The cytokine storm and thyroid hormone changes in COVID-19.

BACKGROUND: COVID-19 is now a worldwide pandemic. Among the many extra-pulmonary manifestations of COVID-19, recent evidence suggested a possible occurrence of thyroid dysfunction. PURPOSE: The Aim of the present review is to summarize available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations. CONCLUSIONS: The repercussions of the thyroid of COVID-19 seem to be related, in part, with the occurrence of a "cytokine storm" that would, in turn, induce a "non-thyroidal illness". Some specific cytokines and chemokines appear to have a direct role on the hypothalamus-pituitary-thyroid axis. On the other hand, some authors have observed an increased incidence of a destructive thyroiditis, either subacute or painless, in patients with COVID-19. The hypothesis of a direct infection of the thyroid by SARS-Cov-2 stems from the observation that its receptor, ACE2, is strongly expressed in thyroid tissue. Lastly, it is highly probable that some pharmaceutical agents largely used for the treatment of COVID-19 can act as confounding factors in the laboratory evaluation of thyroid function parameters.

Pre-pregnancy body mass index, gestational weight gain and adverse birth outcomes: some evidence from Italy.

BACKGROUND: Overweight and obese women present an increased risk of poor maternal and child health outcomes. The aim of this paper is to analyze the joint effects of pre-pregnancy body mass index and inadequate gestational weight gain on birth weight and gestational age in an Italian sample of pregnant women. METHODS: Data were obtained from a sample of about 2,000 pregnant women at the University Teaching Hospital of Perugia University (Italy) in 2013. We used the revised classification proposed by Institute of Medicine to identify gestational weight gains considered as appropriate. Logistic regression models were used to estimate the adjusted odds-ratios of women belonging to any BMI class different from normal (used as the reference category) and of women who increased their weight by an amount smaller or greater than normal, controlling for a large set of observable confounders. RESULTS: Higher probability of low birth weight was associated with both obesity (OR = 1.9124, s.e. = 0.526) and less than normal weight gains (OR = 2.3614, s.e. = 0.388). The probability of fetal macrosomia was found to be positively associated with more than normal weight increases (OR = 2.6232, s.e. = 0.465). Pre-term deliveries were associated with less than normal gestational weight gains (OR 1.7338, s.e. = 0.320). CONCLUSION: Overweight and obesity represent a big issue for public health. In particular, weight management during pregnancy and pre-pregnancy could determine negative health outcomes in newborns. In our study we found that inadequate weight variations during pregnancy, according to the Classification of the Institute of Medicine, negatively influence health conditions at birth. Stronger initiatives, especially in terms of midwifery, nurse training and informative policies should be adopted by policy makers.

Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH-independent hypercortisolism.

OBJECTIVE: To evaluate if the parameters of hypothalamic-pituitary-adrenal (HPA) axis activity could predict the occurrence and duration of post-surgical hypocortisolism (PSH) in patients with Cushing's syndrome (CS) and with adrenal incidentaloma (AI). METHODS: We studied 80 patients (54 females, age 53.3 ± 11 years), who underwent adrenalectomy for CS (17 patients) or for AI (53 patients). Before surgery, we measured adrenocorticotroph hormone (ACTH), urinary free cortisol (UFC) and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) levels. After surgery, all patients were given a steroid replacement therapy, and PSH was searched after 2 months by a low-dose (1 µg, iv) corticotropin stimulation test, that was repeated every 6 months in PSH patients for at least 4 years. RESULTS: The PSH occurred in 82.4 and 46% of CS and AI patients, respectively. In the whole sample and in AI patients separately considered, the PSH was independently predicted by the preoperative cortisol levels after 1 mg-DST, however, with a low (< 70%) accuracy. In AI patients the PSH occurrence was not ruled out even by the cortisol levels after 1 mg-DST lower than 1.8 µg/dL (50 nmol/L). In the 50% of CS patients and in 31% of AI patients the PSH lasted more than 18 months and in 35.7% of CS patients it persisted for more than 36 months. In AI patients, the PSH duration was not predictable by any parameter. However, a PSH duration of at least 12 months was significantly predicted before adrenalectomy (sensitivity 91.7%, specificity 41.2%, positive predictive value 52.4%, negative predictive value 87.5%, p = 0.05) by the presence of at least 2 out of low ACTH levels, increased UFC levels and cortisol levels after 1 mg-DST ≥ 3.0 µg/dL (83 nmol/L). CONCLUSION: The PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.

Health and income inequalities in Europe: What is the role of circumstances?

Equality of opportunity theories distinguish between inequalities due to individual effort and those due to external circumstances. Recent research has shown that half of the variability in income of World population was determined by country of birth and income distribution. Since health and income are generally strictly related, the aim of this paper is to estimate how much variability in income and health is determined by external circumstances. We use data from the Survey of Health, Ageing and Retirement (SHARE) and the English Longitudinal Survey on Ageing (ELSA), two comparable multidisciplinary surveys that provide micro-level data on health and financial resources among the elderly for a large number of European countries. Our baseline estimation shows that about 20% of the variability in income is explained by current country-specific circumstances, while health outcomes range from 12% using BMI to 19% using self-rated health. By including early-life circumstances, the explained variability increases almost 20 percentage points for income and for self-rated health but less for other health outcomes. Finally, by controlling for endogeneity issues linked with effort, our estimates indicate that circumstances better explain variability in health outcomes. Results are robust to some tests, and the implications of these findings are discussed.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

STUDY QUESTION: Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER: A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY: Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION: International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE: We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION: The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. WIDER IMPLICATIONS OF THE FINDINGS: This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. STUDY FUNDING/COMPETING INTERESTS: None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. TRIAL REGISTRATION NUMBER: N/A.

Economic Evaluation of the effect of Quitting Smoking on Weight Gains: Evidence from the United Kingdom.

OBJECTIVE: This article estimated the causal effect of quitting smoking on body weight gains in the United Kingdom to evaluate whether savings in health costs deriving from smoking prevention and its related diseases are greater than the costs associated with increased obesity. METHODS: We used a longitudinal data set extracted from two waves (2004-2006) of the British Household Panel Survey, which includes information on smoking and a large number of sociodemographic variables. We modeled the effect of quitting smoking on body weight accounting for heterogeneous responses from individuals belonging to different clinical classes of body mass index (BMI) (i.e., overweight and obese individuals). National Health Service costs associated with smoking were then used to implement a cost-benefit analysis, comparing the advantages of smoking reductions with the costs associated with increased obesity. RESULTS: The BMI was found to increase by 0.26 points for quitters compared with those who continued to smoke. The estimated BMI increase was larger for overweight (0.49 points) and obese (0.76 points) people. This result does not change when different control groups are examined. From an economic perspective, the National Health Service cost reductions attributable to quitting smoking were £156.81 million whereas the lost benefit for unintended increases in body weight was £24.07 million. CONCLUSIONS: This article found that the health benefits associated with quitting smoking are greater than the costs associated with increased overweight and obesity.

Self-perceived health among Eastern European immigrants over 50 living in Western Europe.

OBJECTIVES: This paper examines whether Eastern European immigrants aged 50 and over living in Northern and Western Europe face a health disadvantage in terms of self-perceived health, with respect to the native-born. We also examined health changes over time (2004-2006-2010) through the probabilities of transition among self-perceived health states, and how they vary according to nativity status and age group. METHODS: Data were obtained from the Survey of Health, Ageing and Retirement in Europe (SHARE). Logistic regressions and probabilities of transition were used. RESULTS: Results emphasise the health disadvantage of Eastern European immigrants living in Germany, France and  Sweden with respect to the native-born, even after controlling for socio-economic status. Probabilities of transition also evidenced that people born in Eastern Europe were more likely to experience worsening health and less likely to recover from sickness. CONCLUSIONS: This paper suggests that health inequalities do not affect immigrant groups in equal measure and confirm the poorer and more steeply deteriorating health status of Eastern European immigrants.

Localization of peripheral autonomic neurons innervating the boar urinary bladder trigone and neurochemical features of the sympathetic component.

The urinary bladder trigone (UBT) is a limited area through which the majority of vessels and nerve fibers penetrate into the urinary bladder and where nerve fibers and intramural neurons are more concentrated. We localized the extramural post-ganglionic autonomic neurons supplying the porcine UBT by means of retrograde tracing (Fast Blue, FB). Moreover, we investigated the phenotype of sympathetic trunk ganglion (STG) and caudal mesenteric ganglion (CMG) neurons positive to FB (FB+) by coupling retrograde tracing and double-labeling immunofluorescence methods. A mean number of 1845.1±259.3 FB+ neurons were localized bilaterally in the L1-S3 STG, which appeared as small pericarya (465.6±82.7 µm2) mainly localized along an edge of the ganglion. A large number (4287.5±1450.6) of small (476.1±103.9 µm2) FB+ neurons were localized mainly along a border of both CMG. The largest number (4793.3±1990.8) of FB+ neurons was observed in the pelvic plexus (PP), where labeled neurons were often clustered within different microganglia and had smaller soma cross-sectional area (374.9±85.4 µm2). STG and CMG FB+ neurons were immunoreactive (IR) for tyrosine hydroxylase (TH) (66±10.1% and 52.7±8.2%, respectively), dopamine beta-hydroxylase (DßH) (62±6.2% and 52±6.2%, respectively), neuropeptide Y (NPY) (59±8.2% and 65.8±7.3%, respectively), calcitonin-gene-related peptide (CGRP) (24.1±3.3% and 22.1±3.3%, respectively), substance P (SP) (21.6±2.4% and 37.7±7.5%, respectively), vasoactive intestinal polypeptide (VIP) (18.9±2.3% and 35.4±4.4%, respectively), neuronal nitric oxide synthase (nNOS) (15.3±2% and 32.9±7.7%, respectively), vesicular acetylcholine transporter (VAChT) (15±2% and 34.7±4.5%, respectively), leu-enkephalin (LENK) (14.3±7.1% and 25.9±8.9%, respectively), and somatostatin (SOM) (12.4±3% and 31.8±7.3%, respectively). UBT-projecting neurons were also surrounded by VAChT-, CGRP-, LENK-, and nNOS-IR fibers. The possible role of these neurons and fibers in the neural pathways of the UBT is discussed.

Neurochemical features of boar lumbosacral dorsal root ganglion neurons and characterization of sensory neurons innervating the urinary bladder trigone.

Porcine lumbosacral dorsal root ganglion (DRG) neurons were neurochemically characterized by using six neuronal markers: calcitonin gene-related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), neurofilament 200kDa (NF200), transient receptor potential vanilloid 1 (TRPV1), and isolectin B4 (IB4) from Griffonia simplicifolia. In addition, the phenotype and cross-sectional area of DRG neurons innervating the urinary bladder trigone (UBT) were evaluated by coupling retrograde tracer technique and immunohistochemistry. Lumbar and sacral DRG neuronal subpopulations were immunoreactive (IR) for CGRP (30 ± 3% and 29 ± 3%, respectively), SP (26 ± 8% and 27 ± 12%, respectively), nNOS (21 ± 4% and 26 ± 7%, respectively), NF200 (75 ± 14% and 81 ± 7%, respectively), and TRPV1 (48 ± 13% and 43 ± 6%, respectively), and labeled for IB4 (56 ± 6% and 43 ± 10%, respectively). UBT sensory neurons, which were distributed from L2 to Ca1 DRG, had a segmental localization, showing their highest density in L4-L5 and S2-S4 DRG. Lumbar and sacral UBT sensory neurons expressed similar percentages of NF200 immunoreactivity (64 ± 33% and 58 ± 12%, respectively) but showed a significantly different immunoreactivity for CGRP, SP, nNOS, and TRPV1 (56 ± 9%, 39 ± 15%, 17 ± 13%, 62 ± 10% vs. 16 ± 6%, 16 ± 11%, 6 ± 1%, 45 ± 24%, respectively). Lumbar and sacral UBT sensory neurons also showed different IB4 labeling (67 ± 19% and 48 ± 16, respectively). Taken together, these data indicate that the lumbar and sacral pathways probably play different roles in sensory transmission from the UBT. The findings related to cell size also reinforced this hypothesis, because lumbar UBT sensory neurons were significantly larger than sacral ones (1,112 ± 624 µm(2) vs. 716 ± 421 µm(2) ).

Impact of immigration on burden of tuberculosis in Umbria: a low-incidence Italian region with high immigrants rates.

INTRODUCTION: In Italy, Tubercolosis (TB) has increasingly become a disease for specific population subgroups such as immigrants. The objective of this paper is to describe the trend in TB incidence from 1999 to 2008 in Umbria: a low-incidence Italian region with high immigrants rates. METHODS: Data were obtained from the Regional Information System for Infectious Diseases. Using a linear regressions model we estimated trends for number of cases and incidence rates; with a logistic regression model we estimated the effect of a set of covariates on the probability of being affected by TB. RESULT: 590 TB cases were reported of whom 254 (43%) were foreign. In 2008 39.7 new cases per 100.000 were registered among foreign-born subjects. TB incidence among Italians was 3.8/100.000 Italians. But a linear regression analysis showed a statistically significant decreasing trend in the notification rate among foreign-born people (coef: -7.32, r2:0.57, p < 0.05). The probability to be affected by extra-pulmonary is significantly larger in foreign patients (OR = 0.72, CI = 0.48-1.07). Foreign unskilled workers report a higher probability to be affected by TB (OR = 19.05, CI = 6.01-60.4). DISCUSSION: Increasing immigration rates may affect TB epidemiology. The analysis of incidence trends is an important toolfor monitoring tuberculosis disease control and to identify specific sub-group at risk.

Randomised clinical trial: low-volume bowel preparation for colonoscopy - a comparison between two different PEG-based formulations.

BACKGROUND: Low-volume bowel preparations with polyethylene glycol (PEG) have been shown to provide an equivalent cleansing with improved tolerability as compared with standard PEG bowel preparation for colonoscopy. A new iso-osmotic sulphate-free formulation of PEG-Citrate-Simethicone (PEG-CS) in combination with bisacodyl has been recently developed. AIM: To compare the quality of bowel cleansing with PEG-CS with bisacodyl vs. PEG-Ascorbate (PEG-ASC) in adult out-patients undergoing colonoscopy. METHODS: Randomised, observer-blind, parallel group study in adult out-patients undergoing colonoscopy in five Italian centres. Both preparations were taken the evening before the procedure. Subjects were instructed to take 2-4 tablets of 5 mg bisacodyl at 16:00 hours and 2 L of PEG-CS at 20:00 hours or 2 L of PEG-ASC plus 1 L of additional water the day before colonoscopy. Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale (≥6 scores were considered as 'clinical success'), and mucosal visibility according to a 3-point scale. Tolerability, acceptability and compliance were also evaluated. RESULTS: Four hundred and eight patients were randomly allocated to PEG-CS and bisacodyl (n = 204, male patient 48%, mean age 59.1 years) or PEG-ASC (n = 204, male patient 51%, age 59.4 years). In the planned per-protocol analysis, the rate of successful preparation was 79.1% following PEG-CS with bisacodyl, and 70% following PEG-ASC (P < 0.05). Mucosal visibility was evaluated as optimal in 56.1% in the PEG-CS and bisacodyl and 46.3% in the PEG-ASC group (P < 0.05). There were no serious adverse events (AE) in each of the two experimental groups. Two subjects in the PEG-ASC group discontinued the study because of AE. CONCLUSIONS: Polyethylene glycol-Citrate-Simethicone in combination with bisacodyl was more effective for bowel cleansing than PEG-ASC for out-patient colonoscopy. Tolerability, safety, acceptability and compliance of the two low-volume bowel preparations were similar.

Experimental study on the location of neurons associated with the first sacral sympathetic trunk ganglion of the pig.

The neurons associated with the left first sacral sympathetic trunk ganglion (STG S1), an autonomic ganglion particularly concerned in the innervation of the smooth and striated musculature associated with pelvic organs, were identified in the pig, using the non-trans-synaptic fluorescent retrograde neuronal tracer Fast Blue. The labelled neurons were located mostly ipsilaterally, in the intermediolateral nucleus of the spinal cord segments T10-L5, in the sympathetic trunk ganglia L3-Co1, in the caudal mesenteric ganglia, in the pelvic ganglia, and in the spinal ganglia T13-S4. Our results could indicate the existence of visceral neuronal circuits concerning the ganglia of the sympathetic trunk and the caudal mesenteric, pelvic and spinal ganglia with or without the intervention of the central nervous system, whose identification and preservation during surgical treatments could be helpful in reducing the risk of subsequent urinary and sexual disfunctions.

Proposal for a systematic preoperative assessment of pelvic endometriosis.

AIM: Severe endometriosis represents one of the most challenging clinical and surgical cases in gynecology. Preoperative assessment of the extension of the disease is of key relevance to opt for medical or surgical therapy and, sometimes, to plan a multidisciplinary approach. METHODS: A systematic diagnostic approach is proposed and evaluated in a tertiary referral centre. It is based on an initial clinical evaluation and a second level ultrasound of the pelvis. Further exams, whenever required, have to be aimed at demonstrating specific involvements of organs other than ovaries and peritoneum such as bowel, urinary tract and nerves. RESULTS: The application of the proposed protocol has led to a reduction of the number of non-radical surgical procedures due to incomplete consent associated with missed diagnosis over the years (P<0.001). CONCLUSION: Our findings support the efficacy of a systematic diagnostic approach to endometriosis. This allows a correct planning of therapy with a multidisciplinary approach when necessary.

Evaluation of colonic involvement in endometriosis: double-contrast barium enema vs. magnetic resonance imaging.

BACKGROUND: The purpose of the study was to compare the accuracy of double-contrast barium enema (DCBE) and magnetic resonance imaging (MRI) in the diagnosis of intestinal endometriosis using the histological examination on resected specimen as comparative standard. METHODS: Eighty-three consecutive patients with suspected intestinal endometriosis, resected between 2005 and 2007, were prospectively evaluated. All of the women underwent preoperative DCBE and MRI on the same day. We evaluated number, site (rectum, sigmoid, cecum), and size of the lesions. The imaging findings were correlated with those resulting at pathology. RESULTS: Among the 65 women who underwent surgery, 50/65 (76.9%) were found to have bowel endometriosis, with 9/50 (18%) patients presenting two lesions; DCBE allowed to detect 50/59 (84.7%) lesions. MRI allowed to detect 42/59 (71.1%) lesions. DCBE showed sensibility, specificity, PPV, NPV, and accuracy of respectively 84.7, 93.7, 98.0, 62.5, and 86.6%, MRI of 71.1, 83.3, 93.3, 46.8, and 74.6%. CONCLUSION: DCBE is more accurate than unenhanced MRI in the diagnosis of bowel endometriosis, and should be preferred in the preoperative management of this disease, since it usually enables a proper surgical planning.

Laparoscopic treatment of bowel endometriosis in infertile women.

BACKGROUND: The purpose of the study was to determine the influence of bowel endometriosis on fertility, and to study whether its removal improves fecundity in women with endometriosis-associated infertility. METHODS: Three groups of infertile patients were included in the study. Group A (60 women) consisted of patients who underwent surgery for endometriosis with colorectal segmental resection. In group B, 40 patients with evidence of bowel endometriosis underwent endometriosis removal without bowel resection. Group C consisted of 55 women who underwent surgery for moderate or severe endometriosis with at least one endometrioma and deep infiltrating endometriosis but without bowel involvement. The women were clinically evaluated before laparoscopy and then at 1 month, at 6 months and at each year up to 4 years after surgery. Main outcome measures were surgical complications as well as post-operative pregnancy rate, time to conception and monthly fecundity rate. RESULTS: The monthly fecundity rates (MFR) in groups A, B and C were 2.3, 0.84 and 3.95%, respectively. The difference in the MFR between groups was significant (P < 0.05). CONCLUSIONS: The presence of bowel infiltration by endometriosis seems to negatively influence the reproductive outcome in women with endometriosis-associated infertility. The complete removal of endometriosis with bowel segmental resection seems to offer better results in terms of post-operative fertility.

National pathfinder survey on children's oral health in Italy: pattern and severity of caries disease in 4-year-olds.

This paper describes the dental health status of Italian 4-year-olds in 2004/2005 and analyzes the association between caries in preschool children and some background characteristics in children and parents. Caries was recorded according to WHO criteria. 5,538 subjects were examined. Information on the children's and their parents' social, behavioral, ethnic and demographic status was obtained through a series of closed questions. Bivariate analysis was performed to investigate the association between caries and background characteristics. The probability of being an extra zero for the dmfs index was estimated via the zero-inflated negative binomial regression model (ZINB). 78.4% (95% CI = 77.2-79.6) of the children were caries-free. The national mean dmfs index was 1.36 (95% CI = 1.15-1.57), ranging from 1.22 (95% CI = 1.03-1.42) in the Italian North-East to 1.73 (95% CI = 0.83-2.63) in the South section. Significant bivariate associations between caries experience and risk factors were observed for parents' nationality (not Italian vs. Italian: p < 0.001), parents' educational levels (low vs. high: p < 0.001), preterm birth (yes vs. no: p = 0.011), prolonged breastfeeding (13 months: p = 0.038) and early tooth eruption (<6 months as reference: p = 0.004). Multivariable analysis (ZINB) showed that children with a low caries risk level had a higher probability of being an extra zero; in particular, children from fathers with a high educational level showed a probability of being an extra zero of 0.22. The results suggest a need to plan preventive programs to reduce oral health disparities among Italian preschool children, based on educational intervention with parents and children concerning oral health and caries prevention.

Targeted therapy with trastuzumab in dysplasia and adenocarcinoma arising in Barrett's esophagus: a translational approach.

AIM: Human epidermal growth factor receptor (HER2) protooncogene, overexpressed/ amplified in preneoplastic lesions and in adenocarcinoma (ADC) of the esophagus, can be considered a target for treatment of esophageal dysplasia/ADC. The aim of this study was to evaluate the therapeutic role of the anti-HER2 monoclonal antibody, trastuzumab, in the management of ADC originating from HER2-positive Barrett's esophagus (BE). METHODS: Two patients with high-grade dysplasia and ADC of the esophagus after esophageal mucosectomy and no metastatic disease were studied. Patients were not eligible for radical surgery or chemo-radiotherapy because of age and comorbidities. HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. Additional immunohistochemical analyses were performed. The whole panel was analysed at baseline, after treatment and at follow-up. RESULTS: At baseline, the two patients showed HER-2 overexpression/amplification in all areas of dysplasia and ADC but not in BE. Six months after treatment no significant differences in terms of endoscopical and histological patterns of the disease were found. HER-2, EGFR, TOPOII-alpha and anti-ssDNA analysis demonstrated a down-regulation of these markers and increased apoptosis. CONCLUSION: This study demonstrates that this treatment is feasible. No clear evidence of dysplasia regression was observed. However, HER2 and TopoII-alpha downregulation and induction of apoptosis occurring 6 months after treatment encourages further investigation.

[The birth certificate as an instrument for pregnancy]. / Il Certificato di assistenza al parto come strumento informativo per una analisi del percorso nascita.

The birth certificate is a valid source of information on pregnancy, birth, the newborn and the parents: such information could be useful to identify and eventually to improve the sanitary, social and economic conditions in which this event takes place and which could have negative effects on pregnancy outcome. In this paper the authors present and analyze the results of a number of births in some sanitary structures in the Umbria region (Italy), carried out through the revision of data reported in the birth certificates during the year 2004.