Cortelezzi A.,University of Milan |
Sciume M.,University of Milan |
Liberati A.M.,University of Perugia |
Vincenti D.,University of Milan |
And 22 more authors.
Leukemia | Year: 2014
We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m 2) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features. © 2014 Macmillan Publishers Limited.
Gharavi A.G.,Columbia University |
Kiryluk K.,Columbia University |
Choi M.,Howard Hughes Medical Institute |
Li Y.,Columbia University |
And 51 more authors.
Nature Genetics | Year: 2011
We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 -10'26 and 4.84-10'9 and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures. © 2011 Nature America, Inc. All rights reserved.
PubMed | University of Rome La Sapienza, University of Genoa, University of Piemonte Orientale, San Giovanni Battista Hospital and 13 more.
Type: Clinical Trial, Phase II | Journal: Leukemia | Year: 2014
We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dellAdulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m(2)) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade 3 neutropenia was observed in 61.7% of patients; however, grade 3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features.
Lamberti I.,University of Modena and Reggio Emilia |
Buzzetti E.,University of Modena and Reggio Emilia |
Cristani A.,Azienda Ospedaliero Universitaria Policlinico di Modena
Recenti Progressi in Medicina | Year: 2013
It is well known that strenuous exercise training can induce an overproduction of reactive oxygen species with subsequent impairment of cellular macromolecules and metabolism, leading to cellular dysfunction. In elite athletes, reactive oxygen species can add to other injurious factors for muscle tissue; therefore special precautions are required to avoid an increase in injury risk.
Marchioni D.,Azienda Ospedaliero Universitaria Policlinico di Modena |
Alicandri-Ciufelli M.,Azienda Ospedaliero Universitaria Policlinico di Modena |
Molteni G.,Azienda Ospedaliero Universitaria Policlinico di Modena |
Genovese E.,Azienda Ospedaliero Universitaria Policlinico di Modena |
Presutti L.,Azienda Ospedaliero Universitaria Policlinico di Modena
Laryngoscope | Year: 2010
Objectives: Patients undergoing endoscopic middle ear surgery require reconstruction procedures that are able to give adequate functional results, with particular attention to ventilation of middle ear routes and mastoid tissue preservation. Study Design: Outcome research on a prospective case series in a tertiary university referral center. Methods: A case series of 27 patients with attic retraction pockets underwent endoscopic middle ear surgical procedures. Three kinds of tympanoplasty were selected and performed. Results: In all 27 subjects, it was possible to preserve the mastoid bone and the epitympanic-mastoid mucosa by performing a transcanal endoscopic approach. In total, 21 of 27 (77.7%) subjects presented no recurrence of the disease at 20.1 months mean follow-up. Conclusions: Three main types of endoscopic tympanoplasty can be performed for surgical treatment of attic retraction pockets, preserving as much as possible the ventilation routes, physiology, and anatomy of the middle ear. © 2010 The American Laryngological, Rhinological and Otological Society, Inc.
PubMed | Azienda Ospedaliero Universitaria Policlinico di Modena
Type: Journal Article | Journal: Logopedics, phoniatrics, vocology | Year: 2011
OBJECTIVES. Vocal fold paralysis can have a significant impact on a patients quality of life. The aim of this study was to analyze, in terms of vocal improvement and motility recovery, the post-vocal treatment results of patients with unilateral vocal fold paralysis (UVFP) who underwent early voice therapy. Study design. A 7 years prospective study of patients with an UVFP who underwent our multidimensional diagnostic-therapeutic assessment. MATERIAL AND METHODS. Seventy-four patients with UVFP were included in the study. All patients underwent a voice therapy based on forcible exercises supplemented by manipulations and maneuvers. A pre and post-treatment objective voice evaluation and self-assessment was made.Out of 74 patients with UVFP, 51 (68.9%) recovered vocal fold motility. In 23 (31.1%), UVFP persisted after voice therapy. In this group of patients, a complete glottal closure was seen in 5 before voice therapy and in 13 after; An important and significant (p <0.0001) reduction in fundamental frequency (F(o)) was found; a manifest improvement was seen for the mean values of Jitter (Jitt%; p = 0.001), Shimmer (Shim%; p <0.0001) and noise-to-harmonic ratio (NHR) (p <0.0001). The same statistical comparisons calculated for male patients alone was not significant for Jitt% (0.102), Shim% (0.112) and NHR (0.155), as a result of the reduced number of patients in this group. Voice Handicap Index (VHI) values showed a clear and significant improvement and mean maximum phonation time (MPT) increased significantly. CONCLUSION. Early voice therapy based on an energetic approach, combined with patient co-operation, motivation and understanding through educated participation in the voice restoration process, strengthen the idea that patients with UVFP have a good chance of recovering vocal fold motility or improving their voice quality.
PubMed | Azienda Ospedaliero Universitaria Policlinico di Modena
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2014
Telaprevir (TVR) plus peg interferon (PEG-IFN) and ribavirin (RBV) substantially increase treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection but data about its safety in HIV patients with cirrhosis are lacking. Our purpose was to evaluate estimated Glomerular Filtration Rates (eGFR) variations during combination therapy in a difficult-to-treat HIV/HCV population with advanced fibrosis/cirrhosis through three different scores commonly used in clinical practice: CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), Modification of Diet in Renal Disease (MDRD) scores (that consider gender, ethnicity, age, serum creatinine level [SCL]) and MDRD 6 variable (that considers the previous parameters plus blood urea nitrogen and serum albumin). Second objective was to identify any association between creatinin clearance and haemoglobin (Hb) variation during combination therapy.We conducted an observational retrospective study including 18 HIV/HCV patients attending our clinic who started combination therapy for HCV, including in the analysis the first 16 weeks of therapy. Treatment included TVR 1125 mg BID (twice a day) for 12 weeks, PEG-IFN -2a 180 mcg QW and RBV daily dose according to body weight (800 mg in individuals <60 kg; 1000 mg in individuals 60-75 kg; 1200 mg in individuals >75 kg). Advanced fibrosis was defined as Metavir score=F3 or Ishak 3-4 and cirrhosis was defined as Metavir score F4 or Ishak 5-6 assessed by liver biopsy or transient elastography respectively. P per trend were assessed to evaluate any change of SCL and eGFR (according to different formulas). Multilevel linear regression analysis was performed to estimate factors associated with reduction of Hb.Baseline characteristics and HCV virological responses were collected. Figure 1 shows median SCL and eGFR trends across follow-up period: SCR p-per-trend was 0.28, for CKD-EPI was 0.50, for MDRD was 0.48, for MDRD-6 variables was 0.27. Hb trend was also assessed and a significant decrease of Hb across follow-up (p per trend <0.001) was noted. Multilevel regression analysis found an association between SCL and Hb change, after adjustment for age, sex, basal BMI, tenofovir exposure and proteinuria (assessed at baseline) as shown in Table 1.In our experience, combination therapy with TPV in cirrhotic HIV-HCV patients did not significantly affect renal function. As expected, Hb levels decreased during treatment and it is likely related to RBV exposure. In multivariable analysis, reduction of Hb appeared to be related to SCL higher levels, thus suggesting even a mild decrease of renal function.
PubMed | Azienda Ospedaliero Universitaria Policlinico di Modena
Type: Journal Article | Journal: Anticancer research | Year: 2015
Aim of the study was to evaluate feasibility and toxicities of exclusive radiosurgery using tomotherapy in patients with brain oligo-metastases.Between 2008 and 2013 68 patients underwent stereotactic radiosurgery (SRS). Mean patient age was 63 years. Brain was the only site involved in 32 patients, while 36 had extracranial disease. Pre-SRS MRI 56 patients had sovratentorial lesions, 10 subtentorial and 2 patients had both. Fifty-two patients had 1 brain lesion, 11 had 2, and 5 patients had three. All patients underwent SRS using Tomotherapy. The median delivered dose was 18 Gy.After a mean follow-up of 13 months, 14 patients were alive, while 54 patients had died. Two patients had complete response, 32 had partial response, 21 stable disease and 13 disease progression. Overall response rate was 80.9%. One- and two-year overall survival were 41,2% and 24,7%, while local control 61.5% and 37.7%. Toxicity was acceptable.SRS using tomotherapy has been proven feasible as non-invasive exclusive treatment for oligometastatic patients with good prognostic score.
PubMed | Azienda Ospedaliero Universitaria Policlinico di Modena, Modena University Hospital and Karolinska University Hospital
Type: Journal Article | Journal: Journal of plastic, reconstructive & aesthetic surgery : JPRAS | Year: 2016
Reconstruction of composite orbital defects must address the orbit and an exposed skull base and/or maxillary region. The orbit should not only be covered but also reshaped to accommodate the orbital contents or an epithesis when warranted. This study presents a rationale for a near-anatomical reconstruction of the orbit, together with adjacent dead space obliteration, using the segmentalized osteo-fascia-cutaneous fibula flap. Before the flap transfer, a cutting template for the fibula is made according to the measures and requirements of the facial defect. The segmentalized bone is then osteosynthesized to the facial skeleton and revascularized. Thus, an orbital depth is created by the bony fibula, whereas the fascio-cutaneous part of the flap may be used for lining the orbit and obliteration of the skull base or the maxillary region, or resurface the palate and/or the nasal cavity.
PubMed | Azienda Ospedaliero Universitaria Policlinico di Modena, University of Bologna and Instituto Oncologico Veneto Iov Irccs
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2013
Mutations of genes encoding the subunits of the succinate dehydrogenase (SDH) complex were described in KIT/PDGFRA wild-type GIST separately in different reports. In this study, we simultaneously sequenced the genome of all subunits, SDHA, SDHB, SDHC, and SDHD in a larger series of KIT/PDGFRA wild-type GIST in order to evaluate the frequency of the mutations and explore their biological role. SDHA, SDHB, SDHC, and SDHD were sequenced on the available samples obtained from 34 KIT/PDGFRA wild-type GISTs. Of these, in 10 cases, both tumor and peripheral blood (PB) were available, in 19 cases only tumor, and in 5 cases only PB. Overall, 9 of the 34 patients with KIT/PDGFRA wild-type GIST carried mutations in one of the four subunits of the SDH complex (six patients in SDHA, two in SDHB, one in SDHC). WB and immunohistochemistry analysis showed that patients with KIT/PDGFRA wild-type GIST who harbored SDHA mutations exhibited a significant downregulation of both SDHA and SDHB protein expression, with respect to the other GIST lacking SDH mutations and to KIT/PDGFRA-mutated GIST. Clinically, four out of six patients with SDHA mutations presented with metastatic disease at diagnosis with a very slow, indolent course. Patients with KIT/PDGFRA wild-type GIST may harbor germline and/or de novo mutations of SDH complex with prevalence for mutations within SDHA, which is associated with a downregulation of SDHA and SDHB protein expression. The presence of germline mutations may suggest that these patients should be followed up for the risk of development of other cancers.