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Proton pump inhibitors (PPIs) are widely prescribed in all age groups, and their use is increasing. However, their safety profile has been frequently questioned.The aim of this study was to analyze the characteristics of PPI-related adverse drug reactions (ADRs) reported to the Italian spontaneous reporting system (SRS) database and relative to an Italian region (Sicily).A 20-year observational, retrospective study was conducted, evaluating PPI-related ADR reports from Sicily between January 1st, 2001, and June 30th, 2021. The factors associated with ADR seriousness were investigated.A total of 148 spontaneous reports of ADRs related to PPIs were analyzed. Lansoprazole was the drug with the highest number of associated reports (30.87%). The most frequently reported ADRs were cutaneous (24.56%) and/or gastrointestinal manifestations (18.10%), the latter especially in the case of lansoprazole-related ADRs (p0.006). The great majority of ADR reports were relative to on-label prescriptions. Serious ADRs were 39 (26.35%). Serious ADRs were more common in reports including omeprazole than in reports containing other PPIs (p0.008) and in reports presenting PPIs combined with other drugs than in reports with PPI single therapies (p0.001).Most PPI-related ADRs are non-serious. Omeprazole and combination therapy seem to be associated with ADR seriousness.

The vaccination of pregnant women against influenza and COVID-19 may reduce the risk of severe illness in both the women of this population and their babies. Although the risks of non-vaccination are more serious than the side effects, maternal immunization is still the least-used method of prevention due to a lack of information leading to concerns about the safety and efficacy of vaccines, resulting in a low prevalence rate among pregnant individuals. Our study investigates vaccination coverage and the knowledge, attitudes and perceptions of COVID-19 in pregnant women at a university hospital. A questionnaire was created with the following three scores: a vaccination propensity score, a knowledge score and a hesitancy score. The first observation in the results was the very low number of immunized women (only 4.7% received their first dose). The main barrier towards vaccination was found to be fear of adverse events. We noticed a low percentage of influenza and diphtheria tetanus pertussis vaccination compared to other studies. Vaccination propensity was higher when healthcare workers educated their patients. As immunization is a crucial part of public health policy, measuring coverage to identify gaps and monitor trends, especially for individuals considered at high risk, and developing new strategies in order to increase awareness of vaccination during pregnancy is particularly timely and relevant.

Objectives Treatment approach of myasthenia gravis (MG) is still debated; corticosteroids alone or in combination with immunosuppressive agents are the most used drugs. Azathioprine (AZA) has been shown to be effective for MG with a significant steroid-sparing activity, although burdened by side effects. Few studies on methotrexate (MTX) administration showed controversial results. In this cohort, we evaluated the role of MTX as a effective steroid-sparing agent. Methods Fifteen MG patients treated with MTX, previously treated with AZA for at least 12 months, with poor benefits and uncomfortable side effects AZA related, have been selected. Each patient was evaluated through MG-Activity of Daily Living and Quantitative MG scores 5 times/yr. Results Patients treated with MTX had a significant improvement of MG-Activity of Daily Living and Quantitative MG scores. Furthermore, all patients reduced prednisone dosage, and none complained of side effects. Conclusions We suggest MTX is effective and well tolerated and could be considered as a steroid-sparing agent in MG treatment.

Aims The objective of this study was to evaluate the impact of the first Italian COVID-19 lockdown on patients with chronic migraine (CM). Material and methods The study was based on an e-mail survey addressed to CM patients of our headache center. The survey evaluated demographic, life style, sleep, psychological, and migraine features during the COVID-19 lockdown period and the month before. The outcomes were migraine impact on daily life and variation in attack frequency, attack duration, migraine pain intensity, migraine symptomatic drugs use per week, and efficacy. Results Ninety-two patients completed the survey. During the lockdown period, attack frequency was stable in 40,2%, increased in 33,7%, and reduced in 26,1% of patients; attack duration was stable in 55,4%, increased in 23,9%, and reduced in 20,7%. Migraine pain was stable or reduced in 65,2% and increased in 34,8%; number of symptomatic drugs per week was stable in 50%, reduced in 29,3%, and increased in 20,7%; migraine drug efficacy was stable in 73,9%, reduced in 17,4%, and increased in 8,7%. Patients had a HIT-6 score of 64,63 ± 8,81. Significant associations were found with remote working, smoke, education, discontinuation of the therapy performed within headache center, migraine familiarity, sleep, anxiety, perceived stress, concern about future, and COVID-19. Conclusion During the lockdown, approximately half of the patients had a clinical stability, a quarter an improvement, and another quarter a worsening. We identified different migraine-influencing elements; in particular, the remote working could represent an easy way to ameliorate migraineurs’ life. Supplementary Information The online version of this article contains supplementary material available (10.1007/s10072-021-05521-7).

The objective of the present study was to evaluate sleep features and sleep-modifying factors in patients with chronic migraine (CM) during the first Italian COVID-19 lockdown.The study was based on an e-mail survey addressed to CM patients of our headache center. The survey investigated demographic, life-style, sleep, psychological, and migraine features during the first COVID-19 lockdown period and the month before. The outcomes were sleep quality (measured using PSQI) and variation in sleep quality, duration, and latency.Ninety-two patients were included. The mean PSQI was 11.96. Sleep quality was improved in 14.1%, stable in 47.8%, and worsened in 38.0%. Sleep latency was reduced in 5.4%, stable in 46.7%, and increased in 47.8%. Sleep duration was reduced in 29.3%, stable in 34.8%, and increased in 35.9%. Significant associations were found with age, work/study, remote working, job loss, meal quality change, smoking variation, COVID-19 province prevalence, home-inhabitant relationship, ratio of house size/number of people, stress, state anxiety, anxiety/depression variation, future concern variation, computer hours, internet hours, and television hours.The study described sleep features of chronic migraineurs during COVID-19 lockdown, pinpointing the main factors involved in sleep quality and sleep changes. Our findings revealed that migraineurs' sleep was closely linked with life-style and psychological features. Several modifiable factors came to light and they should be considered in order to develop an optimal management of CM. An appropriate and more aware treatment of sleep problems could be a way to improve migraineurs' life.

Pulmonary opacities are described in many chest radiograph reports in stroke patients and are often asymptomatic. The aim of this study is to investigate the clinical features associated with asymptomatic pulmonary opacities (APO) and evaluate APO prognostic value in ischemic stroke.We prospectively analyzed patients with acute ischemic stroke without pneumonia symptoms referred to our stroke center. All patients underwent a chest x-ray within 48 hours after admission. We divided patients with APO (defined as asymptomatic area of increased pulmonary attenuation) and patients without APO. Firstly, we compared clinical, laboratory, and echocardiographic parameters between groups; secondly, APO were evaluated as a possible predictor of the neurological severity at discharge and functional outcome at 90 days.We included 162 patients, 78 of whom had APO. On univariate analysis, we observed a significant difference between patients with APO and patients without APO in terms of neutrophils (73,56±10,10 vs 69,72±12,29; p=0,031), atrial fibrillation (AF, paroxysmal 27,4% vs 25,6%; permanent 19% vs 2,6%; p0,002), cardioembolic etiology (37,2% vs 22,7%, p0,033), thrombectomy (58,3% vs 42,9%, p0,05), dysphagia/vomit (34,5% vs 14,10%, p0,005), admission NIHSS (14,20±5,98 vs 10,29±5,82, p=0,001), discharge NIHSS (8,68±6,73 vs 5,64±6,20; p=0,003), and 90 days mRS (3,47±2,12 vs 2,31±1,93; p=0,001). On multivariate analysis, APO were significantly associated with admission NIHSS and AF. APO were a predictor of outcome on univariate analysis, but not on multivariate.APO in acute ischemic stroke are associated with AF. APO were not a predictor of neurological and functional outcome.

Purpose: To assess utility of computed tomography perfusion (CTP) protocols for selection of patients with acute ischemic stroke (AIS) for reperfusive treatments and compare the diagnostic accuracy (ACC) in predicting follow-up infarction, using time-to-maximum (Tmax) maps. Methods: We retrospectively reviewed consecutive AIS patients evaluated for reperfusive treatments at comprehensive stroke center, employing a multimodal computed tomography. To assess prognostic accuracy of CTP summary maps in predicting final infarct area (FIA) in AIS patients, we assumed the best correlation between non-viable tissue (NVT) and FIA in early and fully recanalized patients and/or in patients with favorable clinical response (FCR). On the other hand, the tissue at risk (TAR) should better correlate with FIA in untreated patients and in treatment failure. Results: We enrolled 158 patients, for which CTP maps with Tmax thresholds of 9.5s and 16s, presented sensitivity of 82.5%, specificity of 74.6%, and ACC of 75.9%. In patients selected for perfusion deficit in anterior circulation territory, CTP-Tmax > 16s has proven relatively reliable to identify NVT in FCR patients, with a tendency to overestimate NVT. Similarly, CTP-Tmax > 9.5s was reliable for TAR, but it was overestimated comparing to FIA, in patients with unfavorable outcomes. Conclusions: In our experience, Tmax thresholds have proven sufficiently reliable to identify global hypoperfusion, with tendency to overestimate both NVT and TAR, not yielding satisfactory differentiation between true penumbra and benign oligoemia. In particular, the overestimation of NVT could have serious consequences in not selecting potential candidates for a reperfusion treatment.

Severe Acquired Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) infection represents an unprecedented public health problem and, at present, vaccination is the only weapon available to combat the infection. The simplest and most immediate method to quantify the response of the subject's immune system to vaccination and / or infection is the serological assessment of the antibody titer. The objective of our study was 1) to evaluate the presence of antibody responses in a sample of healthcare workers subjected to a complete vaccination course as per ministerial provisions (double dose for negatives and single dose for ex-SARS-CoV subjects -2 positive) with Comirnaty vaccine (Pfizer / BioNTech) 2) evaluate the presence of statistically significant associations for sex, age and previous positive swab.the antibody levels of both nucleocapsid antibodies and anti-Sars-CoV2 Spike antibodies of the study subjects were examined with the electrochemiluminescent immunoassay (ECLIA) method developed by Roche®. The cut-off value, as suggested by the manufacturer, for anti-nucleocapsid antibodies was 1 COI, while the Ig Spike value was 0.8 I / mL. The study sample was stratified by age (≤45 years, 46-55, ≥56 years old), previous positive molecular swab, gender and IgG S1 / S2 values ​​at the completed vaccination course (≤200, ≥200 AU / mL ). Statistical analyzes were carried out with the R software.almost all of the sample (89.45%) showed IgG Spike values200 AU / mL with statistically significant associations in relation to sex (greater in females, p≤0.05), to previous swab positivity in the presence of a vaccine dose (n = 44; p0.001) and at age (with greater antibody response in subjects under 45; p0.001).The current study confirms what is reported in the literature. In the light of the results obtained, it could be interesting to promote studies that evaluate the antibody titers trend over time a) in women of childbearing age and postmenopausal age b) in particular categories of subjects with chronic degenerative diseases to assess the actual need for doses booster, it being understood that the immune system response is guaranteed by both cellular and humoral immunity and that the antibody titer does not faithfully reflect the protection obtained.

Background: Acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) represents 1–4% of all ischemic strokes. BAO results in strokes associated with a high risk of a poor functional outcome and, in 86–95% of the untreated cases, it results in death because of the vital cerebral structures involved. Diagnosis can be delayed because of the variability in presenting symptoms, and acute treatment is often attempted even beyond 6 h from symptoms onset because of the high risk of a fatal prognosis. Objective: In this observational study, we retrospectively analyzed patients with AIS due to BAO referred to the stroke center of the University Hospital of Messina. We aimed to assess prognostic factors and to evaluate the association between clinical outcome and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) and collateral status. Method: BAO was confirmed by cerebral computed tomography (CT) angiography or cerebral angiography. All patients underwent CT scan and magnetic resonance imaging (MRI). We assessed the pc-ASPECTS on diffusion-weighted imaging (DWI) MR images and the Posterior Circulation Collateral Score (PC-CS) for every patient. Functional outcome was assessed at 3 months using the modified Rankin Scale (mRS). Results: The study population consisted of 27 patients; 16 males and 11 females. The mean age was 66 (±14) years. We observed a favorable outcome (mRS 0–3) in 40.7% of cases, 25.9% reached mRS 0–2, and 29.6% had a poor clinical outcome (mRS 4–5). Patient survival was 70.4%, whereas 8 patients died (29.6%). In 7 patients, pc-ASPECTS was ≥7. According to the PC-CS, 33.3% had moderate collaterals and 63.0% had good collateral status prior to receiving the treatment. Favorable outcome was significantly associated with age, NIHSS score at admission, pc-ASPECTS, hypercholesterolemia, and female sex but not with the other risk factors. Conclusions: In our study, we found that younger age, low NIHSS score at admission, and high pc-ASPECTS, but not onset to treatment time, are associated with a favorable clinical outcome. Transferred patients did not have a significantly poorer outcome. These findings confirm that acute stroke treatment improves clinical outcome in BAO patients, in spite of a delayed diagnosis and an extended therapeutic window, considering lesion volume and localization in DWI MRI.

We aim to provide prevalence and pattern of anatomical variants of circle of Willis in over one thousand ischemic stroke patients compared to an age- and sex-matched control group, and to determine their role in the severity and in-hospital prognosis. Two groups of neuroradiologists evaluated all vascular images of ischemic stroke patients and controls to identify anatomical variants using a preexisted classification. We collected data concerning patient characteristics, stroke severity on admission and discharge, in-hospital mortality, hemorrhagic transformation, acute treatment performed, and etiology. We included 1131 patients with acute ischemic stroke and 562 controls. Among stroke patients, 702 (62.1%) had one or more vascular variants, compared to 308 (54.8%) of the control group (p

Background The use of proton pump inhibitors (PPIs) has increased in the last ten years in children. Data regarding their safety profile are limited. The aim of this study was to analyze data from the Italian spontaneous reporting system (SRS) database to evaluate the incidence and characteristics of PPI-related adverse drug reactions (ADRs) in children. Research design and methods This was an observational, retrospective study analyzing PPI-related ADR reports in children in the Italian SRS database between January 1st, 2001, and December 31st, 2020. ADRs were coded according to the system organ class term level. Factors associated with ADR seriousness were investigated. Results Seventy spontaneous reports of ADRs related to PPIs were analyzed. Esomeprazole and lansoprazole caused the highest number of ADRs equally (27% respectively), and the most frequently reported ADRs presented with gastrointestinal (24%) and/or skin manifestations (21.3%). More than a half of PPI prescriptions were off label for pediatric population. Serious ADRs were 19 (27.1%). Serious ADRs were more frequent in reports presenting PPIs combined with other drugs in comparison to reports with PPI single therapies (p=0.03). Conclusions PPI-related ADRs in children are mostly not serious, and combination therapy seems to be associated with ADR seriousness.

Objective: Up to 30% of pediatric patients with Crohn's disease (CD) require surgery. The aim of the study was to evaluate long-term health-related quality of life (HRQoL) outcome in children with CD who have had ileocolonic resection.Materials and methods: This was a retrospective cross-sectional study on all pediatric patients who had undergone surgery for CD between January 2015 and December 2017 in the Pediatric Surgery and Gastroenterology Units of the University Hospital of Messina. Surgical treatment was represented by laparoscopic ileocecal resection with latero-lateral anastomosis. Patients were asked to fill in a modified version of the IMPACT III questionnaire made up of 15 closed questions before and after surgery. The questionnaire was scored on a five-point scale with 5 reporting “not a problem” and 1 “a very severe problem.” The total score ranged from 15 (worst HRQoL) to 75 (best HRQoL). Frequency of relapses, reoperations, complications during follow-up, and postoperative bowel function were also studied.Results: Data were obtained in 10 patients (9 males), who underwent surgery at a median age of 13.5 years (range 13–18), after a median post-diagnosis period of 2.5 years (range 0–8). Preoperative scores were low in all 4 domains of the questionnaire. Postoperatively, HRQoL measures improved significantly (p < 0.05) about symptoms, school attendance, social and emotional functioning. Overall, nearly all patients were completely satisfied with the surgical outcome.Conclusions: HRQoL is low in CD children referred for possible operation, and surgery may positively affect the overall HRQoL. Collecting HRQoL data provides insight into the impact of treatment on children health status.

BACKGROUND Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is the recommended elective surgery for children with ulcerative colitis (UC). The aim of this study was to evaluate functional and long-term health-related quality of life (HRQoL) outcomes of surgery in paediatric patients with UC. METHODS We reviewed the hospital records of all paediatric patients who had undergone surgery for UC between January 2009 and December 2016 in the Units of Paediatric Gastroenterology and Surgery, of both the University Hospital of Messina, and the Gaslini Children's Hospital of Genoa. Surgical treatment was represented by restorative proctocolectomy and laparoscopic IPAA. Patients and parents were interviewed by telephone before and after surgery and responded to the modified IMPACT III questionnaire about health outcomes and HRQoL. The questionnaire was scored on a five-point scale with higher scores indicating a better HRQoL. The total score ranged from 35 (worst HRQoL) to 175 (best HRQoL). RESULTS Data were obtained in 30 patients (16 males), with a median age of 12 (range 3- 16). The median amount of time elapsed after the operation was 3 years (range 1-4.5). Preoperative scores were very low in all 4 domains of the questionnaire. Postoperatively, HRQoL measures improved significantly (p

Previous studies demonstrated the benefits of motor exercise and physical activity in neuromuscular disorders. However, very few papers assessed the effects of sport practise. The aim of this multicentre study was to assess the impact of sport activity on self-esteem and emotional regulation in a cohort of athletes with neuromuscular disorders. The 38 patients with Duchenne, Becker or other types of muscular dystrophy or spinal muscular atrophy practising sport (aged 13–49 years) and 39 age-, gender-, disability- and disease-matched patients not practising sport were enrolled. Testing procedures to assess self-esteem, anxiety and depression disorder, personality trait and quality of life (QoL) were used. Patients practising sport had a significantly higher self-esteem, lower level of depression, greater social own identity and adherence and QoL. Frequency of sport activity may represent a complementary therapy in neuromuscular disorders to improve mental and social well-being.

ObjectiveWe conducted a study to describe food profile, health status and stroke risk factors in the population of the Aeolian Islands.DesignSelf-administrated questionnaires regarding eating habits, health status and stroke risk factors were obtained from a sample of the general Aeolian population. We analysed the difference from common healthy eating habits indicated by the Italian Institute of Nutrition.SettingCurrent evidence finds the Mediterranean diet is a protective factor for cardio- and cerebrovascular diseases. The Aeolian Islands are an interesting study setting because of their peculiarity in the epidemiology of cerebrovascular and neurodegenerative diseases.ParticipantsIndividuals (n586; age range 15–93 years; mean 52 (sd18) years) living in the Aeolian Islands.ResultsWe found low fish consumption in 13·3% and vitamin intake deficiency in 5·8% of participants. A marked excess of saturated fats was observed in 71·0% of participants. Sodium excess was reported almost in half of participants (49·0%). Eating habits were characterized by high consumption of fruits and vegetables, consistent use of olive oil and scanty use of cured meat. Health status as evaluated by the General Health Questionnaire was characterized by ‘normal distress’ level in the majority of participants.ConclusionsStudy findings show the eating habits and health status of the Aeolian people in an interesting setting of low incidence of cerebrovascular disease. This nutrition regimen has been proved to be protective against cerebrovascular disease. Nutrition is likely to contribute to the low incidence of stroke in this population.

Background: Child obesity is today one of the greatest health emergencies, on such a large scale as to be considered a global epidemic by the WHO and, unfortunately, Italy holds the worst European record. Methods: We conducted an observational study to investigate the effects of early and late risk factors on the development of primary childhood obesity. We collected anthropometric parameters, information about early risk markers and late risk factors on a sample of 280 children from March 2016 to December 2017. Results: Statistically significant associations emerged between: child's BMI and education level of the mother (p

Background Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is the recommended elective surgery for children with ulcerative colitis (UC). The aim of the present study was to evaluate health outcomes of children with UC and undergone restorative proctocolectomy with IPAA and to compare preoperative and postoperative health-related quality of life (HRQoL). Methods We reviewed the hospital records of all paediatric patients who had undergone surgery for UC between January 2009 and December 2016 in the Units of Paediatric Surgery and Gastroenterology of the University Hospitals of Messina and Genoa. Surgical treatment was represented by restorative proctocolectomy and laparoscopic IPAA. Patients and parents were interviewed by telephone before and after surgery, and responded to the modified IMPACT III questionnaire about health outcomes and HRQoL. The final version was made up of 15 closed questions of functional outcomes and HRQoL. All of the issues were grouped into 5 domains, such as gastrointestinal functional aspects (7 questions), school functioning (2 questions), social functioning (3 questions), emotional functioning (3 questions). The questionnaire was scored on a five-point scale with higher scores indicating a better HRQoL. The total score ranged from 35 (worst HRQoL) to 175 (best HRQoL). Results Data were obtained in 30 patients (16 males), who underwent surgery after a median post-diagnosis period of 3 years (range 1–4.5), at a median age of 12 (range 3–16). The most common indication for colectomy was acute severe colitis (63%, n = 19). Table 1 shows all the functioning total scores before and after IPAA. HRQoL scores showed a statistically significant improvement after IPAA. This difference was observed in all dimensions of HRQoL (symptoms, school attendance, social activities, and emotional functioning). Overall, nearly all were completely satisfied with the outcome of colectomy. No operation-related mortality was reported. By the end of the follow-up, one patient developed pouchitis 1 month after colectomy, and responded well to antibiotic therapy. Conclusion Our data confirmed that HRQoL is low in children with UC referred for possible operation, and showed that surgical treatment may positively affect the overall HRQoL.

Background Behçet’s disease is a rare multi-systemic inflammatory disease with unknown etiology which involves principally oral and genital mucosa, skin and eyes. Average age at onset of the disease is about 25-30 years, but it may be diagnosed before the age of 16. It is not very rare in Italy, even though there are limited data concerning epidemiology. Aim of this study is to describe the baseline data of an Italian cohort of patients with as having BD or probable BD. Methods We described the baseline data of the first national epidemiological study on children coming from 16 Italian Pediatric Rheumatologic Centers diagnosed by the treating physicians as having Behçet’s Disease. Data on demographic characteristics, clinical features and therapy were collected. We then compared our findings to those of international pediatric cohort studies and also retrospectively evaluated the ability to diagnose BD using ISG, ICBD and, for the first time, the new PEDBD criteria. Results The study included 110 patients (62 M, 48F). Average age at onset was 8.34±4.11 years. The frequencies of signs/symptoms were: recurrent oral aphtosis 94.5%, genital ulcers 33.6%, ocular 43.6%, gastrointestinal 42.7%, musculoskeletal 42.7%, neurological 30.9% and vascular involvement 10%. Thirty-two patients (29.1%) fulfilled ISG, 78 (70.9%) ICBD, 50 (45.5%) PEDBD criteria and 31 (28%) didn’t fulfill any of them. The most frequently used treatments were colchicine and corticosteroids followed by immunosuppressants. Four patients received biologic therapy (anti TNF-α and anti-IL-1) to treat severe organ involvement. Conclusions Recurrent oral aphtosis was the most frequent clinical manifestation, followed by ocular involvement. Gastrointestinal lesions were more frequent in Italy than in non-European countries as opposed to genital ulcers. Skin, ocular and vascular manifestations had a higher frequency in males and genital ulcers in females. Constitutional symptoms were present in 44.5% and recurrent fever in one third of our population.

Some studies have shown a direct relationship between nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting, defined as a percentage of the ideal body weight for age, has been shown to be an independent predictor of mortality in CF. With respect to height only two studies were performed and these studies suggested that stunting is an important determinant of survival but both did not adjust statistical analysis for confounding variables. We aimed at determining the association between stunting and risk of mortality in CF patients.393 CF patients older than 6 years of age, 95 deceased, as cases, and 298 live, as controls, were enrolled in a nested case-control study. Stunting was defined by a height percentile5th. We performed a multivariate statistical analysis including height percentile and the following possible confounding variables: age, gender, Body Mass Index (BMI), Forced Expiratory Volume in 1 s (FEV1), genotype, pancreatic status, CF-related diabetes, colonization with Pseudomonas aeruginosa and/or Burkholderia cepacia.In the adjusted analyses stunting (OR 2.22 [IC 95%1.10-4.46]), wasting (OR 5.27 [IC 95% 2.66-10.41]), and FEV1 40% of predicted (OR 10.60 [IC 95% 5.43-20.67]) resulted the covariates that significantly predict the risk of mortality.Our study shows, for the first time, that stunting is a significant and independent risk factor for mortality in CF patients, and warrants an intervention of nutritional rehabilitation. Considering that nutritional interventions in stunted patients should be prolonged, are invasive and expensive, and might affect self-esteem and body image, their efficacy should be fully assessed by Randomised Controlled Trials.

Objective To evaluate the serum melatonin levels in critically ill pediatric patients and to test the effect of light on the melatonin's circadian rhythm. Data on melatonin secretion in critically ill pediatric subjects are lacking. Study design We investigated the serum melatonin levels of 16 sedated and mechanically ventilated patients in a pediatric intensive care unit. Children (mean age, 5.1 ± 3.1 years) were randomly assigned to a dark-exposed or to a light-exposed group to evaluate the effects of light on serum melatonin concentrations. Blood samples for serum melatonin analysis were collected at 10 p.m., 1 a.m., 3 a.m., 5 a.m., 8 a.m., and 12 p.m. Results The melatonin circadian rhythm was severely disrupted in critically ill children; light exposure lowered serum melatonin even in a context of highly altered circadian cycle; melatonin peaks were greater for healthy age-matched children. Conclusion The high melatonin levels in the critically ill children may be a response to counteract the elevated oxidative stress associated with serious diseases. Whether these elevated melatonin levels confer any beneficial effects in pediatric critically ill patients remains unknown.

Objectives: Surgical site infections (SSIs) are a frequent complication of surgical procedures and one of the most common forms of hospital acquired infection (HAI). National/international guidelines and recommendations have been issued for prevention. The objective of this study was to observe the behaviour of healthcare workers engaged in surgical procedures and hence assess compliance with SSI guidelines. Methods: An observational descriptive study was conducted at a University hospital in southern Italy. A specifically designed form was used to record the actions of the surgical team during randomly selected surgical operations. Observations comprised the use of surgical attire, the frequency of doors opening and the number of staff in the operating room. Results: A total of 308 operating room personnel was observed during 402 surgical procedures: 127 surgeons (41%), 39 anaesthesiologists (13%), 62 nurses (20%) and 80 students in training (26%). 96% of the surgical team wore scrubs, 93% of health workers wore a mask and of these 78% wore it correctly in order to completely cover the nose, mouth and beard (when present), 99% wore a cap (only in 48% was the hair completely covered), 50% of the operators wore gloves, 95% wore shoes dedicated to the operating theater and 23% also wore shoe covers, 56% wore gowns, and 22% had eye protection. Furthermore, the average number of health personnel in the operating theater was 8, the doors remained closed in 261 (65%) surgical operations. Conclusion: As the results indicated a low adherence to international guidelines among the personnel, it is suggested that training courses should be provided to increase staff awareness on prevention and management of HAI.

The aim of this study was to determine the effects of inhaled NO with different oxygen concentrations on the inflammatory cascade in newborns with hypoxic respiratory failure secondary to persistent pulmonary hypertension.60 newborns received iNO and 30 of them received an initial oxygen concentration of 45% (group 1), while the other 30 newborns received an initial oxygen concentration of 80% (group 2). The levels of inflammatory cytokines (IL-6, IL-8, TNF-α) were measured. The clinical outcome was also recorded.The findings show that interleukin concentrations (IL-6, IL-8, TNF-α) were significantly decreased between 0 and 72 hours (p0.01) in the newborns exposed to initial oxygen concentration of 45% and significantly increased in the other group.When inhaled, NO was co-administered with concentration of O(2)45%, anti-inflammatory responses occurred, in accord with evidence in the published literature. The benefits of iNO on the clinical outcome in the current study demonstrate that inhaled NO in both groups was associated with improved short-term oxygenation.

Repeated invasive procedures occur routinely in neonates who require intensive care, causing pain at a time when it is developmentally unexpected. Multiple lines of evidence suggest that repeated and prolonged pain exposure alters their subsequent pain processing, long-term development, and behaviour. Primary outcome of this study was to evaluate the reduction of procedural pain induced by “heel-lances” in preterm newborns with three different treatment [administration of fentanyl (FE, 1–2 μg/kg), facilitated tucking (FT), sensorial saturation (SS)]. Secondary outcome was the measurement of the levels of cytokines as markers of stress correlated to pain. A prospective randomized controlled trial (RCT) comparing three different pharmacological or non-pharmacological treatments was performed involving 150 preterm newborn (gestational age 27–32 weeks). No other analgesic treatment was performed during the study. CRIES score was used to evaluate the procedural pain. The results showed that the reduction in the pain score was greater in FE and SS groups than FS group. The differences were statistically significant (p < 0.01). The levels of IL-6, IL-8, and TNF-α were higher in the FT individuals than in the FE or SS-treated infants at 1 day (p < 0.01), at 3 days (p < 0.01), and at 7 days (p < 0.01) of life. Conclusions: The findings of this study suggest that FE and SS provide a superior analgesia in preterm neonates during procedural pain. In particular, sensorial saturation seems to be an important non-pharmacological alternative treatment to prevent and reduce the procedural pain in preterm newborn.

Endotracheal intubation is a common painful procedure in newborn care. Neonates are more sensitive to pain than older infants, children, and adults, and this hypersensitivity is further exacerbated in preterm neonates. The aim of this study was to evaluate the analgesic activity of melatonin during endotracheal intubation of the newborn by using the Neonatal Infant Pain Scale (NIPS) and Premature Infant Pain Profile (PIPP) score. Secondary outcome was an evaluation of melatonin as inflammatory responses. This was performed by measuring the levels of pro- and anti-inflammatory cytokines implicated in the pain. Sixty preterm infants were enrolled in the study and were randomly divided into two groups: 30 infants treated with melatonin plus common sedation and analgesia recommended by Italian Society of Neonatology (group 1) and 30 infants treated with only common sedation and analgesia. The sedative and analgesic drugs included atropine, fentanyl, and vecuronium. The reduction in pain score (NIPS) was similar in both groups at an early phase, while it (PIPP score) was lower in melatonin-treated group infants than the other newborns at a late phase, during intubation and mechanical ventilation. The differences were statistically significant at 12, 24, 48, and 72 hr (P < 0.001). Pro-inflammatory and anti-inflammatory cytokines (IL-6, IL-8, IL-10 and IL-12) were higher in the common sedation and analgesia group than in melatonin-treated infants at 24, 48, 72 hr and 7 days (P < 0.001). This study suggests the use of melatonin as an adjunct analgesic therapy during procedural pain, especially when an inflammatory component is involved.

Glutamine is an important substrate for critical cells of the immune system, in particular lymphocytes and macrophages, and it is considered a conditionally essential amino acid. Several studies have indicated that glutamine-enriched total parenteral nutrition improves immunologic status and shortens length of stay of critically ill patients. We investigated the effect of total parenteral nutrition supplemented with glutamine on the immune system in anorectic patients.Thirty-six anorectic patients were randomized to receive standard parenteral nutrition or parenteral nutrition supplemented with glutamine 0.18 g kg(-1) d(-1) for 20 d. To evaluate the immune system status, we determined serum levels of neopterin and insulin growth factor-1 and lymphocyte count at baseline and after 10 and 20 d from the beginning of the therapy.The results showed a significant increase of the serum levels of neopterin after 10 d of treatment with glutamine (26.44 +/- 3.08 versus 6.75 +/- 1.73 nmol/L, P0.001), thus proving a probable stimulating action carried out by glutamine on the immune system, as testified by the increase of lymphocytes.

We designed a pilot study to assess as primary end point the safety and efficacy of a new phosphorylcholine-coated, closed cardiopulmonary bypass (CPB) system (extracorporeal circulation, optimized [ECC.O], Dideco, Mirandola, Italy). The secondary end point was to compare results with two retrospectively matched cohorts of patients who underwent isolated coronary artery by-pass graft (CAGB) with nonphosphorylcholine-bonded circuits and cardiotomy suction (Group II, n = 32) and off-pump coronary artery by-pass (OPCAB) (Group III, n = 26). In January 2005, 30 patients (Group I) undergoing first-time CABG were assigned to the ECC.O group. Five minutes after CPB, initial hematocrit levels were significantly and consistently highest in Group I relative to Group II (Group I, 29.7 +/- 4.4 vs. Group II, 22.7 +/- 4.1; P < 0.001). Red blood cell transfusion rate was reduced drastically in Group I versus Group II (P < 0.001). High differences were also observed in C-reactive protein levels at 24 h after surgery (Group I vs. Group II-P < 0.001 and vs. Group III-P < 0.001) and at 72-h peak value (Group I vs. Group II-P < 0.001 and vs. Group III-P < 0.001). The routine clinical use of the ECC.O system has been demonstrated to be both clinically safe and efficacious. An intensive training program for surgeons, perfusionists, and anesthesiologists is required.

ObjectivesThe purposes of this study were to evaluate the clinical safety and efficacy of 10F, 15F, and 19F Blake drains (Ethicon, Sommerville, NJ) in a pediatric population after cardiac surgery and to compare their clinical effect with that of conventional chest drains.MethodsFrom January 2002 through December 2004, a prospective randomized trial was conducted on 189 patients who underwent surgical intervention for congenital heart disease at our institution. Statistical analyses were conducted to test the null hypothesis that there was no difference in the incidence of pericardial or pleural effusion requiring drainage. Secondary end points included total volume of drainage, drain size, and time to drain removal.ResultsNinety-eight patients (group A) received Blake drains, and 91 patients (group B) received conventional chest drains. There were no statistically significant difference in age, weight at the time of surgical intervention, open- and closed-heart procedures, and number of drains applied. Statistically significant differences were detected in the frequency of pericardial effusion (group A: 1.1% vs group B: 4.8%, P < .01), pleural effusion (group A: 1.1% vs group B: 5.3%, P < .01), size of the drain (group A: 12.37 French ± 1.72 French vs group B: 16.81 French ± 0.70 French, P < .001), and time to removal (group A: 43.75 ± 20.76 hours vs group B: 55.62 ± 26.48 hours, P < .001).ConclusionsBlake drains are safer and more efficient than conventional chest tubes in pediatric populations after cardiac surgery. In comparison with conventional chest tubes, they showed fewer occurrences of effusions and the same amount of fluid drained but smaller size and earlier removal.

Background Systemic hypertension is one of the main risk factors for atherothrombosis. Tissue factor (TF) is found in the adventitia of blood vessels and in the lipid core of atherosclerotic plaques, and is specifically expressed on monocyte or macrophage cell membrane surfaces. TF plays a pivotal role in blood clotting physiology and is involved in pro-inflammatory action and atherosclerotic plaque destabilization. Objective In this study we investigated whether there is any relationship between TF messenger RNA expression and activity in blood monocytes isolated from hypertensive patients with clinical signs of atherosclerosis, uncomplicated hypertensive individuals and normotensive control subjects. Methods Eighty subjects (41 men and 39 women, mean age 41 ± 12 years) with untreated essential hypertension and 41 control subjects matched for sex and age were enrolled in the study. Patients were classified according to whether they had a normal (≤ 1 mm, 41 patients) or abnormal (>1 mm, 39 patients) intima-media thickness (IMT). Results TF mRNA expression and activity in hypertensive individuals with no carotid atherosclerosis were no different from control subjects in unstimulated and stimulated monocytes. Abnormal IMT patients showed a higher TF mRNA expression compared with normal IMT hypertensive subjects (P

Several researches has focused the hypothesis that low blood lead levels could be asso- ciated with an increased risk of hypertension. To assess the relation between occupational lead exposure and elevated blood pressure a group of 27 workers, age range from 27 to 62 years, mean (SD) 36.52 (± 8.16) yr; length of employment mean (DS) 2.97 (± 1.67) yr, were recruited as study subjects. The following variables were measured: blood lead concentration (BPb), δ- Aminolevulinic Acid Dehydratase (ALAD) activity, Zinc Protoporphirin (ZPP), creatinine, hema- tocrit, Body Mass Index (BMI) and Systolic Blood Pressure (SBP) and Diastolic Blood (DBP) Pressure. The results showed that long term occupational exposure was related to a slight increase of systolic and diastolic blood pressure among workers who had been exposed to high- er level of lead with respect to workers exposed to lower level of lead. Furthermore, blood lead concentration (BPb) and ZPP resulted higher among workers exposed to higher level of ambi- ent lead, while in the same group of workers ALAD activity resulted more inhibited. The authors concluded long term cumulative lead exposure can significantly increase blood pressure in low level Pb exposed workers.

Despite the efforts made, a serum marker reliable for the screening and follow-up of patients with gastric cancer has not yet been identified. The aim of this preliminary study was to test the role of pro-inflammatory cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha in patients with gastric cancer and in control groups. The statistical analysis of cytokines serum levels in the group with gastric cancer versus control groups has shown considerable differences (p < 0.001) in their mean rates. The results indicate that the cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha might perhaps act as diagnostic markers in patients with gastric cancer. Therefore, it is hypothesized that after more extended trials, their use in the screening and prognostic assessment of these patients could be a possibility.

Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity has been reported following statin treatment.In the present study the following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(-107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment.205 Sicilian subjects with primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were concurrently enrolled. Hypercholesterolaemic patients were randomly divided into two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group. Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase, oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in LDL, PON1 activity and genotypes in both HCh and control subjects were determined at baseline. The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups.HCh subjects showed significantly lower LDL resistance to oxidation, vitamin E content and PON1 activity levels than controls. A strong association was found among PON1 T(-107)C genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity. After treatment, the atorvastatin group displayed a significant decrease in total cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an increase in vitamin E content and PON1 activity, compared with baseline values. Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed.These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism.

Background and Objectives: Increased plasma low-density lipoprotein-cholesterol (LDL-C) levels in hypercholesterolemic subjects are associated with enhanced LDL oxidation that represents an additional risk for atherosclerotic disease. Human serum paraoxonase (PON1), a high-density lipoprotein (HDL) associated enzyme, has been shown to protect LDL from oxidation, thus playing an important role in reducing the risk of atherosclerosis. PON1 gene polymorphisms have been found to be associated with the variations in serum PON1 levels and activities, and with the risk for coronary artery disease (CAD). This study was performed to evaluate the contribution of the PON1 promoter (� 107)T>C and the coding region Gln 192 Arg (Q192R) and Leu 55 Met (L55M) polymorphisms to the presence of carotid atherosclerosis in 208 Sicilian subjects with primary hypercholesterolemia. Methods: Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The subjects were classified according to whether they have a normal (V1 mm) or an abnormal (>1 mm) IMT. Subjects were also investigated for physical and biochemical parameters, including PON1 activity. Results: No significant differences were detected among the PON1 genotypes with respect to age, sex, BMI, plasma lipids, systolic blood pressure in both groups of patients. There were significant differences between PON1 genotypes with respect to PON1 activity. The 192QQ, 55MM and (� 107)TT genotypes showed lower PON1 activity compared to the RR, LL and CC genotypes. The PON1 (� 107)T>C genotype distribution in both IMT groups showed no significant differences in percentage of TT, CT and CC genotypes. Similar results were obtained analyzing the Q192R and L55M genotype frequencies. Stepwise forward logistic regression analysis confirmed the lack of association between PON1 genotypes and carotid abnormalities. Conclusions: In conclusion, our data provided no evidence of a significant association between either PON1 promoter (� 107)T>C or coding region, Q192R and L55M, polymorphisms and early carotid atherosclerosis in Sicilian hypercholesterolemic subjects. D 2004 The Canadian Society of Clinical Chemists. All rights reserved.

Background: Strong evidence has been reported that a high plasmatic level of fibrinogen plays a central role in the development of coronary heart disease. Many researches showed that stressful life events lead to an increase in plasmatic fibrinogen. The present investigation examined the relationship between plasmatic fibrinogen level and stressful life events. Sampling and Methods: A sample of 40 middle-aged women employed as teachers underwent a general objective examination, a venous puncture for plasma fibrinogen level evaluation, and completed a questionnaire regarding health behaviours, at baseline and 1-year follow-up. The stressful life events were recorded using the Paykel’s interview for recent life events. Results: At the baseline assessment, the distribution of teachers in the two stress exposure groups was 16 women for the non-exposed group of teachers, and 24 for the exposed teachers, while at the 1-year follow-up assessment, it was 10 for the non-exposed and 30 for the exposed group. The number of teachers exposed to stress was significantly higher at the 1-year follow-up than at the baseline assessment (30 and 24, respectively; p < 0.05). Average levels of plasmatic fibrinogen were significantly higher in stress-exposed women than in non-exposed women both at baseline assessment (p < 0.01) and at 1-year follow-up (p < 0.002). Moreover, the mean value of fibrinogen at the follow-up assessment showed a higher increase in stressed women compared with non-stressed women with an annual increase of 10.71 and 5.40%, respectively. Conclusions: Stress may trigger the hypercoagulable state evidenced by an increased plasmatic fibrinogen level. This mechanism may help explain the adverse impact of stress on the cardiovascular system.

This study was carried out to determine whether the administration of antithrombin III decreases the risk of intraventricular hemorrhage in premature infants. In a randomized study, 60 infants born before 30 weeks of gestation were assigned to receive a loading dose of antithrombin III or placebo. There was no significant difference in the incidence of intraventricular hemorrhage between the antithrombin III and the placebo group (27.5 vs. 32%). Partial thromboplastin time, Quick’s prothrombin time and platelet count were also not significantly different between the 2 groups. We conclude that the administration of antithrombin III during the first 2 days of life does not decrease incidence of intraventricular hemorrhage. Antithrombin III is a very expensive therapy and its benefits should be carefully investigated before being recommended as valuable therapy.

Objective. The assessment of sedation le vel in critically ill patient remains a challenge for the intensivists in order to avoid over- or under-sedation phenomena. Scoring systems commonly used still show some limitation; the intro- duction of BispectralIndex (an EEG parameter) could bring potentialadvantages in monitoring sedation. According to the reports, Bispectral Index correlates with levels of sedation on the Ramsay Scale. We report our personal experience in this topic. Methods. Twenty patients, diagnosed with chronic obstructive pulmonary disease (COPD), were involved in the study. For an optimaladaptation to respiratory prothesis, they were sedated (with Propofolby continuous infusion at an initial dose of 2 mg/kg/h, which could be modulated with steps of 0.5 mg/kg/h), in order to maintain a Ramsay score of 4^5. BIS value was continuously recorded, and manually calculated on a mean average of a minute during the measur- ing of Ramsay score (T0) and every 30 0 for 24 hours on par with Ramsay score. EEG, SpO2, non invasive arterialpres- sure, ventilatory module, ETCO2 ,F IO2 were also recorded. For the statistic analysis, Friedman test and Spearman coef- ¢cient were utilized. Values of p < 0.05 were considered signi¢cant. Results. 980 observations were carried out. The variation range of Ramsay Score was between 2 and 6. BIS range varied from 34 to 98. Statistic analysis of the data obtained pointed out some signi¢cative correlations, partic- ularly between Ramsay Score and BIS (p < 0.01), and between BIS and dosage of Propofol( p < 0.01). Conclu- sions. The results of the study are consistent with those found in the literature on this topic of study. In fact, this study demonstrates the utility of BIS to track levels of consciousness in ICU patients while still maintaining the use of the score systems to care for ICU patients.

We sought to determine whether treatment with felbamate was capable to reduce the accumulation of putrescine induced by transient forebrain ischemia in the Mongolian gerbil. Gerbils underwent 10 min ligation of common carotid arteries followed by recirculation. Immediately after the release of the arterial occlusion, felbamate (75 and 150 mg kg(-1) i.p.) was administered. Putrescine and polyamine levels were measured in hippocampus and striatum at 1, 8, 24 and 48 h after recirculation. Putrescine levels appeared enhanced already 8 h after the release of the arterial occlusion and kept increasing up to 48 h in the hippocampus and striatum. No significant changes in spermidine levels during recirculation were detected. Conversely, spermine appeared to decrease in the hippocampus while it did not show changes in the striatum. Felbamate significantly reduced the ischemia induced changes in putrescine brain content only at the dose of 150 mg kg(-1) i.p.

Bis(2-ethylhexyl) phthalate (DEHP) is a compound widely used in plastics technology to impart flexibility to rigid polymers. We sought to determine whether the oral exposure of female rats to DEHP during gestation and suckling produces alterations in the litter. Female rats were exposed to different concentrations of DEHP suspended in drinking water (32.5 and 325 μ l/litre) from day 1 of pregnancy to day 21 after delivery. Pup body weight gain and kidney, liver and testes weight was measured at different times (21, 28, 35, 42 and 56 days) after birth. Plasma concentrations of DEHP and histopathological alterations in kidneys, liver and testes were also studied. In addition, the ability of female pups (1 month of age) to perform a learned avoidance test, the ‘beam walking’ test, was evaluated. Perinatal exposure to DEHP produced no statistically significant changes in the body weight gain of offspring. Conversely, it produced a significant decrease in kidney and testes relative weight (organ/body weight) with a significant increase in relative liver weight. Signs of histological damage in kidneys, liver, and particularly testes, were observed. Pups exposed perinatally to the highest concentration of DEHP elicited a significant increase in the time necessary to perform the beam walking test.

1062 Background: TNBC is an aggressive subset of breast cancer (BC) with central nervous system and visceral metastatic involvement and it represents a molecular subtype without specific target therapy. Methods: This observational, retrospectivestudy included 45 TNBC. The aim of this study was to evaluate the expression of some molecular determinants such as the AR, E-cadherin and Ki-67 in relation to histological type, time to relapse and overall survival.Immunohistochemistry (IHC) was carried out on formalin-fixed paraffin-embedded tumor samples obtained from patients (pts) defined TNBC, since ER and PgR were 0% and HER2 negative (IHC score 0/1 or FISH not amplified). Results: Median age was 58.8 years (range 39-77). The main histological type was ductal in 35 pts (77.7%), lobular in 7 (15.5%), medullary in 3(6.6%). 29 pts (64.4%) had a G3 tumor. Tumor stage was: I 6/45 (13.3%), IIA 21/45 (46.6%), IIIA 11/45 (24.4%), IIIB 3/45 (6.6%) and IV 4/45 (8.8%). All patients received treatments; the most frequently used regimens were anthracycline and taxanes. The androgen receptor was positive (IHC >10%) in 12/45 (26.6%). E-cadherin expression was semi-quantitatively analyzed according to the percentage of cells showing membrane positivity: 0 (0 to 10%); 1+ (10 to 30%); 2+ (30 to 70%); 3+ (> 70%). E-cadherin expression was considered positive if the score was ≥ 2, and negative when score was ≤ 1. This expression was negative in 24/45 (53.3%) cases. The Ki-67 index was ≥ 25% in 17/45(37.7%). The statistical analysis showed that patients with AR negative and Ki-67 positive expression have a significant correlation with the ductal histotype and G3 tumors (p < 0.001). Multivariate analysis showed that the patients with AR and E-cadherin negative but Ki-67 positive expression showed significantly (p < 0.001) worse overall survival time than those with either AR and E-cadherin positive but Ki-67 negative expression. Conclusions: Our data suggest that the combination of AR and E-cadherin expression as well as Ki-67 status might be useful prognostic markers in TNBC.

Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Among our group of CCM Italian patients, we selected a cohort of sporadic cases negative for mutations in CCM genes. In this cohort, five variants in CCM2 gene were detected, which proved to be the known polymorphisms in intronic regions (IVS2-36AG and IVS8 +119 CT) and in coding sequence (c.157 GA in exon 2, c.358 GA in exon 4 and c.915 GA in exon 8). Therefore, we undertook a case-control study to investigate the possible association of these polymorphisms with sporadic CCMs. The five polymorphisms were identified in 91 CCM sporadic patients and in 100 healthy controls by direct sequencing methods using lymphocyte DNA. Polymorphisms IVS2-36AG and c.915 GA showed statistically significant differences in frequencies between patients and controls [(χ2, 6.583; P0.037); (χ2, 14.205; P0.001)]. The prevalence of the wild-type genotype was significantly lower in the CCM group than in the control sample. Patients with the A/G and G/G genotypes (IVS2-36AG) had a significant increase for CCM risk (OR, 3.08; 95% CI, 1.5-5.9 and OR, 4.3; 95% CI, 1.4-22.6) and the same was observed for the polymorphism c.915 GA (genotype G/A OR, 6.1; 95% CI, 3.0-12.6 and genotype A/A OR, 2.79). In addition, the polymorphisms c.358 GA in exon 4 (χ2, 15.977; P0.04) and c.915 GA in exon 8 (χ2, 18.109; P0.02) were significantly associated with different types of symptoms. Haplotype analysis, performed only on polymorphisms c.358 GA (p.Val120Ile), c.915 GA (p.Thr305 Thr) and IVS2-36AG, shows that haplotype GAG (+--) significantly increased among CCM sporadic patients compared to the control group. Significant differences between patients and controls were observed only for IVS2-36AG and c.915 GA polymorphisms indicating their possible association with sporadic CCMs and an increased risk of CCM. On the other hand, polymorphisms c.358 GA and c.915 GA were associated with a more benign course of the disease. These data were confirmed by the haplotype GAG (+--) frequencies.

Endotracheal intubation is a common painful procedure in newborn care. Neonates are more sensitive to pain than older infants, children, and adults, and this hypersensitivity is further exacerbated in preterm neonates. The aim of this study was to evaluate the analgesic activity of melatonin during endotracheal intubation of the newborn by using the Neonatal Infant Pain Scale (NIPS) and Premature Infant Pain Profile (PIPP) score. Secondary outcome was an evaluation of melatonin as inflammatory responses. This was performed by measuring the levels of pro- and anti-inflammatory cytokines implicated in the pain. Sixty preterm infants were enrolled in the study and were randomly divided into two groups: 30 infants treated with melatonin plus common sedation and analgesia recommended by Italian Society of Neonatology (group 1) and 30 infants treated with only common sedation and analgesia. The sedative and analgesic drugs included atropine, fentanyl, and vecuronium. The reduction in pain score (NIPS) was similar in both groups at an early phase, while it (PIPP score) was lower in melatonin-treated group infants than the other newborns at a late phase, during intubation and mechanical ventilation. The differences were statistically significant at 12, 24, 48, and 72 hr (P0.001). Pro-inflammatory and anti-inflammatory cytokines (IL-6, IL-8, IL-10 and IL-12) were higher in the common sedation and analgesia group than in melatonin-treated infants at 24, 48, 72 hr and 7 days (P0.001). This study suggests the use of melatonin as an adjunct analgesic therapy during procedural pain, especially when an inflammatory component is involved.

We evaluated the effects on cerebral ischemia of a treatment with fructose-1,6-bisphosphate, a compound known to possess protective effects on acute ischemic injury in a variety of different tissues. We investigated the ability of the compound, administered either 15 minutes before or 15 minutes after the ischemic insult, in reducing the ischemia-induced changes in polyamine brain levels. The experiments were performed in adult, chloral hydrate-anesthetized Mongolian gerbils that underwent a 15 minutes ligation of the common carotid arteries followed by recirculation. Animals were sacrificed 1, 8 and 24 hours and immediately after the release of the occlusion. Polyamine brain levels were not modified during ischemia. Putrescine began to increase after eight hours from the release of the occlusion and we found it significantly increased after 24 hours in the hippocampus and striatum. We did not detect any significant changes in spermidine brain levels either during ischemia or during recirculation. Conversely, spermine appeared to decrease in the hippocampus while it did not show changes in striatum and medulla-pons. The activity of ornithine decarboxylase, a key enzyme in the biosynthesis of polyamines, resulted enhanced at the end of the ischemic period in all the brain regions tested and showed a peak at eight hours of recirculation in striatum and hippocampus whereas returned to control values in the medulla-pons. Fructose-1,6-bisphosphate significantly reduced the ischemia induced changes in polyamine brain content when administered before the ischemic insult while did not show protective properties when administered post-ischemically.

The treatment of peritoneal malignancies in elderly patients with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is an ongoing question due to the high associated surgical risk.Thirty patients, 11 (36.7%) older than 65 years, were submitted to CRS plus HIPEC. Criteria of patient eligibility were: peritoneal carcinomatosis of different origin, T3-4 gastric cancer, ECOG performance status ≤2, no extra-abdominal extension and no evidence of bowel obstruction. The median follow-up was 21.5 months (range: 1-63). The purpose of this retrospective study, was to evaluate the feasibility of this approach in elderly patients, with special reference to postoperative morbidity, mortality and survival.We have recorded, in elderly patients, higher grade 3 and 4 morbidity and mortality, similar mean duration of cytoreductive surgery, of postoperative hospital stay, of median survival and of overall survival rates.Since there no statistical differences, in terms of morbidity and mortality, CRS with HIPEC may also be suitable for elderly patients.