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In the frame of Earth observation remote-sensing data analysis, synergistic retrieval (SR) and complete data fusion (CDF) are techniques used to exploit the complementarity of the information carried by different measurements sounding the same air mass and/or ground pixel. While more difficult to implement due to the required simultaneous access to measurements originating from different instruments, the SR method is sometimes preferred over the CDF method as the latter relies on a linear approximation of the retrieved states as functions of the true atmospheric and/or surface state. In this work, we study the performance of the SR and CDF techniques when applied to simulated measurements of the Far-infrared Outgoing Radiation Understanding and Monitoring (FORUM) and the Infrared Atmospheric Sounding Interferometer – New Generation (IASI-NG) missions that will be operational in a few years, from two polar-orbiting satellites. The study is based on synthetic measurements generated for the two missions in clear-sky atmospheres. The target parameters of the inversion are the vertical profiles of temperature, water vapor and ozone mixing ratios, surface temperature, and spectral emissivity. We find that for exact matching of the measurements, the results of the SR and CDF techniques differ by less than 1/10 of their errors estimated through the propagation of measurement noise. For measurements with a realistic mismatch in space and time, the two methods provide more different results. Still in this case, however, the differences between the results are within the error bars due to measurement noise. We conclude that, when applied to FORUM and IASI-NG missions, the two methods are equivalent from an accuracy point of view.

The new platforms for Earth observation from space are characterized by measurements made at great spatial and temporal resolutions. While this abundance of information makes it possible to detect and study localized phenomena, it may be difficult to manage this large amount of data for the study of global and large-scale phenomena. A particularly significant example is the use by assimilation systems of Level 2 products that represent gas profiles in the atmosphere. The models on which assimilation systems are based are discretized on spatial grids with horizontal dimensions of the order of tens of kilometres in which tens or hundreds of measurements may fall in the future. A simple procedure to overcome this problem is to extract a subset of the original measurements, but this involves a loss of information. Another option is the use of simple averages of the profiles, but this approach also has some limitations that we will discuss in the paper. A more advanced solution is to resort to the so-called fusion algorithms, capable of compressing the size of the dataset while limiting the information loss. A novel data fusion method, the Complete Data Fusion algorithm, was recently developed to merge a set of retrieved products in a single product a posteriori. In the present paper, we apply the Complete Data Fusion method to ozone profile measurements simulated in the thermal infrared and ultraviolet bands in a realistic scenario. Following this, the fused products are compared with the input profiles; comparisons show that the output products of data fusion have smaller total errors and higher information contents in general. The comparisons of the fused products with the fusing products are presented both at single fusion grid box scale and with a statistical analysis of the results obtained on large sets of fusion grid boxes of the same size. We also evaluate the grid box size impact, showing that the Complete Data Fusion method can be used with different grid box sizes even if this possibility is connected to the natural variability of the considered atmospheric molecule.

When the complete data fusion method is used to fuse inconsistent measurements, it is necessary to add to the measurement covariance matrix of each fusing profile a covariance matrix that takes into account the inconsistencies. A realistic estimate of these inconsistency covariance matrices is required for effectual fused products. We evaluate the possibility of assisting the estimate of the inconsistency covariance matrices using the value of the cost function minimized in the complete data fusion. The analytical expressions of expected value and variance of the cost function are derived. Modelling the inconsistency covariance matrix with one parameter, we determine the value of the parameter that makes the reduced cost function equal to its expected value and use the variance to assign an error to this determination. The quality of the inconsistency covariance matrix determined in this way is tested for simulated measurements of ozone profiles obtained in the thermal infrared in the framework of the Sentinel-4 mission of the Copernicus programme. As expected, the method requires sufficient statistics and poor results are obtained when a small number of profiles are being fused together, but very good results are obtained when the fusion involves a large number of profiles.

Abstract Background Over the years it has been widely stated that approximately one-third of asthmatic women experience worsening of the disease during pregnancy. However, the literature has not been reviewed systematically and the meta-analytic reviews include old studies. This study aimed to examine whether the prevalence of worsening asthma during pregnancy is still consistent with prior estimate or it has been reduced. Methods A detailed Clinical Questionnaire on respiratory symptoms, medical history, medication, use of services, occupation, social status, home environment and lifestyle was administered to random samples of the Italian population in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Only clinical data belong to 2.606 subjects that completed the clinical stage of the GEIRD study, were used for the present study. Results Out of 1.351 women, 284 self-reported asthma and 92 of them had at least one pregnancy. When we considered the asthma course during pregnancy, we found that 16 women worsened, 31 remained unchanged, 25 improved. Seven women had not the same course in the different pregnancies and 13 did not know. The starting age of ICS use almost overlaps with that of asthma onset in women with worsening asthma during pregnancy (19 years ± 1.4), unlike the other women who started to use ICS much later (30.3 years ± 12). In addition, the worsening of asthma was more frequent in women with an older age of onset of asthma (18 years ± 9 vs 13 years ± 10). Among women who completed the ACT during the clinical interview, the 50% of women who experienced worsening asthma during pregnancy (6/12) had an ACT score below 20. Conclusion Asthma was observed to worsen during pregnancy in a percentage much lower to that generally reported in all the previous studies. There is still room in clinical practice to further reduce worsening of asthma during pregnancy by improving asthma control, with a more structured approach to asthma education and management prepregnancy.

The complete data fusion (CDF) method is applied to ozone profiles obtained from simulated measurements in the ultraviolet and in the thermal infrared in the framework of the Sentinel 4 mission of the Copernicus programme. We observe that the quality of the fused products is degraded when the fusing profiles are either retrieved on different vertical grids or referred to different true profiles. To address this shortcoming, a generalization of the complete data fusion method, which takes into account interpolation and coincidence errors, is presented. This upgrade overcomes the encountered problems and provides products of good quality when the fusing profiles are both retrieved on different vertical grids and referred to different true profiles. The impact of the interpolation and coincidence errors on number of degrees of freedom and errors of the fused profile is also analysed. The approach developed here to account for the interpolation and coincidence errors can also be followed to include other error components, such as forward model errors.

Surface reflectance has a central role in the analysis of land surface for a broad variety of agricultural, geological and urban studies. An accurate atmospheric correction, obtained by an appropriate selection of aerosol type and loading, is the first requirement for a reliable surface reflectance estimation. The aerosol type is defined by its micro-physical properties, while the aerosol loading is described by optical thickness at 550 nm. The aim of this work is to evaluate the radiative impact of the aerosol model on the surface reflectance obtained from CHRIS (Compact High Resolution Imaging Spectrometer) hyperspectral data over land by using the specifically developed algorithm CHRIS@CRI (CHRIS Atmospherically Corrected Reflectance Imagery) based on the 6SV radiative transfer model. Five different aerosol models have been used: one provided by the AERONET inversion products (used as reference), three standard aerosol models in 6SV, and one obtained from the output of the GEOS-Chem global chemistry-transport model (CTM). As test case the urban site of Bruxelles and the suburban area of Rome Tor Vergata have been considered. The results obtained encourages the use of CTM in operational retrieval and provides an evaluation of the role of the aerosol model in the atmospheric correction process, considering the different microphysical properties impact.

Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. Methods: The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. Results: The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months ( p < 0.001) and at 1 year ( p = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses ( p < 0.05). Conclusions: ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated.

Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described., Competing Interests: The authors declare no conflicts of interest.

Niemann-Pick Disease (NPD) is a rare autosomal recessive disease belonging to lysosomal storage disorders. Three types of NPD have been described: NPD type A, B, and C. NPD type A and B are caused by mutations in the gene SMPD1 coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase activity. These diseases have been thus classified as acid sphingomyelinase deficiencies (ASMDs). NPD type C is a neurologic disorder due to mutations in the genes NPC1 or NPC2 , causing a defect of cholesterol trafficking and esterification. Although all three types of NPD can manifest with pulmonary involvement, lung disease occurs more frequently in NPD type B, typically with interstitial lung disease, recurrent pulmonary infections, and respiratory failure. In this sense, bronchoscopy with broncho-alveolar lavage or biopsy together with high-resolution computed tomography are fundamental diagnostic tools. Although several efforts have been made to find an effective therapy for NPD, to date, only limited therapeutic options are available. Enzyme replacement therapy with Olipudase α is the first and only approved disease-modifying therapy for patients with ASMD. A lung transplant and hematopoietic stem cell transplantation are also described for ASMD in the literature. The only approved disease-modifying therapy in NPD type C is miglustat, a substrate-reduction treatment. The aim of this review was to delineate a state of the art on the genetic basis and lung involvement in NPD, focusing on clinical manifestations, radiologic and histopathologic characteristics of the disease, and available therapeutic options, with a gaze on future therapeutic strategies.

Background: Severe alpha1-antitrypsin (AAT) deficiency (AATD) is associated with a high risk of airflow obstruction and emphysema. The risk of lung disease in those with intermediate AAT deficiency is unclear. Our aims were to compare pulmonary function, time of onset of symptoms, and indicators of quality of life among patients with severe AATD (PI*ZZ), patients with intermediate AATD (PI*MZ) from the Italian Registry of AATD with a chronic obstructive pulmonary disease (COPD) cohort of patients without AATD (PI*MM)., Methods: We considered a total of 613 patients: 330 with the PI*ZZ genotype, 183 with the PI*MZ genotype and 100 with the PI*MM genotype. Radiological exams, pulmonary function test, and measurement of quality of life have been performed on all cohorts of patients., Results: The three populations differ significantly in terms of age at COPD/AATD diagnosis (P=0.00001), respiratory function (FEV1, FVC, DLCO P<0.001), quality of life (P=0.0001) and smoking history (P<0.0001). PI*ZZ genotype had 24.9 times a higher likelihood of developing airflow obstruction. The MZ genotype is not associated with a significant early risk of airflow obstruction., Conclusions: The comparison of populations with PI*ZZ, MZ and MM genotypes allows to delineate the role of alpha1-antitrypsin deficiency on respiratory function and on the impact on quality of life, in relation to other risk factors. These results highlight the crucial role of primary and secondary prevention on smoking habits in PI*MZ subjects and the importance of an early diagnosis.

Background: Positive microbiological fungal culture from bronchoalveolar-lavage-fluid (BAL) for Aspergillus or tissue biopsy and the detection of high levels of Aspergillus Galactomannan (GM) are commonly considered standard for diagnosing Invasive Pulmonary Aspergillosis (IPA). However, Aspergillus infection induces both cellular and humoral immune responses, characterized by the production of specific immunoglobulins, which can be easily detected in serum and accurately measured. This study hypothesized that Aspergillus-specific IgE, IgG, including IgG4, assays could be adopted as a rapid preliminary screening tool in patients with suspected Aspergillus-related lung disease in order to help in the identification of patients who require more invasive procedures (bronchoscopy, biopsy)., Methods: We prospectively stored 447 serum specimens of patients admitted for suspected IPA from 1 January 2010 to 31 July 2021. Serum total IgE and serum IgE, IgG and IgG4 specific for Aspergillus fumigatus and Aspergillus niger were determined for each sample. In addition, bronchoscopy with BAL for microbiologic culture and Aspergillus Galactomannan (GM) antigen were performed in all patients., Results: Patients with IPA, diagnosed by detection of a positive BAL culture for Aspergillus and/or a positive GM, showed higher serum levels of specific Aspergillus fumigatus and Aspergillus niger immunoglobulins. Serum-specific Aspergillus fumigatus IgG at a cut-off of 22.6 mgA/L showed the highest sensitivity in predicting IPA, though quite moderate (AUC 0.62). Nonetheless, the simultaneous presence of values below the cut-off of Aspergillus IgE, IgG and IgG4 showed a negative predictive value greater than 90% both towards positive BAL culture and positive GM., Conclusions: In patients with suspected IPA, Aspergillus-specific immunoglobulins assay could be tested as a preliminary screening tool to support more invasive procedures, i.e. BAL.

Background: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19., Methods: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled., Results: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer., Conclusion: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home., (© 2023. The Author(s).)

Background: Chronic cough is a common symptom, addressed in the clinical setting by empirical treatment together with some laboratory investigations. The aim of the present study was to investigate the value of testing eosinophilic cationic protein (ECP) serum levels combined with other diagnostic procedures and empirical treatment in the diagnostic workup of chronic cough., Methods: In this study, we evaluated 194 patients with chronic cough. No subject had received any anti-inflammatory treatment before clinical evaluation, and none was an active smoker. ECP was measured with a commercially available fluoroenzyme immunoassay and results were expressed as µg/L., Results: The analysis of variance showed that mean ECP level differs among the various diagnosis categories (P<0.001). Mean ECP level was significantly higher in asthmatic patients, particularly in the active disease., Conclusions: Serum ECP concentration could represent a useful biomarker in the clinical work-up of chronic cough, managing to differentiate asthma from other chronic disorders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 19 (COVID-19). COVID-19 can manifest with a heterogenous spectrum of disease severity, from mild upper airways infection to severe interstitial pneumonia and devastating acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection may induce an over activation of the immune system and the release of high concentrations of pro-inflammatory cytokines, leading to a "cytokine storm", a recognized pathogenetic mechanism in the genesis of SARS-CoV-2-induced lung disease. This overproduction of inflammatory cytokines has been recognized as a poor prognostic factor, since it can lead to disease progression, organ failure, ARDS and death. Moreover, the immune system shows dysregulated activity, particularly through activated macrophages and T-helper cells and in the co-occurrent exhaustion of lymphocytes. We carried out a non-systematic literature review aimed at providing an overview of the current knowledge on the pathologic mechanisms played by the immune system and the inflammation in the genesis of SARS-CoV-2-induced lung disease. An overview on potential treatments for this harmful condition and for contrasting the "cytokine storm" has also been presented. Finally, a look at the experimented experimental vaccines against SARS-CoV-2 has been included.

Idiopathic pulmonary fibrosis (IPF) is a rare disease of the lung with a largely unknown etiology and a poor prognosis. Intriguingly, forms of familial pulmonary fibrosis (FPF) have long been known and linked to specific genetic mutations. There is little evidence of the possible role of genetics in the etiology of sporadic IPF. We carried out a non-systematic, narrative literature review aimed at describing the main known genetic and epigenetic mechanisms that are involved in the pathogenesis and prognosis of IPF and FPF. In this review, we highlighted the mutations in classical genes associated with FPF, including those encoding for telomerases ( TERT , TERC , PARN , RTEL1 ), which are also found in about 10-20% of cases of sporadic IPF. In addition to the Mendelian forms, mutations in the genes encoding for the surfactant proteins ( SFTPC , SFTPA1 , SFTPA2 , ABCA3 ) and polymorphisms of genes for the mucin MUC5B and the Toll-interacting protein TOLLIP are other pathways favoring the fibrogenesis that have been thoroughly explored. Moreover, great attention has been paid to the main epigenetic alterations (DNA methylation, histone modification and non-coding RNA gene silencing) that are emerging to play a role in fibrogenesis. Finally, a gaze on the shared mechanisms between cancer and fibrogenesis, and future perspectives on the genetics of pulmonary fibrosis have been analyzed.

Despite low rates of bacterial co-infections, most COVID-19 patients receive antibiotic therapy. We hypothesized that patients with positive pneumococcal urinary antigens (PUAs) would benefit from antibiotic therapy in terms of clinical outcomes (death, ICU admission, and length of stay). The San Matteo COVID-19 Registry (SMACORE) prospectively enrolls patients admitted for COVID-19 pneumonia at IRCCS Policlinico San Matteo, Pavia. We retrospectively extracted the data of patients tested for PUA from October to December 2020. Demographic, clinical, and laboratory data were recorded. Of 469 patients, 42 tested positive for PUA (8.95%), while 427 (91.05%) tested negative. A positive PUA result had no significant impact on death (HR 0.53 CI [0.22-1.28] p -value 0.16) or ICU admission (HR 0.8; CI [0.25-2.54] p -value 0.70) in the Cox regression model, nor on length of stay in linear regression (estimate 1.71; SE 2.37; p -value 0.47). After adjusting for age, we found no significant correlation between urinary antigen positivity and variations in the WHO ordinal scale and laboratory markers at admission and after 14 days. We found that a positive PUA result was not frequent and had no impact on clinical outcomes or clinical improvement. Our results did not support the routine use of PUA tests to select COVID-19 patients who will benefit from antibiotic therapy.

Niemann-Pick Disease type B (NPDB) is a rare autosomal recessive disease belonging to the family of lysosomal storage disorders. NPDB is caused by mutations of sphingomyelin phosphodiesterase 1 gene (SMPD1) and is characterized by hepatosplenomegaly, interstitial lung disease, recurrent pulmonary infections, and neurologic disorders. Bronchiectasis are atypical. Until now, only three cases of lung transplantation for severe respiratory impairment have been reported. We describe a case of NPDB that was diagnosed after lung transplantation for cystic bronchiectasis. In 2016, a 31-year-old woman who was experiencing hypoxemic respiratory failure and recurrent pulmonary infections due to cystic bronchiectasis received a double-lung-transplantation. Histopathologic study on removed lungs revealed clusters of CD68 foamy lipid-laden macrophages with concentric and palisade arrangement, compatible with the diagnosis of NPDB, which was confirmed after SMPD1 genetic sequencing. Twenty-three months after transplantation, allograft function is stable (FEV 1 was 100% of best-FEV 1 ). The singularity of this case lies in the presence of bronchiectasis, which is an unprecedently described phenotype of NPDB. This finding was accompanied by the detection of a novel SMPD1 mutation (p.Ala46=) of uncertain meaning., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis., (Copyright © 2020 Tirelli, Morandi, Valentini, La Carrubba, Dore, Zanframundo, Morbini, Grignaschi, Franconeri, Oggionni, Marasco, De Stefano, Kadija, Mariani, Codullo, Alpini, Scirè, Montecucco, Meloni and Cavagna.)

Background: Over the years it has been widely stated that approximately one-third of asthmatic women experience worsening of the disease during pregnancy. However, the literature has not been reviewed systematically and the meta-analytic reviews include old studies. This study aimed to examine whether the prevalence of worsening asthma during pregnancy is still consistent with prior estimate or it has been reduced., Methods: A detailed Clinical Questionnaire on respiratory symptoms, medical history, medication, use of services, occupation, social status, home environment and lifestyle was administered to random samples of the Italian population in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Only clinical data belong to 2.606 subjects that completed the clinical stage of the GEIRD study, were used for the present study., Results: Out of 1.351 women, 284 self-reported asthma and 92 of them had at least one pregnancy. When we considered the asthma course during pregnancy, we found that 16 women worsened, 31 remained unchanged, 25 improved. Seven women had not the same course in the different pregnancies and 13 did not know. The starting age of ICS use almost overlaps with that of asthma onset in women with worsening asthma during pregnancy (19 years ± 1.4), unlike the other women who started to use ICS much later (30.3 years ± 12). In addition, the worsening of asthma was more frequent in women with an older age of onset of asthma (18 years ± 9 vs 13 years ± 10). Among women who completed the ACT during the clinical interview, the 50% of women who experienced worsening asthma during pregnancy (6/12) had an ACT score below 20., Conclusion: Asthma was observed to worsen during pregnancy in a percentage much lower to that generally reported in all the previous studies. There is still room in clinical practice to further reduce worsening of asthma during pregnancy by improving asthma control, with a more structured approach to asthma education and management prepregnancy.

To analyze how food values and other variables related to dietary acculturation affect international university students' food buying decisions, this article provides an in-depth review of relevant literature related to the food buying decisions of groups of sojourners, which suggest several research hypotheses. The data collection targeted international university students in Spain and used factorial analysis of the main components together with linear parametric regressions. The resulting findings offer distinct insights, according to sojourners' continent of origin. Specifically, whereas European students exhibit a higher propensity to value sustainable production practices in the food choices, American students emphasize flavor and exhibit a greater degree of adaptation. These findings in turn suggest some key managerial recommendations and research guidelines for both private and public operators in related fields., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Considering the clinical benefit of trastuzumab in advanced breast cancer, fi ve prospective adjuvant randomized trials have recently been completed and early results have been published. Two of them, (NSABP-B31 and NCCTG N9831), employed anthracycline-containing regimens with sequential paclitaxel, with or without trastuzumab. The third study, HERA trial, randomized patients after adjuvant chemotherapy into an observational arm, one or two years of trastuzumab. Results of these studies, after a median follow up of 2-3 years confirm a DFS and OS benefit for the experimental arms. The worst rate of cardiotoxicity, in terms of incidence of CHF, with the use of trastuzumab and anthracycline based regimens was 4.1% in the trastuzumab arm of the NSABP-B31 trial. Among the fi ve trastuzumab trials, two, BCIRG 006 and FinHer, employed docetaxel-based regimens. The innovative BCIRG 006 trial compared ACdocetaxel (T) with two trastuzumab-containing regimens, ACTH, and a non-anthracycline-containing regimens, TCH, with a clear advantage in DFS for both trastuzumab arms. Data from the second interim analysis indicate that, in the subgroup of patients without co-amplification of topoisomerase 2 (TOPO-2), the arm without trastuzumab (ACT) showed a DFS significantly poorer that in the other arms; moreover, if we consider the lower toxicity of TCH regimen in comparison with anthracycline-containing arms, the innovative statements offered by BCIRG 006 trial appear evident, and these findings opened an important question about the consolidated employment of anthracyclines in adjuvant setting.The FinHer trial was a small trial testing a short course of trastuzumab (9 weeks) concomitantly with a chemotherapy including docetaxel, and there was a significant advantage in DFS for the trastuzumab based arms, without relevant toxicity and without any cardiotoxicity. Although data from all trastuzumab adjuvant trials, and without particulary from BCIRG-006 and FinHer trials, appear very intriguing, further follow-up is required.

The role of sentinel lymph node biopsy (SLNB) in pT1a and "microinvasive" breast cancer has not been extensively studied. We report our experience with SLNB in patients with "minimal" breast cancer to determine the incidence and type of SLN metastases, and to study the potential impact on their surgical or oncological management. Among some 3387 women operated upon for primary breast cancer who underwent sentinel lymph node biopsy at nine institutions participating in the Rome Breast Cancer Study Group, 251 were staged pT1a or pT1mic (7.4%). There were 13 cases of sentinel lymph node metastases identified in this group of patients (5.2%), seven macrometastases and six micrometastases. Additionally, ITC were diagnosed by immunohistochemistry in four cases (1.6%). The incidence of SLN metastases was 7/174 (4%) and 6/77 (7.8%) in patients with pT1a and pT1mic tumors, respectively (p=0.2). Age and histological grade were predictive factors for SLN metastases. Chemotherapy was seldom directed by axillary node status (8/38 patients). As the incidence of SLN metastases in these patients is very small, particularly in the pT1a group, the indications for even a minimally invasive procedure, such as sentinel lymph node biopsy, should be probably individualized.

Background and Objectives: Breast-conserving treatment (BCT) is the elective approach to early stage breast cancer. We report on our 24 years of experience., Methods: Between 1975 and 1998, 980 conservative surgical procedures in 962 patients for limited-sized infiltrating breast cancer (T1 to "small" T2, N0-N1, M0) were performed. BCT consisted of a local wide excision, axillary dissection and postoperative radiation therapy to the entire breast (50 Gy). An adjuvant systemic treatment (chemo- and/or hormonotherapy) was administered to the large majority of patients. Data on age, menopausal status, histologic subtype of tumor, quadrant site of cancer, tumor size (Tla, T1b, T1c, or T2), axillary nodal status (N- or N+, with involvement of 1-3 nodes, or more), and follow-up were stored for each patient. Overall, N+ patients constituted 29.2% of the total number. Survival data were analyzed using the Berkson-Gage actuarial method., Results: The 15-year overall and disease-free survival rates were 72% and 67%, respectively. Nevertheless, the more interesting results concern survival rates in relation to T and N parameters. T-related survival showed a sharp distinction among the subgroups T1a + T1b and T1c, with values of 90% for the former versus 62% for the latter. Even more significative results were achieved by comparing N with survival. In fact, it was 84% for N-patients and 31% for N+ patients; for N+ patients, outcome was poor for the subgroup showing an involvement of more than 3 nodes, with no patient surviving at 15 years. None of the other evaluated parameters proved to be related to survival. The validity of our protocol is confirmed by the low number of local relapses: only 33 (3.4%) of 980 total treated cases. Cosmetic results were excellent or good in a high percentage of patients (>80%)., Conclusions: These results unquestionably confirm the validity of BCT, provided certain prerequisites are fulfilled.

Sexual dysfunction after colorectal cancer surgery may be severe and occurs in 25% to 100% of cases. Thirty-eight patients underwent colorectal resection; eight (21%) who were totally impotent and two (5%) who had ejaculatory failure were therefore studied to better understand the neurophysiological alterations related to this type of surgery. The patients were evaluated after surgery with electrophysiological testing, including examination of the sacral reflex (SR), pudendal somatosensory evoked potential (PEP), and motor evoked potential (MEP) responses. Sudomotor skin response (SSR) was also studied in a group of patients. Of the 38 patients studied, 29 showed abnormalities: six of SR, three of PEP, six of MEP, and fourteen of SSR. Only a combination of all these tests permits correct evaluation of the sexual dysfunction.

N-Acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase were measured in the serum of 70 patients with breast and digestive-tract neoplasms and in 70 healthy subjects. The mean value of the NAG activity was significantly (P < 0.001) elevated in patients with gastric, liver and pancreas cancer as compared with the reference population. In patients with liver and pancreas cancer the very high sensitivity contrasted with a low specificity. NAG elevations above normal were observed in 14 (78%) patients with breast cancer, in 11 (100%) with gastric cancer, in 17 (70%) with colorectal cancer, in 8 (100%) with liver cancer and in 9 (100%) with pancreas cancer. In patients with breast and gastric cancer the enzyme shows a good specificity and sufficient sensitivity as a tumor marker. beta-Glucuronidase appeared less sensitive and was significantly elevated (100%) only in patients with pancreas cancer.

Unlabelled: We herein present a study conducted on 14 patients presenting cancer of the lower rectum or of the anal canal (10 adenocarcinomas and 4 squamous-cell carcinomas) and submitted to the Miles abdominal perineal resection in which a new perineal sphincter was constructed., Purpose: The aim of this study was to evaluate the efficacy of this new perineal sphincter constructed by transposing the gracilis muscles around an orthotopic colostomy in the attempt to avoid a permanent abdominal colostomy., Methods: In all cases both gracilis muscles were employed. The right one was placed along the posterior wall of the pelvis and fixed to the contralateral ischiatic tuberosity, creating a sling comparable to the levator ani muscles. The left gracilis was passed around the colon and attached to the ipsilateral or contralateral tuberosity according to its length, reconstructing a muscular ring. The entire procedure was performed in one step in nine cases and in more steps in the remaining five., Results: Of the 14 operated patients, 2 died of vascular disease and 1 developed necrosis of the colonic stump which required reconversion to an abdominal colostomy. Of the remaining 11 patients available for long-term evaluations, 8 showed adequate stool control. The remaining three manifested an incomplete level of continence. During the three-year follow-up period, all patients were evaluated by clinical examination, defecography, endoluminal ultrasonography, nuclear magnetic resonance, CT scan, and endoluminal manometry., Conclusion: This neosphincter realizes an elastic stenosis responsible for an efficient level of continence. Best results are observed in the young and educated patients submitted to surgery in two steps. Contraindications to this surgery seem to be advanced cancer, old age, and obesity.

Alanine aminopeptidase (AAP), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) were measured in 40 patients with breast and thyroid cancer and in 40 patients suffering from benign tumors and benign noninflammatory diseases. AAP activity was significantly increased (P < 0.001) in all cancer patients considered together. TPA shows a remarkable diagnostic sensitivity but a low specificity. For CEA an inverse situation is observed. Evaluation of the predictive value of the assay of AAP revealed a sufficient sensitivity, a good specificity, a sufficient predictive value of both positive and negative results, and a good efficiency. We believe that the test, if supported by other information, can be useful in the diagnosis of breast and thyroid cancer.

Serum values of retinol, carotenoids, tocopherol and ascorbic acid were assayed in healthy adult females (Group A: 20 cases) and in subjects with fibrocistic mastopathy (Group B: 20 cases), benign breast neoplasms, as fibroadenomas and intraductal papillomas (Group C: 18 cases), and breast carcinoma in situ (Group D: 36 cases). Retinol and carotenoids were evaluated by spectrophotometry using trifluoroacetic acid. Tocopherol was determined by a colorimetric method involving the reduction of Fe to Fe++ by tocopherol with the formation of a red complex of the Fe++ with alpha, alpha'-dipirydyl. Ascorbic acid was estimated by a colorimetric method after derivatization with 2,4-dinitrophenylhydrazine. Our results point out that there is a highly significant decrease (p less than 0.001) of average retinol serum levels in all three patient groups as compared with group A, whereas carotenoids resulted decreased but not significantly. Tocopherol was found to be significantly lower only in groups B (p less than 0.05) and D (p less than 0.01), ascorbic acid in groups B (p less than 0.01) C (p less than 0.05) and D (p less than 0.001).