Long-term outcomes in survivors of acute respiratory distress syndrome ventilated in supine or prone position.

PURPOSE: The aim of this study is to examine long-term pulmonary function and quality of life in survivors of acute respiratory distress syndrome (ARDS) previously enrolled in a randomized multicenter trial testing prone compared with supine positioning (PSII study) at five Italian centers. DESIGN: Observational prospective study. SUBJECTS AND MEASUREMENTS: Pulmonary function [spirometric test, gas exchange, carbon monoxide diffusion capacity (DLCO)], high-resolution computed tomography (CT) scan, and health-related quality of life [Short Form-36 (SF-36) and St. George's Respiratory Questionnaire] were evaluated at 12 months. RESULTS: Twenty-six patients (13 in each group, mean age 54.1 ± 2.8 years, body mass index 24.5 ± 1.4 kg/m(2), PaO(2)/FiO(2) 117 ± 49 mmHg) were evaluated. There were no significant differences in demographic data, illness severity, or outcome between the prone and supine groups. The overall survival rate was 40%. Pulmonary function was in the normal range without any differences between the two groups. Quantitative lung CT scan analysis showed similar amounts for not aerated (8.1 ± 3.2% versus 7.3 ± 3.4%), poorly aerated (15.3 ± 3.6% versus 17.1 ± 4.9%), and well-aerated (64.0% ± 8.4 versus 70.2 ± 8.4%) lung regions, while overaerated lung region was slightly higher in the prone compared with the supine group (12.5 ± 6.5% versus 5.3 ± 5.5%). Health-related quality of life was similar to in healthy population. However, these patients showed reduction in daily activity specifically due to pulmonary disease as measured by the St. George's Respiratory Questionnaire. CONCLUSIONS: No differences in pulmonary function or quality of life were observed in this small group of ARDS survivor patients treated in prone versus supine position.

Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results.

BACKGROUND: Anti-tumour necrosis factor-alpha antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor-alpha suppressive properties. AIM: To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. METHODS: Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5-2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. RESULTS: Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). CONCLUSIONS: Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension.

Side effects of GnRH analogue treatment in childhood.

There are a few reports of side-effects of LHRHa treatment in childhood, the mechanisms of which remain little understood. Such effects can be local reactions: erythema, induration, wheal and sterile abscess formation, which can be possible causes of therapy failure. There are negative effects on growth velocity and final height requiring rhGH therapy or a suppressive treatment when bone age >13 years. Excessive weight gain can occur by various mechanisms: menopausal-like phenomena, or LHRHa influence on hypothalamic and/or leptin-mediated control of body weight. Other possible adverse effects involve increased ovarian volume with possible POS development; however, there is no evidence correlating LHRHa, hyperandrogenism and POS. The latter appears related to CPP onset with pre-existing hyperandrogenism, although lengthier follow-up is necessary to confirm this. Bone density decreases during therapy, but final peak bone mass is in the normal range. Frequent transitory side-effects include headaches, hot flushes, depression and irregular menses.

Chronic exposure to either somatostatin (SS) or octreotide, a long-lasting SS analogue, affects SS expression in the postnatal visual cortex of the rat.

The peptide somatostatin (SS) is widely distributed in the mammalian brain where it modulates neuronal activity through interactions with specific membrane-bound receptor subtypes (ssts). Five different ssts were characterized so far (sst1-5) and their selective agonists were developed on the basis of their binding specificity. SS and ssts are transiently expressed in the developing brain, suggesting a functional role of somatostatinergic systems in neuronal maturation. In the present study, we investigated the effects of chronic exposure to either the SS synthetic analogue, SS-14 or octreotide (a long-acting sst2-preferring analogue) on the maturation of SS-immunoreactivity (-ir) in the primary visual cortex of the rat. SS-ir maturation was investigated both by an evaluation of the number of SS-immunoreactive cells and by radioimmunoassay (RIA) to measure the levels of SS in the postnatal visual cortex. In the visual cortex of normal rats, the number of SS-positive cells markedly increased during the second postnatal week and then significantly decreased until the adult value was reached at the third week. Early and repeated intracerebroventricular (i.c.v.) injections of either SS-14 or octreotide prevented the increase in the number of SS-positive cells, with adult values reached at the end of the first postnatal week. Similarly, administration of either SS-14 or octreotide significantly decreased the SS content of the visual cortex, measured at the end of the second postnatal week. These results show that high local concentrations of either SS-14 or octreotide interfere with SS expression in developing cortical neurons in a restricted postnatal period.

Endoscopic management of inveterate esophageal perforations and leaks.

The endoscopic management of four selected patients with inveterate esophageal perforations or leaks is presented. One patient had a perforation of the cervical esophagus following endoscopic removal of a foreign body already treated with surgical drainage; two patients had a leak following diverticulectomy and esophagogastrostomy, respectively, persistent after multiple surgical repairs; the last patient had a spontaneous perforation of the thoracic esophagus persistent after two transthoracic repairs. The mean time elapsed between the diagnosis of perforation and the endoscopic treatment was 19 days. In one patient, transesophageal drainage of a mediastinal abscess was performed. In the other three patients, a stent was placed to seal the leak in combination with gastric and esophageal aspiration. Two of these patients underwent endoscopy in critical condition and could have not been candidates for major surgical procedures. All patients received enteral nutrition. No morbidity or mortality related to the endoscopic procedure was recorded; the treatment was effective in all patients who recovered and resumed oral feeding within 3 weeks. We conclude that endoscopic transesophageal drainage and stenting are effective procedures in the management of patients with inveterate esophageal perforations or leaks.

[Bronchopulmonary dysplasia in very low birth weight infants]. / La displasia bronco-polmonare nei nati di peso molto basso.

The reported incidence of Bronchopulmonary dysplasia (BPD) varies from 5% to 68%. The different criteria used to define BPD are responsable for these discrepancies: some Authors include only patients with a clinical and radiological picture that fits the stage IV, as originally described by Northway, others use a more liberal approach and include all patients with manifestations of chronic pulmonary disease. We observed BPD in 12 of 22 (54%) survivors infants of very low birth weight (mean 1115 gm) and gestational age (mean 29,2 weeks). The infants were all born between November 1979 and March 1981. According to Ehrenkranz et al., we classified the radiological findings as severe, moderate and mild. We believe that the etiology of BPD in very low birth weight infants is multifactorial. However, pulmonary oxygen toxicity and immaturity are the most important causes.