Children with medical complexity and paediatric palliative care: a retrospective cross-sectional survey of prevalence and needs.

BACKGROUND: Children with medical complexity (CMC) have been defined (Cohen et al., Pediatrics 127: 529-538, 2011.) as an emerging population potentially eligible for PPC. The current study investigated the prevalence of children with medical complexities eligible for a local palliative care network, including a paediatric hospice. METHODS: A retrospective cross-sectional survey has been conducted using children clinical charts from 14 local health authorities of our region (Emilia Romagna, Italy). RESULTS: The total number of children with life-limiting conditions was 601, with a mean age of 7.4 ± 4.8 years, a prevalence of 8.4/10.000 residents < 19 years of age and a heterogeneous presentation among the provinces in the region. Neurological diseases affect 51% of patients, followed by congenital diseases (21%) and pathologies originating in the perinatal period (6%), while only 4% of the patients had a cancer diagnosis. Patients are dependent from many devices and supports: 32% had a gastrostomy, 22% a respiratory support and 15% of patients had both of them. CONCLUSIONS: Observed regional prevalence of complex needs is lower than that published from other European countries. More research is needed to raise awareness of palliative care for children with medical complexities in order to address specific needs.

Imbibition of Femtoliter-Scale DNA-Rich Aqueous Droplets into Porous Nylon Substrates by Molecular Printing.

This work presents the first reported imbibition mechanism of femtoliter (fL)-scale droplets produced by microchannel cantilever spotting (µCS) of DNA molecular inks into porous substrates (hydrophilic nylon). Differently from macroscopic or picoliter droplets, the downscaling to the fL-size leads to an imbibition process controlled by the subtle interplay of evaporation, spreading, viscosity, and capillarity, with gravitational forces being quasi-negligible. In particular, the minimization of droplet evaporation, surface tension, and viscosity allows for a reproducible droplet imbibition process. The dwell time on the nylon surface permits further tuning of the droplet lateral size, in accord with liquid ink diffusion mechanisms. The functionality of the printed DNA molecules is demonstrated at different imbibed oligonucleotide concentrations by hybridization with a fluorolabeled complementary sequence, resulting in a homogeneous coverage of DNA within the imbibed droplet. This study represents a first step toward the µCS-enabled fabrication of DNA-based biosensors and microarrays into porous substrates.

Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section.

Following studies on the properties of spontaneous plants in Sardinia we have evaluated the tissue regenerating action of a mixture of oily extracts of Hypericum perforatum and Calendula arvensis on surgical wounds from childbirth with caesarean section.

Bilateral laryngeal pseudoparalysis in xanthoma disseminatum treated by endoscopic laser medial arytenoidectomy.

Xanthoma disseminatum is a rare non-Langerhans' cell histiocytosis, characterized by papular cutaneous eruption, possible mucosal involvement, and frequent association with vasopressin-sensitive diabetes insipidus. Herein we report a case of xanthoma disseminatum with pharyngolaryngeal involvement. In this patient, mucosal xanthomas involving the arytenoid cartilages and the interarytenoid area resulted in laryngeal stenosis and severe impairment of both cricoarytenoid joints' motility. Endoscopic CO2 laser medial arytenoidectomy, according to the technique described by Crumley (1993), and vaporization of interarytenoid xanthomas were successfully performed, thus reestablishing bilateral cordal motility and the laryngeal airway. Four years later, a CO2 laser revision was necessary because of recurrence of xanthomas in the posterior larynx. Two years after the latter operation, the patient has no signs of laryngeal obstruction and has a normal voice quality. This case report suggests that endoscopic medial arytenoidectomy may be successfully used in the treatment of bilateral laryngeal pseudoparalysis secondary to xanthoma disseminatum.

Clinical experience with the treatment of T1b glottic cancer by means of horizontal glottectomy.

This study describes the oncological and functional results of horizontal glottectomy performed in a series of 37 similar patients with T1b glottic cancers. The 5-year overall and disease-free survival rates were, respectively, 85.4% and 91.0%. Decannulation was always possible within a mean period of 16.2 days, and no patient developed laryngeal stenosis. A bypass naso-gastric tube was removed a mean 4.9 days after surgery, and adequate swallowing was soon obtained. The mean duration of post-operative hospitalization was 16 days and no major post-operative complications were observed. Satisfactory vocal function was obtained in all cases. On the basis of these results, horizontal glottectomy was found to be a reliable and safe procedure for the management of T1b glottic cancer.

A multicenter trial of specific local nasal immunotherapy.

OBJECTIVE: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters. STUDY DESIGN: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months. METHODS: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen. The specific treatments were self-administered using an insufflator in two phases (phase 1: increasing doses; phase: 2, maintenance dose). Patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test results confirmed that this difference was statistically significant. The rhinomanometric analysis gave positive results for the treated group mainly in LNIT for mites. No differences in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is effective for allergic rhinitis and appears to offer considerable advantages over other hyposensitization methods. It can be done at home, patient compliance is good, and the treatment is safe.

The predictive value of p53, MDM-2, cyclin D1 and Ki67 in the progression from low-grade dysplasia towards carcinoma of the larynx.

To evaluate the predictive role of the oncogenes p53, MDM-2 and cyclin D1, and the proliferative marker Ki67, in the progression from low-grade dysplasia to carcinoma of the larynx. We studied immunohistochemically a series of 32 low-grade pre-neoplastic laryngeal lesions, 10 of which progressed to invasive carcinoma. Immunoreactivity in more than 10 per cent of the dysplastic cells was detected in five cases immunostained with anti-p53 (approximately 15 per cent), in two with anti-MDM-2 (approximately six per cent), and 11 with anti-Ki67 antibodies (approximately 34 per cent), whereas none of the cases showed cyclin D1 overexpression. No significant association was found between p53 and MDM-2 immunoreactivity and the evolution to carcinoma; on the contrary, Ki67 expression was detectable in all but one of the 10 cases developing an infiltrative tumour (90 per cent), and in two of the 22 cases that did not progress (approximately nine per cent) (p = 0.01). These findings indicate that immunohistochemical assessment of the proliferative index in bioptic samples of dysplastic laryngeal mucosa may be useful in selecting patients who should undergo a more specific follow-up evaluation.

p53 and cyclinX D1 protein expression in carcinomas of the parotid gland.

BACKGROUND: p53 and cyclin D1 genes play a central role in the regulation of the G1 phase of the cell-cycle, and are frequently involved in head and neck tumorigenesis. MATERIALS AND METHODS: By means of immunohistochemistry, we retrospectively investigated the overexpression of cyclin D1 and p53 genes in a series of 28 parotid gland carcinomas. The immunohistochemical analysis was performed using the ABC method and the antibodies DCS6 (for cyclin D1) and CM1 (for p53). RESULTS: p53 was overexpressed in 12 (42.9%) and cyclin D1 in 6 cases (21.4%). No significant association was found between p53 or cyclin D1 expression and the evaluated clinicopathological parameters of tumor extension, clinical stage, and lymph node or distant metastases. Nevertheless, it is worth noting that all of the patients with a high expression of p53 died of their disease. CONCLUSIONS: The present data confirm the role of p53 abnormalities in the pathogenesis of salivary gland carcinoma and report, for the first time, the involvement of cyclin D1 gene in these tumors.

Clinical relevance of p53 and bcl-2 protein over-expression in laryngeal squamous-cell carcinoma.

We investigated immunohistochemically the clinical relevance of the over-expression of the apoptosis-regulating proteins p53 and bcl-2 in a homogeneous series of 149 laryngeal squamous-cell carcinomas. p53 was over-expressed in 75 cases and bcl-2 in 39 cases. p53 and bcl-2 co-expression was found in 21 cases. p53 and bcl-2 immunoreactivity was significantly associated with poor histological differentiation and lymph-node metastases. Moreover, a significant statistical correlation was found between bcl-2 expression, supraglottic tumor site and advanced disease stage. p53/bcl-2 co-expression was significantly associated with poor differentiation, tumor extension, the presence of lymph-node metastases and advanced clinical stage. Univariate analysis showed that a lower probability of survival was significantly associated with supraglottic site, tumor extension, advanced clinical stage and p53/bcl-2 co-expression, but not with p53 or bcl-2 considered separately. In multivariate analysis, only tumor extension and supraglottic site retained their prognostic value. Our data suggest that clinical staging remains the most reliable predictive indicator of survival in patients with laryngeal carcinoma.

Cyclin D1 protein expression is related to clinical progression in laryngeal squamous cell carcinomas.

The expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell carcinomas (LSCCs) in order to determine its clinical and prognostic value. Overexpression of cyclin D1 was detected immunohistochemically using DCS6 monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin D1 expression was detected in 22 of the 74 cases investigated (30 per cent), thirteen of which presented nodal metastases (59 per cent); of the patients without any detectable cyclin D1 protein expression, six presented nodal metastases (12 per cent). Cyclin D1 protein expression was found in five per cent of the specimens of normal mucosa, eight per cent of those with low-grade dysplasia and 20 per cent of those with high-grade dysplasia. A statistically significant association was found between cyclin D1 expression and the supraglottic site (p < 0.05), tumour extension (p < 0.001), the presence of lymph node metastases (p < 0.001), and advanced clinical stage (p < 0.001). Cyclin D1 expression analysis is an important tool in the selection of LSCC patients with an aggressive clinical course.

DNA content and thymidine labeling index correlate with prognosis in squamous cell carcinoma of the larynx.

The prognostic value of proliferative activity was determined in 48 cases of squamous cell carcinoma of the larynx. Tumor samples were obtained during surgery: DNA content was determined by static cytometry with an image analysis program, and cell kinetics were analyzed by the in vitro thymidine labeling index (T-LI). The DNA content analysis visualized a diploid cellular population in 32 cases and an aneuploid cellular population in 16 cases. The DNA content was not significantly related to the sex and the age of the patients or the TN stage of the tumors, but to histological grade (p = 0.03). Similarly significant correlation was found between T-LI and age of the patients, indeed the median value was higher in patients older than 59 (p = 0.024). T-LI was not related to the sex of the patients, or to the histological grade or the TN stage of the tumors. In multivariate analysis, using the Cox model, T-LI was the most important prognostic parameter (p = 0.015), superior to DNA content (p = 0.021) and to TN stage (p = 0.047; p = 0.043). From the data obtained in this study it can be concluded that evaluation of DNA content and thymidine labeling index in squamous cell carcinoma of the larynx may be new independent parameters of prognosis and may contribute to optimal and individualized therapy.

p53 protein expression in laryngeal squamous cell carcinomas bearing wild-type and mutated p53 gene.

We performed an immunohistochemical analysis to investigate the expression of p53 protein in a panel of 18 laryngeal squamous cell carcinomas, 15 primary tumours and three in relapse, previously analysed by us for the presence of p53 gene mutations. Dysplastic and/or normal surrounding mucosa was evaluated in 15 different tumours. The results of our study are the following: (1) expression of p53 protein was observed in one out of five tumours positive for p53 gene mutations (20%) and in 10 out of 13 (80%) negative cases; (2), p53 protein over-expression was frequently observed in normal and/or dysplastic mucosa surrounding either wild-type (7/11) or mutated p53 tumours (2/4); (3), p53 immunoreactive cells showed a pattern of distribution in normal and mildly/ moderately dysplastic mucosa (basal layers), different from that in severely dysplastic mucosa (whole thickness). These data further support the hypothesis that p53 protein over-expression may be a marker of the earliest phases of multistep tumorigenesis in laryngeal squamous cell carcinoma.

Extracorporeal electromagnetic shock-wave lithotripsy for salivary gland stones.

Sialoadenectomy for sialolithiasis is necessary when the stone cannot be removed through the salivary duct. In addition, extracorporeal. shock-wave lithotripsy has recently become available for this purpose. The safety and efficacy of this method was assessed in 52 outpatients bearing stones with an average diameter of 6.76 mm in the submandibular or parotid gland. Anesthetics, sedatives, and analgesics were not required. Twenty-four of the 36 patients with submandibular gland calculi and all 16 with parotid sialolithiasis had complete stone disintegration or fragmentation of the calculi, with possible spontaneous clearance. Untoward effects were observed in 15 patients, namely localized skin petecchiae, transitory swelling of the gland, and self-limiting bleeding from the duct. No persistent damage of the salivary glands or adjacent structures was noted during a mean follow-up period of 10 months.

[Liver damage and obesity in pediatric age]. / Alterazioni epatiche e obesità in età pediatrica.

In adult obese patients both an increase of aminotranspherase values and hepatic steatosis have been frequently showed. Conversely in childhood the existence of a liver's damage is often not investigated. To assess the prevalence of hepatic alterations in obese children, we studied 135 subjects, all affected by simple obesity, showing in a 20% of them the presence of ultrasonographic evidence of hepatic steatosis and/or hyperaminotransferasemia. Our study demonstrates the existence of silent hepatic alterations also in obese children and suggests to improve the treatment of obesity in childhood to prevent the progression of liver's damage.

Multiple genetic lesions in laryngeal squamous cell carcinomas.

BACKGROUND: To understand the molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs), this study investigated the involvement of various protooncogene loci (bcl-1, int-2, c-erbB-1, c-myc, ras) and the p53 tumor suppressor gene in 18 patients with LSCC (15 at clinical presentation, 3 in clinical relapse). METHODS: For all patients, the mutations affecting the p53 and the H-, K-, and N-ras genes were evaluated by polymerase chain reaction (PCR), single-strand conformation polymorphism, and the direct sequencing of PCR-amplified fragments. The bcl-1, int-2, c-erbB-1, and c-myc loci of 15 patients were investigated using Southern blot analysis. RESULTS: A mutation of the p53 gene was detected in 5/18 patients (approximately 28%), bcl-1 locus amplification in 4/15 (approximately 26%), c-erbB-1 locus amplification in 2/15 (approximately 13%), and c-myc locus amplification in 1/15 (approximately 6%). The simultaneous presence of more than one genetic lesion was observed in four patients; two showed int-2/bcl-1 coamplification, and two int-2/c-erbB-1 coamplification, one of whom also showed a p53 gene mutation. A novel p53 mutation involving the splice acceptor site of exon 6 was detected in one patient. Two of the five patients positive for p53 mutations had clinical relapses of primary tumors. bcl-1 locus amplification only was observed in patients with lymph node metastases (4/6). All but one of the patients with molecular genetic lesions showed a peculiar infiltrating pattern. CONCLUSIONS: Overall, these results show that alterations of known protooncogenes and the p53 tumor suppressor gene are involved in a large proportion of LSCCs (11/18; approximately 60%) and may suggest that distinct molecular pathways occur in the pathogenesis of these tumors.

[Dermatitis herpetiformis and latent celiac disease in two siblings]. / Dermatite erpetiforme e malattia celiaca silente in due fratelli.

The association between coeliac disease (CD) and dermatitis herpetiformis (DH) is well known. Moreover, this cutaneous disease may be the only sign of an otherwise asymptomatic CD. Subjects presenting with both CD and DH generally show an HLA pattern in which A1, B8, DR2, DR7, DQw2 are the most frequent antigens one can find. We report about 2 brothers presenting with DH, clinically asymptomatic, without antigliadin serum antibodies (AGA), but positive to the research of antiendomysial (EMA) ones. The biopsy performed by digestive endoscopy showed a complete atrophy of duodenal villi and the diagnosis of CD was confirmed according to the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) criteria. The diet without gluten caused the DH to recovery and the duodenal villi microscopic aspect to normalize as well. Both the brothers had the same HLA pattern: A1, B8, DR3-DR2, DQw2. Our clinical study suggests that it is very important, especially for the general practitioner, to recognize a DH and in every child presenting with a dermatitis like that it will be mandatory to perform a laboratory research of both AGA and EMA.

[Autoimmune endocrinopathies and Down's syndrome: a case report]. / Endocrinopatie autoimmuni e sindrome di Down: descrizione di un caso.

The authors refer about a girl, 16 years old, affected by Down's syndrome which developed diabetes mellitus (type I) and soon after hypothyroidism following autoimmune thyroiditis. They underline the usefulness of monitoring endocrine function in these patients.

A multicentre clinical study of nimesulide in inflammatory diseases of the ear, nose and throat.

940 male and female patients aged 15 to 77 years were enrolled in a multicentre noncomparative study in order to assess the efficacy and tolerability of nimesulide in otorhinolaryngological inflammatory diseases. 309 patients were affected by otitis media and 631 by upper respiratory tract inflammation. All the patients were treated with orally administered granular nimesulide 100mg twice daily for a mean period of 10 days. Nimesulide significantly reduced the intensity of signs and symptoms, thus allowing functional recovery. The drug was well tolerated, and of the 75 patients who reported adverse effects, only 26 had to be withdrawn from treatment.