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Purpose:  This prospective, single-center study aims to evaluate the safety and effectiveness of NEAUVIA Intense, a PEG cross-linked polymeric hydrogel, in correcting moderate-to-severe nasolabial folds (NLF) in a routine clinical setting. The study investigates the aesthetic outcomes, patient satisfaction, and adverse events associated with the injectable filler., Patients and Methods: Seventy patients were initially enrolled, with 60 meeting study parameters. The post-market study involved a single session treatment, employing NEAUVIA Intense on each side of the NLF. Assessments utilized the Modified Fitzpatrick Wrinkle Scale (MFWS), Global Aesthetic Improvement Scale (GAIS), and Visual Analogical Scale (VAS)., Results:  The study demonstrated a statistically significant improvement in tissue depression immediately post-injection (p < 0.001), with sustained effects up to 6 months. MFWS assessments revealed that responder patients were 96.6% immediately after treatment, 76.6% one month, 48.3% after 3 months, and 28.3% at 6 months (p < 0.001). Additionally, there was a significant change in the frequency distribution of MFWS scores post-treatment (p < 0.001), with the majority of patients experiencing improvement in tissue depression. Maximum improvement was observed at 30- and 90-days post-treatment based on GAIS assessments. Patient and physician satisfaction, measured by VAS, remained stable over time, with fluctuations at 4 and 24 weeks after treatment (p < 0.001, Anova; p < 0.05, Wilcoxon). Throughout the entire follow-up duration of the patients enrolled in the study, no adverse effects related to the use of the product were observed., Conclusion:  NEAUVIA Intense proved to be an effective solution for correcting NLF, providing significant and lasting improvements in tissue depression and aesthetic outcomes. The study underscores the necessity for continuous assessment in aesthetic medicine to align outcomes with evolving patient expectations and optimize long-term results. The findings contribute to the understanding of this specific hydrogel filler and highlight the broader context of injectable fillers in comprehensive facial aesthetic strategies., Competing Interests: UB-CARE S.R.L. is part of the Matex Lab Group. Dr. Nicola Zerbinati is the scientific director of MatexLab. The authors report no other conflicts of interest in this work., (© 2024 Zerbinati et al.)

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold ( p = 0.047; IC 0.99-6.8) and 5.4-fold ( p = 0.002; CI 1.9-16), respectively. Conclusions : In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells.

Common complications of coronavirus disease 2019 (COVID-19) related ARDS and ventilation are barotrauma-induced pneumothorax, pneumatocele and/or empyema. We analysed indications and results of video-assisted thoracoscopic surgery (VATS) in complicated COVID-19 patients. This is a retrospective single-institution study analysing a case series of patients treated by VATS for secondary spontaneous pneumothorax (SSP), pneumatocele and empyema complicating COVID-19, not responding to drainage in Lodi Maggiore Hospital between February 2020 and May 2021. Out of 2076 patients hospitalized in Lodi Maggiore Hospital with COVID-19, nine Males (0,43%; mean age 58,1-33-81) were treated by VATS for complications of pneumonia (6 SSP and 3 empyema; 1 case complicated by haemothorax). 7 patients (77%) had CPAP before surgery for 21.3 days mean (4-38). Mean Operative time was 80.9 min (38-154). Conversion rate was 0%. 3 (33%) patients were admitted to ICU before VATS. Treatments were: bullectomy in six patients (66%), drainage of the pleural space in all patients, pleural decortication and fluid aspiration in five cases (55%). two patients (22%) needed surgery interruption and bilateral ventilation to restore adequate oxygenation. Mortality was 1/9 (11%) due to respiratory failure for persistent pneumonia. In one patient (11%) redo surgery was performed for bleeding. Mean postop Length of Stay (LOS) was 37.9 days (10-77). Our report shows that VATS can be considered an extreme, but effective treatment for COVID-19 patients with SSP, pneumatocele or empyema, for patients who can tolerate general anaesthesia. Attention must be paid to the aerosol-generation of infected droplets., (© 2022. Italian Society of Surgery (SIC).)

Introduction: The aim of this study was to assess the safety of bronchoscopic microwave ablation (MWA) of peripheral lung parenchyma using the NEUWAVE™ FLEX Microwave Ablation System, and robotic-assisted bronchoscopy (RAB) using the MONARCH™ Platform in a swine model., Methods: Computed tomography (CT)-guided RAB MWA was performed in the peripheral lung parenchyma of 17 Yorkshire swine (40-50 kg) and procedural adverse events (AEs) documented. The acute group (day 0, n  = 5) received 4 MWAs at 100 W for 1, 3, 5, and 10 min in 4 different lung lobes. Subacute and chronic groups (days 3 and 30, n  = 6 each) received one MWA (100 W, 10 min) per animal., Results: The study was completed without major procedural complications. No postprocedural AEs including death, pneumothorax, bronchopleural fistula, hemothorax, or pleural effusions were observed. No gross or histological findings suggestive of thromboembolism were found in any organ. One 3-Day and one 30-Day swine exhibited coughing that required no medication (minor AEs), and one 30-Day animal required antibiotic medication (major AE) for a suspected lower respiratory tract infection that subsided after two weeks. CT-based volumetric estimates of ablation zones in the acute group increased in an ablation time-dependent (1-10 min) manner, whereas macroscopy-based estimates showed an increasing trend in ablation zone size., Conclusion: The NEUWAVE FLEX and MONARCH devices were safely used to perform single or multiple RAB MWAs. The preclinical procedural safety profile of RAB MWA supports clinical research of both devices to investigate efficacy in select patients with oligometastatic disease or primary NSCLC.

Enhanced weathering (EW) is one of the most promising negative emissions technologies urgently needed to limit global warming to at least below 2 °C, a goal recently reaffirmed at the UN Global Climate Change conference (i.e., COP26). EW relies on the accelerated dissolution of crushed silicate rocks applied to soils and is considered a sustainable solution requiring limited technology. While EW has a high theoretical potential of sequestering CO 2 , research is still needed to provide accurate estimates of carbon (C) sequestration when applying different silicate materials across distinct climates and major soil types in combination with a variety of plants. Here we elaborate on fundamental advances that must be addressed before EW can be extensively adopted. These include identifying the most suitable environmental conditions, improving estimates of field dissolution rates and efficacy of CO 2 removal, and identifying alternative sources of silicate materials to meet future EW demands. We conclude with considerations on the necessity of integrated modeling-experimental approaches to better coordinate future field experiments and measurements of CO 2 removal, as well as on the importance of seamlessly coordinating EW with cropland and forest management.

Background: Haemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs)., Methods: Observational, prospective, multicentre, Italian study., Results: 451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence., Conclusions: Our study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding., Trial Registration: NCT02045394., (© 2021. The Author(s).)

To describe radiographic key patterns on Chest X-ray (CXR) in patients with SARS-CoV-2 infection, assessing the prevalence of radiographic signs of interstitial pneumonia. To evaluate pattern variation between a baseline and a follow-up CXR. 1117 patients tested positive for SARS-CoV-2 infection were retrospectively enrolled from four centers in Lombardy region. All patients underwent a CXR at presentation. Follow-up CXR was performed when clinically indicated. Two radiologists in each center reviewed images and classified them as suggestive or not for interstitial pneumonia, recording the presence of ground-glass opacity (GGO), reticular pattern or consolidation and their distribution. Pearson's χ 2 test for categorical variables and McNemar test (χ 2 for paired data) were performed. Patients mean age 63.3 years, 767 were males (65.5%). The main result is the large proportion of positive CXR in COVID-19 patients. Baseline CXR was positive in 940 patients (80.3%), with significant differences in age and sex distribution between patients with positive and negative CXR. 382 patients underwent a follow-up CXR. The most frequent pattern on baseline CXR was the GGO (66.1%), on follow-up was consolidation (53.4%). The most common distributions were peripheral and middle-lower lung zone. We described key-patterns and their distribution on CXR in a large cohort of COVID-19 patients: GGO was the most frequent finding on baseline CXR, while we found an increase in the proportion of lung consolidation on follow-up CXR. CXR proved to be a reliable tool in our cohort obtaining positive results in 80.3% of the baseline cases., (© 2020. The Author(s).)

Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors.

Diffuse alveolar hemorrhage (DAH) is an acute often life-threatening condition characterized by a variable combination of hemoptysis, dyspnoea, diffuse and bilateral ground glass pulmonary opacities, anemia and hypoxemia, that can be induced by different causes, including several drugs. We report here the case of a 25-year-old woman who has been admitted to our pulmonary clinic for the onset of chest pain, cough and haemoptysis, started one week after her first treatment with alemtuzumab for multiple sclerosis. Computed tomography (CT) scan of the chest at the admission showed diffuse and bilateral ground glass pulmonary opacities. Her symptoms resolved completely without any treatment, after the interruption of alemtuzumab, and CT scan of the chest performed one month later showed total disappearance of the pulmonary opacities.

Hydrogels based on hyaluronic acid are used to restore volume, hydration, and skin tone, as well as to correct scars, asymmetries or defects of the soft tissue. Hyaluronic acid is often chemically crosslinked with different crosslinking agents in order to improve its mechanical and biological properties. Here we focused on defining the chemical and mechanical characterization of a new hydrogel with specific characteristics: hyaluronic acid polyethylene glycol (PEG)-crosslinked with a high concentration of hyaluronic acid (28 mg/mL), manufactured by MatexLab Spa, via Carlo Urbani 2, ang Via Enrico Fermi, Brindisi, Italy. We made a quantitative and qualitative analysis of the content of sodium hyaluronate in the hydrogel after polymerization and sterilization processes and also evaluated histologically the bio integration of these hydrogels in the cutaneous soft tissues. The results suggest that hyaluronic acid hydrogel PEG-crosslinked have great bio integration, great chemical and mechanical properties, compared with other products available on the market, that are cross-linked with different cross-linking agents. The nontoxicity and nonimmunogenicity of PEG guarantee the lack of allergic and immunological reactions. The PEG-crosslinking technology guarantees a high duration time of the implanted hydrogel because of more resistant physiological degradation., (© 2020 Wiley Periodicals LLC.)

European SARS-CoV-2 pandemic epicenter was detected in Northern Italy, in a little Italian town of Lodi province, the Lodi Hospital was therefore rapidly saturated, and in particularly the departments of respiratory diseases and Intensive Care Unit had been largely involved. In this paper, we describe how the first Sub-intensive Respiratory Unit in Europe completely dedicated to COVID-19 patients was organized and managed in our hospital. From February 25 th to April 30 th 2020, 156 patients were admitted to our Respiratory Sub-intensive Unit. Among them, 100 were discharged, 28 dead and 28 transferred to ICU for intubation., (©Copyright: the Author(s).)

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern., Objective: We explored the clinical management of inpatients with COVID-19 in Italy., Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed., Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%., Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available., (© 2020 S. Karger AG, Basel.)

Introduction: The aim of the study was to assess the effects of chronic inflammation on incretin levels, inflammatory markers, and enteric neuronal function measured in isolated preparations of smooth muscle of rat., Material and Methods: We induced experimental colitis using 2,4-dinitrobenzenesulfonic acid (DNBS) in 17 Albino male Sprague-Dawley rats, while 16 rats were used as a control. They were housed in temperature-controlled rooms in a 12-h light/dark cycle at 22-24°C and 50 to 60% humidity. We evaluated in both inflamed and healthy rats: fasting plasma glucose concentration, fasting plasma insulin, myeloperoxidase, active glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and GLP-2 levels, adiponectin, and C-reactive protein (CRP). We also evaluated colonic longitudinal smooth muscle contractile activity., Results: Intrarectal administration of DNBS reduced body weight gain in inflamed rats. We recorded higher levels of fasting plasma glucose, and insulin in inflamed rats. We observed higher levels of myeloperoxidase and CRP, and lower levels of ADN in inflamed rats. We recorded higher levels of GIP, GLP-1, and GLP-2 in inflamed rats compared to the healthy ones. Regarding functional response of colon intestinal smooth muscle after electrical stimulation, we recorded a lower functional response of colon intestinal smooth muscle after electrical stimulation in inflamed rats., Conclusions: We can conclude that chronic inflammation leads to an increase of incretin levels and to a decrease of functional response of colon intestinal smooth muscle after electrical stimulation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

Background: Hyaluronic acid (HA) based hydrogels for esthetic applications found widespread use. HA should be crosslinked for this application to achieve the correct viscoelastic properties and avoid fast degradation by the hyaluronidase enzyme naturally present in the skin: these properties are controlled by the amount of crosslinker and the fraction that is effectively crosslinked (i.e. that binds two HA chains)., Aim: Crosslinking by polyethylene glycol diglycidyl ether (PEGDE) has been more recently introduced and showed attractive features in terms of viscoelastic properties and reduced biodegradation. Aim of this paper is to define a method for the determination of the crosslinking properties of these recently introduced fillers, method that is lacking at the moment., Material and Method: The percentage of crosslinker and the fraction that is effectively crosslinked were determined by proton Nuclear Magnetic Resonance (1H NMR) and by 13C NMR, respectively. The filler were preliminarily washed with acetonitrile to remove residual PEG and then digested by hyaluronidase to obtain a sample that can be analysed by NMR., Results: The crosslinking parameters were determined in four samples of NEAUVIA PEG-crosslinked dermal fillers (produced by MatexLab S.p.A., Italy). The percentage of crosslinker was between 2.8% and 6.2% of HA, whereas the effective crosslinker ratios were between 0.07 and 0.16 (ratio between the moles of effectively crosslinked PEG and total moles of PEG). Moreover, a digestion procedure alternative to enzymatic digestion, based on acidic hydrolysis, was successfully tested for the determination of crosslinker percentage., Conclusions: The proposed method successfully determined the two crosslinking parameters in PEG-crosslinked dermal fillers. The estimated percentage of crosslinker is similar to previously reported data for other crosslinkers, whereas the effective crosslinker ratio is lower for PEG crosslinked hydrogels.

Background: Bronchoscopy plays a key role to diagnose the etiology, to localize the site, and to identify the sources of the bleeding in patients with hemoptysis, but the ideal timing of an endoscopic examination is still unclear., Methods: We performed a secondary analysis of an observational and multicenter study, aimed at evaluating the epidemiology of hemoptysis in Italy and the diagnostic yield of the most frequently prescribed examinations. The aim of the study was to evaluate whether an early bronchoscopy (i.e., performed during active bleeding/≤48 h after hemoptysis stopped) helps localize bleeding (i.e., site, lobe, lung) and increase diagnostic yield in comparison with a delayed examination., Results: Four hundred eighty-six consecutive adult patients (69.2% males; median [IQR] age: 67 [53-76] years) with hemoptysis requiring an etiological diagnosis and undergoing bronchoscopy were recruited. Bleeding focus could be located more frequently in case of moderate-severe bleedings than in cases of mild hemoptysis (site: 70/154, 45.4%, VS. 73/330, 22.1%; p-value < 0.0001; lobe: 95/155, 61.3%, VS. 95/331, 28.7%; p-value < 0.0001; lung: 101/155, 65.1%, VS. 111/331, 33.5%; p-value < 0.0001). Early bronchoscopy showed a higher detection rate of bleeding source in comparison with delayed examination (site: 76/214, 35.5%, VS. 67/272, 24.6%; p-value = 0.01; lobe: 98/214, 45.8%, VS. 92/272, 33.8%; p-value = 0.007; lung: 110/214, 51.4%, VS. 102/272, 37.5%; p-value = 0.002). Early bronchoscopy did not provide any advantages in terms of increased diagnostic yield, in the total cohort (113/214, 52.8%, VS. 123/272, 45.2%; p-value = 0.10) and in the severity subtypes (mild: 56/128, 43.8%, VS. 88/203, 43.4%; p-value = 0.94; moderate-severe: 57/86, 66.2%, VS. 35/69, 50.7%; p-value = 0.051)., Conclusions: Early bronchoscopy helps detect bleeding sources, particularly in cases of moderate-severe hemoptysis, without increasing diagnostic accuracy., Trial Registration: ClinicalTrials.gov (identifier: NCT02045394 ).

Neauvia Intense is biocompatible, injectable hyaluronic acid (HA) filler PEG cross-linked for facial soft-tissue augmentation that provides volume to tissues. The aim of the present study is to evaluate the sensitivity of Neauvia Intense in hyaluronidase from bovine testes in a time-course analysis. The test is based on the colourimetric determination of the N-acetyl - D - glucosamine (NAG) released by the hyaluronidase in standardised conditions. The in vitro conditions involve the treatment of Neauvia Intense with a known concentration of the enzyme (6080U/ml). The NAG content was determined at different times to assess the kinetics of the degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h); the Ehrlich's reagent was used for the colourimetric quantification, by the method described by Reissing and colleagues. The intensity of the violet colour developed after the chemical reaction was proportional to the NAG present in each sample. A microplate reader at 585 nm read the absorbance. The amount of NAG released by the product was proportional to the time of incubation with bovine hyaluronidase, reaching a plateau after 168 hours.

Aesthetic surgery of female external genitalia has gained increasing popularity over the past decade, with reduction of the labia minora (labiaplasty) being the procedure most commonly requested and performed. Female external genitalia lose elasticity and volume with age, but few studies describe the techniques for labia majora augmentation. Currently, very few studies have investigated the effectiveness and safety of labia majora augmentation with hyaluronic acid (HA) injection. This study aims to evaluate the effectiveness and safety of labia majora augmentation with hyaluronic acid filler injection. We retrospectively analyzed 37 patients affected by hypotrophy of the labia majora, treated with HA dermal filler 28mg/ml PEG crosslinked (Neauvia® Intense Rose, Matex Lab, Switzerland) between May 2015 and July 2016. Global evaluation of the aesthetics of the intimate area and clinical data were investigated with VAS (Visual Analogic Scale) ad hoc. Adverse events and complications were recorded. A total of 37 women affected by labia majora hypotrophy were treated with 28mg/ml HA dermal filler. A significant clinical improvement was observed in the score provided by both patients and doctor. Only mild adverse events and complications were recorded. HA hydrogel with a novel crosslinking agent is able to provide a considerable rejuvenation with a simple outpatient procedure and to bring a significant clinical improvement. HA-based filler infiltration treatment in labia majora is repeatable, has virtually no complications, and is reversible.

Background: There has been a dramatic increase in the number of pancreatic cystic lesions observed in the past two decades but data regarding the prevalence of cysts in the general population are lacking., Methods: All the individuals who undergo CT at the San Marino State Hospital are residents of the Republic of San Marino; their demographic distribution is available and precise. CT scans carried out over 1 year at the State Hospital were reviewed for asymptomatic pancreatic cysts., Results: 1061 relevant CT scans were carried out on 814 patients; 762 individuals were eligible for the study and 650 patients underwent contrast-enhanced CT. Thirty-five patients had at least one cyst at contrast-enhanced CT (5.4%). The prevalence of cysts increased with increasing age up to 13.4% (95% CI 6.6-20) in individuals 80-89 years of age (p < .001). Cyst prevalence was significantly higher in patients who underwent CT for malignancy (p = .038) but this difference was no longer significant in multivariate analysis. The odds of a cyst being present increased by 1.05 (95% CI 1.02-1.09) for each increasing year of age (p = .002). Approximately a quarter of the patients with cysts died within 1 year after CT from non pancreas-related disease. The estimated standardized age-adjusted cyst prevalence is 2194 per 100,000 people., Conclusions: The likelihood of having a pancreatic cyst correlates with increasing age, not with the presence of extra-pancreatic malignancies. The estimated prevalence of CT-detectable asymptomatic pancreatic cysts in the general population is 2.2%., (Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The aims of this study were to develop a kinematic model of the spine, seen as a continuous deformable body and to identify the smallest set of surface markers allowing adequate measurements of spine motion. The spine is widely considered as a rigid body or as a kinematic chain made up of a smaller number of segments, thereby introducing an approximation. It would be useful to have at our disposal a technique ensuring accurate and repeatable measurement of the shape of the whole spine. Ten healthy subjects underwent a whole-spine radiographic assessment and, simultaneously, an optoelectronic recording. Polynomial interpolations of the vertebral centroids, of the whole set of markers were performed. The similarity of the resulting curves was assessed. Our findings indicate that spine shape can be reproduced by 5th order polynomial interpolation. The best approximating curves are obtained from either 10- or 9-marker sets. Sagittal angles are systematically underestimated., (Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Aim: The aim of the paper was to perform a 64-slice CT evaluation of the main anatomic variants of paranasal sinuses., Methods: From April 2005 to January 2006, 100 patients were chosen among all those that had undergone a paranasal sinuses CT examination. They were 45 women and 55 men, all aged between 18 and 70 years, mean age 46 years; they were all caucasian. This research has been conducted using a 64-slice Siemens Somatom Volume-Zoom multidetector Spiral CT. Para-nasal sinuses CT examination has been performed through a thin axial acquisition; the patient was lying on his back and the images were processed with multiplanar reconstruction (MPR). The anatomic variants considered in this study are: concha bullosa, Haller cells, uncinate process abnormalities, agger nasi cells, ethmoidal bulla, Onodi cell, middle turbinate curvature abnormalities., Results: In this research it has been noticed that 29% of patients are affected by concha bullosa, 5% by Haller cells and again 5% by uncinate process abnormalities; 52% are affected by agger nasi cells, 15% by ethmoidal bulla, 9% by Onodi cell and 11% by middle turbinate curvature abnormalities., Conclusion: By using a 64-slice CT you can get a better quality of images in terms of spatial and temporal resolution. Osteomeatal complex structures are often featured by many anatomic variants. The most of the time, percentages are the same as recent researches have shown.

Mechanisms underlying the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) have been extensively investigated, whereas those leading to intestinal damage are not completely understood. Several hypotheses have been put forward on the pathophysiology of intestinal damage by NSAIDs: enhanced intestinal permeability, inhibition of cyclooxygenase (COX), enterohepatic recirculation, and formation of adducts. The effects of COX-2 selective inhibitors, which appear to have better gastric tolerability when compared to nonselective NSAIDs, on normal and inflamed intestinal mucosa (as in Crohn's disease or ulcerative colitis) are still largely unexplored. If COX-2 inhibition plays a key role in suppressing the inflammatory process, recent evidence suggests that COX-2 products are involved in maintaining the integrity of intestinal mucosa, in the healing of gastrointestinal ulcers and in the modulation of inflammatory bowel disease (IBD). Animal models of intestinal inflammation have so far yielded conflicting results on the effects of COX-2 selective inhibitors on the intestinal mucosa. It is now clear that NSAIDs do not act through cyclooxygenase inhibition, but also have different targets such as nuclear factor-kappaB and/or peroxisome proliferator-activated receptors gamma. The peculiar pharmacological profile of each compound may help to explain the different impact of each NSAID on the inflammatory process and on IBD. Notably, the salicylic acid derivative 5-ASA is widely used in the treatment of IBD and is believed to act through nuclear factor-kappaB inhibition. Although the use of COX-2 selective inhibitors remains contraindicated in patients with IBD, studying their effects on intestinal mucosa may offer new insights into their subcellulars mechanisms of action and open new avenues for the development of novel therapies for IBD.

Sumatriptan is a 5-HT1B/D receptor agonist of documented efficacy in relieving migraine and associated symptoms such as nausea and vomiting. In the past decade, several studies reported an important delay of gastric emptying induced by sumatriptan in healthy humans. The impact of this gastric motor effect of sumatriptan in migraineurs is difficult to predict: a further delay in gastric emptying could be detrimental (i.e. increased nausea and epigastric symptoms) in patients already having delayed gastric emptying. However, in patients with functional dyspepsia, sumatriptan is also reported to improve gastric accommodation to a meal and reduce perception of gastric distention, hence relieving epigastric symptoms. Thus, reduced visceral perception could be a mechanism involved in reducing nausea during a migraine attack. Paradoxically, sumatriptan is reported both to relieve the nausea of a migraine attack and to have nausea as a side effect. Although careful analysis of the time of onset of nausea may offer a clue as to the origin of this symptom, available data do not support definite conclusions, all the more so because the gastric motor effect of second-generation triptans are still unexplored. Taken together, the available evidence warrants further studies to clarify the following issues: first, the mechanism responsible for the gastric motor effect of sumatriptan [receptor subtype(s) involved; central vs peripheral mechanism]; secondly, the effects on gastric motility/visceral sensitivity of second-generation triptans (which are 5-HT1B/D receptor agonists) and more recent selective 5-HT1D receptor agonists (proposed as investigational antimigraine agents with less potential to induce coronary vasoconstriction through 5-HT1B receptors); finally, the possible use of drugs improving gastric accommodation to a meal in the management of those dyspeptic patients with impaired fundic relaxation/altered visceral sensitivity., (Copyright 2001 Academic Press.)

Purpose: To evaluate the effect of oxcarbazepine (OCBZ) on the pharmacokinetic profile of steroid oral contraceptives., Methods: Twenty-two healthy women aged 18-44 years were recruited, and 16 of them completed the study. By using a randomized double-blind crossover design, each woman was studied in two different menstrual cycles, during which placebo or OCBZ (maintenance dosage, 1,200 mg/day) was given in randomized sequence for 26 consecutive days with a washout of at least one cycle in between. A steroid oral contraceptive containing 50 microg ethinylestradiol (EE) and 250 microg levonorgestrel (LN) was taken for the first 21 days of each cycle. Plasma concentrations of EE and LN were measured by gas chromatography-mass spectrometry in samples collected at regular intervals on days 21-23 of each cycle., Results: Compared with placebo, areas under the plasma concentration curves (AUC(0-24h, geometric means) decreased by 47% for both EE (from 1,677 to 886 pg.h/ml; p < 0.01) and LN (from 137 to 73 ng.h/ml; p < 0.01), during OCBZ treatment. Peak plasma EE concentrations decreased from 180 pg/ml during the placebo cycle to 117 pg/ml during the OCBZ cycle (p < 0.01), whereas peak plasma LN concentrations decreased from 10.2 to 7.7 ng/ml (p < 0.01). The half-lives of EE and LN also decreased from 13.6 to 7.9 h (p < 0.01) and from 28.8 to 15.8 h, respectively (p < 0.01)., Conclusions: OCBZ reduces plasma concentrations of the estrogen and progestagen components of steroid oral contraceptives, presumably by stimulating their CYP3A-mediated metabolism in the liver or gastrointestinal tract or both. Because this may lead to a decreased efficacy of the contraceptive pill, women treated with OCBZ should receive preferentially a high-dosage contraceptive and should be monitored for signs of reduced hormonal cover.

Purpose: Malignant pericardial effusion, although highly variable, is an uncommon complication of cancer. It is often associated with symptoms like dyspnea, chest pain, and cough, which may be severe and disabling. We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder., Patients and Methods: Patients with malignant pericardial effusions were treated with intracavitary thiotepa (15 mg on days 1, 3, and 5) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0. Responses were assessed by clinical examination, computed tomographic (CT) scan, and echocardiography before treatment, 1 month after treatment, and every 2 months thereafter. Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure., Results: Nine patients with breast cancer, 11 with lung cancer, two with an unknown primary tumor, and one with metastatic melanoma were treated. In all but three patients, systemic medical treatment was started after completion of intracavitary therapy. Nineteen patients responded to treatment (83%; 95% confidence interval, 61% to 95%) with a rapid improvement of symptoms. The median time to pericardial effusion progression was 8.9 months (range, 1 to 26). No significant side effects were registered, except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia., Conclusion: A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion.

Purpose: This study was conducted to determine whether vigabatrin affects in vivo indices of hepatic microsomal enzyme activity and the pharmacokinetics of steroid oral contraceptives in healthy subjects., Methods: Under double-blind conditions, 13 female healthy volunteers received, in random order and with a washout interval of > or = 4 weeks, two oral 4-week treatments with vigabatrin (VGB) (maintenance dosage, 3,000 mg daily) and placebo, respectively. The clearance and half-life of antipyrine (a broad marker of drug oxidation capacity), the urinary excretion of 6-beta-hydroxycortisol (a selective marker of cytochrome CYP3A-mediated oxidation), and the activity of serum gamma-glutamyltransferase (a nonspecific index of microsomal enzyme activity) were determined after 3 weeks of each treatment. The single-dose kinetics of a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel were also determined after 3 weeks of treatment by specific radioimmunologic assays., Results: VGB treatment had no influence on antipyrine clearance (28 +/- 5.6 vs. 30 +/- 4.5 ml/h/kg on placebo), antipyrine half-life (15.5 +/- 3.5 vs. 14.1 +/- 2.1 h), urinary 6-beta-hydroxycortisol excretion (488 +/- 164 vs. 470 +/- 228 nmol/ day), 6-beta-hydroxycortisol-to-cortisol concentration ratio (6.8 +/- 3.1 vs. 6.1 +/- 3.1) and serum gamma-glutamyltransferase activity (12 +/- 3 vs. 11 +/- 3 IU/L). No difference in pharmacokinetic parameters between VGB and placebo sessions were found for ethinyl estradiol (half-life, 12.5 +/- 3.2 vs. 13.9 +/- 3.2 h; AUC, 874 +/- 301 vs. 939 +/- 272 ng/ L/h) and levonorgestrel (half-life, 17.7 +/- 5.2 vs. 23.1 +/- 9.8 h; AUC, 27.5 +/- 9.6 vs. 30.0 +/- 12.0 micrograms/L/h). Two subjects, however, showed a 50 and a 39% reduction in ethinyl estradiol AUC during VGB treatment., Conclusions: At therapeutic dosages, VGB did not modify in vivo indices of hepatic microsomal enzyme activity and did not interfere significantly with the CYP3A-mediated metabolism of ethinyl estradiol and levonorgestrel. Based on these data, VGB is unlikely to affect consistently the efficacy of steroid oral contraceptives or interact pharmacokinetically with drugs that are eliminated mainly by oxidative pathways, particularly those involving cytochrome CYP3A.

Purpose: To assess whether phenytoin affects the pharmacokinetics of the dihydropyridine calcium antagonist nisoldipine., Methods: Twelve patients with epilepsy receiving chronic phenytoin therapy and 12 healthy control subjects matched for age and gender received a single oral dose of nisoldipine (40 and 20 mg, respectively). Blood samples were collected for up to 48 h for estimation of plasma nisoldipine levels by capillary gas chromatography., Results: Mean plasma nisoldipine concentrations were much lower in the patients. Geometric means for areas under the concentration-time curve (AUC0-tn) normalized to a 20-mg dose were 1.6 micrograms/L/h (95% confidence intervals, 0.6-3.8 micrograms/L/h) in the patients compared with 15.2 (10.7-21.6) micrograms/L/h in control subjects (p < 0.002)., Conclusions: These results suggest that phenytoin increases the first-pass metabolism of nisoldipine to a clinically important extent. In view of the magnitude and variability of interaction, use of nisoldipine in patients receiving chronic phenytoin therapy is contraindicated.

To assess potential ethnic and gender-related differences in the expression of cytochrome CYP1A2-mediated activity, the pharmacokinetics of phenacetin (a CYP1A2 substrate) and its metabolite paracetamol were compared in 20 Caucasian and 20 Chinese subjects after administration of a single oral 900 mg phenacetin dose. Peak plasma concentrations and apparent oral clearance values for phenacetin did not differ between the two groups (geometric means: 3.4 micrograms/ml and 1.56 ml h-1 kg-1, respectively, for Caucasians vs. 4.7 micrograms/ml and 1.25 ml h-1 kg-1, respectively, for Chinese, after excluding one Caucasian with aberrantly low plasma phenacetin values). Pharmacokinetic parameters for metabolically derived paracetamol were also similar in the two groups. When subjects were divided into subgroups according to gender, phenacetin apparent oral clearance values were found to be lower in Chinese women compared with both Chinese men and Caucasian subjects of either sex. It is concluded that there are no major interethnic differences in the expression of CYP1A2-related activity between Caucasians and Chinese, although Chinese women as a subgroup may exhibit comparatively lower enzyme activity.

The effect of fluvoxamine on the pharmacokinetics of diazepam and metabolically derived N-desmethyl-diazepam was investigated in eight healthy volunteers. Each subject received a single oral dose of diazepam (10 mg) in a control session and on the fourth day of a 16-day treatment with fluvoxamine maleate (100 to 150 mg daily). Compared with the control session, concurrent fluvoxamine intake was associated with increased mean peak plasma diazepam concentrations (from 108 to 143 ng/ml, geometric means, difference not significant), with a marked reduction in apparent oral diazepam clearance (from 0.40 to 0.14 ml/min/kg; p < 0.01) and with a prolongation in diazepam half-life (from 51 to 118 hours; p < 0.01). Although peak plasma N-desmethyldiazepam levels were similar in the two sessions, the time required for the metabolite to reach a peak was longer during fluvoxamine intake than in the control session (206 versus 62 hours; p < 0.01). N-Desmethyldiazepam area under the plasma concentration-time curve values were also significantly increased during fluvoxamine treatment. These data suggest that fluvoxamine inhibits the biotransformation of diazepam and its active N-demethylated metabolite. The magnitude of this interaction is likely to have considerable clinical significance.

The forensic interest in the use of food colours is related to health rights and safeguard of the consumer, as established in national legislations. The regulations related to food dyes consider the health of human beings and the adulteration of foodstuffs and economic needs connected with quantitative restrictions on imports. Efficient analytical methods are required for evaluating toxicity and authenticity or adulteration, in order (a) to determine whether there are synthetic dyes present in foods and whether they are permitted, (b) to determine the levels, (c) to confirm the absence of added dyes in foods where they are not declared and (d) to check on the stability of dyes during processing and storage. Recent HPLC methods for the identification and determination of natural and synthetic dyes and of carcinogenic amines contained as impurities in synthetic dyes are reviewed.

Omeprazole has been reported to increase cytochrome P450IA2 (CYP1A2) activity in vitro, but whether this effect also occurs in vivo is controversial. To clarify this issue, the effect of omeprazole (20 mg/day for 8 days) on the kinetics and metabolism of phenacetin, an in vivo marker of CYP1A2 activity, was examined in 10 healthy volunteers. The pharmacokinetic parameters of phenacetin and metabolically derived paracetamol on the 8th day of omeprazole administration were very similar to those observed in a control session in the absence of omeprazole administration, the only significant difference being a higher peak plasma phenacetin concentration during omeprazole treatment. It is concluded that at the dosage used omeprazole does not increase the rate of oxidative and conjugative reactions involved in the metabolism of phenacetin and paracetamol respectively. These data are consistent with the hypothesis that omeprazole is generally devoid of inducing effects on CYP1A2 activity in vivo, at least in a Caucasian population with a low prevalence of the omeprazole-mephenytoin poor metabolizer phenotype.

Eighteen myasthenic patients have been operated on under general anaesthesia; 14 subjected to thymectomy and 2 to emergency procedures (caesarean section and laparotomy because of intestinal obstruction). Atracurium (0.3 mg/kg) and vecuronium (0.06 mg/kg) exhibited a long duration of action only in the two cases affected by the more severe signs and symptoms of the disease.

We calculated the annual noise dose absorbed by machine drivers engaged in wine and cereal growing. In order to do that it has been measured the average daily noise dose in the various mechanized operations and then calculated in respect of its duration in a working year. The days spent in manual works were also taken in account. The annual dose of noise became somewhat higher than 90 dB(A) in wine growing, while in cereal growing it was a bit higher than 95 dB(A). The reliability of these data was confirmed by an epidemiological study of hearing damage. In 106 tractor-drivers, employed in farms where wine and cereal growings are done, it was found that the hearing threshold shift due to noise (average 1000-2000-4000 Hz) in relation to the years of employment, had a similar course to that forecasted by the Normative ISO-DIS 1999 in those exposed to a noise dose of 95 dB(A).

The bronchodilator response to inhaled fenoterol (400 micrograms) was examined in the morning and in the afternoon before and during oral sustained-release aminophylline treatment in eight patients with chronic reversible airway obstruction. Bronchodilatation was evaluated by measuring serial peak expiratory flow rates (PEFR) for eight hours after inhaled fenoterol and calculating the area under the time-response curves and the percentage increment from the baseline values. The patients showed an enhancement of the bronchodilatation achieved with fenoterol in the morning during aminophylline treatment. In the afternoon, instead, the effect of the fenoterol was not improved by oral aminophylline. This different effect of oral aminophylline might depend on the variable degree of potential reversibility present or diurnal variation in the bronchial response.