RESUMEN
Post-transplantation cyclophosphamide (PTCy) demonstrated effectiveness to prevent GVHD after haploidentical hematopoietic cell transplantation (HCT). Reducing toxicities with a maximized efficacy is still challenging in HCT. In this retrospective study, we analyzed the safety and efficacy of transplantation from a 1-antigen HLA-mismatched unrelated donor (9/10 MMUD) in 80 patients with hematological disorders between 2010 and 2018; 22 patients received PTCy with a reduced dose of 40 mg/kg, cyclosporine A, and mycophenolate mofetil (MMF); 58 patients received anti-thymocyte globulin (ATG), cyclosporine A, and either methotrexate or MMF for GVHD prophylaxis. Cumulative incidence (CI) of acute GVHD grades II-IV in the PTCy group was significantly lower (15% vs. 50%, p = 0.006); however, CI of chronic GVHD was (not significantly) lower in the PTCy group (26% vs. 35%, p = 0.137). One-year OS was significantly longer (p = 0.008) in the PTCy group with a similar 1-year PFS (p = 0.114) in both groups. Rates of 1-year relapse and non-relapse mortality were similar. Median time to neutrophil engraftment was comparable in both GVHD prophylaxis groups (14 days vs. 16 days, respectively, p = 0.107). Our results show that a lower dose of PTCy-based prophylaxis is an effective and safe strategy to prevent acute GVHD in HCT with 9/10 MMUD compared to ATG.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Anemia Aplásica/terapia , Enfermedades de la Médula Ósea/terapia , Trastornos de Fallo de la Médula Ósea , Ciclofosfamida/administración & dosificación , Ciclosporina/uso terapéutico , Evaluación de Medicamentos , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemoglobinuria Paroxística/terapia , Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Neoplasias/terapia , Estudios Retrospectivos , Linfocitos T/inmunología , Donantes de TejidosRESUMEN
Hematopoietic cell transplantation - essentials on indication, patient referral and long term follow up Abstract. Both, autologous and allogeneic hematopoietic cell transplantation (HCT) are established treatment components for a large number of predominantly hemato- and lymphopoietic disorders. Diagnosis and disease status, the timing for referral to a transplant center and comorbidities are crucial factors for the patients' outcome. Survivorship care plans are an important contribution to improve intermediate and long-term outcome. Although these are mainly guided by the transplant center, family and referring physicians play an important role in prevention, early detection and treatment of late effects. This review discusses «HCT-essentials¼ for non-transplant physicians for referral and follow up of transplant patients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Atención a la Salud , Estudios de Seguimiento , Humanos , Derivación y Consulta , Trasplante HomólogoRESUMEN
BACKGROUND: Little is known about the function of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca(2+) release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated after Gαq-protein-coupled receptor stimulation, affecting Ca(2+) cycling, enhancing myocyte performance, and potentially favoring an increase in the incidence of arrhythmias. METHODS AND RESULTS: IP3R function was determined in human left ventricular myocytes, and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electric and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human left ventricular myocytes. After Gαq-protein-coupled receptor activation, Ca(2+) mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action potential, and occurrence of early afterdepolarizations. Ca(2+) transient amplitude and cell shortening are enhanced, and extrasystolic and dysregulated Ca(2+) elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that Gαq-protein-coupled receptor activation provides inotropic reserve, which is hampered by electric instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca(2+) load by IP3Rs promote Ca(2+) extrusion by forward-mode Na(+)/Ca(2+) exchange, an important mechanism of arrhythmic events. CONCLUSIONS: The Gαq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias.
Asunto(s)
Potenciales de Acción/fisiología , Señalización del Calcio/fisiología , Insuficiencia Cardíaca/fisiopatología , Receptores de Inositol 1,4,5-Trifosfato/fisiología , Miocitos Cardíacos/fisiología , Adulto , Animales , Arritmias Cardíacas/fisiopatología , Células Cultivadas , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/fisiología , Insuficiencia Cardíaca/genética , Ventrículos Cardíacos/citología , Humanos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Contracción Miocárdica/fisiología , Miocitos Cardíacos/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/fisiología , Retículo Sarcoplasmático/fisiología , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive. METHODS: Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo. RESULTS: Human lungs contain undifferentiated human lung stem cells nested in niches in the distal airways. These cells are self-renewing, clonogenic, and multipotent in vitro. After injection into damaged mouse lung in vivo, human lung stem cells form human bronchioles, alveoli, and pulmonary vessels integrated structurally and functionally with the damaged organ. The formation of a chimeric lung was confirmed by detection of human transcripts for epithelial and vascular genes. In addition, the self-renewal and long-term proliferation of human lung stem cells was shown in serial-transplantation assays. CONCLUSIONS: Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease. (Funded by the National Institutes of Health.).
Asunto(s)
Pulmón/citología , Células Madre/fisiología , Adulto , Animales , Células Clonales , Femenino , Humanos , Pulmón/embriología , Pulmón/fisiología , Ratones , Ratones Endogámicos C57BL , Células Madre Pluripotentes , Proteínas Proto-Oncogénicas c-kit/análisis , Regeneración , Trasplante de Células Madre , Células Madre/químicaAsunto(s)
Insuficiencia Cardíaca/etiología , Leucemia Prolinfocítica de Células T/complicaciones , Miocarditis/etiología , Anciano , Alemtuzumab/efectos adversos , Alemtuzumab/uso terapéutico , Citocinas/metabolismo , Diagnóstico Tardío , Resultado Fatal , Humanos , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/patología , Masculino , Miocarditis/patologíaRESUMEN
RATIONALE: According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening. OBJECTIVE: Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration. METHODS AND RESULTS: Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs. CONCLUSIONS: The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the "mother" DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.
Asunto(s)
Cromátides/fisiología , Segregación Cromosómica/fisiología , Corazón/fisiología , Infarto del Miocardio/terapia , Miocardio/citología , Regeneración/fisiología , Trasplante de Células Madre , Células Madre/citología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Bromodesoxiuridina , Proliferación Celular , Células Cultivadas , Niño , Preescolar , Cromátides/ultraestructura , ADN/fisiología , Femenino , Humanos , Técnicas In Vitro , Lactante , Masculino , Persona de Mediana Edad , Modelos Animales , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Ratas , Ratas Endogámicas F344 , Células Madre/fisiología , Telómero/ultraestructura , Adulto JovenRESUMEN
The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to qualify comorbidities to predict non-relapse mortality (NRM) of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). HSCT procedures continue to improve. Therefore, the predictive value of HCT-CI needs to be re-evaluated. Our study is a retrospective analysis of pre-existing comorbidities assessing the relevance of the HCT-CI on the outcome of consecutive patients (n = 1102) undergoing allo-HSCT from 2006-2021. HCT-CI was classified as low (HCT-CI 0), intermediate (HCT-CI 1-2) and high-risk (HCT-CI ≥ 3). At 10 years, NRM for low, intermediate, and high-risk HCT-CI group was 21.0%, 26.0%, and 25.8% (p = 0.04). NRM difference was significant between low to intermediate (p < 0.001), but not between intermediate to high-risk HCT-CI (p = 0.22). Overall survival (OS) at 10 years differed significantly with 49.9%, 39.8%, and 31.1%, respectively (p < 0.001). In multivariate analysis of HCT-CI organ subgroups, cardiac disease was most strongly associated with NRM (HR = 1.73, p = 0.02) and OS (HR = 1.77, p < 0.001). All other individual organ comorbidities influenced NRM to a lesser extent. Further, donor (HR = 2.20, p < 0.001 for unrelated and HR = 2.17, p = 0.004 for mismatched related donor), disease status (HR = 1.41, p = 0.03 for advanced disease) and previous HSCT (HR = 1.55, p = 0.009) were associated with NRM. Improvement in transplant techniques and supportive care may have improved outcome with respect to comorbidities.
RESUMEN
BACKGROUND: Two opposite views of cardiac growth are currently held; one views the heart as a static organ characterized by a large number of cardiomyocytes that are present at birth and live as long as the organism, and the other views the heart a highly plastic organ in which the myocyte compartment is restored several times during the course of life. METHODS AND RESULTS: The average age of cardiomyocytes, vascular endothelial cells (ECs), and fibroblasts and their turnover rates were measured by retrospective (14)C birth dating of cells in 19 normal hearts 2 to 78 years of age and in 17 explanted failing hearts 22 to 70 years of age. We report that the human heart is characterized by a significant turnover of ventricular myocytes, ECs, and fibroblasts, physiologically and pathologically. Myocyte, EC, and fibroblast renewal is very high shortly after birth, decreases during postnatal maturation, remains relatively constant in the adult organ, and increases dramatically with age. From 20 to 78 years of age, the adult human heart entirely replaces its myocyte, EC, and fibroblast compartment ≈8, ≈6, and ≈8 times, respectively. Myocyte, EC, and fibroblast regeneration is further enhanced with chronic heart failure. CONCLUSIONS: The human heart is a highly dynamic organ that retains a remarkable degree of plasticity throughout life and in the presence of chronic heart failure. However, the ability to regenerate cardiomyocytes, vascular ECs, and fibroblasts cannot prevent the manifestations of myocardial aging or oppose the negative effects of ischemic and idiopathic dilated cardiomyopathy.
Asunto(s)
Insuficiencia Cardíaca/fisiopatología , Desarrollo de Músculos/fisiología , Miocitos Cardíacos/fisiología , Adolescente , Adulto , Anciano , Envejecimiento , Niño , Preescolar , Células Endoteliales/fisiología , Fibroblastos/fisiología , Corazón/fisiología , Humanos , Persona de Mediana Edad , Miocitos Cardíacos/citología , Regeneración , Donantes de Tejidos , Adulto JovenAsunto(s)
Janus Quinasa 2/genética , Mutación Missense , Dolor , Policitemia Vera , Sustitución de Aminoácidos , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico por imagen , Dolor/enzimología , Dolor/genética , Dolor/fisiopatología , Policitemia Vera/diagnóstico por imagen , Policitemia Vera/enzimología , Policitemia Vera/genética , Policitemia Vera/fisiopatologíaRESUMEN
Introduction: Vaccine-induced myocarditis is a rare complication of messenger RNA (mRNA) COVID-19 vaccines. Case presentation: We report a case of acute myopericarditis in a recipient of allogeneic hematopoietic cells following the first dose of the mRNA-1273 vaccine and the successful administration of a second and third dose while on prophylactic treatment with colchicine to successfully complete the vaccination. Conclusion: Treatment and prevention of mRNA-vaccine-induced myopericarditis represent a clinical challenge. The use of colchicine is feasible and safe to potentially reduce the risk of this rare but severe complication and allows re-exposure to an mRNA vaccine.
RESUMEN
BACKGROUND: Cardiac stem cells (CSCs) delivered to the infarcted heart generate a large number of small fetal-neonatal cardiomyocytes that fail to acquire the differentiated phenotype. However, the interaction of CSCs with postmitotic myocytes results in the formation of cells with adult characteristics. METHODS AND RESULTS: On the basis of results of in vitro and in vivo assays, we report that the commitment of human CSCs (hCSCs) to the myocyte lineage and the generation of mature working cardiomyocytes are influenced by microRNA-499 (miR-499), which is barely detectable in hCSCs but is highly expressed in postmitotic human cardiomyocytes. miR-499 traverses gap junction channels and translocates to structurally coupled hCSCs favoring their differentiation into functionally competent cells. Expression of miR-499 in hCSCs represses the miR-499 target genes Sox6 and Rod1, enhancing cardiomyogenesis in vitro and after infarction in vivo. Although cardiac repair was detected in all cell-treated infarcted hearts, the aggregate volume of the regenerated myocyte mass and myocyte cell volume were greater in animals injected with hCSCs overexpressing miR-499. Treatment with hCSCs resulted in an improvement in ventricular function, consisting of a better preservation of developed pressure and positive and negative dP/dt after infarction. An additional positive effect on cardiac performance occurred with miR-499, pointing to enhanced myocyte differentiation/hypertrophy as the mechanism by which miR-499 potentiated the restoration of myocardial mass and function in the infarcted heart. CONCLUSIONS: The recognition that miR-499 promotes the differentiation of hCSCs into mechanically integrated cardiomyocytes has important clinical implications for the treatment of human heart failure.
Asunto(s)
Células Madre Adultas/citología , MicroARNs/fisiología , Infarto del Miocardio/terapia , Miocitos Cardíacos/citología , Trasplante de Células Madre , Células Madre Adultas/fisiología , Animales , Diferenciación Celular/fisiología , División Celular/fisiología , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Uniones Comunicantes/fisiología , Expresión Génica/fisiología , Humanos , Infarto del Miocardio/patología , Miocitos Cardíacos/fisiología , Proteína de Unión al Tracto de Polipirimidina , Proteínas de Unión al ARN/genética , Ratas , Regeneración/fisiología , Factores de Transcripción SOXD/genéticaAsunto(s)
Aminopterina/análogos & derivados , Antineoplásicos/uso terapéutico , Células Dendríticas/patología , Trastornos Mieloproliferativos/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Aminopterina/uso terapéutico , Humanos , Masculino , Trastornos Mieloproliferativos/patología , Recurrencia , Neoplasias Cutáneas/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cyclosporine A (CsA) is commonly used for Graft versus Host Disease (GvHD) prophylaxis at a recommended starting dose of 3 mg/kg/d: Evidence for the effect of different CsA starting doses on GvHD risk is limited. We therefore estimated the association of 5 mg/kg/d (CsA5) and 3 mg/kg/d (CsA3) CsA starting doses with GvHD risk in two consecutive cohorts of allogeneic hematopoietic cell transplantation (allo-HCT) patients, exploring potential risk factors for incident acute GvHD, with a focus on CsA starting dose. We analyzed 519 patients within CsA5 (n = 153) and CsA3 (n = 366). The cumulative incidence function of acute GvHD grade ≥2 was higher in the CsA3 compared to the CsA5 group (41% vs. 33%, respectively; p = 0.043), without impacting chronic GvHD. In multivariable analysis, a CsA starting dose of 3 mg/kg/d, no ATG use, unrelated donor and high to very high disease risk index were significantly associated with acute GvHD grade ≥2. A higher CsA starting dose of 5 mg/kg/d was independently associated with lower acute GvHD risk, and higher CsA levels in the early period after allo-HCT were reached.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estudios de Cohortes , Ciclosporina/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Donante no EmparentadoRESUMEN
BACKGROUND/AIM: We report three adult patients with primary immunodeficiency (PID) treated with reduced-intensity allogenic hematopoietic cell transplantation (HCT) with fludarabine/treosulfan conditioning and graft-versus-host disease (GvHD) prophylaxis with alemtuzumab and a calcineurin inhibitor. CASE REPORT: Patient 1, a 51-year-old male, had common variable immunodeficiency (CVID) with protein-losing enteropathy. Patient 2 was a 29-year-old woman with STAT3 (signal transducer and activator of transcription 3)-dependent hyper-IgE syndrome (HIES). Patient 3 was a 25-year-old male with XIAP (X-linked inhibitor of apoptosis)-deficiency presenting as treatment-refractory granulomatous enteropathy. Engraftment occurred in all three patients, with 100% donor chimerism in blood. Two patients survived, whereas the patient with CVID died due to infection. CONCLUSION: This series highlights issues of transplantation for PID in adults and treosulfan-based conditioning, which is feasible for PID patients; infectious complications are the major issue of concern.
Asunto(s)
Busulfano , Trasplante de Células Madre Hematopoyéticas , Enfermedades de Inmunodeficiencia Primaria , Adulto , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de Inmunodeficiencia Primaria/epidemiologíaRESUMEN
: Background: The Somnotouch-Non-Invasive-Blood-Pressure (NIBP) device delivers raw data consisting of electrocardiography and photoplethysmography for estimating blood pressure (BP) over 24 hours using pulse-transit-time. The study's aim was to analyze the impact on 24-hour BP results when processing raw data by two different software solutions delivered with the device. METHODS: We used data from 234 participants. The Somnotouch-NIBP measurements were analyzed using the Domino-light and Schiller software and compared. BP values differing > 5 mmHg were regarded as relevant and explored for their impact on BP classification (normotension vs. hypertension). RESULTS: Mean (±standard deviation) absolute systolic/diastolic differences for 24-hour mean BP were 1.5 (±1.7)/1.1 (±1.3) mm Hg. Besides awake systolic BP (p = 0.022), there were no statistically significant differences in systolic/diastolic 24-hour mean, awake, and asleep BP. Twenty four-hour mean BP agreement (number (%)) between the software solutions within 5, 10, and 15 mmHg were 222 (94.8%), 231 (98.7%), 234 (100%) for systolic and 228 (97.4%), 232 (99.1%), 233 (99.5%) for diastolic measurements, respectively. A BP difference of >5 mmHg was present in 24 (10.3%) participants leading to discordant classification in 4-17%. CONCLUSION: By comparing the two software solutions, differences in BP are negligible at the population level. However, at the individual level there are, in a minority of cases, differences that lead to different BP classifications, which can influence the therapeutic decision.
RESUMEN
BACKGROUND: Survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increased but so have long-term sequelae. New-onset post-transplant diabetes mellitus (PTDM) occurs frequently following allo-HSCT. PATIENTS AND METHODS: Study endpoints were incidence and risk factors of PDTM. We studied 599 adult patients suffering from either acute myeloid leukemia n=220), acute lymphoblastic leukemia (n=79), chronic myeloid leukemia (n=22), myelodysplastic syndrome/myeloproliferative neoplasm (n=105), chronic lymphocytic leukemia (n=37), lymphoma/myeloma (n=116, or non-malignant disorders (e.g. bone marrow failure, hemoglobinopathies) (n=20) who underwent myeloablative (466; 77.8%) or non-myeloablative (131; 21.9%) allo-HSCT between 2006 and 2016. RESULTS: Altogether, 39 patients (6.5%) developed PTDM. In a competing-risk analysis, time to PTDM was associated with acute grade 2-4 graft-versus-host-disease (p=0.017). Further cardiovascular risk factors were hypertension (n=145; 24.2%), coronary artery disease (n=36, 6%), dyslipidemia (n=139; 23.3%), and stroke (n=12; 2%). CONCLUSION: After allo-HSCT, a significant number of patients developed PTDM and patients with acute graft-versus-host-disease were found to have a higher risk for PTDM. Long-term and continuous follow-up for diabetes and cardiovascular risk factors after HSCT is important in order to be able to provide timely and appropriate treatment.
Asunto(s)
Diabetes Mellitus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Sobrevivientes , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: Dyslipidemia is common after hematopoietic stem cell transplantation (HSCT). Few data regarding the time course of lipid profiles after HSCT, the effect of multiple transplantations, and efficacy and safety of lipid-lowering treatments are available. OBJECTIVE: The objective of the study was to determine the prevalence and treatment of dyslipidemia over a 25-year period in a large, single-center cohort. METHODS: One thousand one hundred ninety-six adult patients (≥16 years) who underwent HSCT during 1973 to 2013 and who survived ≥100 days were studied retrospectively. RESULTS: The prevalence of dyslipidemia before transplantation was 36% and 28% in the autologous and allogeneic groups, respectively (P < .001). Three months after HSCT, the prevalence rose to 62% and 74% (P < .001), and at 25 years, it was 67% and 89%. Lipid profiles were similar after first and subsequent transplants. Baseline dyslipidemia (odds ratio [OR] = 2.72), allogeneic transplant (OR = 2.44), and age ≥ 35 years (OR = 2.33) were independent risk factors for dyslipidemia at 1 year. Lipid-lowering treatment was given to 223 (19%) patients, primarily in the form of statins (86%) and was associated with a decrease in total cholesterol from 246 to 192 mg/dL (P < .01) and from 244 to 195 mg/dL (P < .001) in the autologous and allogeneic groups, respectively. There were 10 cases (4%) of muscle symptoms prompting cessation of lipid-lowering therapy, including 1 case of rhabdomyolysis. The OR for dyslipidemia among patients who suffered a cardiovascular event (conditional logistic regression) was 3.5 (95% confidence interval = 1.6-7.7, P = .002). CONCLUSION: This study confirms that dyslipidemia is a common and long-lasting phenomenon among both allogeneic and autologous HSCT patients. Statins are effective, generally well-tolerated and should be highly recommended for the management of post-HSCT dyslipidemia.
Asunto(s)
Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/métodos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Adulto , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/etiología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Triglicéridos/sangreRESUMEN
OBJECTIVE: To assess the incidence and outcome of clinically significant aspiration pneumonitis in intensive care unit (ICU) overdose patients and to identify its predisposing factors. DESIGN: Retrospective cohort study. SETTING: Medical ICU of an academic tertiary care hospital. PATIENTS: A total of 273 consecutive overdose admissions. MEASUREMENTS AND RESULTS: Clinically significant aspiration pneumonitis was defined as the occurrence of respiratory dysfunction in a patient with a localised infiltrate on chest X-ray within 72 h of admission. In our cohort we identified 47 patients (17%) with aspiration pneumonitis. Importantly, aspiration pneumonitis was associated with a higher incidence of cardiac arrest (6.4 vs 0.9%; p = 0.037) and an increased duration of both ICU stay and overall hospital stay [respectively: median 1 (interquartile range 1-3) vs 1 (1-2), p = 0.025; and median 2 (1-7) vs 1 (1-3), p < 0.001]. In multivariate logistic regression analysis, Glasgow Coma Scale (GCS) score [odds ratio (OR) for each point of GCS 0.8; 95% confidence interval (CI) 0.7-0.9; p = 0.001], ingestion of opiates (OR 4.5; 95% CI 1.7-11.6; p = 0.002), and white blood cell count (WBC) (OR for each increase in WBC of 10(9)/l 1.05; 95% CI 1.0-1.19; p = 0.049) were identified as independent risk factors. CONCLUSIONS: Clinically relevant aspiration pneumonitis is a frequent complication in overdose patients admitted to the ICU. Moreover, aspiration pneumonitis is associated with a higher incidence of cardiac arrest and increased ICU and total in-hospital stay.
Asunto(s)
Sobredosis de Droga/complicaciones , Neumonía por Aspiración/epidemiología , Neumonía por Aspiración/etiología , Adulto , Distribución de Chi-Cuadrado , Femenino , Paro Cardíaco/epidemiología , Paro Cardíaco/etiología , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neumonía por Aspiración/diagnóstico por imagen , Radiografía , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na(+) current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca(2+) cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca(2+) transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly.