Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

OBJECTIVE: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. METHODS: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. RESULTS: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. CONCLUSIONS: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

Persistence of bDMARD therapy in Rheumatoid Arthritis after first-line TNF-inhibitor failure: the RECORD study of the Italian Society for Rheumatology.

OBJECTIVE: The optimal choice of a second biological disease-modifying anti-rheumatic drug (bDMARD) after failure with first line tumour necrosis factor inhibitor (TNFi) represents a critical therapeutic challenge. This study aims to evaluate the persistence with treatment using second line bDMARDs with different mechanisms of action in rheumatoid arthritis (RA) patients with inadequate response to first line TNFi. METHOD: A retrospective cohort study on administrative healthcare databases was conducted. We analysed the relationship between different bDMARDs and persistence with treatment in RA patients who started second line bDMARD therapy according to two different strategies: cycling (second TNFi) or switching [change in mechanism of action: abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX)] with or without concomitant conventional synthetic (cs) DMARDs. RESULTS: The cohort comprised 1434 patients. The mean age was 53.8 years and 1142 (79.6%) were women. Among second line bDMARDs, 969 patients (67.6%) started TNFi, 204 (14.2%) ABA, 145 (10.1%) RTX, and 116 (8.1%) TCZ. A bDMARD was prescribed as monotherapy in 359 patients (25.0%). The switching strategy showed a lower overall discontinuation rate [hazard ratio (HR) 0.72], while switching compared to cycling showed significantly better survival for ABA (HR 0.61) and RTX (HR 0.76), but no significant difference for TCZ (HR 0.82). A lower impact of better drug survival in the switching strategy occurred in patients with concurrent methotrexate. CONCLUSIONS: Among RA patients failing a first TNFi, switching is associated with marginally better persistence, in particular for ABA and RTX, with only marginal differences in patients on concurrent csDMARDs.

Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

COVID-19 cumulative incidence, intensive care, and mortality in Italian regions compared to selected European countries.

BACKGROUND: The high contagiousness and rapid spreading of the coronavirus disease 2019 (COVID-19) has caused a high number of critical to severe life-threatening cases, which required urgent hospital admission and treatment in intensive care units (ICUs). The pandemic has been a tough test for all European national health systems and their capability to provide an adequate reaction. METHODS: The present work aims to reveal correlations between parameters such as COVID-19 incidence, ICU bed occupancy, ICU excess area, and mortality in Italian regions. Public data for the period of March 1 to July 16, 2020, were analyzed using several mathematical and statistical methods. RESULTS: The analysis defined two separate groups of Italian regions. The examined variables considered within these groups were interlinked and dependent on each other. The regions of the two groups shared the same kind of fitted model (linear) explaining mortality as a function of cumulative incidence, but with higher value of the constant in one group, so characterized by a high intrinsic "strength" of the pandemic, certainly playing a major role in the generation of a large number of severe and life-threatening cases. These results are confirmed at European level. Other factors may condition mortality and be linked to incidence, such as ICU saturation and excess. CONCLUSIONS: These quantitative results could be a very helpful tool to set up preventive measures and optimize biomedical interventions before the pandemic, in its recurrent waves, could overcome the reaction capacity of any public health system.

Reply to the Letter to the Editor: The Italian Society of Rheumatology clinical practice guidelines for the management of polymyalgia rheumatica.

Not available.

The Italian Society of Rheumatology clinical practice guidelines for the management of polymyalgia rheumatica.

OBJECTIVE: to provide evidence-based up-to-date recommendations for the management of patients with a definite diagnosis of polymyalgia rheumatica (PMR). METHODS: A systematic literature review was performed to find the existing clinical practice guidelines (CPGs) on PMR and the framework of the Guidelines International Network Adaptation Working Group was used to appraise (AGREE II), synthesize, and customize the recommendations according to the needs of the Italian healthcare context. Rheumatologists on behalf of the Italian Society of Rheumatology (SIR) and from the SIR Epidemiology Unit joined the working group and identified the key health questions on PMR to guide the systematic literature review. Physicians, including general practitioners and specialists, and health professionals who manage PMR in the clinical practice were the target audience. The final recommendations were rated externally by a multi-disciplinary and multi-professional group of stakeholders. RESULTS: From the systematic search in databases (Medline, Embase) and grey literature, 3 CPGs were identified and appraised by two independent raters. Combining the statements and the evidence from these CPGs, 9 recommendations were developed by endorsement or adaptation in response to the initial key health questions. The quality of evidence was graded and the working group discussed the final recommendations in view of their implementation in the Italian healthcare context. CONCLUSIONS: In absence of national guidelines so far, these recommendations are the first to provide guidance for the management of patients with a diagnosis of PMR in Italy and they are expected to ensure the best evidence-based clinical practice for this disease.

Application of guidelines for the management of nonalcoholic fatty liver disease in three prospective cohorts of HIV-monoinfected patients.

OBJECTIVES: Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients. METHODS: We analysed three prospective screening programmes for NAFLD carried out in the following cohorts: the Liver Disease in HIV (LIVEHIV) cohort in Montreal, the Modena HIV Metabolic Clinic (MHMC) cohort and the Liver Pathologies in HIV in Palermo (LHivPa) cohort. In the LIVEHIV and LHivPa cohorts, NAFLD was diagnosed if the controlled attenuation parameter (CAP) was ≥ 248 dB/m; in the MHMC cohort, it was diagnosed if the liver/spleen Hounsfield unit (HU) ratio on abdominal computerized tomography scan was < 1.1. Medium/high-risk fibrosis category was defined as fibrosis-4 (FIB-4) ≥ 1.30. Patients requiring specialist referral to hepatology were defined as either having NAFLD and being in the medium/high-risk fibrosis category or having elevated alanine aminotransferase (ALT). RESULTS: A total of 1534 HIV-infected adults without significant alcohol intake or viral hepatitis coinfection were included in the study. Of these, 313 (20.4%) patients had the metabolic comorbidities (obesity and/or diabetes) required for entry in the diagnostic algorithm. Among these patients, 123 (39.3%) required specialist referral to hepatology, according to guidelines. A total of 1062 patients with extended metabolic comorbidities (any among obesity, diabetes, hypertension and dyslipidaemia) represented most of the cases of NAFLD (79%), elevated ALT (75.9%) and medium/high-risk fibrosis category (75.4%). When the algorithm was extended to these patients, it was found that 341 (32.1%) would require specialist referral to hepatology. CONCLUSIONS: According to current guidelines, one in five HIV-monoinfected patients should undergo detailed assessment for NAFLD and disease severity. Moreover, one in ten should be referred to hepatology. Expansion of the algorithm to patients with any metabolic comorbidities may be considered.

The Italian Society of Rheumatology clinical practice guidelines for the management of polymyalgia rheumatica

To provide evidence-based up-to-date recommendations for the management of patients with a defi-nite diagnosis of polymyalgia rheumatica (PMR).Methods: A systematic literature review was performed to find the existing clinical practice guidelines (CPGs) on PMR and the framework of the Guidelines International Network Adaptation Working Group was used to appraise (AGREE II), synthesize, and customize the recommendations according to the needs of the Italian healthcare context. Rheumatologists on behalf of the Italian Society of Rheumatology (SIR) and from the SIR Epidemiology Unit joined the working group and identified the key health questions on PMR to guide the systematic literature review. Physicians, including general practitioners and specialists, and health profession-als who manage PMR in the clinical practice were the target audience. The final recommendations were rated externally by a multi-disciplinary and multi-professional group of stakeholders.Results: From the systematic search in databases (Medline, Embase) and grey literature, 3 CPGs were identi-fied and appraised by two independent raters. Combining the statements and the evidence from these CPGs, 9 recommendations were developed by endorsement or adaptation in response to the initial key health questions. The quality of evidence was graded and the working group discussed the final recommendations in view of their implementation in the Italian healthcare context. Conclusions: In absence of national guidelines so far, these recommendations are the first to provide guid-ance for the management of patients with a diagnosis of PMR in Italy and they are expected to ensure the best evidence-based clinical practice for this diseas

Cytomegalovirus infection in Systemic Lupus Erythematosus: report of four cases challenging the management of the disease, and literature review.

Cytomegalovirus (CMV) is particularly dangerous in systemic lupus erythematosus (SLE), being a problem both for the differential diagnosis with disease flare and for the management of SLE flare with immunosuppressive drugs. We report on four cases of SLE with concomitant CMV infection, having some common clinical and laboratory characteristics. Our data suggest that lupus patients presenting with symptoms such as fever, diarrhea, and respiratory symptoms, alone or in combination, and laboratory evidence of leukopenia, elevated transaminases, and hyponatremia, especially in the setting of recent immunosuppressive treatments, should be screened for CMV.

The Italian Society for Rheumatology clinical practice guidelines for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterised by chronic joint inflammation, leading to functional disability and increased risk of premature death. Clinical practice guidelines (CPGs) are expected to play a key role in improving management of RA, across the different phases of the disease course. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2011 recommendations on management of RA. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing RA CPGs to the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Research Unit and a committee with experience in RA identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage RA in practice, and the target population includes adult patients diagnosed as having RA. An external multi-disciplinary committee rated the final version of the CPGs. From the systematic search in databases (Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 8 (Management) +6 (Safety) recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the management of RA and to disseminate the best evidence-based clinical practices for this disease.

The sequence of prenatal growth restraint and postnatal catch-up growth: normal heart but thicker intima-media and more pre-peritoneal fat in late infancy.

BACKGROUND: The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES: To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS: Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS: Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2 years. CONCLUSIONS: From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.

The main causes of death contributing to absolute and relative socio-economic inequality in Italy.

OBJECTIVES: Monitoring socio-economic inequality has become a priority for many governments, especially after the socio-economic changes that followed the 2008 financial crisis. This study aimed at detecting the causes of death with the largest socio-economic inequality in relative and absolute terms in Italy. STUDY DESIGN: This is a historical cohort study. METHODS: We used two regression-based measures of socio-economic inequality, the relative index of inequality (RII) and the slope index of inequality (SII), to rank the causes of death with the highest relative and absolute socio-economic inequality. We obtained these measures on a large census-based cohort study with more than 35 million individuals and 452,273 deaths registered in the period 2012-2014. RESULTS: The causes with the highest relative socio-economic inequality were the following: laryngeal cancer (RII: 6.1, 95% confidence interval [CI]: 4.8-7.78), AIDS/HIV (RII: 4.8, 95% CI: 3.1-7.4), chronic liver disease (RII: 4.8, 95% CI: 3.2-7.3), and chronic lower respiratory diseases (RII: 4.8, 95% CI: 3.5-6.5) in men, and diabetes (RII: 6.2, 95% CI: 4.8-7.9), AIDS/HIV (RII: 4.5, 95% CI: 2.7-7.7), genitourinary system (RII: 3.8, 95% CI: 2.6-5.4) and chronic liver diseases (RII: 3.6, 95% CI: 2.9-4.5) in women. In absolute terms, lung cancer and ischemic heart diseases contributed more to the overall socio-economic inequality in men, whereas diabetes and ischemic heart diseases accounted for most of the socio-economic inequality in women. CONCLUSIONS: Our findings call for effective policies to reduce the disparities in mortality from ischemic heart diseases, lung cancer, and diabetes taking into account the sex-specific pattern of inequality.

Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset.

Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.

Dapagliflozin modulates glucagon secretion in an SGLT2-independent manner in murine alpha cells.

AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin. Data were validated in murine and human pancreatic islets. RESULTS: SLC5A2 (the SGLT2-encoding gene) was nearly undetectable in αTC1 cells, not even by a digital PCR technique using different probes. In contrast, SLC5A1 (the SGLT1-encoding gene) was constitutively abundant in αTC1 cells and in islets, and increased with Dapa. This was associated with greater glucagon release, preceded by increased expression of preproglucagon and HNF4α. Looking at the candidate intracellular signalling pathway, reduced PASK and increased AMPK-α2 expression were also detected. GLUT1 and GLUT2, as well as regulators of glucagon release and alpha-cell phenotype (chromogranin A, paired box 6, proprotein convertase 1/2, synaptophysin), were unaffected by Dapa, as were GLP-1 receptor expression and GLP-1 release. Low glucose did not influence the stimulatory effect of Dapa on glucagon release, but was instead almost fully reverted by SLC5A1 silencing. When the effect of Dapa on AMPK and PASK, emerging regulators of lipid and glucose metabolism, was tested, upregulated AMPK-α2 appeared to be involved in molecular signalling. CONCLUSION: Our study has shown that, in αTC1 cells, Dapa acutely upregulates SGLT1 expression and increases glucagon release through an SGLT1-dependent mechanism, with SGLT2 expression virtually undetectable. These results suggest the involvement of SGLT1 in modulating glucagon increases following SGLT2 inhibition.

Circulating microRNAs and diabetes mellitus: a novel tool for disease prediction, diagnosis, and staging?

Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility. Recently, a new class of endogenous non-coding small RNAs, namely microRNAs, have been indicated as putative biomarkers, being released by cells and tissues and found in a cell-free circulating form in many biological fluids, including serum and/or plasma. MicroRNAs have been initially identified as promising biomarkers in cancer, and nowadays their application has been extended to other diseases, including diabetes. Although an increasing number of studies focused on the evaluation of circulating microRNAs in diabetes, few reproducibly identified microRNAs as biomarkers for disease prediction or follow-up. Technological problems as well as the need to obtain highly standardized operating procedures and methods are still an issue in such research field. In this review, we comprehensively resume the main and most recent findings on circulating microRNAs, and their possible use as biomarkers to predict and follow-up diabetes and its complications, as well as the methodological challenges to standardize accurate operating procedures for their analysis.

Correction: Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler.

[This corrects the article DOI: 10.1371/journal.pone.0150152.].

Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler.

INTRODUCTION: Infant anthropometry and body composition have been previously assessed to gauge the impact of intrauterine growth restriction (IUGR) at birth, but the interplay between prenatal Doppler measurements and postnatal development has not been studied in this setting. The present investigation was performed to assess the significance of prenatal Doppler findings relative to postnatal anthropometrics and body composition in IUGR newborns over the first 12 months of life. PATIENTS AND METHODS: Consecutive cases of singleton pregnancies with suspected IUGR were prospectively enrolled over 12 months. Fetal biometry and prenatal Doppler ultrasound examinations were performed. Body composition was assessed by absorptiometry at ages 10 days, and at 4 and 12 months. RESULTS: A total of 48 pregnancies qualifying as IUGR were studied. Doppler parameters were normal in 26 pregnancies. The remaining 22 deviated from normal, marked by an Umbilical Artery Pulsatility Index (UA-PI) >95th centil or Cerebro-placental ratio (CPR) <5th centile. No significant differences emerged when comparing anthropometry and body composition at each time point, in relation to Doppler findings. Specifically, those IUGR newborns with and without abnormal Doppler findings had similar weight, length, body mass index, lean and fat mass, and bone mineral content throughout the first 12 months of life. In a separate analysis, when comparing IUGR newborns by Doppler (abnormal UA-PI vs. abnormal CPR), anthropometry and body composition did not differ significantly. CONCLUSIONS: Infants with IUGR maintain a pattern of body composition during the first year of life that is independent of prenatal Doppler findings. Future studies with larger sample sizes and correlating with hormonal status are warranted to further extend the phenotypic characterization of the various conditions now classified under the common label of IUGR.

The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3-6 years.

BACKGROUND: Infants born small-for-gestational-age (SGA) who develop post-natal weight catch-up are at risk for insulin resistance, central adiposity and cardiovascular disease in later life, even in the absence of overweight. OBJECTIVE: In young (age 3-6 years) non-obese SGA children, we assessed arterial health (as judged by intima-media thickness [IMT]) and abdominal fat distribution (subcutaneous, visceral, preperitoneal and hepatic components by magnetic resonance imaging [MRI] and/or ultrasound [US]) besides a selection of endocrine markers. METHODS: Comparisons of measures in SGA (n = 27) vs. appropriate-for-GA (AGA) children (n = 19) of similar height, weight and body mass index. Longitudinal outcomes (age 3-6 years) were carotid IMT (cIMT); fasting glucose, circulating insulin, IGF-I and high-molecular-weight (HMW) adiponectin; abdominal fat partitioning by US. Cross-sectional outcomes (age 6 years) were aortic IMT (aIMT) and abdominal fat partitioning by MRI. RESULTS: At 3 and 6 years, cIMT and IGF-I results were higher and HMW adiponectin lower in SGA than AGA children; at 6 years, SGA subjects had also a thicker aIMT and more pre-peritoneal and hepatic fat, and were less insulin sensitive (all P values between <0.05 and <0.0001). cIMT correlated positively with pre-peritoneal fat, particularly at 6 years. Post-SGA status and weight gain in early childhood (between 3 and 6 years) were independent predictors of cIMT at 6 years, explaining 48 % of its variance. CONCLUSION: SGA children aged 3-6 years were found to have a thicker intima- media and more pre-peritoneal and hepatic fat than AGA children of comparable size.

Circulating GLP-1 in infants born small-for-gestational-age: breast-feeding versus formula-feeding.

Prenatal growth restraint associates with the risk for later diabetes, particularly if such restraint is followed by postnatal formula-feeding (FOF) rather than breast-feeding (BRF). Circulating incretins can influence the neonatal programming of hypothalamic setpoints for appetite and energy expenditure, and are thus candidate mediators of the long-term effects exerted by early nutrition. We have tested this concept by measuring (at birth and at age 4 months) the circulating concentrations of glucagon-like peptide-1 (GLP-1) in BRF infants born appropriate-for-gestational-age (AGA; n=63) and in small-for-gestational-age (SGA) infants receiving either BRF (n=28) or FOF (n=26). At birth, concentrations of GLP-1 were similar in AGA and SGA infants. At 4 months, pre-feeding GLP-1 concentrations were higher than at birth; SGA-BRF infants had GLP-1 concentrations similar to those in AGA-BRF infants but SGA-FOF infants had higher concentrations. In conclusion, nutrition appears to influence the circulating GLP-1 concentrations in SGA infants and may thereby modulate long-term diabetes risk.

Early Lupus Project - A multicentre Italian study on systemic lupus erythematosus of recent onset.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset that is problematic for a correct and prompt diagnosis. We undertook this project with the purpose of collecting an inception cohort of Italian patients with recent-onset SLE, in order to obtain information on the main clinical and serological characteristics at the beginning of the disease. In this first report we describe the characteristics of this cohort at study entry. METHODS: All patients with a diagnosis of SLE (1997 ACR criteria) and a disease duration less than 12 months were consecutively enrolled between 1 January 2012 and 31 December 2013 in a multicentre prospective study. Information on clinical and serological characteristics at study entry and then every six months was collected into a specific electronic database. Statistical analysis was performed by means of the Openstat program. RESULTS: Among 122 patients enrolled (103 F) 94.3% were Caucasians. Mean age (SD) of patients at study entry was 37.3 (14.3) years, mean age at disease onset was 34.8 (14.3) years, mean age at diagnosis was 36.9 (14.3) years, and mean disease duration was 2.9 (3.9) months. The frequency of the manifestations included in the 1997 ACR criteria was as follows: ANA 97.5%, immunologic disorders (anti-dsDNA, anti-Sm, antiphospholipid antibodies) 85.2%, arthritis 61.8%, haematologic disorders 55.7%, malar rash 31.1%, photosensitivity 29.5%, serositis 27%, renal disorders 27%, oral/nasal ulcers 11.5%, neurologic disorders 8.2%, and discoid rash 5.7%. The cumulative frequency of mucocutaneous symptoms was 77.8%. At enrolment, autoantibody frequency was: ANA 100%, anti-dsDNA 83.6%, anti-SSA 28%, anticardiolipin 24.5%, anti-nRNP 20.4%, anti-beta2GPI 17.2%, lupus anticoagulant 16.3%, anti-Sm 16%, and anti-SSB 13.1%. CONCLUSIONS: In this paper we describe the main clinical and serological characteristics of an Italian inception cohort of patients with recent-onset SLE. At disease onset, mucocutaneous manifestations, arthritis and haematologic manifestations were the most frequent symptoms; ANA, anti-dsDNA and complement reduction were the most frequent laboratory findings. Our data confirm that the diagnosis of SLE is a challenging one, and that SLE is a severe disease even at onset, since the majority of patients require at least a hospitalization before the diagnosis.