Pervasive refusal syndrome or anorexia nervosa: a case report with a successful behavioural treatment.

PURPOSE: Pervasive refusal syndrome (PRS) is a rare psychiatric disease that affects children. It was first described by Lask in 1991 (Arch Dis Child 66:866-869, 1991). Recently, Otasowie and Collaborators reported a systematic review about PRS. Despite this, PRS has not yet been classified in DSM-5 and ICD-11 and the lack of evidence-based treatment makes this syndrome a real challenge for clinicians. The aim of this paper is to present our experience through the description of a case report and its treatment. METHODS AND RESULTS: The case reported is a girl aged 11 years that fits the clinical picture described in the literature of PRS. In previous reports, behavioural treatment was not used or appreciated; our case adds new knowledge regarding the PRS diagnosis and the successful behavioural treatment during hospitalization, which we describe in all its phases. CONCLUSION: PRS is a rare, life-threatening syndrome; it would be extremely important to have an official and evidence-based treatment guide. LEVEL OF EVIDENCE: Level V, case report.

Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). METHODS: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. RESULTS: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. CONCLUSIONS: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Design and conduct of early clinical studies of immunotherapy agent combinations: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies.

The Methodology for the Development of Innovative Cancer Therapies task force considered aspects of the design and conduct of early studies of combinations of immunotherapy agents during their 2018 meeting. The task force defined the relevant data to justify combination clinical trials, which includes a robust hypothesis for the combination, pre-clinical data with evidence of efficacy and an understanding of the pharmacodynamics effects of each agent, and ideally evidence of single agent activity. Evaluation of pharmacodynamic biomarkers is critical in early phase combination trials, and should be incorporated into trial objectives and go/no-go decisions. The task force also identified the need to develop assessment tools and end points that capture the unique patterns of tumour responses to immunotherapy, including pseudoprogression and hyperprogression. At least one additional tumour measurement before baseline and an early CT scan (at 4 weeks for example) would help define the incidence of hyperprogression, although a common definition is needed. Finally, the task force highlighted substantial redundancy and inefficiency in the combination immunotherapy space, and recommended the adoption of innovative trial designs.

Pomological Traits, Sensory Profile and Nutraceutical Properties of Nine Cultivars of Loquat (Eriobotrya japonica Lindl.) Fruits Grown in Mediterranean Area.

In this paper the diversity of fruit quality within nine loquat cultivars, including five international affirmed cultivars (Algerie, Golden Nugget, Peluche, Bueno, El Buenet) and four local cultivars (Sanfilippara, Nespolone di Trabia, BRT20 and Claudia), were investigated in order to discriminate the variation in pomological characteristics, sensory profile, and antioxidant properties. Finally, to evaluate potential bioactivity, antiproliferative activity of hydrophilic extracts from loquat fruits was assessed, at dietary relevant concentrations, against three human epithelial cell lines. Even though the international cultivars confirmed an appropriate level of commercial qualities in association to high levels in antioxidant compounds, the local cultivars revealed the best performances in a wide range of chemical-physical and sensory characteristics. Concerning bioactivity, our results indicate that hydrophilic extracts from all tested cultivars showed concentration-dependent antiproliferative activity with a significant variability of effects between different cell lines and between different cultivars. HeLa cells, the most sensitive and hydrophilic extracts from Peluche, showed the highest inhibitory effect followed by Nespolone di Trabia and Claudia. The results of this trial provide useful information on the pomological traits and the not yet known specific nutritional and functional properties of loquat fruits. Our data, besides helping to promote specific local cultivars, could serve to establish a database that will permit to improve the utilization of specific genetic resources in breeding programs.

Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1ß-exposed human intestinal epithelial cells.

BACKGROUND: Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains substantial amounts of proanthocyanidins and possesses anti-inflammatory activities. PURPOSE: We studied the effects of HPE and of its polymeric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1ß-stimulated Caco-2 cells. METHODS: HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatography. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1ß. Cell viability and parameters associated with nuclear factor-κB (NF-κB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements. RESULTS: HPE decreased prostaglandin (PG)E2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-κB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable to HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers. CONCLUSION: Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-κB activation and occurs in parallel with the adsorption of polymeric proanthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert beneficial effects to gastrointestinal pathophysiology.

Laparoscopic versus laparotomic approach to endometrial cancer.

OBJECTIVE: The aim of our study was to compare the feasibility, morbidity, long-term safety, disease-free survival, and overall survival of the laparoscopic (LPS) approach to early-stage endometrial cancer (EC) compared to the traditional laparotomic approach. METHODS: We reviewed retrospective data of patients who underwent primary surgery from 1997 to 2009. We recorded clinical parameters, surgical stage, histological type, operative and peri-operative complications, time to resumption of normal functions, conversion to laparotomy, overall survival, and disease-free survival. RESULTS: LPS, did not increase operative risk and peri-operative complications even in obese and older women. The number of pelvic lymph and aortic nodes removed was similar for the two groups. One hundred and eight patients had a follow-up of 60 months. The two groups were similar for disease-free survival and overall survival. CONCLUSIONS: Laparoscopic approach to EC provides a reduction in postoperative complications and hospital stay compared to the laparotomic approach.

Cystic fibrosis Δf508 mutation screening in Brazilian women with altered fertility.

Cystic Fibrosis (CF) is an autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator gene (CFTR). The most frequent mutation in CF is ΔF508. The disease is clinically characterized by elevated concentrations of sweat chlorides and abnormally thick mucus. It affects organs such as lung, pancreas, gastrointestinal and reproductive tract. Women with CF commonly present delayed puberty and amenorrhea due to malnutrition. Our objective was to screen the presence of ΔF508 mutation in 24 women with altered fertility. Nine of these women presented reduced fertility without a known cause, four showed polycystic ovaries and two had early menopause. One woman with early menopause was a carrier of the ΔF508 mutation. Our study demonstrates that it is possible that the frequency of CF mutations among patients with altered fertility may be higher than expected. Previous data showed that fibrocystic women can show reduced fertility, maternal mortality associated with pregnancy and increased incidence of spontaneous abortion. We therefore recommend that women with reduced fertility undertake genetic tests for a better evaluation of pregnancy risks and clinical monitoring.

Post-traumatic stress, anxiety, and depressive symptoms in caregivers of children tested for COVID-19 in the acute phase of the Italian outbreak.

BACKGROUND: The recent COVID-19 pandemic pointed out new burdens for researchers on mental health and that evidence-based (EB) studies on vulnerable populations are timely needed. The present paper aims at analysing the impact of suspicious of SARS-COV-2 infection in a cohort of parents presented at 3 major hospitals (spread between north and center of Italy) during the Italian COVID-19 pandemic phase 1. METHODS: Participants of the present cross-sectional, multicenter study were parental couples of children suspected to have COVID-19 who underwent testing with nasopharyngeal swabbing. All subjects were assessed by means of the: Impact of Event Scale-Revised (IES-R), Generalized Anxiety Disorder 7-Item (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in order to evaluate Post-traumatic stress (PTSS), anxiety, and depressive symptoms, respectively. OUTCOMES: Results evidenced that parents whose children tested positive for COVID-19 were more prone to developing PTSS, anxiety and depressive symptoms. The same results emerged for parents who had quarantined as opposed to those who had not. Moreover, patients who suffered economic damage showed a higher prevalence of anxiety and depressive symptoms, whereas PTSS was more common among unemployed subjects and among mothers. INTERPRETATION: This study identified a mental health strain represented by parenting a child who tested positive for SARS-CoV-2 infection. Further EB research is needed to develop evidence-driven strategies to reduce adverse psychological impacts and related psychiatric symptoms in caregivers of COVID-19 infected children during the next phases of the pandemic.

Effects of rituximab therapy on B cell differentiation and depletion.

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell­mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/- immature B cells and IgD-CD38+/- memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127-/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.

Photoelectron emission from yttrium thin films prepared by pulsed laser deposition.

We present the results of our investigation of metallic films as suitable materials for the production of intense electron beams. Thin films of Y prepared for the first time by pulsed laser deposition on Si substrates have been tested as photocathodes in an ultra high vacuum photodiode chamber at 10(-6) Pa. High quantum efficiencies have been obtained for the deposited films, comparable to those of corresponding bulks. The role of the adsorbed gases on the emission performance has been studied. Systematic laser cleaning treatments improved the quantum efficiency (QE) from 10(-6) to 4.5 10(-4). The samples could stay for several months in open air before being tested in a photodiode cell. The deposition process and testing results are presented.

A novel COL1A1 gene-splicing mutation (c.1875+1G>C) in a Brazilian patient with osteogenesis imperfecta.

Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility and deformity, recurrent fractures, blue sclera, short stature, and dentinogenesis imperfecta. Most cases are caused by mutations in COL1A1 and COL1A2 genes. We present a novel splicing mutation in the COL1A1 gene (c.1875+1G>C) in a 16-year-old Brazilian boy diagnosed as a type III osteogenesis imperfecta patient. This splicing mutation and its association with clinical phenotypes will be submitted to the reference database of COL1A1 mutations, which has no other description of this mutation.

Consequences of long-lasting persistent allergic rhinitis in adolescents.

While it is well known that asthma is characterized by airway remodelling, only few studies have investigated this issue in patients affected by allergic rhinitis (AR). The aim of the present study is to investigate functional and structural consequences of long-lasting persistent AR (PER) in a cohort of adolescents. Eighty patients, forty with short-lasting and forty with long-lasting PER were prospectively and consecutively evaluated both clinically and by performing skin prick test, nasal cytology, and rhinomanometry. Eosinophils were significantly higher in patients presenting with long-lasting PER rather than in those with short-lasting PER (P < 0.0001). The degree of inflammation was significantly associated with impaired nasal airflow (rs = -0.81). This study provides evidence that adolescents with long-lasting PER may show a progressive worsening of nasal function depending on the inflammation.

Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group. METHODS: Data from patients with stage I AGCTs were retrospectively collected. Clinicopathological features were evaluated for association with relapse and death. Survival curves were calculated using the Kaplan-Meier method and compared with the log-rank test. The role of clinicopathological variables as prognostic factors for survival was evaluated using Cox's regression model. RESULTS: 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and 29.6% respectively. 7.6% were apparently stage I. Surgical approach was laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was 84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC, incomplete staging, site of primary surgery retained significant prognostic value. CONCLUSION: The present study suggests that surgical route does not affect the oncological safety of patients with stage I AGCTs, with comparable outcomes between laparoscopic and open approach.

[Neurodevelopment and phenocopies of attention deficit hyperactivity disorder: differential diagnosis]. / Neurodesarrollo y fenocopias del trastorno por deficit de atencion/hiperactividad: diagnostico diferencial.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders. Other neurodevelopmental disorders may appear as a comorbidity or mimicking ADHD itself. DEVELOPMENT: This study reviews the high prevalence of other neurodevelopmental disorders (specific learning difficulties, communication disorders, etc.) in patients with ADHD. Moreover, the possible differential diagnoses include the same neurodevelopmental disorders that can occur as a comorbidity. Based on the literature, the study evaluates the role of clinical evaluation and neuropsychology in distinguishing between comorbidity and mimicry. CONCLUSIONS: The clinical evaluation could be insufficient for the comorbid diagnosis of neurodevelopmental disorders. In these cases, a neuropsychological evaluation is generally required, since it can also offer alternative diagnostic hypotheses about the symptoms observed and may therefore be a valuable aid for the differential diagnosis.

TITLE: Neurodesarrollo y fenocopias del trastorno por deficit de atencion/hiperactividad: diagnostico diferencial.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo mas prevalentes. Otros trastornos del neurodesarrollo pueden aparecer de forma comorbida o mimetizar el propio TDAH. Desarrollo. Se revisa la elevada prevalencia de otros trastornos del neurodesarrollo (trastornos especificos del aprendizaje, trastornos de la comunicacion...) en los pacientes con TDAH. Por otro lado, entre los posibles diagnosticos diferenciales se situan los mismos trastornos del neurodesarrollo que pueden aparecer de forma comorbida. Se valorara, de acuerdo a la bibliografia, el papel de la valoracion clinica y la neuropsicologia en la distincion entre comorbilidad y mimetismo. Conclusiones. La valoracion clinica podria ser insuficiente para el diagnostico comorbido de los trastornos del neurodesarrollo. En estos casos, la valoracion neuropsicologica es generalmente necesaria; esta puede igualmente ofrecer hipotesis diagnosticas alternativas de la sintomatologia observada y, por tanto, ser util para el diagnostico diferencial.

Immunotoxicity and sensitizing capacity of metal compounds depend on speciation.

Immunotoxicity of metal compounds is an issue of great importance due to the recent industrial application of metals with unknown toxicity on the immune system and the discovery of metal intermediary compounds not sufficiently studied yet. In this report we show results of our study on the immunotoxicity of the following metals: the Platinum group elements (Platinum, Palladium, Rhodium), Titanium and Arsenic. We applied functional and non functional assays and investigated both innate and adaptive immune systems, in particular, cell proliferation, cytokine production by PBMCs and O*2 production by neutrophils. We obtained the following results: only some Ti compounds (Titanocene, Ti ascorbate and Ti oxalate) show immunotoxicity. Trivalent As compounds (Sodium arsenite and tetraphenyl arsonium chloride) are more immunotoxic than the other investigated As compounds. Genotoxicity of Pt group compounds is in the following order: Pt > Rh > Pd. Immunotoxicity of Pt group compounds is in the following order: Pd > Pt > Rh. Lymphocytes and macrophages show a different reaction of neutrophils to metal toxicity. We can conclude that these studies show that metal immunotoxicity depends on speciation. In general speciation provides additional and often essential information in evaluating metal toxicity. However, there are many difficulties in applying speciation in investigating toxico-kinetic aspects to many metals, mainly due to the lack of information about the existence and significance of species and to the lack of analytical methods for measuring species in biological samples.

Eosinophil recruiting chemokines are down-regulated in peripheral blood mononuclear cells of allergic patients treated with deflazacort or desloratadine.

Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophils-basophils activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic-asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, I-309 (CCL1), MCP-1 (CCL2), MIP1-alpha (CCL3), MIP1-beta (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-alpha and MIP1-beta with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.

Current status and future perspectives in male contraception.

Contraception is a crucial human right for its role on health, development and quality of life. Since the introduction of hormonal female contraception the burden of family planning has fallen mostly on women. The few methods of family planning available for men--namely condoms, vasectomy, periodic abstinence and withdrawal--are hundred year old in concept, are based on preindustrial practices and have low efficacy or are difficult to reverse. In spite of the shortcomings of currently available male contraceptives, 1/3 of the couples that use contraception worldwide rely on male methods suggesting that development of a safe, effective, reversible and affordable contraceptive method for men would meet a critical need. Recent surveys have shown that men want to know more about reproductive health and want to support their partner more actively. In recent decades, there have been exceptional advances in the development of safer and more effective contraceptives. Currently, several methods of contraception for men are under development. This paper summarises the efforts performed over the past decades to develop an effective, safe and reversible male contraceptive.

[Pulmonary physiopathology in scleroderma: study of respiratory function in 86 patients]. / La fisiopatologia polmonare nella sclerodermia: esame della funzionalità respiratoria in 86 pazienti.

OBJECTIVE: To contribute to an early diagnosis of pulmonary involvement in scleroderma by evaluating the correlation between respiratory symptoms and functional respiratory data observed. PATIENTS AND METHODS: 86 patients affected by scleroderma, 76 women and 10 men, age 14-75, underwent lung function tests, blood gas sample, CO diffusing capacity in setting and supine position, respiratory drive measurement through P0.1 and evaluation of the respiratory muscles efficiency with Maximum Inspiratory Pressure (MIP). RESULTS: Data obtained suggested us to divide our patients in four different groups: first group where both spirometric data and pulmonary diffusion were normal; a second group with a clear reduction of pulmonary diffusion likely due to the reduction of vascular bed; a third group where we observed a restrictive ventilatory impairment due to the reduction of the compliance and a reduction of the pulmonary diffusion likely related to interstitial damage; finally, a fourth group where beside a restricted spirometric outline we have detected a more accentuated reduction of pulmonary diffusion likely due to pulmonary hypertension. Moreover, our study has highlighted a progressive decrease of MIP and Maximum Voluntary Ventilation (MVV) shifting from the first to the fourth group, suggesting reduction of the muscular efficiency with an increase of P0.1 index of activity in the respiratory drive. CONCLUSIONS: The results could explain the dyspnea often reported by the patients affected by scleroderma even without spirometric alteration.