High levels of LIGHT/TNFSF14 in patients with Prader-Willi syndrome.

PURPOSE/METHODS: Prader-Willi syndrome (PWS) is a rare genetic disorder displaying different clinical features, including obesity and bone impairment. LIGHT/TNFSF14 is a cytokine produced by immune cells affecting both fat and bone metabolism. The present study aimed to evaluate LIGHT serum levels in 28 children and 52 adult PWS patients compared to age and sex-matched controls, as well as correlations with parameters of bone and fat metabolism. RESULTS: Median serum LIGHT levels were significantly increased in pediatric PWS with respect to controls [255.82 (284.43) pg/ml vs 168.11 (76.23) pg/ml, p ≤ 0.02] as well as in adult PWS compared to controls [296.85 (895.95) pg/ml vs 134.18 (141.18) pg/ml, p ≤ 0.001]. In pediatric PWS, LIGHT levels were positively correlated with weight-SDS, height-SDS, and glucose levels, and negatively with total 25 (OH) vitamin D, cholesterol, LDL cholesterol and triglycerides. Additionally, LIGHT levels were negatively correlated with total BMD and fat mass. In adult PWS, LIGHT levels were positively correlated with weight, HDL cholesterol and PTH, and negatively with glucose, insulin, HOMA-IR, total cholesterol, LDL cholesterol, triglycerides, calcium, phosphorus, 25(OH)Vitamin D as well as with instrumental parameters of bone and fat quality. Consistently, multiple regression analysis showed that LIGHT serum levels in pediatric and adult PWS were predicted by different parameters including 25 (OH) Vitamin D as well as DXA parameters of bone and fat quality. CONCLUSIONS: In PWS children and adults the high levels of LIGHT could represent a marker of the altered bone and fat metabolism.

Role of Wnt-signaling inhibitors DKK-1 and sclerostin in bone fragility associated with Turner syndrome.

PURPOSE: Girls affected with Turner syndrome (TS) present with low bone mineral density (BMD) and osteopenia/osteoporosis. Thus, they have an increased risk to develop fractures compared to normal population. The aim of this study was to deepen the pathophysiology of skeletal fragility in TS subjects by evaluating the serum levels of Dickkopf-1 (DKK-1) and sclerostin, main regulators of bone mass, as well as the percentage of circulating osteoblast precursors (OCPs). METHODS: Thirty-four TS girls and 24 controls were recruited. All subjects underwent anthropometric measures (height, weight, body mass index-BMI). A peripheral venous blood sample was collected to determine serum levels of active intact parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, bone alkaline phosphatase (bALP), osteocalcin, sclerostin, DKK-1, RANKL and OPG. OCPs were detected by flow cytometry. In TS subjects bone mineralization was measured at lumbar spine by dual energy X-ray absorptiometry (DXA). RESULTS: bALP, 25-OH Vitamin D, and osteocalcin levels were significant lower in TS subjects than in the controls. Statistically significant higher levels of sclerostin, DKK-1 and RANKL were measured in patients compared with the controls. The percentage of OCPs did not show significant differences between patients and controls. Sclerostin and DKK-1 levels were related with anthropometric parameters, bone metabolism markers, HRT, rhGH therapy, RANKL and lumbar BMAD-Z-score. CONCLUSION: TS patients showed higher levels of sclerostin and DKK-1 than controls which can be related to HRT, and to reduced bone formation markers as well as the increased bone resorption activity.

Polyphenols and obesity prevention: critical insights on molecular regulation, bioavailability and dose in preclinical and clinical settings.

Obesity represents one of the most important public health challenges of the 21st century and is characterized by a multifactorial etiology in which environmental, behavioral, metabolic, and genetic factors work together. Despite the rapid increase in prevalence of obesity in the last decades, especially in children, it remains a preventable disease. To battle obesity a multisector approach promoting healthier lifestyle in terms of physical activity and nutrition is needed. Specifically, biologically active dietary compounds, as polyphenols, are able to modulate the expression of genes involved in the development and progression of obesity and its comorbidities as demonstrated by multiple studies using different obesity models. However, human studies focusing on the transcriptomic modulation by polyphenols in obese patients are still limited and do not often recapitulate the results obtained in preclinical setting likely due to the underestimation of some variables such as bioavailability, dose and form (native vs. metabolized) of polyphenols used. The aim of this review is to summarize the state-of-art of nutrigenomic in vitro, in vivo and ex vivo studies as well as clinical trials based on dietary polyphenols to fight obesity. We also critical discuss the variables to be considered to fill the gap between preclinical and clinical settings.

Custom made onlay implants in peek in maxillofacial surgery: a volumetric study.

PURPOSE: Facially malformed patients often present a variable degree of facial imbalance even after basal bone correction, and resolution of the residual hard- and soft-tissue deficiencies and asymmetries of the face are of great importance for achieving a satisfactory post-implant procedure result. The use of polyether ether ketone (PEEK) implants for maxillofacial reconstruction has been documented in the literature, but the number of patients who have received them is limited. The aim of this study was to evaluate the overall volumetric results in patients with facial imbalance after onlay custom implant positioning for mandible and fronto-orbital reconstructions. Analysis was performed by confronting volumes with the use of three-dimensional (3D) photogrammetry. METHODS: Fifteen patients were eligible for PEEK implant placements, eight for mandibular angle reconstruction, and seven for fronto-orbital reconstruction. Pre- and post-surgical 3D images of each patient's face were acquired. Facial asymmetry was analyzed by comparing each face with its mirrored copy. RESULTS: Three-dimensional analyses have shown that some degree of volume imbalance was still present in the patients with only 1.32 ± 1.02 mm residual discrepancy after treatment. CONCLUSION: Results of the study were found to fall within clinically acceptable limits since an asymmetry rate of < 3 mm is considered to fall into the norm.

Analysis of Circulating Mediators of Bone Remodeling in Prader-Willi Syndrome.

We tested the hypothesis that the levels of bone remodeling mediators may be altered in Prader-Willi syndrome (PWS). We assessed RANKL, OPG, sclerostin, DKK-1 serum levels, and bone metabolism markers in 12 PWS children (7.8 ± 4.3 years), 14 PWS adults (29.5 ± 7.2 years), and 31 healthy controls matched for sex and age. Instrumental parameters of bone mineral density (BMD) were also evaluated. Lumbar spine BMD Z-scores were reduced in PWS children (P < 0.01), reaching osteopenic levels in PWS adults. PWS patients showed lower 25(OH)-vitamin D serum levels than controls (P < 0.001). Osteocalcin was increased in PWS children but reduced in adults respect to controls (P < 0.005 and P < 0.01, respectively). RANKL levels were higher in both pediatric and PWS adults than controls (P < 0.004), while OPG levels were significantly reduced (P < 0.004 and P < 0.006, respectively). Sclerostin levels were increased in children (P < 0.04) but reduced in adults compared to controls (P < 0.01). DKK-1 levels did not show significant difference between patients and controls. In PWS patients, RANKL, OPG, and sclerostin significantly correlated with metabolic and bone instrumental parameters. Consistently, with adjustment for age, multiple linear regression analysis showed that BMD and osteocalcin were the most important predictors for RANKL, OPG, and sclerostin in children, and GH and sex steroid replacement treatment in PWS adults. We demonstrated the involvement of RANKL, OPG, and sclerostin in the altered bone turnover of PWS subjects suggesting these molecules as markers of bone disease and new potential pharmacological targets to improve bone health in PWS.

News on Climate Change, Air Pollution, and Allergic Triggers of Asthma.

The rising frequency of obstructive respiratory diseases during recent years, in particular allergic asthma, can be partially explained by changes in the environment, with the increasing presence in the atmosphere of chemical triggers (particulate matter and gaseous components such as nitrogen dioxide and ozone) and biologic triggers (aeroallergens). In allergic individuals, aeroallergens stimulate airway sensitization and thus induce symptoms of bronchial asthma. Over the last 50 years, the earth's temperature has risen markedly, likely because of growing concentrations of anthropogenic greenhouse gas. Major atmospheric and climatic changes, including global warming induced by human activity, have a considerable impact on the biosphere and on the human environment. Urbanization and high levels of vehicle emissions induce symptoms of bronchial obstruction (in particular bronchial asthma), more so in people living in urban areas compared than in those who live in rural areas. Measures need to be taken to mitigate the future impact of climate change and global warming. However, while global emissions continue to rise, we must learn to adapt to climate variability.

Severe asthma in adolescents and adults: a national, multicenter registry in real life.

Summary: The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.

Google Trends terms reporting rhinitis and related topics differ in European countries.

Google Trends (GT) searches trends of specific queries in Google and reflects the real-life epidemiology of allergic rhinitis. We compared Google Trends terms related to allergy and rhinitis in all European Union countries, Norway and Switzerland from 1 January 2011 to 20 December 2016. The aim was to assess whether the same terms could be used to report the seasonal variations of allergic diseases. Using the Google Trend 5-year graph, an annual and clear seasonality of queries was found in all countries apart from Cyprus, Estonia, Latvia, Lithuania and Malta. Different terms were found to demonstrate seasonality depending on the country - namely 'hay fever', 'allergy' and 'pollen' - showing cultural differences. A single set of terms cannot be used across all European countries, but allergy seasonality can be compared across Europe providing the above three terms are used. Using longitudinal data in different countries and multiple terms, we identified an awareness-related spike of searches (December 2016).

Thunderstorm-related asthma: what happens and why.

The fifth report issued by the Intergovernmental Panel on Climate Change forecasts that greenhouse gases will increase the global temperature as well as the frequency of extreme weather phenomena. An increasing body of evidence shows the occurrence of severe asthma epidemics during thunderstorms in the pollen season, in various geographical zones. The main hypotheses explaining association between thunderstorms and asthma claim that thunderstorms can concentrate pollen grains at ground level which may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients suffering from pollen allergies may inhale a high concentration of the allergenic material that is dispersed into the atmosphere, which in turn can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events.

Near fatal asthma: treatment and prevention.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Appendiceal mucinous neoplasms: an uncertain nosological entity. Report of a case.

INTRODUCTION: Appendiceal mucocele is a relatively rare condition characterized by progressive dilation of the appendix caused by intraluminal accumulation of mucoid substance. Its incidence is 0.07 - 0,63% of all appendectomies performed. CASE REPORT: We report the case of a 70-year-old man who came to our observation with gravative pain in right lower abdominal region. A computed tomography abdominal scan revealed a cystic/tubular structure like an appendicular mass with wall enhancement but without calcifications suggestive of a mucocele. Into peritoneal cavity we found profuse mucinous material with a 1,5 cm size parietal nodule. We also identified a free perforation of the cecum with consensual spillage of gelatinous material mimicking a pseudomyxoma peritonei. We decided to perform a right hemicolectomy with excision of peritoneal lesion. DISCUSSION: The controversy in the pathologic terminology can give rise to a clinical dilemma in terms of the management and follow-up plans. For mucosal hyperplasia and cystadenoma simple appendectomy is curative. Only in case of large base of implantation it may be necessary the resection of the ileum and caecum or right hemicolectomy. In case of mucinous cystoadenocarcinoma authors perform a right hemicolectomy. CONCLUSION: Appendiceal mucinous neoplasms are different pathological entities. The correct surgical management depends on size and location of lesion. A preoperative diagnosis is obviously needed in order to perform the correct treatment. CT abdominal scan is the better diagnostic tool, but different authors show their inability to reach a preoperative diagnosis in the larger majority of cases.

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.

BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

An unusual case of occupational asthma in a part time magician. He has got an allergy surprise from his top hat!

In this report we describe a case of respiratory allergy induced by an unusual occupational exposure to rabbit. The patient worked as a part-time magician in theatres and private parties and the most popular performance of his show was to pull out a white rabbit from a top hat. Unfortunately, a few minutes after the extraction of rabbit from top hat, the patient experienced the onset of upper and lower airway symptoms, and in some occasions he was forced to stop the show and to use short acting ß2agonists and intramuscular steroids. The results of SPT and evaluation of serological specific IgE (ImmunoCAP and ImmunoCAP ISAC IgE) revealed allergic sensitization to rabbit (Oryctolagus cuniculus) dander as well as to Parietaria and dust mites. ImmunoCAP ISAC IgE excluded allergic sensitization to other cross-reacting animal allergens. Rabbit constitutes a reliable risk factor for allergic sensitization in individuals working as professional / part-time magicians or as animators in some recreational settings (resorts, parties, charity shows, etc).

Sensitization to cockroach allergens in the urban atopic populations living in Campania district (southern Italy). A multicenter study.

BACKGROUND: Although cockroach (CR) is an important cause of allergic sensitization worldwide, only a few data are available in Italy and in a previous study we have observed, in Naples area, a low prevalence of CR sensitization. OBJECTIVES: We sought to perform a prospective study for assessing the prevalence of allergic sensitization to CR in a sample of atopic population living in Campania district area (Southern Italy). METHODS: Ten Allergy Units or Centres of Campania district participated in this cross-sectional study. Each centre was required to collect the results of at least 100 allergy consultations in consecutive outpatients referred for actual or suspected respiratory allergy. We registered demographic data, type and duration of respiratory symptoms, pets ownership, possible exposure to CR allergens, results of the skin prick tests (SPTs). RESULTS: A total of 1477 patients were examined, 985 (66.68%) had a SPTs positivity to at least one allergen. In this context, ninety were sensitized to CR, thus the overall sensitization prevalence in subjects with respiratory allergy was 6.09% ranging between 0-11% and only five patients were mono-sensitized. Thirteen patients reported rhinitis (R) + bronchial asthma (A), twenty-one R + A + conjunctivitis (C), thirty-seven R + C, five only A and eleven individuals only R. Sixty-seven patients exhibited persistent and twenty-three intermittent symptoms. Dust mite constituted the first cause of associated sensitization to CR. CONCLUSIONS: The prevalence of allergic sensitization to CR is not negligible in population living in Campania district and shows a higher trend in comparison to that found recently and some years ago in Naples area. Finally, we suggest atopic individuals and especially those highly sensitized to mite allergens or those living in low-income areas to be tested by SPTs / evaluation of serum specific IgE to CR allergens to exclude the occurrence of CR allergic sensitization.

Endoscopic sclerotherapy for hemostasis of acute esophageal variceal bleeding.

INTRODUCTION: Currently the most widely used methods for endoscopic control of esophageal varices bleeding are sclerotherapy and rubber band ligation. Although the superiority of band ligation (BL) over endoscopic sclerotherapy (SCL) for the secondary prophylaxis of variceal hemorrhage has been proven, the best approach for acute bleeding remains controversial. PATIENTS AND METHODS: We performed a retrospective study between January 2005 and May 2013. We selected 104 patients with gastrointestinal hemorrhage from rupture of esophageal varices treated with endoscopic sclerotherapy. The sclerosing agent used was 1% polidocanol in 89 cases, butyl-cyanoacrylate in 8 cases and sodium tetradecylsulfate in 4 cases. In 3 cases had not been carried sclerosis because it was not possible to identify the bleeding site. RESULTS: Among the 101 patients who underwent endoscopic sclerotherapy 4 presented re-bleeding within 12 hours from first treatment. Other 10 patients (9.9%) presented re-bleeding within a 5-days period. The most frequent complication was ulceration, observed in 4 cases (3.8%). There was only one case of perforation treated conservatively. CONCLUSIONS: The general improvement in the results of the treatment of variceal acute bleeding might be attributed to better clinical management of these patients. In literature no consensus exists regarding the preferred endoscopic treatment. To date, there is no single method applicable to all patients with bleeding esophageal varices, but sclerotherapy is considered effective, safe and repeatable in experienced hands.

Reconstruction of severe atrophic jaws with Fresh Frized Bone Allografts: clinical histologic and histomorphometric evaluation.

OBJECTIVES: Rehabilitation of maxillary edentulism with implant-supported prostheses has come into common clinical practice. Although autologous bone has osteoinductive, osteoconductive and osteogenetic properties, its use is subject to certain disadvantages such as: Increased morbidity Limited amount of bone harvested from each donor site. AIM: The aim of this study is to analyze clinical, histological and histomorphometric results of homologous bone for implantoprosthetic rehabilitation in severe atrophic jaws. PATIENTS AND METHODS: Twenty consecutive patients, 14 female and 6 males, were treated with homologous bone bank. Treatment protocol consist of: first surgycal step, trasversal and vertical volume restore, second surgycal step: screw remove, specimen biopsy and insert implant fixtures. RESULTS: Data show that Fresh Frozen Bone Allografts (FFBA) could be a valuable substitute for autologous bone, in as much as histological and histomorphometric results are widely overlapping. CONCLUSIONS: Homologous bone is a valuable option for its large availability with a low cost, good versatility, no morbidity at the donor site, shorter surgical time and hospital stay.

Improvement of quality of life in allergic rhinoconjunctivitis patients using nasal filters, a preliminary study.

BACKGROUND: Allergic rhinoconjunctivitis is a clinical condition that impairs quality of life. The use of traditional drugs in many cases is not enough to improve quality of life in these patients. METHODS: In this pilot study we used the Sanispira Nasal filters in 15 patients (mean age 34,7 years) affected by allergic rhinoconjunctivitis for 18 days. At each follow-up visit, patients were assessed with a specific quality of life questionnaire, a symptoms form and a drugs form that evaluates the use of antiallergic drugs in the last week. Patients sensitive to environmental allergens wore Sanispira nasal filters during the day, while patients sensitive to domestic allergens wore the device during the night. RESULTS: Thirteen patients completed the study. We found an improvement significative (p=0,0241) of the total score of RQLQ of 23,10 points between baseline and 18 days ( total score at baseline prior to nasal filter insertion= 60,60, at 1 week = 42, 28, at 18 days= 34, 10). A significative improvement in the nasal symptoms domain between baseline and 18 days (in particular stuffy nose p=0,047; runny nose p=0,012; sneezing p=0,0021; ) and one item of practical problems domain, the need to repeatedly blow the nose(p=0,082). The total score of symptoms evaluated with the symptoms form improved significantly from baseline to 18 days. Total symptoms score at baseline was 9,7; at 1 week it was 8,1 and at 18 days it was 4,7. The improvement was statistically significant (p=0,0092). Three of the thirteen patients that completed the study eliminated completely the use of drugs during of the study. CONCLUSIONS: The use of SANISPIRA ®, has shown encouraging results, with an improvement in the quality of life in Rhinoconjunctivitis patients specially an improvement in nasal and ocular symptoms.

A relapse of near-fatal thunderstorm-asthma in pregnancy.

Thunderstorm-related asthma is a dramatic example of the allergenic potential of pollen antigens. Pollen allergic patients who encounter the allergenic cloud of pollen during a thunderstorm are at higher risk of having an asthma attack. Relapse is also possible and we describe here the first case of relapse of near fatal thunderstorm-asthma occurred in a 36 years old, 20 weeks pregnant woman affected by seasonal asthma and sensitized to allergens released by Parietariapollen. Patients suffering from pollen allergy should be alerted of the danger of being outdoors during a thunderstorm in the pollen season and if they experienced an episode of severe thunderstorm-related asthma could be at risk of a relapse during a heavy precipitation event.

Laparoscopic drainage of liver abscess: case report and literature review.

AIM: To evaluate the safety and efficacy of the minimally invasive surgical approach (laparoscopic drainage) of liver abscesses in selected cases. CASE REPORT: Male, 58 years old, from a rural area, presented with epigastric abdominal pain, fever, weight loss, loss of appetite, a palpable mass in the epigastrium and neutrophilic leukocytosis. CT revealed a complex multiloculated liver abscess in segments 2-3. Systemic antibiotic therapy alone was ineffective; percutaneous drainage was excluded due to the characteristics of the lesion. RESULT: Given the complexity of the lesion, a laparoscopic approach was chosen involving complete drainage of the abscess, debridement and irrigation; the cavity was unroofed using electrocautery and samples were obtained for bacterial culture and drug testing. Two drains were left in the cavity for seven days. No complications were observed. DISCUSSION: In accordance with the scientific literature, after thorough imaging we performed laparoscopic drainage of a large, complex liver abscess as a safe, effective alternative to open surgery when antibiotic therapy alone failed and percutaneous drainage was uncertain. CONCLUSION: Not all liver abscesses can be treated with antibiotic therapy or percutaneous drainage. Laparoscopic drainage in association with systemic antibiotic therapy is a safe and effective minimally invasive approach that should be considered in selected patients.

Social networks: a new source of psychological stress or a way to enhance self-esteem? Negative and positive implications in bronchial asthma.

The Internet and, in particular, social networks are an increasingly important part of daily life for both adolescents and adults who maintain a virtual relationship with others sharing interests and goals. Very often, they disclose more about themselves online than they do in person. However, cyberbullying and cyberostracism can be problematic for adolescents and sensitive individuals, who might be negatively affected by social networks. Some studies have shown an increased risk of depression, whereas others suggest beneficial effects through enhanced communication, social connection, and self-esteem. Bronchial asthma is an increasingly frequent disease in the industrialized world, and psychological implications play a role in increasing or in reducing its severity. One year after the case report of an asthma exacerbation that may have been triggered by Facebook, it seems reasonable to analyze the effects of social networks on bronchial asthma.