and lysosomal exocytosis by overexpression of the transcription factor EB (TFEB) gene was effective in improving muscle pathology in PD mice injected intramuscularly with an AAV-TFEB vector. Here we have evaluated the effects of TFEB systemic delivery on muscle pathology and on functional performance, a primary measure of efficacy in a disorder like PD. We treated 1-month-old PD mice with an AAV2.9-MCK-TFEB vector. An animal cohort was analyzed at 3 months for muscle and heart pathology. A second cohort was followed at different timepoints for functional analysis. In muscles from TFEB-treated mice we observed reduced PAS staining and improved ultrastructure, with reduced number and increased translucency of lysosomes, while total glycogen content remained unchanged. We also observed statistically significant improvements in rotarod performance in treated animals compared to AAV2.9-MCK-eGFP-treated mice at 5 and 8 months. Cardiac echography showed significant reduction in left-ventricular diameters. These results show that TFEB overexpression and modulation of autophagy result in improvements of muscle pathology and of functional performance in the PD murine model, with delayed disease progression