University Cattolica ore

Rome, Italy

University Cattolica ore

Rome, Italy
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Birnbaum R.Y.,University of California at San Francisco | Everman D.B.,JC Self Research Institute | Murphy K.K.,University of California at San Francisco | Gurrieri F.,University Cattolica ore | And 2 more authors.
Human Molecular Genetics | Year: 2012

Disruption of distaless homeobox 5 and 6 (Dlx5/6) in mice results in brain, craniofacial, genital, ear and limb defects. In humans, chromosomal aberrations in the DLX5/6 region, some of which do not encompass DLX5/6, are associated with split hand/foot malformation 1 (SHFM1) as well as intellectual disability, craniofacial anomalies and hearing loss, suggesting that the disruption of DLX5/6 regulatory elements could lead to these abnormalities. Here, we characterized enhancers in the DLX5/6 locus whose tissue-specific expression and genomic location along with previously characterized enhancers correlate with phenotypes observed in individuals with chromosomal abnormalities. By analyzing chromosomal aberrations at 7q21, we refined the minimal SHFM1 critical region and used comparative genomics to select 26 evolutionary conserved non-coding sequences in this critical region for zebrafish enhancer assays. Eight of these sequences were shown to function as brain, olfactory bulb, branchial arch, otic vesicle and fin enhancers, recapitulating dlx5a/6a expression. Using a mouse enhancer assay, several of these zebrafish enhancers showed comparable expression patterns in the branchial arch, otic vesicle, forebrain and/or limb at embryonic day 11.5. Examination of the coordinates of various chromosomal rearrangements in conjunction with the genomic location of these tissue-specific enhancers showed a correlation with the observed clinical abnormalities. Our findings suggest that chromosomal abnormalities that disrupt the function of these tissue-specific enhancers could be the cause of SHFM1 and its associated phenotypes. In addition, they highlight specific enhancers in which mutations could lead to non-syndromic hearing loss, craniofacial defects or limb malformations. © The Author 2012. Published by Oxford University Press. All rights reserved.

Mingrone G.,University Cattolica ore | Panunzi S.,National Research Council Italy | De Gaetano A.,National Research Council Italy | Guidone C.,University Cattolica ore | And 8 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed. METHODS:In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy). RESULTS:At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group). CONCLUSIONS:In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures. (Funded by Catholic University of Rome; number, NCT00888836.) Copyright © 2012 Massachusetts Medical Society.

Cellini F.,Policlinico Universitario Campus Bio Medico | Valentini V.,University Cattolica ore
Current Medicinal Chemistry | Year: 2014

Oesophageal cancer is the sixth cause of cancer-related death worldwide. Nowadays radiochemotherapy (RTCT) plays a central role in the treatment settings of such disease. Evaluation of molecular targeted therapies is an attractive opportunity for the management of oesophageal, GEJ and gastric cancers to improve outcomes as for other primary tumours. Clinical trials focused on the potential of many molecular targeted agents included in CT schedules, and also on the possibility, efficacy and tolerance of their use combined with RT. This review will focus on the over 15 more promising agents studied in combination with RT for esophagogastric tumour, describing the mechanism and target of action, evidences and potential future role on over 50 trials evaluated. Mechanisms of action, studies and evidences about Human Epidermal Growth Factor type 2 Targeting Agents (one of the more promising), Epidermal Growth Factor's Receptor Inhibitors (nowadays showing a lower potential than expected), Vascular Endothelial Growth Factor Inhibitors, Mesenchymal Epithelial Transition Factor, Hepatocyte Growth Factor and other targeting agents are reviewed. © 2014 Bentham Science Publishers.

Bujko K.,lodowska Curie Memorial Cancer Center | Glimelius B.,Uppsala University | Valentini V.,University Cattolica ore | Michalski W.,Bioinformatics and Biostatistics Unit | Spalek M.,lodowska Curie Memorial Cancer Center
European Journal of Surgical Oncology | Year: 2015

Background There is no consensus on the role of postoperative chemotherapy in patients with rectal cancer who have received preoperative radio(chemo)therapy. Materials and methods A systematic review and meta-analysis were performed of trials that used preoperative radio(chemo)therapy and randomized patients either between postoperative chemotherapy and observation or between a fluoropyrimidine only (FU-only) and a fluoropyrimidine with oxaliplatin (FU-OXA) as postoperative chemotherapy. Results Five randomized studies compared postoperative chemotherapy with observation in a total of 2398 patients. None of these trials demonstrated a statistically significant benefit of chemotherapy for OS and DFS. The pooled differences in OS and DFS did not differ statistically significantly between the chemotherapy group and the observation group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were 0.95 (CI: 0.82-1.10), P = 0.49 and 0.92 (CI: 0.80-1.04), P = 0.19, respectively. In the subgroup of trials in which randomization was performed after surgery (n = 753), a statistically significant positive pooled chemotherapy effect was observed for DFS (HR = 0.79, 95% CI: 0.62-1.00, P = 0.047), but not for OS (P = 0.39). Four randomized trials compared adjuvant FU-OXA with adjuvant FU-only in 2710 patients. In two trials, the difference in DFS between groups was statistically significant in favour of FU-OXA, and in the other two trials, the difference was not significant. The pooled difference in DFS between the FU-OXA group and the FU-only group was not statistically significant: HR = 0.84 (CI: 0.66-1.06), P = 0.15. Conclusion The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence. © 2015 Elsevier Ltd. All rights reserved.

The aim of this study was to asses the validity of the TCB nomogram for the European population for predicting significant hyperbilirubinemia in healthy term and late-preterm newborns. This observational study was conducted from February 2009 to December 2009 in the well-baby nurseries of Gemelli hospital of Rome. The predictive ability of the skin bilirubin (TCB) nomogram was prospectively assessed in 926 neonates with gestational age ?35 weeks. TCB was measured with Bilichek and total serum bilirubin (TSB) was contemporary assayed by the standard spectrophotometric method. Every neonate was assess for a single TCB and TSB value. The mean TSB values was 8.2 +/- 3.2 mg/dl, while the mean TCB values was 9.5 +/- 3.6 mg/dl A sensitivity of 100% and a negative predictive value of 100% were obtained with a single bilirubin determination applying the 75 degrees percentile of our nomogram. The 75 degrees percentile of the skin bilirubin nomogram for the European population in the first 96 hours of life is able to predict all neonates at risk of severe hyperbilirubinemia. It could facilitate a safe discharge from the hospital and a targeted intervention and follow-up reducing the need for blood samples.

The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior. We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data. We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis. Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.

Tamburrelli F.C.,University Cattolica ore | Genitiempo M.,University Cattolica ore | Logroscino C.A.,University Cattolica ore
European Spine Journal | Year: 2011

Cauda equina syndrome seems to be a very rare complication of spinal manipulations. Only few cases, in fact, were referred in literature in the past decades. Most of them are very old and poorly documented evoking doubts about the pathogenetic relationship between the spinal maneuvers and the onset of the syndrome. We observed and treated a 42-year-old patient who complained a rapid onset of saddle hypoparesthesia and urine retention only a few hours after the spinal manipulation performed for L5-S1 herniated disc. The comparison of the two following MRIs performed before and after the manipulations seems to prove a close pathogenetic relationship. The patient was operated soon after the admission to our emergency department and 1 year later he referred an incomplete recovery of the syndrome. The case offered the opportunity to update the literature. The review revealed only three cases from the beginning of the current century that confirm the rarity of the syndrome. Based on the data emerging from the official literature, safety of the manipulations and its pathogenetic aspects in causing lumbar radiculopathies are discussed. © 2011 Springer-Verlag.

Panunzi S.,CNR Institute of Neuroscience | De Gaetano A.,CNR Institute of Neuroscience | Carnicelli A.,University Cattolica ore | Mingrone G.,CNR Institute of Neuroscience
Annals of Surgery | Year: 2015

Objective: To compare diabetes remission after bariatric surgery in subjects with body mass index (BMI) of 35 kg/m2 or more or BMI of less than 35 kg/m2 to determine which predictors are best. Background: BMI is currently the only selection criterion for bariatric surgery in diabetic subjects.Many studies have challenged BMI for predicting diabetes remission. Methods: Data sources were PubMed, Cochrane Library, and EMBASE databases from January 1980 to June 2013. The selected studies were randomized controlled trials, controlled clinical trials, or cohort studies with 10 or more patients per arm. Of 1437 screened articles, 94 studies were included with 94,579 patients undergoing surgical procedures (4944 with type 2 diabetes mellitus). Weight, BMI, glycated hemoglobin A1c, fasting glucose, and insulin were abstracted by 2 independent reviewers. The effect size was the percent diabetes remission. Results: Meta-analysis was performed for BMI less than 35 kg/m2 (group 1) and BMI 35 kg/m2 or more (group 2). Diabetes remission was 72% [95% confidence interval (CI), 65-80] in group 1 and 71% (95% CI, 65-77) in group 2. Diabetes resolution was 89% (95% CI, 83-94) after biliopancreatic diversion, 77% (95% CI, 72-82) after Roux-en-Y bypass, 62% (95% CI, 46- 79) after gastric banding, and 60% (95% CI, 51-70) after sleeve gastrectomy. The only significant predictor of glycated hemoglobinA1c reductionwaswaist circumference, lower baseline waist associating with higher reduction. Conclusions: Bariatric surgery determines similar diabetes remission rates in patients with BMI of 35 kg/m2 or more or BMI of less than 35 kg/m2. Baseline BMI is unrelated to diabetes remission. The association of baseline waist circumference with glycated hemoglobin A1c reduction is likely due to selection bias. Bariatric or metabolic effects of the surgical procedures appear independent, and different indices are needed to predict them. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.

Legler S.E.,University Cattolica ore | Caffi T.,University Cattolica ore | Rossi V.,University Cattolica ore
Plant Pathology | Year: 2012

Production and development of the chasmothecia of Erysiphe necator on Vitis vinifera leaves were studied using potted plants in controlled and outdoor environments and grapevines in a vineyard. The optimum temperature for ascocarp production was 20°C; fewer chasmothecia were produced at 15°C and even fewer at 25°C; at 10 and 30°C, no or very few chasmothecia were observed, and none reached maturity. Nonlinear equations describing ascocarp development as a function of time and temperature were developed, parameterized with data from experiments at constant temperatures, and evaluated under fluctuating temperatures. Goodness-of-fit showed high agreement between observed and predicted data: the model efficacy ranged from 0·74 to 0·97 (1·0 indicates a perfect fit), and the root mean square error ranged from 0·001 to 0·01 (zero indicates a perfect fit). The high proportion of the observed variability accounted for by these equations (R 2=0·83-0·98) supported the hypothesis that temperature has a predominant role in ascocarp development under natural conditions, when all environmental factors interact. The equations tended to overestimate the production of mature chasmothecia (the coefficient of residual mass was -0·23), but this inconsistency mainly occurred when rainfall apparently washed the mature chasmothecia from leaves during the logarithmic phase of the ascocarp developmental curve. Results from this work will be useful for predicting the development of chasmothecia in a vineyard and for timing the use of natural products, fungicides or biocontrol agents for reducing the population of chasmothecia, which are all more effective when they are applied to immature chasmothecia. © 2011 The Authors. Plant Pathology © 2011 BSPP.

Tamburrelli F.C.,University Cattolica ore | Proietti L.,University Cattolica ore | Logroscino C.A.,University Cattolica ore
European Spine Journal | Year: 2011

Interspinous devices (IDs) were introduced in the 90s. Since then, they have rapidly become very popular for the minimally invasive treatment of lumbar pain disorders. They feature different shapes and biomechanical characteristics, and are used in the spine degenerative pathologies or as motion segment stabilizers (dynamic stabilization) or to obtain the decompression of neurological structures. The indications seem to be rather narrow and still to be verified in terms of their clinical efficacy. However, IDs are being extensively utilized beyond their classical indications with the inevitable risk of a clinical failure. The aim of the present work was to carry out a critical analysis of the causes of failure in a series of 19 patients. From January 2007 to March 2009, 19 patients with residual painful syndrome after the implantation of IDs were observed. The series includes 11 males and 8 females with a mean age of 53.6 years (range 38-84 years) who were operated on elsewhere and who underwent revision surgery at our hospital. The inclusion criteria were low back pain and/or radiculopathy after the device implantation without improvement of the painful symptomatology, radiculopathy with signs of sensory and motor deficit, intermittent neurogenic claudication, and infection. All patients were thoroughly re-assessed with new standard imaging examinations such as MRI and CT scans, considering the following image features: the position of the device with respect to the spinous processes (X-ray), the intervertebral disc disease of the level operated upon or of the adjacent levels (MRI), the segmental instability (dynamic X-rays), the severity of the canal stenosis (CT). The accurate evaluation of the clinical and imaging parameters revealed three main causes of failure: errors of indication, technical errors and the structural failure of the ID. The most frequent cause of failure was a wrong indication. The results of the study are presented and the causes of failure are discussed in detail. © 2011 Springer-Verlag.

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