Boeckxstaens G.E.,Catholic University of Leuven |
Annese V.,Ospedale Casa Sollievo Della Sofferenza |
Des Varannes S.B.,University of Nantes |
Chaussade S.,Cochin University Hospital |
And 8 more authors.
New England Journal of Medicine | Year: 2011
BACKGROUND: Many experts consider laparoscopic Heller's myotomy (LHM) to be superior to pneumatic dilation for the treatment of achalasia, and LHM is increasingly considered to be the treatment of choice for this disorder. METHODS: We randomly assigned patients with newly diagnosed achalasia to pneumatic dilation or LHM with Dor's fundoplication. Symptoms, including weight loss, dysphagia, retrosternal pain, and regurgitation, were assessed with the use of the Eckardt score (which ranges from 0 to 12, with higher scores indicating more pronounced symptoms). The primary outcome was therapeutic success (a drop in the Eckardt score to ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for retreatment, pressure at the lower esophageal sphincter, esophageal emptying on a timed barium esophagogram, quality of life, and the rate of complications. RESULTS: A total of 201 patients were randomly assigned to pneumatic dilation (95 patients) or LHM (106). The mean follow-up time was 43 months (95% confidence interval [CI], 40 to 47). In an intention-to-treat analysis, there was no significant difference between the two groups in the primary outcome; the rate of therapeutic success with pneumatic dilation was 90% after 1 year of follow-up and 86% after 2 years, as compared with a rate with LHM of 93% after 1 year and 90% after 2 years (P = 0.46). After 2 years of follow-up, there was no significant between-group difference in the pressure at the lower esophageal sphincter (LHM, 10 mm Hg [95% CI, 8.7 to 12]; pneumatic dilation, 12 mm Hg [95% CI, 9.7 to 14]; P = 0.27); esophageal emptying, as assessed by the height of barium-contrast column (LHM, 1.9 cm [95% CI, 0 to 6.8]; pneumatic dilation, 3.7 cm [95% CI, 0 to 8.8]; P = 0.21); or quality of life. Similar results were obtained in the per-protocol analysis. Perforation of the esophagus occurred in 4% of the patients during pneumatic dilation, whereas mucosal tears occurred in 12% during LHM. Abnormal exposure to esophageal acid was observed in 15% and 23% of the patients in the pneumatic-dilation and LHM groups, respectively (P = 0.28). CONCLUSIONS: After 2 years of follow-up, LHM, as compared with pneumatic dilation, was not associated with superior rates of therapeutic success. (European Achalasia Trial Netherlands Trial Register number, NTR37, and Current Controlled Trials number, ISRCTN56304564.) Copyright © 2011 Massachusetts Medical Society.
Lo-Coco F.,University of Rome Tor Vergata |
Lo-Coco F.,Santa Lucia Foundation |
Avvisati G.,Biomedical University of Rome |
Vignetti M.,Data Center |
And 39 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity. METHODS: We conducted a phase 3, multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk (white-cell count, ≤10×109per liter). Patients were randomly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA- idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA. The study was designed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5%. RESULTS: Complete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated (100%) and in 75 of 79 patients in the ATRA-chemotherapy group (95%) (P = 0.12). The median follow-up was 34.4 months. Two-year event-free survival rates were 97% in the ATRA-arsenic trioxide group and 86% in the ATRA-chemotherapy group (95% confidence interval for the difference, 2 to 22 percentage points; P<0.001 for noninferiority and P = 0.02 for superiority of ATRA-arsenic trioxide). Overall survival was also better with ATRA-arsenic trioxide (P = 0.02). As compared with ATRA-chemotherapy, ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity. CONCLUSIONS: ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. Copyright © 2013 Massachusetts Medical Society.
PubMed | Hopital Robert Debre, Otto Von Guericke University of Magdeburg, Ospedale Casa Sollievo della Sofferenza, University of Belgrade and 11 more.
Type: | Journal: Human mutation | Year: 2017
Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu
Salvador R.,University of Padua |
Annese V.,Ospedale Casa Sollievo della Sofferenza |
Bruley Des Varannes S.,University of Nantes |
Chaussade S.,Cochin University Hospital |
And 5 more authors.
Gastroenterology | Year: 2013
Background & Aims: Patients with achalasia are treated with either pneumatic dilation (PD) or laparoscopic Heller myotomy (LHM), which have comparable rates of success. We evaluated whether manometric subtype was associated with response to treatment in a large population of patients treated with either PD or LHM (the European achalasia trial). Methods: Esophageal pretreatment manometry data were collected from 176 patients who participated in the European achalasia trial. Symptoms (weight loss, dysphagia, retrosternal pain, and regurgitation) were assessed using the Eckardt score; treatment was considered successful if the Eckardt score was 3 or less. Manometric tracings were classified according to the 3 Chicago subtypes. Results: Forty-four patients had achalasia type I (25%), 114 patients had achalasia type II (65%), and 18 patients had achalasia type III (10%). After a minimum follow-up period of 2 years, success rates were significantly higher among patients with type II achalasia (96%) than type I achalasia (81%; P <.01, log-rank test) or type III achalasia (66%; P <.001, log-rank test). The success rate of PD was significantly higher than that of LHM for patients with type II achalasia (100% vs 93%; P <.05), but LHM had a higher success rate than PD for patients with type III achalasia (86% vs 40%; P =.12, difference was not statistically significant because of the small number of patients). For type I achalasia, LHM and PD had similar rates of success (81% vs 85%; P =.84). Conclusions: A higher percentage of patients with type II achalasia (based on manometric tracings) are treated successfully with PD or LHM than patients with types I and III achalasia. Success rates in type II are high for both treatment groups but significantly higher in the PD group. Patients with type III can probably best be treated by LHM. Trialregister.nl number NTR37; ISRCTN56304564. © 2013 AGA Institute.
PubMed | Ospedale Casa Sollievo Della Sofferenza, Azienda Ospedaliera Universitaria Verona, Azienda Ospedaliera Universitaria, Ospedali Civili di Brescia and 8 more.
Type: | Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | Year: 2016
This registry was created to describe the experience of 76 Italian centres with a large cohort of recipients of multipoint pacing (MPP) capable cardiac resynchronization therapy (CRT) devices.A total of 507 patients in whom these devices had been successfully implanted were enrolled between August 2013 and May 2015. We analysed: (i) current clinical practices for the management of such patients, and (ii) the impact of MPP on heart failure clinical composite response and on the absolute change in ejection fraction (EF) at 6 months. Multipoint pacing was programmed to ON in 46% of patients before discharge. Methods of optimizing MPP programming were most commonly based on either the greatest narrowing of the QRS complex (38%) or the electrical delays between the electrodes (34%). Clinical and echocardiographic follow-up data were evaluated in 232 patients. These patients were divided into two groups according to whether MPP was programmed to ON (n = 94) or OFF (n = 138) at the time of discharge. At 6 months, EF was significantly higher in the MPP group than in the biventricular-pacing group (39.1 9.6 vs. 34.7 7.6%; P < 0.001). Even after adjustments, early MPP activation remained an independent predictor of absolute increase in LVEF of 5% (odds ratio 2.5; P = 0.001). At 6 months, an improvement in clinical composite score was recorded in a greater proportion of patients with MPP-ON than in controls (56 vs. 38%; P = 0.009). On comparing optimal MPP and conventional vectors, QRS was also seen to have decreased significantly (P < 0.001).This study provides information that is essential in order to deal with the expected increase in the number of patients receiving MPP devices in the coming years. The results revealed different practices among centres, and establishing the optimal programming that can maximize the benefit of MPP remains a challenging issue. Compared with conventional CRT, MPP improved clinical status and resulted in an additional increase in EF.http://www.clinicaltrial.gov/. Unique identifier: NCT02606071.
PubMed | University of Turin, Ospedale Casa Sollievo della Sofferenza, University of New South Wales, University of Bonn and 13 more.
Type: Journal Article | Journal: Hepatology (Baltimore, Md.) | Year: 2016
A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio = 1.39, 95% confidence interval 1.04-1.87, and odds ratio = 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection.The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (Hepatology 2016;64:34-46).
Zuccarello D.,University of Padua |
Dallapiccola B.,Bambino Gesu Pediatric Hospital |
Novelli A.,Ospedale Casa Sollievo della Sofferenza |
Foresta C.,University of Padua
European Journal of Medical Genetics | Year: 2010
A mosaic ring chromosome 22 (mos 46,XY,r(22)/45,XY,-22) was found in an euploid azoospermic otherwise phenotypically normal individual. Testicular cytological analysis showed hypospermatogenesis with a complete spermatogonial arrest. The majority of subjects with constitutional r(22) are dysmorphic and mentally retarded due to deletion of a sizable segment of the chromosome 22q. Only a few cases of r(22) chromosome are known in which deletion of the very distal telomeric regions is associated with unremarkable phenotype and fertility, both in males and females. The present patient is the first example of male infertility associated with this cytogenetic anomaly. It is likely that infertility arose from a mechanical block of meiosis, resulting from pairing failure of chromosomes 22, similarly to azoospermia occurring in few known males with r(21) chromosomes. © 2010 Elsevier Masson SAS.
Eslam M.,University of Sydney |
Leung R.,University of Sydney |
Romero-Gomez M.,Hospital Universitario Of Valme |
Mangia A.,Ospedale Casa Sollievo della Sofferenza |
And 15 more authors.
Journal of Hepatology | Year: 2014
Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.