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The association between environmental conditions and pregnancy outcome has been under investigation for a long time, but results appear to be inconclusive regarding damage to either the newborn or the mother. The aim of this study was to evaluate the distribution of hospitalization of newborns with low birthweight (

Background Effective screening for colorectal cancer can reduce mortality by early detection of tumours and colonic polyps. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a potential non‐invasive diagnostic tool for detection of cancer. The aim of this study was to evaluate the reliability of breath‐testing for colorectal cancer screening and early diagnosis using an advanced breath sampler. Methods The exhaled breath of patients with colorectal cancer and non‐cancer controls with negative findings on colonoscopy was collected using the ReCIVA® Breath Sampler. This portable device is able to capture the alveolar breath fraction without environmental contamination. VOCs were desorbed thermally and analysed by gas chromatography–mass spectrometry. The discriminatory ability of VOCs in detecting colorectal cancer was evaluated by receiver operating characteristic (ROC) curve analysis for each VOC, followed by cross‐validation by the leave‐one‐out method, and by applying stepwise logistic regression analysis. Results The study included 83 patients with colorectal cancer and 90 non‐cancer controls. Fourteen VOCs were found to have significant discriminatory ability in detecting patients with colorectal cancer. The model with the diagnosis of cancer versus no cancer resulted in a statistically significant likelihood of discrimination of 173·45 (P, Available screening methods for colorectal cancer have poor reliability and low patient compliance. Cancer cells produce altered metabolites, which are transported in the bloodstream and released in the alveoli; these volatile organic compounds (VOCs) can be detected in exhaled breath. This study used a new‐generation breath sampler, capable of selecting the alveolar fraction of the breath and preventing environmental contamination. A pattern of 14 VOCs was able to discriminate patients with colorectal cancer from healthy controls, with a true predictive value of 93 per cent, irrespective of cancer stage. Breath test signature in colorectal cancer

Italy was one of the nations most affected by SARS-CoV-2. During the pandemic period, the national government approved some restrictions to reduce diffusion of the virus. We aimed to evaluate changes in in-hospital mortality and its possible relation with patient comorbidities and different restrictive public health measures adopted during the 2020 pandemic period. We analyzed the hospital discharge records of inpatients from public and private hospitals in Apulia (Southern Italy) from 1 January 2019 to 31 December 2020. The study period was divided into four phases according to administrative restriction. The possible association between in-hospital deaths, hospitalization period, and covariates such as age group, sex, Charlson comorbidity index (CCI) class, and length of hospitalization stay (LoS) class was evaluated using a multivariable logistic regression model. The risk of death was slightly higher in men than in women (OR 1.04, 95% CI: 1.01–1.07) and was lower for every age group below the &gt, 75 years age group. The risk of in-hospital death was lower for hospitalizations with a lower CCI score. In summary, our analysis shows a possible association between in-hospital mortality in non-COVID-19-related diseases and restrictive measures of public health. The risk of hospital death increased during the lockdown period.

Autism Spectrum Disorder (ASD) has historically been studied, known, and diagnosed in males. Females tend to remain unidentified, especially those with average intelligence abilities. This sex/gender difference might be partially explained by biological risk factors, but it is probably also bound to methodological issues. The present study aims to examine phenotypic characteristics (cognitive, emotive, socio-communicative, and academic) of a group of 54 females with ASD matched to a group of 55 males with ASD (3–18 years), all without cognitive impairment. Results suggest that there are subtle, yet potentially meaningful, quantitative, and qualitative phenotypic differences between females and males that common screening tests are not always sensitive enough to recognize. Further studies to improve practice and course for the assessment of females, reducing sex/gender-based inequities in ASD care, are required.

The emergence of link between periodontal disease and diabetes has created conditions for analyzing new interdisciplinary approach making toward tackling oral health and systemic issues. As periodontal disease is a readily modifiable risk factor this association has potential clinical implications. The aim of this paper was systematically review the extant literature related to analytics data in order to identify the association between type 1 diabetes (T1DM) in childhood and adolescence with periodontal inflammation. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a database search between 2004 and 2019. A manual search of the literature was conducted as an additional phase of the search process, with the aim of identifying studies that were missed in the primary search. One hundred and thirty-nine records were screened and 10 fulfilled the inclusion criteria. Most studies were of moderate methodological quality. Outcomes included assessments of diabetes and periodontal status. In diabetic populations, compared to healthy subjects, interindividual differences in periodontal status are reflected in higher severity of periodontal inflammation. The most reported barriers to evidence uptake were the intrinsic limits of cross-sectional report data and relevant research, and lack of timely research output. Based on the evidence presented within the literature, the aforementioned biomarkers correlate with poor periodontal status in type 1 diabetic patients. Whilst the corpus of the evidence suggests that there may be an association between periodontal status and type 1 diabetes, study designs and methodological limitations hinder interpretation of the current research.

Since Hans Asperger’s first description (Arch Psych Nervenkrankh 117:76–136, 1944), through Lorna Wing’s translation and definition (Psychol Med 11:115–129, 1981), to its introduction in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM, 1994), Asperger Syndrome has always aroused huge interest and debate, until vanishing in the DSM fifth edition (2013). The debate regarded its diagnostic validity and its differentiation from high functioning autism (HFA). The present study aimed to examine whether AS differed from HFA in clinical profiles and to analyze the impact of DSM-5’s innovation. Differences in cognitive, language, school functioning and comorbidities, were revealed when 80 AS and 70 HFA patients (3–18 years) were compared. Results suggested that an AS empirical distinction within autism spectrum disorder should be clinically useful.

Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.

Osteoarthritis (OA) is a chronic disease that requires a multimodal therapeutic approach. The aim of this study was to evaluate the effects of undenatured type II collagen (UC-II) as compared to robenacoxib in dogs affected by OA. Our hypothesis was that the two compounds would be similar (non-inferiority) in improving mobility. To test this hypothesis, a complete orthopedic examination, x-ray and the Liverpool Osteoarthritis in Dogs (LOAD) survey were performed in dogs affected by OA before and after the treatments. The study was designed as a clinical, randomized, controlled and prospective study. Sixty client-owned dogs were randomized in the R group (n = 30, robenacoxib 1 mg/kg/day for 30 days) and in the UC-II group (n = 30, UC-II 1 tablet/day for 30 days). Thirty days after the beginning of the treatment (T30), the dogs were reassessed for the LOAD, MOBILITY and CLINICAL scores. Based on the data obtained from the study, a significant reduction in LOAD and MOBILITY scores was recorded between T0 and T30 with a similar magnitude among the two groups (R = 31.5%, p &lt, 0.001, UC-II = 32.7%, p = 0.013). The results of this study showed that UC-II and robenacoxib were able to similarly improve mobility of dogs affected by OA.

Though scantly investigated, Leishmania infantum infection and clinical cases of leishmaniasis in cats have been recently reported in several countries of the Mediterranean basin, with large variability in prevalence data. A major limitation in the comparability of the data available is attributed to the differences in diagnostic techniques employed and cat populations sampled. The aim of this study was to assess the prevalence of L. infantum infection in owned cats across Italy by serological and molecular tests and the identification of potential risk factors. Blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum, by an immunofluorescence antibody test and for the parasites’ DNA, by real-time PCR. Samples were additionally screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) proviral DNAs. An overall cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or qPCR (0.8%), with a higher rate (10.5%) in southern Italy. The risk of L. infantum infection in cats was significantly associated to the geographical areas (South vs North and Centre; p, Author summary Zoonotic visceral leishmaniasis is a potentially fatal parasitic disease, which is caused by Leishmania infantum. Its distribution is associated with the occurrence of the sand fly vectors and reservoir hosts. Since L. infantum infection can occur in cats with clinical or subclinical outcomes, the role of cats in the epidemiology of zoonotic visceral leishmaniasis needs to be thoroughly assessed. This study aimed to evaluate the prevalence and associated risk factors for infection with L. infantum in a large subset of cats across Italy, a known endemic area with records of human cases of visceral leishmaniasis. Serum and blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum and parasites’ DNA, respectively. A cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or real-time PCR (0.8%). The risk of L. infantum infection in cats was associated to the geographical areas, age class, neutering status and feline immunodeficiency virus infection. These findings reveal that cats are exposed to and/or infected by this protozoan across the country, warranting further investigation to assess their role in the epidemiology of zoonotic visceral leishmaniasis to refine surveillance and prevention strategies against this veterinary and medically important ailment.

To evaluate, in patients stimulated with recombinant FSH and GnRH antagonists, whether triggering the final maturation of oocytes affects IVF outcomes.Five hundred and six IVF procedures were divided into three groups according to the timing of hCG administration: when at least 2 follicles reached the diameter of 17 mm, at least 2 follicles reached 18 mm and at least 2 follicles reached 20 mm. The main outcome was the number of mature oocyte that was the dependent variable of a multivariate model whose independents were, age, AFC, hCG timing, E2 levels at hCG day, number of follicles in different categories of dimension. Secondary endpoints were to compare fertilization, implantation and pregnancy rates in a multilevel multivariate model whose covariates were age, BMI, AFC, embryo quality and cause of infertility.Timing did not result a statistically significant factor influencing the number of oocytes collected, which was influenced by age, AFC, number of follicles between 12.1 and 15.9 mm and E2 levels. Implantation rate and pregnancy rate appear to be affected only by embryo quality.The number of oocytes collected and the probability of pregnancy are not associated with the time of hCG administration.

Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD children and adolescents with comorbid ASD, comparing them with 40 ones affected by ADHD without ASD. Treatment lasted from 6 to 156 months (longer than 24 months in more than three quarters of patients). Efficacy and safety were measured by clinical global impression and children global assessment scales; influence of intellectual functioning was examined. Comparisons between groups were made by Wilcoxon or Friedmann tests; relationships between functioning scores and other characteristics were analyzed by ordinal logistic and linear regression. Results demonstrated that MPH in patients with ASD was associated with significative reduction of illness severity, clinical improvement and amelioration of global functioning, without significant differences with patients having ADHD without ASD. The trend of reduction of illness severity and increase of global functioning were favorably related with intellectual functioning. No serious adverse events were reported. The findings showed that long-term MPH was effective and well-tolerated in ADHD children and adolescents with comorbid high functioning ASD.

Background The physiological effects of high-flow nasal cannula O2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure. In this study, we compared the effects of HFNC and conventional low-flow O2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure. Methods This was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies. After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O2 therapy via a face mask. The inspiratory fraction of oxygen was titrated to achieve an arterial O2 saturation target of 88–92%. Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTPDI/min)) were recorded. Results EAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 μV switching from HFNC1 to conventional O2, and then returned to 15.2 ± 6.4 μV during HFNC2 (conventional O2: p

Background: Cancer Antigen 15-3 (CA 15-3) is a tumor-associated antigen used as serum marker for breast cancer surveillance in patients and for monitoring the response to treatment. Aim of this study was to retrospectively evaluate CA 15-3 as a prognostic factor in early detection of breast cancer relapse as well as to analyze the statistical correlation between CA 15-3 levels and clinical-pathological parameters including staging, grading, estrogen and progesterone receptors. Methods: Sera of 726 women with breast carcinoma obtained preoperatively and postoperatively were assayed for CA 15- 3 by chemoluminescent immunometric assay. Results: We found that the mean serum CA 15-3 levels in patients before surgery were significantly higher (36.59 U/ml) compared with those of CA 15-3 after surgery (27.11 U/ml). We also found that elevated preoperative serum levels of CA 15-3 were significantly correlated with the presence of metastatic disease. In particular, among 305/700 patients (43,6%) that displayed over cut-off (>40U/ml) preoperative levels of CA 15-3, 94 patients (30,8%) developed advanced disease (metastases to distant sites). By contrast, in a subgroup of 395/700 patients (56.4%) with CA 15.3 serum levels < 40U/ml, only 32/305 patients (8%) showed signs of advanced disease during follow-up. Cox regression analysis revealed that only the presence of metastasis and the increased serum levels of CA 15-3 after surgery are significant risk factors for relapse of disease. Conclusion: Elevated preoperative concentrations of CA 15-3 may be a useful predictive factor for cancer progression in postoperative patients.

The combination of pegylated interferon (Peg-IFN) and ribavirin is currently the gold standard therapy in patients with HCV chronic infection. The duration of therapy, as well as the therapeutic dosage, depend on the genotype. Identification of the genotype and rapid virological response (RVR) are widely accepted as the most important predictors of clinical outcome during antiviral therapy but to optimize cost-benefits and to reduce possible side effects, further prognostic factors are needed. Squamous cell carcinoma antigens immunocomplex (SCCA-IC) has been reported to be increased in the serum of patients with liver cancer. In this multicentric prospective study, we investigated the serum levels of SCCA-IC in 103 patients with HCV chronic infection. Serum HCV-RNA was detected before the beginning of treatment, after 4, 12, 24 or 48 weeks, and at week 24 during follow-up. RVR, early virological response and sustained virological response (SVR) were assessed following the international guidelines. SCCA-IC levels were higher in responders (238 AU, interquartile difference 130-556 AU) and decreased significantly to 125 AU (70-290 AU). The mean baseline value in nonresponders was 149 AU (86.5-306.5 AU), but after 4 weeks of treatment the serum levels decreased to 115 AU (80-280 AU): the profile of reduction was different between patients with or without a positive SVR. Logistic regression with SVR as dependent variable identified as significant independent variables: the reduction in SCCA-IC after 1 month (OR = 4.82; 95% CI 1.39-16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21-0.42; P = 0.002); sex and age were also significant factors influencing SVR. SCCA-IC seems to be a reliable independent prognostic marker of therapeutic effectiveness in anti-HCV positive patients undergoing antiviral therapy.

Endometriosis is an estrogen-correlated benign disease characterized by a marked ability of endometrial-like cells to invade and proliferate outside uterine cavity, resembling for some invasive aspect the cancer growth. The molecular mechanisms regulating endometrial cell invasiveness are mostly unknown, although interactions between extracellular matrix (ECM) proteins and their transmembrane receptors, integrins, are likely to play a central role. In particular, laminin (Ln)-5 could be closely involved, as it is in cancer. We have investigated the expression of Ln-1, Ln-5, and collagen IV (Coll IV) ECM proteins and their receptors, alpha3beta1 and alpha6beta4 integrins, in atrophic, proliferative, and secretive endometrium and in endometriosis. The results show that Ln-5, but not Ln-I and Coll IV, is altered in secretive endometrium as well as in endometriosis tissues. No alterations are observed in atrophic or proliferative endometrium. Consistently, the polarization of both integrin subunits alpha3 and beta1, but not alpha6 and beta4, is altered in secretive endometrium and endometriosis tissues, but not in atrophic and proliferative endometrium. These results seem to suggest that Ln-5 and alpha3beta1 could be involved in the invasive mechanism of endometriosis. The altered expression of Ln-5, by upregulating matrix metalloproteases activity, suggest an invading process similar to that of many cancer processes.

Background The increase in costs related to the diagnosis and treatment of chronic-degenerative diseases requires a better knowledge of the true care pathway of patients. The study objective was to explore, using multi-state modeling, how analyses of drug prescriptions and data obtained from hospital discharge sheets can be used in combination to build a model of patients health care pathway in a non experimental setting. The model was applied to Chronic Obstructive Pulmonary Disease (COPD). Methods Based on the GOLD guidelines, access to hospitalization for COPD and prescription pharmaceuticals were awarded to seven transients states theoretically progressive. The intensity of transition were estimated with the non-parametric method proposed by Aalen and Johansen for multi-state Markov models non-homogeneous in time. Results The COPD patients included in the study are 111190. Patients admitted with a diagnosis of non acute COPD had a growing probability over time of needing prescriptions for inhaled corticosteroids (ICS) or the set combination of long-acting beta-agonists (LABA) and ICS; they also had a rising probability of an exacerbation. The use of ICS alone or in combination with LABA delays a hospital admission for acute respiratory failure by about 6 months, as compared to short-acting beta-agonists or anticholinergics. Conclusion The probabilities of a transition and their distribution in relation to time, sex, age and clinical status can be a helpful tool for those operating in the health care sector, who are called upon to carry out decisions from the standpoints of both efficacious clinical management and an efficient use of resources.

The purpose of this study was to evaluate the prevalence of intestinal parasites in 277 healthy subjects in the city of Mamuras (Albania, South Eastern Europe) and the correlation between parasitic infections and possible risk factors. Faecal samples collected with sodium-acetate-formalin fixative were concentrated by formalin ethylacetate sedimentation and examined as wet mounts, permanent stains and by anti-Giardia/Cryptosporidium fluorescent antibodies. Data concerning age, sex, level of education, availability of piped water, number of people living in the same house, and residence in rural or urban area were collected for each subject. Statistical analysis was performed by chi-square test and regression logistic analysis. The overall prevalence of intestinal parasites was 183/277 (66.06%). In particular, pathogenic protozoa or helminths were found in 67 subjects (24.18%), including Trichuris trichiura in 34 (12.27%), Giardia duodenalis in 31 (11.19%), Hymenolepis nana in 5 (1.8%), Ascaris lumbricoides in 3 (1.08%). A significant correlation was observed only between parasite colonization and older age and between Trichuris trichiura infection and residence in rural areas.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Because of its increased incidence in the last decade and the estimated further increase in the next 2 decades, HCC is arousing great interest. In Europe and North America, it commonly develops on cirrhotic livers, and surveillance programs have therefore been suggested to identify early HCC, at a stage when it remains suitable for surgical therapy and has a better clinical outcome. The only serologic marker used in clinical practice is alpha-fetoprotein (alpha-FP), but its sensitivity is poor. In our study, 120 patients with HCC and 90 patients with liver cirrhosis were investigated. We report for the first time to our knowledge that as a marker of HCC, the squamous cell carcinoma (SCCA) antigen has high sensitivity (84.2%) but low specificity (48.9%). However, the combination of alpha-FP and SCCA yielded a correct serologic diagnosis in 90.83% of the HCC patients. A small percentage of patients remain undetected, likely because of the low specificity of SCCA. In conclusion, the combined use of alpha-FP and SCCA antigen represents a more powerful tool for the serologic detection of HCC.

The occurrence of metastasis severely affects prognosis and survival of breast cancer patients. In order to metastasize, breast cancer cells need to cross the basement membrane (BM) tissue boundaries. Matrix metalloproteases (MMPs) are enzymes with proteolytic activity towards extracellular matrix components (ECM) of the BM, that are blocked by physiological tissue inhibitors (TIMPs). Cancer metastasis occurs as a result of an imbalance between MMPs, in particular MMP-2 and MMP-9, and TIMPs, in particular TIMP-2 and TIMP-1. This is the first study to report that pro-MMP-9 and TIMP-1 serum concentrations are inversely correlated in breast cancer patients. In the same patients, we determined the pro-MMP-9, the TIMP-1, the pro-MMP-2 and TIMP-2 before and after surgical eradication of the breast cancer. Our results show that after surgery, when the breast cancer tissue was removed, pro-MMP-9 concentrations dramatically decreased and TIMP-1 concentrations strongly increased, with statistically significant differences, so that a new balance was established. No statistically significant differences were observed regarding pro-MMP-2 and TIMP-2. Also, no correlation was found between pro-MMP-2, pro-MMP-9, TIMP-1 and TIMP-2 and a number of clinical and pathological parameters. In conclusion, our study suggests that pro-MMP-9 and TIMP-1 could be used as markers of disease during the follow-up of breast cancer patients and possibly as prognostic markers, although more studies are needed to address this issue.

Background: Acute coronary syndrome is a major cause of death, morbidity and access in emergency departments (ED). Methods: We evaluated a point-of-care testing (POCT) for the determinations of cardiac markers in an emergency department (ED), defining the clinical efficiency (management of patient with chest pain) and economic effectiveness (rationalization of preanalytical phase) related to data of Core Lab. Results: The results of analytical performances showed a good correlation (cTnI r2=0.89, myoglobin r2=0.84, CK-MB r2=0.9) between POCT and Core Lab and a significant decrease of the turn around time (TAT): difference of medians=−54 min, 95% CI from −48 to −60 min. Conclusions: Our data confirmed that the accurate utilization of POCT in the ED assumes an effective triage of patient with chest pain and the improvement of preanalytical phase out of the laboratory (delivery of specimens) and within the laboratory reception, centrifugation. However, efficiency must be linked to methodological and quality control of the Core Lab, mainly through connectivity.

Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib. These identified mRNA were validated in 78 frozen HCC samples and in 26 ex-vivo HCC tissues treated in culture with galunisertib. Respective protein levels in patients blood were measured by enzyme-linked immunosorbent assay. SKIL, PMEPA1 ANGPTL4, SNAI1, Il11 and c4orf26 were strongly upregulated by TGF-β1 and downregulated by galunisertib in different HCC cell lines. In the 78 HCC samples, only SKIL and PMEPA1 (Pβ1. In ex-vivo samples, SKIL and PMEPA1 were strongly downregulated (PPβ1. SKIL and PMEPA1 mRNA expression in tumor tissues was significantly increased compared with controls and not correlated with protein levels in the blood of paired HCC patients. SKIL and PMEPA1 mRNA levels were positively correlated with TGF-β1 mRNA concentrations in HCC tissues and strongly downregulated by galunisertib. The target genes identified here may serve as biomarkers for the stratification of HCC patients undergoing treatment with galunisertib.

Epidemiological studies suggest a possible association between BMI, diagnosis and clinical-pathological breast cancer characteristics but biological bases for this relationship still remain to be ascertained. Several biological mechanisms play a role in the genesis and progression of breast cancer. This study aimed to investigate relationships between BMI and breast cancer diagnosis/progression in a Southern Italian population and to try to interpret results according to the serum proteomic profile of healthy and breast cancer patients. BMI, presence or absence of breast cancer and its clinical-pathological characteristics were analyzed in a series of 300 breast cancer women and compared with those of 300 healthy women prospectively. To investigate whether obesity is associated with alterations in serum protein profile, SELDI-ToF approach was applied. Alcohol consumption (22.7% vs 11.3%; p = 30 respect to normal weight: OR = 2.49, 95% CI 1.25–4.99, p = 0.0098) and a higher probability of having positive axillary lymph node (OR = 3.67, CI 95% 2.16–6.23, p

Background If spatial representations of hospitalization rates are used, a problem of instability arises when they are calculated on small areas, owing to the small number of expected and observed cases. Aim of this study is to assess the effect of smoothing, based on the assumption that hospitalization rates, when calculated at the municipal level, may be influenced by both the neighboring municipalities and the health service organization, as well as by environmental risk factors associated with the disease under study. Methods To smooth rates we hypothesize that each municipality belongs to two independent hierarchical levels; at one of these levels subjects may belong to a plurality of superior hierarchical objects. Two different models, so-called Multilevel Multimembership Models, are fitted. In the first the structure of random effects was: the municipality heterogeneity, the spatial dependence of the municipalities and the local health service organization. In the second we replaced the local health service organization effect with the environmental risk effect for each municipality area. The models were applied to spatially represent the rates of hospitalization for lung cancer and chronic obstructive pulmonary disease, determined through the hospital discharge forms recorded in Apulia for the year 2006. Results The effect of smoothing was greater in smaller municipalities and in those with a more unstable Risk Adjusted Rate (RAR) due to the small number of cases and of population at risk. When a hierarchical level representing the ASL is inserted, the model fits the data better. Conclusion Maps of hospitalization rates for lung cancer and chronic obstructive pulmonary disease, shaded with the rates obtained at the end of the smoothing procedure, change the visual picture of the disease distribution over the whole territory, and if detected by the model, seem to express a geographical distribution pattern in specific areas of the region. In the case of lung cancer, the models show a clear difference between RAR and smoothed RAR. The inclusion of a random effect indicating the ASL contributed to improve the graphic representation of the results, whereas the environmental risk was not found to be a better hierarchical level than the municipality for fitting of the model.

The open lung strategy aims at reopening (recruitment) of nonaerated lung areas in patients with acute respiratory distress syndrome, avoiding tidal alveolar hyperinflation in the limited area of normally aerated tissue (baby lung).We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung.Twenty-five anesthetized, mechanically ventilated pigs were studied. Four lung-healthy pigs served as controls and the remaining 21 were divided into three groups (n = 7 each) in which lung injury was produced by surfactant lavage, lipopolysaccharide infusion, or hydrochloride inhalation. Computed tomography scans, respiratory mechanics, and gas exchange parameters were recorded under three conditions: at baseline, during lung recruitment maneuver, and at end-expiration and end-inspiration when ventilating after an open lung protocol.During recruitment maneuver and open lung protocol, the gas volume entering the insufficiently aerated compartment was 96% (75-117%) and 48% (41-63%) (median [interquartile range]) of the functional residual capacity measured before and at zero end-expiratory pressure, respectively. Nonetheless, the volume of hyperinflated lung increased during both recruitment maneuver (by 1-28% of total lung volume; P0.01) and open lung protocol ventilation at end-inspiration (by 1-15% of total lung volume; P0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P0.01).Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.

Background This study aimed to investigate squamous cellular carcinoma antigen (SCCA) in serum and in tumoral and paired peritumoral tissues. We studied 27 patients with liver cirrhosis (LC) and 55 with HCC: 20 with a single nodule < 3 cm (s-HCC) and 35 with a single nodule > 3 cm or multifocal (l-HCC). Methods Serum SCCA was measured by the ELISA kit, and in frozen tissues by immunohistochemistry, quantified with appropriate imaging analysis software and expressed in square microns. Continuous variables are reported as means and 95% confidence intervals. Comparisons between independent groups were performed with a generalized linear model and Tukey grouping. Pearson's correlation coefficients were determined to evaluate relations between markers. Qualitative variables were summarized as count and percentage. Statistical significance was set at p-value < 0.05. Results Serum SCCA values in LC patients were 0.41 (0.31–0.55) ng/ml and statistically different from both HCC groups: 1.6 (1.0–2.6) ng/ml in s-HCC, 2.2 (1.28–2.74) ng/ml in l-HCC. SCCA in hepatic tissue was 263.8 (176.6–394.01) μm2 in LC patients, statistically different from values in s-HCC: 1163.2 (863.6–1566.8) μm2 and l-HCC: 625.8 (534.5–732.6). All pairwise comparisons between groups yielded statistically significant differences. Tumoral SCCA resulted linearly related with nodule size, showing a statistically significant inverse relation between the two variables (b = -0.099, p = 0.024). Conclusion There was no statistically significant correlation between tissue and serum levels of SCCA. The significantly stronger expression of SCCA in smaller compared to larger HCC could be important for early HCC detection. However, the increased expression in peritumoral tissue could affect the significance of serological detection.

Summary Objective To examine whether obesity, body fat distribution and insulin resistance have an independent effect on serum TSH and free thyroid hormones (FT3 and FT4) in a cohort of euthyroid women, represented by overweight and obese patients. Design and patients A total of 201 women, aged 18–68 years, with body mass index (BMI) ≥ 25·0 kg/m2 and TSH levels

Background Alpha-fetoprotein (AFP), the only serological marker currently available for the detection of hepatocellular carcinoma (HCC), is unsatisfactory because of its poor sensitivity, as are other recently proposed markers. Therefore new biomarkers are badly needed. Squamous cell carcinoma antigen (SCCA), a serine protease inhibitor physiologically present in the skin, has recently been reported to be present in HCC patients, as also the immunocomplexed (IC) forms of SCCA and AFP: SCCAIC and AFPIC, respectively. Methods To determine the diagnostic accuracy of new serum biomarkers for the diagnosis of HCC a rapid, simple ELISA test was applied in 961 patients. Sensitivity and specificity were determined for each marker and for all the markers combined in detecting smaller and larger HCC versus liver cirrhosis. Results In smaller HCC, receiver operating characteristics analysis yielded the following AUC: AFP 0.714 (CI 95% 0.679–0.748), AFPIC 0.691 (CI95% 0.655–0.748), SCCA 0.703 (CI95% 0.667–0.736), SCCAIC 0.694 (CI 95% 0.659–0.728). SCCA was inversely correlated with size. The combined use of AFPIC, SCCA and SCCAIC in patients displaying low levels of AFP ( Conclusion This study suggests that the use of a combination of all these markers in clinical practice provides a non invasive and simple test that could increase the accuracy of HCC diagnosis.

A role of cadmium exposure in prostate cancer etiology has been suggested by epidemiologic and laboratory studies, but conclusive evidence on this topic is still lacking. We investigated the relation between cadmium exposure, estimated by determining toenails cadmium levels, and prostate cancer risk in forty patients newly diagnosed with prostate cancer and fifty-eight hospital controls recruited in two provinces from southern and northern Italy. We found an excess cancer risk in subjects in the third and fourth (highest) quartiles of toenail cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with subjects in the bottom quartile. Results were basically unchanged when limiting the analysis to each province or entering toenail cadmium concentrations as continuous values in the regression model (P=0.004). Despite the limited statistical stability of the point estimates, these findings appear to support the hypothesis that cadmium exposure increases prostate cancer risk.

Background Thyroid nodules and thyroid cancer occur more frequently in people exposed to radiation for therapeutic purposes, and to nuclear fallout. Furthermore, it is known that a moderate degree of iodine deficiency may be responsible for an increased prevalence of thyroid nodules, while it is suspected that radiation exposure could induce changes in thyroid autoimmunity. The iodine intake of people resident in Bari, S. Italy, is mildly deficient, which could be presumed to cause a higher prevalence of thyroid pathology. This study was conducted to evaluate the prevalence of thyroid nodules in a population occupationally exposed to radiation, in an area of mild iodine deficiency. Methods A cross-sectional study was designed to evaluate the prevalence of thyroid nodules in radiation exposed workers, compared with a stratified sample of non exposed workers. After giving written consent to participate in the study, all the recruited subjects (304 exposed and 419 non exposed volunteers) were interviewed to fill in an anamnestic questionnaire, and underwent a physical examination, ultrasound thyroid scan, serum determinations of fT3, fT4 and TSH, fine needle aspiration biopsy. The sample was subdivided into one group exposed to a determined quantity of radiation (detected by counter), one group exposed to an undetectable quantity of radiation, and the non exposed control group. Results The prevalence of thyroid nodules Instead, the prevalence of thyroid nodules > 1 cm in diameter resulted statistically different in exposed and non exposed health staff: 18.68% in non exposed males vs exposed: 3.76% (determined dose) and 9.09% (undetectable dose) in males, and 20.30% in non exposed females versus 3.23% (detected dose) and 9.52% (undetectable dose) in exposed females. There was a higher proportion of healthy staff in the exposed group than in the non exposed: (80.45% vs 68.68% in males; 80.65% vs 57.87% in females). Conclusion In our study, occupational exposure to radiation combined with mild iodine deficiency did not increase the risk of developing thyroid nodules. The statistically significant higher prevalence of thyroid nodules in the non exposed group could be explained by the high percentage (22%) of people with a familial history of, and hence a greater predisposition to, thyroid disease. The endemic condition of mild iodine deficiency, demonstrated in other studies, played a major role in determining the thyroid pathology in our study groups.

To achieve rapid assessment of chest pain in emergency/cardiology departments, a short turnaround time for cardiac marker testing is necessary. Nevertheless, Total Quality Management principles must be incorporated into the management of point-of-care testing (POCT); in this setting we implemented the Stratus CS assay as POCT for cardiac markers in our emergency/cardiology department. The analytical performance of the troponin I method was evaluated; information connectivity between the Stratus CS data management system and the laboratory information system was implemented and practical training of testing personnel was carried out at the POCT site. A total of 41 non-ST-segment elevation patients admitted to the hospital were followed to evaluate the appropriateness of hospital admission, formulated on the basis of the cardiac troponin-I level measured at the POCT site by clinical staff. Our preliminary clinical data suggest that the high sensitivity of the Stratus CS troponin method could play an important role in the early identification of patients with acute myocardial infarction in a low to intermediate-risk population for acute coronary syndrome. Our POCT model suggests that the central laboratory could ensure that the POCT program remains in compliance with quality requirements. Nevertheless, our comparison studies suggest that the implementation of POCT requires a high level of integration between cardiologists and pathologists to guarantee appropriate interpretation of the monitoring results for suspected ACS patients.

Fifty eight consecutive untreated patients with locally advanced cervical carcinoma (LACC) received neoadjuvant chemotherapy (NACT) with cisplatin (CDDP) 80 mg/sqm (day 1) + vinorelbine (VRL) 25 mg/sqm (day 1 and 8). Three cycles of chemotherapy were planned every 21 days. Within 28 days from the completion of chemotherapy patients in complete or partial response were submitted to radical hysterectomy with pelvic lymphadenectomy. On 155 cycles, hematologic toxicity was mild (G3-4 neutropenia and anemia occurred in 16% and 5%, respectively). Forty-seven patients (81%) were submitted to radical surgery; eight (14%) patients were deemed ineligible for surgery because of poor response to treatment, two (3%) for anesthesia contraindications and one (2%) refused surgery. At pathologic examination 12 patients (25%) had a complete response, one (2%) in-situ carcinoma, six (13%) residual microinvasive disease, and 28 (60%) a partial response. None had extracervical disease. Eight patients (14%) had microscopic lymph node metastases. The number of cycles administered was significantly associated with a good pathologic response. Association of CDDP and VRL as NACT in LACC appears safe and effective. Low cost and modest toxicity would support the initiation of a multicenter randomized phase III trial to compare this association with cisplatin alone.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Despite improvements in diagnostic and therapeutic interventions, prognosis and survival are still poor. To identify factors influencing survival, we retrospectively examined 150 consecutive patients with HCC from the time of first diagnosis of cirrhosis to death. In a multivariate analysis, we found that patients with larger HCC lesions had shorter survival, while other pathologic features had no predictive value. The most important and reliable prognostic factor was the occurrence of tumor thrombus of the portal vein (P

Background The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD. Methods Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP. Results Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination. Conclusion We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.

Background The analysis of non-fatal recurring events is frequently found in studies on chronic-degenerative diseases. The aim of this paper is to estimate the probability of readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) or with Respiratory Failure (RF). Methods The Repeated hospital admissions of a patient are considered as a Markov Chain. The transitions between the states are estimated using the Nelson-Aalen estimator. The analysis was carried out using the Puglia Region hospital patient discharge database for the years 1998–2005. Patients were selected on the basis of first admission between 01/01/2001 and 31/12/2005 with ICD-9-CM code of COPD or RF as principal and/or secondary diagnosis. For those selected two possible transitions were considered in the case they had the second and third admission with an ICD-9-CM code of COPD or RF as principal diagnosis. Results The probability of readmission is increased in patients with a diagnosis of RF (OR = 1.618 in the first transition and 1.279 in the second) and also in those with a diagnosis of COPD or RF as the principal diagnosis at first admission (OR = 1.615 in the first transition and 1.193 in the second). The clinical gravity and the ward from which they were discharged did not significantly influence the probability of readmission. Conclusion The time to readmission depends on the gravity of the pathology at onset. In patients with a grave clinical picture, either COPD or Respiratory Failure, when treated and controlled after the first admission, they become minor problems and they are indicated among secondary diagnoses in any further admission.

To establish the seroprevalence of antibodies to C. burnetii, Leptospira and Brucella in subjects at risk of exposure, 128 workers exposed to farm animals and 280 healthy blood donors were studied. Antibodies to C. burnetii, Leptospira and Brucella were determined by indirect immunofluorescence assay, by microagglutination test (MAT) and by standard tube agglutination test, respectively. Of subjects exposed to farm animals 73.4 % were positive for anti C. burnetii IgG (titeror = 20) compared to 13.6 % of control subjects (p0.0001). The seroprevalence was found mainly among the veterinarians (100 %) and the animal breeding workers (84 %). The trend of percentage of positivity to antibodies to C. burnetii is significant only in the group of workersor = 70 years, when adjusted for sex and occupation. None of the subjects examined had antibodies to Leptospira and Brucella. Further improvements in the occupational hygiene of the work environment is advisable.

Background and aim. Chronic Obstructive Pulmonary Disease (COPD), although largely preventable, is a great health burden in all the countries worldwide. Statistics of morbidity and mortality of COPD show the need for correct management of the disease. Chronic Obstructive Respiratory Diseases (DRG 88) are in 9th place for discharge in in-patient hospital admission. It is necessary to establish specific indicators which are efficacious and relevant for the patient, the doctor and the health manager. This study will analyse the information in respect of hospital admissions (Hospital discharge database) in Puglia for the period 2000-2005. Methods. The analysis was carried out utilising the Puglia Region hospital patient discharge database, selecting those patients with admission for chronic respiratory disease as principal or secondary diagnosis. Results. Chronic respiratory diseases are more frequent in males and in people over 45 years old with frequency increasing with age. Geographical distribution shows that there are greater rates of hospitalisation in big cities and in the neighbourhood of industrial areas. Although the trend over time is slight. A higher percentage of re-admission has been found for patients with COPD, and the interval between the two admissions occurs within one or two months; the diagnosis at the second admission is the same as for the first. 10.6% of discharge forms report one diagnosis, especially in patients older than 65 years of age. Little could be said about diagnostic procedures because these are not reported on the discharge form. Conclusion. Hospitalisation data confirms expectations regarding age and sex of patients. The high hospitalisation rates indicate that in-patients care still remains the only viable treatment for COPD and other chronic respiratory diseases. The high number of exacerbations reflect the absence of out-patients service or community care, and the same diagnosis in more than one episode shows the lack of efficiency of health services and disease management. This data is necessary to understand disease distribution and the modification of disease management in order to reduce health care costs, to increase efficacy in disease control and to limit repeated exacerbation and so to obtain the maximum benefit for the patients.

Background Health service databases of administrative type can be a useful tool for the study of progression of a disease, but the data reported in such sources could be affected by misclassifications of some patients' real disease states at the time. Aim of this work was to estimate the transition probabilities through the different degenerative phases of liver cirrhosis using health service databases. Methods We employed a hidden Markov model to determine the transition probabilities between two states, and of misclassification. The covariates inserted in the model were sex, age, the presence of comorbidities correlated with alcohol abuse, the presence of diagnosis codes indicating hepatitis C virus infection, and the Charlson Index. The analysis was conducted in patients presumed to have suffered the onset of cirrhosis in 2000, observing the disease evolution and, if applicable, death up to the end of the year 2006. Results The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients was 1.5% per year. The probability of developing HCC is higher in males (OR = 2.217) and patients over 65 (OR = 1.547); over 65-year-olds have a greater probability of death both while still suffering from cirrhosis (OR = 2.379) and if they have developed HCC (OR = 1.410). A more severe casemix affects the transition from HCC to death (OR = 1.714). The probability of misclassifying subjects with HCC as exclusively affected by liver cirrhosis is 14.08%. Conclusions The hidden Markov model allowing for misclassification is well suited to analyses of health service databases, since it is able to capture bias due to the fact that the quality and accuracy of the available information are not always optimal. The probability of evolution of a cirrhotic subject to HCC depends on sex and age class, while hepatitis C virus infection and comorbidities correlated with alcohol abuse do not seem to have an influence.