RESUMEN
BACKGROUND: Allogeneic transplant is an effective salvage therapy in patients with Hodgkin lymphoma (HL) relapsed or refractory (R/R) to previous treatments. In recent years, immunotherapies (conjugated antibody and checkpoint inhibitors [CPI]) showed interesting results and were used as bridge therapies to allotransplant. AIM: The aim of this retrospective study in Lazio region was to evaluate the impact of these new therapies on outcome after allogeneic hematopoietic stem cell transplantation (allo-SCT) in comparison with standard chemotherapies used in the past. METHODS: We selected all consecutive patients with diagnosis of HL transplanted in four hematology transplant units, and we collected data obtained from patients' records concerning all the treatments before allo-SCT. RESULTS: A total of 56 patients were enrolled in this study. All patients underwent allo-SCT for R/R HL. Seventeen patients (30%) received chemotherapy prior to allo-SCT (group B); they were treated between 2008 and 2015; and 39 patients (70%) received brentuximab vedotin (BV), CPI, or both before allo-SCT as a bridge to transplant (group A); they were treated between 2012 and 2020. Twenty-five patients were treated with BV alone, 2 with CPI alone, and 12 first with BV and then with CPI. No patient received concomitant BV and CPI. At 5 years from allo-SCT, overall survival (OS) was 59% and progression-free survival (PFS) was 65%. No statistical differences in OS or PFS were observed between patients in groups A and B. Relapse was significantly associated with a lower survival. The only factor associated with a reduced risk of relapse was development of any grade acute graft versus host disease (GVHD) (p > 0.02). CONCLUSIONS: This regional real-world experience shows the changes that have taken place in the last 10 years in R/R HL using new drugs to render a patient eligible for allo-SCT. This strategy appears to guarantee an impressive disease control with an increased risk of complications, for example, aGVHD, that appear to nullify this advantage at least in part.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Terapia Recuperativa/métodos , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Recurrencia Local de Neoplasia , Brentuximab Vedotina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
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 serotonin3 receptor antagonist (5-HT3-RA) with dexamethasone and neurokin1 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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Antieméticos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Náusea/prevención & control , Acondicionamiento Pretrasplante/efectos adversos , Vómitos/prevención & control , Aloinjertos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adhesión a Directriz , Encuestas de Atención de la Salud , Humanos , Italia , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Náusea/inducido químicamente , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Trasplante Autólogo , Vómitos/inducido químicamenteRESUMEN
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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Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Enfermedades Hematológicas/complicaciones , Micosis/complicaciones , Micosis/tratamiento farmacológico , Voriconazol/farmacocinética , Voriconazol/uso terapéutico , Adolescente , Adulto , Factores de Edad , Anciano , Antifúngicos/sangre , Antifúngicos/toxicidad , Peso Corporal , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Micosis/sangre , Resultado del Tratamiento , Voriconazol/sangre , Voriconazol/toxicidad , Adulto JovenRESUMEN
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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Antifúngicos/farmacocinética , Leucemia/complicaciones , Micosis/prevención & control , Plasma/química , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversos , Triazoles/farmacocinética , Administración Oral , Adolescente , Adulto , Anciano , Antifúngicos/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Triazoles/administración & dosificación , Adulto JovenAsunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbapenémicos/farmacología , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Pruebas de Sensibilidad Microbiana , Porinas/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
Purpose: Overcrowding is a problem that affects emergency departments (ED) all over the world; it occurs due to a disproportion between user demand and the physical, human and structural resources available. Essential prerequisites to assessing and managing the phenomenon are its accurate measurement and an understanding of its impact. The objective of this systematic review is to identify the characteristics of the problem, analyzing the proposed strategies aimed at improving patient flow, delay in services provided and overcrowding of emergency departments. Methods: To achieve our objectives, a manual computerized search was performed in the bibliographic databases using as keywords "Emergency Department", "Overcrowding", "Emergency Room", "Emergency Service", "Emergency Unit"",Emergency Ward", "Emergency Outpatient Unit", "Emergency Hospital", "Crowding", "Mass Gathering", "Management" and "Comprehensive Health Care". Two independent reviewers analyzed abstracts, titles and full text articles for admissibility, according to the selected inclusion and exclusion criteria. Results: The process lead to include 19 articles. It was possible to group the solutions proposed in five categories: work organization, investment in primary care, creation of new dedicated professional figures, work and structural modifications and implementation of predictive simulation models using mathematical algorithms. Conclusion: The most effective measures to guarantee an improvement in the flow of patients are represented by both improving the efficiency of human resources and by developing predictive mathematical models, regardless of the type of hospital and its location. Considering the complexity of EDs and the multiple characteristics of overcrowding and that the causes of crowding are different and site-specific, a careful examination of the specifics of each ED is necessary to identify improving fields.
RESUMEN
The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.
RESUMEN
Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.
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Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Anciano , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Sistema de Registros , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodosRESUMEN
The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia/terapia , Estudios Prospectivos , Recurrencia , Tiotepa/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapéuticoRESUMEN
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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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Médula Ósea , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Mieloma Múltiple/terapia , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Estados Unidos , Donante no EmparentadoRESUMEN
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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Enfermedad de Alzheimer/genética , Demencia Vascular/genética , Metaloproteinasas de la Matriz/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/etiología , Apolipoproteínas E/genética , Estudios Transversales , Demencia Vascular/etiología , Femenino , Genotipo , Humanos , Masculino , Polimorfismo GenéticoRESUMEN
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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Factores Inmunológicos/genética , Polimorfismo Genético , Accidente Cerebrovascular/genética , Anciano , Biomarcadores/análisis , Proteína C-Reactiva/genética , Estudios de Casos y Controles , Quimiocina CCL2/genética , Selectina E/genética , Femenino , Genotipo , Humanos , Mediadores de Inflamación/análisis , Molécula 1 de Adhesión Intercelular/genética , Interleucina-6/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Masculino , Metaloproteinasa 3 de la Matriz/genética , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/inmunologíaRESUMEN
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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Enfermedad de Alzheimer/genética , Quimiocina CCL2/genética , Polimorfismo Genético , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/inmunología , Apolipoproteínas E/genética , Estudios de Casos y Controles , Quimiocina CCL2/inmunología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Homocigoto , Humanos , Molécula 1 de Adhesión Intercelular/genética , Interleucina-6/genética , Italia , Modelos Logísticos , MasculinoRESUMEN
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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Neoplasias/psicología , Relaciones Médico-Paciente , HumanosAsunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Fúngicas Invasoras/etiología , Enfermedad Aguda , Adolescente , Niño , Análisis de Datos , Femenino , Enfermedad Injerto contra Huésped , Humanos , Infecciones Fúngicas Invasoras/mortalidad , Italia , Leucemia/terapia , Masculino , Profilaxis Posexposición , Estudios Prospectivos , Factores de Riesgo , Donantes de Tejidos , Trasplante Homólogo/efectos adversosRESUMEN
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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Casas de Salud/estadística & datos numéricos , Sarcopenia/epidemiología , Anciano , Anciano de 80 o más Años , Composición Corporal , Índice de Masa Corporal , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/epidemiología , Estudios Transversales , Femenino , Evaluación Geriátrica/estadística & datos numéricos , Humanos , Masculino , Actividad Motora , Debilidad Muscular/epidemiología , Estado Nutricional , Osteoartritis/complicaciones , Osteoartritis/epidemiología , Prevalencia , Factores de Riesgo , Sarcopenia/etiología , Factores SexualesRESUMEN
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.
Asunto(s)
Envejecimiento/fisiología , Causas de Muerte , Hogares para Ancianos , Casas de Salud , Sarcopenia/epidemiología , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Cohortes , Comorbilidad , Femenino , Anciano Frágil/estadística & datos numéricos , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Fuerza Muscular/fisiología , Aptitud Física/fisiología , Medición de Riesgo , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Índice de Severidad de la Enfermedad , Factores Sexuales , Estadísticas no Paramétricas , Tasa de SupervivenciaRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Inflamación/genética , Polimorfismo Genético , Accidente Cerebrovascular/epidemiología , Adulto , Edad de Inicio , Anciano , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Fumar/efectos adversos , Accidente Cerebrovascular/genéticaRESUMEN
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.