Publications by authors named "Anna Proia"

18 Publications

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GITMO REGISTRY STUDY ON ALLOGENEIC TRANSPLANTATION IN PATIENTS AGED OVER 60 FROM 2000 TO 2017. IMPROVEMENTS AND CRITICISMS.

Transplant Cell Ther 2021 Nov 21. Epub 2021 Nov 21.

Unit of Haematology and Stem Cell Transplant Centre, "San Camillo" Hospital, Rome, Italy.

Background: Nowadays, allogeneic stem cell transplantation (Allo-SCT) can be offered to patients up to the age of 70-72 years and represents one of the most effective curative treatments for many hematological malignancies.

Objectives: The primary objective of the study is to collect data from the allo-SCTs performed in Italy from 2000 to 2017 in patients over 60 years of age to evaluate the changes in safety and efficacy outcomes as well as their distribution and characteristics over time.

Study Design: The GITMO AlloEld study (ClinicalTrials.gov: NCT04469985) is a retrospective, analysis of the allo-SCTs performed 30 Italian transplant Centers on older patients (≥ 60 years) from 2000 to 2017 (n=1,996).

Results: For the purpose of analysis, patients were grouped into three time periods: time A: 2000-2005, n=256 (12%); time B: 2006-2011, n=584 (29%); and time C: 2012-2017, n=1156 (59%). After a median follow-up of 5.6 years, the 5-year Non Relapse Mortality (NRM) remained stable (time A: 32.8%; time B: 36.2%; and time C: 35.0%, p = 0.5); the Overall Survival (OS) improved (time A: 28.4%; time B: 31.8%; and time C: 37.3%, p = 0.012); and the Cumulative Incidence of Relapse (CIR) reduced (time A: 45.3%; time B: 38.2%; time C: 30.0%, p < 0.0001). The 2-year incidence of extensive cGVHD reduced significantly (time A: 17.2%; time B: 15.8%; and time C: 12.2%, p = 0.004). Considering times A and B together (2000-2011), the 2-year NRM was positively correlated to the HCT-CI score; patients with HCT-CI of 0, 1 or 2, or ≥3 had rates of NRM of 25.2%, 33.9%, and 36.1%, respectively, (p < 0.001). Meanwhile, after 2012, the HCT-CI score was not significantlly predictive of NRM.

Conclusions: The study shows that the transplant procedure in elderly patients became more effective over time. Relapse incidence remains the major problem and strategies to prevent it are under investigation (e.g. post-transplant maintenance). Today, the selection of patients aged over 60 could be improved by combining HCT-CI and frailty assessments to better predict NRM.
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http://dx.doi.org/10.1016/j.jtct.2021.11.006DOI Listing
November 2021

Post-Transplantation Cyclophosphamide for Graft-versus- Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation: First Comparison by Donor Type. A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

Transplant Cell Ther 2021 Sep 17. Epub 2021 Sep 17.

Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.

Graft-versus-host disease (GVHD) remains among the major causes of treatment failure in patients with multiple myeloma (MM) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The use of post-transplantation cyclophosphamide (PT-Cy) is now a well-established and widely used method for GVHD prophylaxis after HLA haploidentical HCT. However, the rationale for using PT-Cy in the setting of matched donor transplantation is less apparent, given the lesser degree of bidirectional alloreactivity. In this retrospective study, we investigated the role of PT-Cy as GVHD prophylaxis in patients with multiple myeloma underoing allo-HCT, among different donor types, to determine cumulative incidence of acute and chronic GVHD and impact on engraftment, progression-free survival (PFS), GVHD-free/relapse- free survival (GRFS), overall survival (OS), and NRM A total of 295 patients with MM underwent allo-HCT using grafts from a matched related donor (MRD; n = 67), matched unrelated donor (MUD; n = 72), mismatched related or unrelated donor (MMRD/MMUD, 1 antigen; n = 27), or haploidentical donor (haplo; n = 129) using PT-Cy between 2012 and 2018. In addition to PT-Cy, agents used in GVHD prophylaxis included calcineurin inhibitors in 239 patients (81%), with mycophenolate mofetil in 184 of those 239 (77%). For grade II-IV acute GVHD, the cumulative incidence at day +100 was 30% (95% confidence interval [CI], 25% to 36%), 9% (95% CI, 5% to 12%) for grade III-IV acute GVHD, and 27% (95% CI, 21% to 32%) for chronic GVHD (limited, 21%; extensive, 6%), with no differences by donor type. The median time to neutrophil engraftment was 19d (95% CI, 18-19), with no significant difference by donor type. The median time to platelet engraftment was delayed in haploidentical donor graft recipients (27 days versus 21 days; P < .001). Two-year OS, PFS, GRFS, and NRM were 51% (95% CI, 45% to 58%), 26% (95% CI, 20% to 32%), 24% (95% CI, 18% to 30%), and 19% (95% CI, 14% to 24%), respectively, with no significant difference between different donor types. In multivariable analyses, compared with the haplo donors, the use of MRDs was associated with significantly better OS (hazard ratio [HR], 0.6; 95% CI, 0.38 to 0.95; P = .029), and the use of MUDs was associated with a significantly higher GRFS (HR, 0.63; 95% CI, 0.42 to 0.97; P = .034). There was a trend toward improved PFS with use of MUDs (HR, 0.69; 95% CI, 0.46 to 1.04; P = .08). Our data show that PT-Cy in MM patients undergoing allo-HCT resulted in low rates of acute and chronic GVHD and led to favorable survival, especially in the matched related donor setting. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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http://dx.doi.org/10.1016/j.jtct.2021.09.008DOI Listing
September 2021

Antiemetic prophylaxis in patients undergoing hematopoietic stem cell transplantation: a multicenter survey of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) transplant programs.

Ann Hematol 2020 Apr 8;99(4):867-875. Epub 2020 Feb 8.

SODc Terapie Cellulari e Medicina Trasfusionale, AOU Careggi, Florence, Italy.

A survey within hematopoietic stem cell transplant (HSCT) centers of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) was performed in order to describe current antiemetic prophylaxis in patients undergoing HSCT. The multicenter survey was performed by a questionnaire, covering the main areas on chemotherapy-induced nausea and vomiting (CINV): antiemetic prophylaxis guidelines used, antiemetic prophylaxis in different conditioning regimens, and methods of CINV evaluation. The survey was carried out in November 2016, and it was repeated 6 months after the publication of the Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) specific guidelines on antiemetic prophylaxis in HSCT. The results show a remarkable heterogeneity of prophylaxis among the various centers and a significant difference between the guidelines and the clinical practice. In the main conditioning regimens, the combination of a serotonin receptor antagonist (5-HT-RA) with dexamethasone and neurokin receptor antagonist (NK1-RA), as recommended by MASCC/ESMO guidelines, increased from 0 to 15% (before the publication of the guidelines) to 9-30% (after the publication of the guidelines). This study shows a lack of compliance with specific antiemetic guidelines, resulting mainly in under-prophylaxis. Concerted strategies are required to improve the current CINV prophylaxis, to draft shared common guidelines, and to increase the knowledge and the adherence to the current recommendations for CINV prophylaxis in the specific field of HSCT.
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http://dx.doi.org/10.1007/s00277-020-03945-3DOI Listing
April 2020

Voriconazole treatment in adults and children with hematological diseases: can it be used without measurement of plasma concentration?

Med Mycol 2018 Apr;56(3):263-278

Dipartimento di Scienze della Salute, Sezione di farmacologia Clinica e Oncologia, Università degli Studi di Firenze oppure Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Italy.

Indication and timing of trough plasma-voriconazole (VCZ)-concentration (t-PVC) measurement during VCZ treatment is a debated issue. Patterns of t-PVC were prospectively evaluated in pediatric (50 courses) and adult (95 courses) hematologic patients. Efficacy patterns were defined: adequate, t-PVC always ≥1 mcg/ml; borderline, at least one t-PVC measurement <1 mcg/ml but median value of the measurements ≥1 mcg/ml; inadequate, median value of the measurements <1 mcg/ml. Toxicity patterns were defined: favorable, t-PVC always ≤5 mcg/ml; borderline, one or more t-PVC measurements >5 mcg/ml but median value of the measurements ≤5 mcg/ml; unfavorable, median value of the measurements >5 mcg/ml. In children and adults the mean t-PVCs were higher during intravenous treatments. The t-PVC efficacy pattern was adequate, borderline and inadequate in 48%, 12%, and 40% of courses, respectively, in children, and in 66.3%, 16.8%, and 16.8% of courses, respectively, in adults. Adequate efficacy pattern was more frequent in children with body weight above the median (≥25 kg) (OR 4.8; P = .011) and in adults with active hematological disease receiving intravenous therapy (OR 3.93; P = .006). Favorable toxicity pattern was more frequent in children receiving VCZ daily dosage below the median (<14 mg/kg) (OR 4.18; P = .027) and in adults with body weight below the median (<68 kg) (OR 0.22; P = .004). T-PVC measurement is generally needed, however, a non t-PVC guided approach may be considered in heavier adults receiving intravenous VCZ. The risk of supratherapeutic levels does not seem an absolute indication for t-PVC monitoring.
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http://dx.doi.org/10.1093/mmy/myx053DOI Listing
April 2018

Posaconazole oral suspension primary prophylaxis in acute leukemia and allogeneic stem cell transplant patients: can it be used without measurement of plasma concentration?

Med Mycol 2016 Jul 11;54(5):445-58. Epub 2016 Feb 11.

Dipartimento di Farmacologia Preclinica e Clinica Mario Aiazzi Mancini, University of Florence, Florence, Italy.

Posaconazole oral suspension (PCZ-susp) can display a variable degree of inter and intra-individual absorption. However, there is no agreement on the need of plasma-posaconazole-concentration (PPC) monitoring as a routine practice in patients receiving PCZ-susp. In this prospective, multicenter study we evaluated the variability of PPCs in hematologic patients receiving PCZ-susp prophylaxis with the aim to define conditions at different risk of subtherapeutic PPCs. Overall, 103 acute leukemia (AL) patients submitted to intensive chemotherapy (115 courses) and 46 allogeneic stem cell transplant (allo-SCT) recipients (47 courses) receiving PCZ-susp prophylaxis were considered. The adequacy of PPC pattern after the steady state (≥day 7 of treatment) in courses with two or more PPC measurements was defined as follows: inadequate pattern: PPC < 0.5 mcg/ml at least once; borderline pattern: PPC always ≥0.5mcg/ml but < 0.7 mcg/ml at least once; adequate pattern: PPC always ≥0.7 mcg/ml. The PPC pattern was evaluable in 83 and 37 AL and allo-SCT patients, respectively. It was adequate, borderline and inadequate in 63.9%, 14.5%, and 21.7% of courses, respectively, in AL, and in 62.2%, 10.8%, and 27.0% of courses, respectively, in allo-SCT. In both groups, an inadequate PPC pattern was associated with the development of diarrhea. In absence of diarrhea, the probability of an inadequate PPC pattern was 11.9% in AL and 17.2% in allo-SCT patients. PCZ-susp might be used without stringent need of PPC monitoring in patients without diarrhea.
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http://dx.doi.org/10.1093/mmy/myw001DOI Listing
July 2016

Unrepaired Tetralogy of Fallot in a 73 year old woman.

Int J Cardiol 2013 Sep 25;168(2):e60-2. Epub 2013 Jul 25.

Department of Geriatrics, Orthopaedics and Neurosciences, Catholic University of Sacred Heart, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2013.07.081DOI Listing
September 2013

Sarcopenia and mortality among older nursing home residents.

J Am Med Dir Assoc 2012 Feb;13(2):121-6

Department of Gerontology and Geriatrics, Catholic University of Sacred Heart, Roma, Italy.

Background And Aims: Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. At present, no data are available on sarcopenia in the nursing home population. The aim of the current study was to explore the relationship between sarcopenia and all-cause mortality in a population of elderly persons aged 70 years and older living in a nursing home in Italy.

Methods: This study was conducted among all subjects (n = 122) aged 70 years and older who lived in the teaching nursing home of Catholic University of Rome between August 1, 2010, and September 30, 2010. According to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was diagnosed in presence of low muscle mass plus either low muscle strength or low physical performance. The primary outcome measure was survival after 6 months.

Results: Forty residents (32.8%) were indentified as affected by sarcopenia. This condition was more common in men (68%) than in women (21%). During the follow-up period, 26 (21.3%) patients died. After adjusting for age, gender, cerebrovascular diseases, osteoarthritis, chronic obstructive pulmonary disease, activity of daily living impairment, and body mass index, residents with sarcopenia were more likely to die compared with those without sarcopenia (adjusted hazard ratio 2.34; 95% confidence interval 1.04-5.24).

Conclusions: The present study suggests that among subjects living in a nursing home, sarcopenia is highly prevalent and is associated with a significantly increased risk of all-cause death. The current findings support the possibility that sarcopenia has an independent effect on survival among nursing home residents.
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http://dx.doi.org/10.1016/j.jamda.2011.07.004DOI Listing
February 2012

Prevalence and risk factors of sarcopenia among nursing home older residents.

J Gerontol A Biol Sci Med Sci 2012 Jan 10;67(1):48-55. Epub 2011 Mar 10.

Department of Gerontology and Geriatrics, Catholic University of Sacred Heart, Roma, Italy.

Background And Aims: Sarcopenia has been indicated as a reliable marker of frailty and poor prognosis among the oldest individuals. At present, there are no data on sarcopenia in nursing home population. We evaluated the prevalence of sarcopenia and its association with functional and clinical status in a population of elderly persons aged 70 years and older living in nursing homes.

Methods: This study was conducted selecting all the participants (n = 122) living in the teaching nursing homes of Catholic University of Rome who were aged 70 years and older from August 1, 2010, to September 30, 2010. The European Working Group on Sarcopenia in Older People (EWGSOP) criteria were adopted. Accordingly, diagnosis of sarcopenia required the documentation of low muscle mass plus the documentation of either low muscle strength or low physical performance.

Results: Forty residents (32.8%) were identified as affected by sarcopenia. The multivariate logistic regression analysis showed a high increase in risk of sarcopenia for male residents (odds ratio [OR] 13.39; 95% confidence interval [CI] 3.51-50.63) and for residents affected by cerebrovascular disease (OR 5.16; 95% CI 1.03-25.87) or osteoarthritis (OR 7.24; 95% CI 2.02-25.95). Residents who had a body mass index higher than 21 kg/m(2) had a lower risk to be sarcopenic (OR 0.76; 95% CI 0.64-0.90) relative to those with body mass index less than 21 kg/m(2). Similarly, sarcopenia was less likely to be present among participants involved in leisure physical activity for 1 hour or more per day (OR 0.40; 95% CI 0.12-0.98).

Conclusions: The present study suggests that among participants living in nursing homes, sarcopenia is highly prevalent and it is more represented among male residents (68%) than among female residents (21%). Our findings support the hypothesis that muscle mass is strongly associated with nutritional status and physical activity in nursing homes, too.
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http://dx.doi.org/10.1093/gerona/glr035DOI Listing
January 2012

Combined effect of inflammatory gene polymorphisms and the risk of ischemic stroke in a prospective cohort of subjects with type 2 diabetes: a Go-DARTS study.

Diabetes 2010 Nov 9;59(11):2945-8. Epub 2010 Jul 9.

Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.

Objective: We have previously observed that genetic profiles determined by the combination of five functionally significant single nucleotide polymorphisms (SNPs) (rs1800795, rs5498, rs5361, rs1024611, and rs679620) of genes encoding prototypical inflammatory molecules are associated with history of ischemic stroke. Here we tested the ability of this multigenic model to predict stroke risk in a large population-based prospective cohort of subjects with type 2 diabetes.

Research Design And Methods: This study was conducted using a prospective cohort of individuals with type 2 diabetes participating in the Go-DARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) study, which includes genetic and clinical information of patients with diabetes within the Tayside region of Scotland, U.K. The above-mentioned inflammatory SNPs were investigated in 2,182 Go-DARTS participants. We created an inflammatory risk score (IRS), ranging from 0 to 5, according to the number of "at-risk" genotypes concomitantly carried by a given individual. The primary outcome was the occurrence of fatal or nonfatal stroke of any kind. Mean follow-up time was 6.2 ± 1.1 years.

Results: The incidence of stroke increased according to the IRS. The IRS was significantly and independently associated with increased stroke risk after adjustment for other conventional risk factors (hazard ratio 1.34 [95% CI 1.1-1.7]; P = 0.009). The highest hazard ratio for stroke was found in subjects concomitantly carrying > 3 proinflammatory variations and in subjects without previous cardiovascular diseases.

Conclusions: This large prospective cohort study provides evidence that SNPs of genes encoding prototypical inflammatory molecules may be used to create multigenic models that predict stroke risk in subjects with type 2 diabetes.
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http://dx.doi.org/10.2337/db09-1690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963555PMC
November 2010

Hepatitis B and C in hematopoietic stem cell transplant.

Mediterr J Hematol Infect Dis 2009 Dec 3;1(3):e2009016. Epub 2009 Dec 3.

Pediatric Hematology Hematology Departments, San Camillo Hospital, Circonvallazione Gianicolense 87, 00152 Rome, Italy.

Although the risk of acquisition of hepatitis B or hepatitis C virus through blood products has considerably reduced since the last decade, some infected patients are candidates to stem cell transplantation. Others may have no alternative than an infected donor. In all these cases, recipients of transplant are prone to short and long term liver complications. The evolution of liver tests under chemotherapy before transplant may give useful information to anticipate on the risk of hepatitis reactivation after transplant, both for HBv and HCv. More than sixty percent of the patients who are HBsAg-positive before transplant reactivate after transplant, and 3% develop acute severe liver failure. Because both viral replication and immune reconstitution are the key factors for reactivation, it is crucial to closely follow liver function tests and viral load during the first months of transplant, and to pay a special attention in slowly tapering the immunosuppression in these patients. Lamivudine reduces HBv viremia, but favors the emergence of HBv polymerase gene mutants and should be individually discussed. Both in case of HBv or HCv hepatitis reactivation with ALT ≥ 10N concomitantly to an increase in viral load at time of immune reconstitution, steroids should be given. In case there is no alternative than a HBv or HCv positive geno-identical donor, the risk of viral hepatitis, including acute liver failure and late complications, should be balanced with the benefit of transplant in a given situation.
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http://dx.doi.org/10.4084/MJHID.2009.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033124PMC
December 2009

Analysis of functional polymorphisms of metalloproteinase genes in persons with vascular dementia and Alzheimer's disease.

J Gerontol A Biol Sci Med Sci 2006 Oct;61(10):1065-9

Istituto di Medicina Interna e Geriatria, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, L.go A. Gemelli 8, 00168 Rome, Italy.

Background: Vascular dementia (VAD) and Alzheimer's disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD. Expression and activity of MMPs may be genetically influenced by common polymorphisms in the promoter regions of the corresponding genes. The purpose of this study was to evaluate whether functional polymorphisms of MMP genes are associated with dementia.

Methods: This is a cross-sectional study including a total of 599 individuals: 193 with VAD, 183 with AD, and 223 controls. Polymorphisms of the MMP-1, MMP-3, and MMP-9 genes were studied.

Results: MMP-1 2G2G, MMP-1 1G2G, MMP-3 5A5A, and MMP-9 TT genotypes were significantly and independently associated with VAD (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4-4.4, OR = 1.7, 95% CI, 1.0-2.7, OR = 2.9, 95% CI, 1.5-5.9, and OR = 6.8, 95% CI, 1.3-35.1, respectively). MMP-1 2G2G and MMP-3 5A5A genotypes were associated with increased risk of AD only in persons who carry the apolipoprotein E (APOE) epsilon4 allele (OR = 6.0, 95% CI, 2.3-15.5, and OR = 14.3, 95% CI, 3.2-63.0, respectively). Interestingly, the odds of VAD and AD was further increased in persons concomitantly carrying more than one MMP gene variation, compared to individuals that only had one high-risk genotype.

Conclusions: Our study suggests that MMP gene polymorphisms are associated with VAD and AD, although these results need to be treated with caution until replicated. MMP genotypes may influence the risk of dementia and merit further investigation as potential genetic markers of disease.
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http://dx.doi.org/10.1093/gerona/61.10.1065DOI Listing
October 2006

Proinflammatory genetic profiles in subjects with history of ischemic stroke.

Stroke 2004 Oct 12;35(10):2270-5. Epub 2004 Aug 12.

Laboratory of Vascular Biology and Genetics, . Gemelli University Hospital, Università Cattolica del Sacro Cuore, School of Medicine, Rome, Italy.

Background And Purpose: Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins.

Methods: The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls. The polymorphisms of the C-reactive protein (CRP), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin (E-sel), and matrix metalloproteinase-3 (MMP-3) genes were studied.

Results: IL-6 GG, IL-6 GC, MCP-1 GG, ICAM-1 EE, E-sel AA, and MMP-3 5A5A genotypes were significantly and independently associated with stroke history. The odds of stroke increased with the number of high-risk genotypes: carrying 1 proinflammatory gene variant conferred a risk of 3.3 (1.6 to 6.9), whereas individuals concomitantly carrying 2 and 3 proinflammatory gene variants had adjusted odds ratios of 21.0 (7.6 to 57.5) and 50.3 (10.2 to 248.1), respectively.

Conclusions: Proinflammatory genetic profiles are significantly more common in subjects with stroke history. Synergistic effects between proinflammatory genotypes might be potential markers for cerebrovascular diseases.
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http://dx.doi.org/10.1161/01.STR.0000140740.19421.feDOI Listing
October 2004

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians.

Exp Gerontol 2004 Aug;39(8):1249-52

Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy.

Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position -2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case-control study to test whether the risk for AD might be influenced by the -2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals (P<0.0001) A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE 4 high-risk allele, nor by the presence of other gene variations associated with a pro-inflammatory phenotype. These findings indicate that the -2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders.
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http://dx.doi.org/10.1016/j.exger.2004.05.001DOI Listing
August 2004

Polymorphisms of the macrophage inhibitory factor and C-reactive protein genes in subjects with Alzheimer's dementia.

Dement Geriatr Cogn Disord 2004 29;18(3-4):261-4. Epub 2004 Jul 29.

Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy.

Neuroinflammation is a central feature of Alzheimer's disease (AD). C-reactive protein (CRP) is a key molecule of the acute phase of inflammation that has been localized in the two characteristic lesions of AD brain, senile plaque and neurofibrillary tangles. On the other hand, the macrophage migration inhibitory factor (MIF) is a cytokine with multiple biological activities, including the ability to act as potent amyloid beta (A-beta)-binding protein. Two common polymorphisms have been recently detected in the genes encoding for CRP and MIF and have been associated with significant modifications of plasma levels and activity of the corresponding proteins. Following these observations, we hypothesized that CRP and MIF gene polymorphisms might contribute to the development and progression of neurodegenerative disorders and evaluated their association with AD. CRP and MIF gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis in 116 Italian subjects affected by probable AD and 184 age- and sex-matched controls. We did not find a statistically significant difference in the distribution of CRP and MIF genotypes and alleles between AD subjects and controls. Although these data need further confirmation, they indicate that CRP and MIF gene polymorphisms are not associated with AD.
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http://dx.doi.org/10.1159/000080026DOI Listing
February 2005

Peripheral nerve ischemia: apolipoprotein E deficiency results in impaired functional recovery and reduction of associated intraneural angiogenic response.

Exp Neurol 2003 Nov;184(1):264-73

Laboratory of Vascular Biology and Genetics, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy.

Apolipoprotein E-knockout (apoE KO) mice have peripheral sensory nerve defects, reduced and delayed response to noxious thermal stimuli, abnormal morphology of unmyelinated fibers, and impaired blood-nerve and blood-brain barriers. In this study, we show that, compared to wild-type mice, peripheral nerves of apoE KO mice have impaired ability to respond to ischemia, as demonstrated by measurement of motor and sensory conduction velocity. In addition, mice lacking apoE exhibit a deficit of reinnervation of ischemic epidermis, evaluated by immunofluorescent staining for the pan-neuronal marker PGP 9.5. Also regional nerve blood flow, measured by laser Doppler, and intraneural angiogenesis after ischemia are significantly compromised in apoE-deficient mice. Finally, upregulation of the angiogenic cytokine vascular endothelial growth factor (VEGF), which physiologically occurs after ischemia in the peripheral nerve of wild-type mice, is severely impaired in apoE KO mice. Among the several neural defects that have already been described in mice lacking apoE, this is the first demonstration that functional recovery to ischemia is impaired in the peripheral nerves of these animals. This deficit is mirrored by the inability of upregulating VEGF and mounting an appropriate intraneural angiogenic response following injury. These findings provide new evidence of possible interdependent relationships between VEGF, angiogenesis, and nerve function and regeneration and may provide new important information on the role of apoE in the nervous system.
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http://dx.doi.org/10.1016/s0014-4886(03)00260-7DOI Listing
November 2003

[Dynamics of communication between physician and the oncologic patient].

Authors:
Anna Proia

Recenti Prog Med 2002 Feb;93(2):108-12

Sezione di Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma.

The informed consent of patients is ethically and legally required for all medical practice. The disclosure of information to cancer patients is one of the most important issues mostly in oncological practice. Because most patients now want to know the truth about their diagnosis and prognosis, the ability to discuss the cancer diagnosis, disease recurrence, or treatment failure, and to solicit patients' views about resuscitation or hospice care, are important verbal skills for oncologists and other oncology care providers. If clinicians involved in cancer care are able to well communicative with patients, these ones and their families can achieve a good level of quality of life and psychological adjustment. Moreover, the ability to clearly articulate a treatment plan or elicit patient preferences for treatment are prerequisite to informed consent. Despite these imperatives, clinicians do not routinely receive training in key communication skills that could enable them to accomplish these tasks. Disclosure of information needs to be individualized, and social and cultural background has to be taken into consideration. This review considers deficiencies in the conduct of key communication tasks and their consequences. The reasons for these deficiencies are explored and guidelines to resolve these issues and to further new alternative methods are proposed.
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February 2002
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