Publications by authors named "Stefania Maffei"

12 Publications

  • Page 1 of 1

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome.

J Stroke Cerebrovasc Dis 2021 Jul 5;30(7):105800. Epub 2021 May 5.

Stroke Unit, Neurology Unit, Department of Neuroscience, Ospedale Civile, Azienda Ospedaliera Universitaria di Modena, Via Giardini 1355, Modena, Emilia Romagna 41126, Italy. Electronic address:

Objectives: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting.

Materials And Methods: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors.

Results: We included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 - 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 - 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 - 203.14).

Conclusion: We found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105800DOI Listing
July 2021

Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients.

Eur Stroke J 2020 Jun 13;5(2):138-147. Epub 2019 Nov 13.

Stroke Center and Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.

Introduction: Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous.

Patients And Methods: In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3-6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: <12 g/dl; male: <13 g/dl) and polyglobulia (female: >15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male: <11 g/dl). Normal haemoglobin level (female: 12.0-15.5 g/dl, male: 13.0-17.0 g/dl) served as reference group. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated with logistic regression models.

Results: Among 6866 intravenous thrombolysis-treated stroke patients, 5448 (79.3%) had normal haemoglobin level, 1232 (17.9%) anaemia - of those 903 (13.2%) had mild and 329 (4.8%) moderate/severe anaemia - and 186 (2.7%) polyglobulia. Anaemia was associated with poor outcome (OR 1.25 (1.05-1.48)) and mortality (OR 1.58 (1.27-1.95)). In anaemia subgroups, both mild and moderate/severe anaemia independently predicted poor outcome (OR 1.29 (1.07-1.55) and 1.48 (1.09-2.02)) and mortality (OR 1.45 (1.15-1.84) and OR 2.00 (1.46-2.75)). Each haemoglobin level decrease by 1 g/dl independently increased the risk of poor outcome (OR 1.07 (1.02-1.11)) and mortality (OR 1.08 (1.02-1.15)). Anaemia was not associated with occurrence of symptomatic intracranial haemorrhage. Polyglobulia did not change any outcome.

Discussion: The more severe the anaemia, the higher the probability of poor outcome and death. Severe anaemia might be a target for interventions in hyperacute stroke.

Conclusion: Anaemia on admission, but not polyglobulia, is a strong and independent predictor of poor outcome and mortality in intravenous thrombolysis-treated stroke patients.
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http://dx.doi.org/10.1177/2396987319889468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313367PMC
June 2020

Clinical features of colorectal cancer patients in advanced age: a population-based approach.

Intern Emerg Med 2016 Mar 19;11(2):191-7. Epub 2015 Oct 19.

Medicina 1, Dipartimento di Medicina Diagnostica, Clinica e Sanità Pubblica, Università di Modena e Reggio Emilia, Policlinico, Via del Pozzo n.71, 41100, Modena, Italy.

In the immediate future, the number of geriatric patients will continue to rise; consequently we should expect an increase of colorectal cancer, a disease of the elderly population. Through the data of a Cancer Registry, we examined (a) the effect of ageing on the main features of colorectal cancer; (b) changes in management, especially for individuals older than 80 years; and (c) changes in prognosis and survival in subgroups of patients with different age. The Registry provided information on colorectal cancer up to 2010 (27 years). A total of 5293 patients were registered; these were divided into three groups: A (0-64 years), B (65-79) and C (80 or more). Three periods of observation were chosen: 1 (1984-1992), 2 (1993-2001) and 3 (2001-2010). Group A included 1571 patients (29 %), Group B 2539 (48 %) and Group C 1183 (22.3 %). The fraction of old individuals increased during the 27 years of the investigation. In these patients, tumours were predominantly localized to the right colon (42.6 %). The rate of surgery and ratio between curative and palliative approaches were similar among the three groups (p < 0.38). There was disparity (p < 0.002) in the administration of chemotherapy (5.8 % of the elderly vs 34.4 % in remaining patients). Survival increased over time in all three groups. In the elderly, average 5-year survival was 31 % in period 1 and 55 % in period 3. These data show that in Western countries, the standard of care for colorectal cancer diagnosed in geriatric patients has improved over the last 30 years.
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http://dx.doi.org/10.1007/s11739-015-1286-5DOI Listing
March 2016

Incidence, clinical features and possible etiology of early onset (≤40 years) colorectal neoplasms.

Intern Emerg Med 2014 Sep 9;9(6):623-31. Epub 2013 Aug 9.

Dipartimento di Medicina Diagnostica, Clinica e Sanità Pubblica, Università di Modena e Reggio, Emilia, Italy.

The aim of the study was to investigate the clinical features, including survival, of patients with colorectal malignancies developed at a very early age (≤40 years), together with possible factors involved in the pathogenesis of these rare neoplasms. The study took advantage of the existence of a specialized colorectal cancer Registry active from 1984. 57 patients met the criteria of early onset cancer; main epidemiological data, morphology, stage, familial aggregation, possible role of inheritance and survival were analyzed. Despite the relevant increase over time of all registered patients, joiningpoint analysis of crude incidence rate of early onset colorectal neoplasms revealed a certain stability of these tumors (EAPC: 2.4, CI 14-22) with a constant prevalence of the male sex. Stage at diagnosis did not show significant variations between early onset and maturity onset colorectal neoplasms. Hereditary as well as familial cases were significantly (P < 0.005 and 0.03) more frequent among patients with early onset tumors, although in the majority of them no specific etiological factor could be identified. Survival was more favorable in patients with early onset tumors, though this had to be attributed to the higher presence of some histological types in early onset cases. Survival was significantly more favorable for patients of all ages registered in the last decade. Incidence of early onset colorectal cancer was relatively stable between 1984 and 2008. A male preponderance was evident through the registration period. Hereditary and familial cases were significantly more frequent among early onset case. A well defined etiology could be observed in 16% of the cases (versus 2-3% in older individuals). Five-year survival showed a significant improvement over time.
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http://dx.doi.org/10.1007/s11739-013-0981-3DOI Listing
September 2014

Disease presentation, treatment and survival for Italian colorectal cancer patients: a EUROCARE high resolution study.

Eur J Public Health 2014 Feb 31;24(1):98-100. Epub 2013 May 31.

1 Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

We analysed presentation, treatment and survival in a representative population-based sample of 3753 Italian colorectal cancer cases, diagnosed 2003-05: 70% were >65 years, 44% stage I-II, 27% stage IV and 92% received surgery. Chemotherapy was given to 58% of stage III colon cases, radiotherapy to 25% of rectal cases. Four percent of surgical cases underwent endoscopic polypectomy, and in 57% ≥11 lymph nodes were examined. Five-year relative survival was good (60%), independent of sex and site. Adherence to treatment guidelines was satisfactory, but wider use of faecal blood testing and colonoscopy will anticipate stage at diagnosis and likely improve survival.
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http://dx.doi.org/10.1093/eurpub/ckt056DOI Listing
February 2014

Altered expression of apoptosis biomarkers in human colorectal microadenomas.

Cancer Epidemiol Biomarkers Prev 2010 Feb;19(2):351-7

Department of Anatomy and Histology, University of Modena and Reggio Emilia, Modena, Italy.

Human colorectal microadenomas are considered the earliest detectable premalignant lesions in the colon. They can be identified as aggregates of enlarged crypts with thicker epithelial linings and elongated luminal openings on the colonic mucosal surface after methylene blue staining and observation under a dissecting microscope. Multiple lines of evidence suggest that a central role in neoplastic development is played by the inhibition of apoptosis, followed by disruption of DNA repair. Understanding the early mechanisms of colorectal carcinogenesis may help develop new approaches of colorectal cancer prevention and treatment. The aim of the present study was to quantify poly-ADP ribose polymerase 1 (PARP-1)-positive cells and to evaluate apoptotic control mechanisms through Caspase-3 active and Bcl-2 protein expression in human microadenomas and in normal colorectal mucosa using immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments. The mean percentage of PARP-1-positive epithelial cells was 3.0 +/- 0.37% (SD) and 15.67 +/- 0.40% in microadenoma and in normal mucosa, respectively. Proteins involved in programmed cell death were differently expressed in microadenoma and in normal mucosa. Indeed, by semiquantitative immunofluorescence analysis, confirmed by Western blot, microadenoma showed low levels of Caspase-3 active and high levels of Bcl-2 expression, whereas the opposite was true for normal colorectal mucosa [corrected]. In the stroma of normal colorectal mucosa, fibroblast-like cells and neutrophils were the cells that underwent apoptosis to a greater extent. In conclusion, malfunction of the control mechanisms of programmed cell death seems present in the early stages of colorectal cancer development.
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http://dx.doi.org/10.1158/1055-9965.EPI-09-0438DOI Listing
February 2010

Relative role of APC and MUTYH mutations in the pathogenesis of familial adenomatous polyposis.

Scand J Gastroenterol 2009 ;44(9):1092-100

Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Objective: Familial adenomatous polyposis (FAP) is an interesting model for the study of colorectal tumour. Two genes contribute to the FAP phenotype - APC and MUTYH - but their relative role is still undefined. The objective of this study was to evaluate the contribution of the two genes to the pathogenesis of FAP by means of a series of FAP families.

Material And Methods: Sixty-one unrelated families with a diagnosis of FAP and a total of 187 affected individuals were evaluated. After extracting DNA, APC and MUTYH genes were sequenced.

Results: In the whole series of patients, colectomy with ileorectal anastomosis was the most frequent surgery, although the number of patients treated by total proctocolectomy and ileoanal anastomosis was increasing. Duodenal and jejunal-ileal adenomas were present in more than half of the patients. Constitutional mutations were detected in 37 of the 45 families (82.2%); there were 33 families with APC and 4 with MUTYH alterations. Age at onset of polyposis and age at surgery were 10-15 years delayed for carriers of MUTYH mutations; cancer at diagnosis was frequent, and extracolonic manifestations were diagnosed in the majority of MUTYH-positive families. MUTYH-associated polyposis showed the horizontal transmission expected for recessive inheritance (at variance with the dominant pattern seen with APC mutations).

Conclusions: At least two genes are associated with the FAP phenotype. APC mutations account for the majority of cases, while MUTYH mutations can be observed in 10% of patients. There are few but definite differences between APC- and MUTYH-associated FAP, such as age at diagnosis and pattern of transmission.
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http://dx.doi.org/10.1080/00365520903100481DOI Listing
February 2010

BRAF mutations in multiple sebaceous hyperplasias of patients belonging to MYH-associated polyposis pedigrees.

J Invest Dermatol 2007 Jun 1;127(6):1387-91. Epub 2007 Feb 1.

Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.

The characteristics of sebaceous gland hyperplasia (SGH) consist of yellowish or skin-colored papules and nodules. Chronic sun exposure and immunosuppressed conditions are the main environmental risk factors, whereas chronological aging regulated by hormones and molecular changes are the intrinsic risk factors. We have evaluated the contribution of BRAF, K-Ras, and N-Ras mutations to the pathogenesis of SGHs in four patients belonging to three MYH-associated polyposis (MAP) pedigrees. MAP is an autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. Immunohistochemistry of mismatch repair and APC proteins was performed. DNA isolated from blood lymphocytes and formalin-fixed or paraffin-embedded SGHs was PCR amplified and sequenced. In the SGH patients, we detected T1796A heterozygous substitution (V600E) in the BRAF gene. Compound biallelic germline MYH mutations (Y165C/G382D, R168H/379delC, and Y90X/delGGA464) were detected in the MAP patients. In contrast to the majority of melanocytic lesions, activating hotspot mutations in BRAF have not been involved so far in the pathogenesis of SGH. BRAF mutation is not a specific marker of melanocytic cancerogenesis, and it can also be involved in SGHs. In both melanocytic and non-melanocytic skin tumors, BRAF mutation is linked to early tumorigenesis events.
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http://dx.doi.org/10.1038/sj.jid.5700723DOI Listing
June 2007

Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis.

Gastroenterology 2006 Aug;131(2):439-44

Division of Pathology, Hospital of Carpi, Modena, Italy.

Background & Aims: MYH-associated polyposis is a recently described, autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. There are only few immunohistochemical studies of the MYH protein. We investigated the expression pattern of the MYH protein to evaluate whether a immunohistochemical approach could be used in clinical practice to screen patients for germline mutations in the MYH gene.

Methods: The expression of MYH, MSH2, MLH1, and MSH6 proteins was studied by immunohistochemistry in 20 samples (colorectal adenomas or cancer) from 18 patients with biallelic MYH mutation, in 11 samples from patients with germline adenomatous polyposis coli (APC) mutations, in 20 samples from patients with sporadic colorectal cancers, and in 10 samples from patients with normal colonic mucosa without malignancies.

Results: In all cases the mismatch repair proteins were expressed normally. Nuclear and cytoplasmic immunoreactivity for the MYH protein were observed in normal colorectal mucosa, in sporadic colorectal carcinomas, and in adenomas and carcinomas from patients carrying APC germline mutations. Adenomas and carcinomas from patients with MYH biallelic mutation showed a different pattern of expression: a strong granular cytoplasmic staining was observed without any nuclear expression. The same immunophenotype was observed in the surrounding normal mucosa.

Conclusions: Patients with biallelic MYH mutations showed disappearance of staining from the nucleus, and segregation of immunoreactivity in the cytoplasm, both in neoplastic and surrounding healthy mucosa. Because this pattern of expression seems to be specific for biallelic mutations, it follows that immunohistochemistry might be used in clinical practice to screen patients at risk for MYH-associated polyposis.
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http://dx.doi.org/10.1053/j.gastro.2006.05.049DOI Listing
August 2006

Microsatellite instability and colorectal cancer prognosis.

Clin Cancer Res 2005 Dec;11(23):8332-40

Department of Medicine and Medical Specialties, University of Modena and Reggio Emilia, Modena, Italy.

Purpose: Many studies have evaluated the role of high levels of microsatellite instability (MSI) as a prognostic marker and predictor of the response to chemotherapy in colorectal cancer (CRC); however, the results are not conclusive. The aim of this study was to analyze the prognostic significance of high levels of MSI (MSI-H) in CRC patients in relation to fluorouracil-based chemotherapy.

Experimental Design: In three different institutions, 1,263 patients with CRC were tested for the presence of MSI, and CRC-specific survival was then analyzed in relation to MSI status, chemotherapy, and other clinical and pathologic variables.

Results: Two hundred and fifty-six tumors were MSI-H (20.3%): these were more frequently at a less advanced stage, right-sided, poorly differentiated, with mucinous phenotype, and expansive growth pattern than microsatellite stable carcinomas. Univariate and multivariate analyses of 5-year-specific survival revealed stage, tumor location, grade of differentiation, MSI, gender, and age as significant prognostic factors. The prognostic advantage of MSI tumors was particularly evident in stages II and III in which chemotherapy did not significantly affect the survival of MSI-H patients. Finally, we analyzed survival in MSI-H patients in relation to the presence of mismatch repair gene mutations. MSI-H patients with hereditary non-polyposis colorectal cancer showed a better prognosis as compared with sporadic MSI-H; however, in multivariate analysis, this difference disappeared.

Conclusions: The type of genomic instability could influence the prognosis of CRC, in particular in stages II and III. Fluorouracil-based chemotherapy does not seem to improve survival among MSI-H patients. The survival benefit for patients with hereditary non-polyposis colorectal cancer is mainly determined by younger age and less advanced stage as compared with sporadic MSI-H counterpart.
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http://dx.doi.org/10.1158/1078-0432.CCR-05-1030DOI Listing
December 2005

Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes.

Am J Gastroenterol 2005 Oct;100(10):2280-7

Department of Pathology, University of Modena and Reggio, Emilia, Italy.

Objectives: Colorectal cancer (CRC) occurs rarely in young individuals (<45 yr) and represents one of the criteria for suspecting hereditary cancer families. In this study we evaluated clinical features and molecular pathways (chromosomal instability [CIN] and microsatellite instability [MSI]) in early-onset CRC of 71 patients.

Methods: Detailed family and personal history were obtained for each patient. Expression of APC, beta-catenin, p53, MLH1, MSH2, and MSH6 genes was evaluated by immunohistochemistry. MSI analysis was performed and constitutional main mutations of the mismatch repair (MMR) genes were searched by gene sequencing.

Results: Fourteen (19.7%) out of the 71 cases showed both MSI and altered expression of MMR proteins. In the 57 MSI-negative (MSI-) lesions altered expression of APC, beta-catenin, and p53 genes were found more frequently than in MSI-positive(MSI+) tumors. Seven (50%) out of the 14 patients with MSI+ tumors presented clinical features of Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) and in all but one, constitutional mutations in MLH1 or MSH2 genes could be detected. The same mutations were also found in other family members.

Conclusions: Our study demonstrates the involvement of CIN in a majority of early-onset colorectal tumors. Furthermore, we identified Lynch syndromes in seven cases (50%) of early-onset colorectal carcinomas with impairment of the MMR system. These results suggest that patients with early-onset CRC should be screened for hereditary cancer syndrome through clinical and molecular characterizations.
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http://dx.doi.org/10.1111/j.1572-0241.2005.00223.xDOI Listing
October 2005

MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients.

AIDS 2003 Jul;17(11):1696-8

Department of Biomedical Sciences, University of Modena and Reggio Emilia School of Medicine, via Campi 287, 41100 Modena, Italy.

P-glycoprotein, a membrane-localized protein transporter, codified by the MDR1 gene, influences the response to pharmacological treatments, including antiretroviral drugs. MDR1 polymorphism C3435T is correlated with the functionality of the protein. We investigated the influence of this polymorphism in the reconstitution of the peripheral CD4 T cell pool in 149 drug-naive HIV-positive patients starting highly active antiretroviral therapy. The MDR1 C3435Tpolymorphism did not influence response to therapy, suggesting no disadvantages for individuals with a different genotype.
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http://dx.doi.org/10.1097/00002030-200307250-00016DOI Listing
July 2003